When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

 

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

 

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Clomipramine	150-200 mg/d
Fluoxetine	40-80 mg/d
Sertraline	50-200 mg/d
Fluvoxamine	200-300 mg/d
Paroxetine	40-60 mg/d
Citalopram	40-60 mg/d
The higher end of the dosage ranges shown above is preferred if tolerated. All clinical trials with SRIs for OCD should last at least 10 weeks.

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

 

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Likely effective ♦♦	Possibly effective (insufficient data for adequate assessment of efficacy) ♦
Neuroleptics	Clonidine
Busipirone	Fenfluramine
Clonazepam	Nortriptyline
Lithium	Pindolol
	Trazodone
	Tryptophan
Dosage for these agents has not been adequately studied for augmentation of SRIs. Clinical trial length should be for 2 to 8 weeks.

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Drug	Dosage	Duration	Comments
Clonazepam	0.5-5 mg/d	≥ 4 weeks	extrapolated from experience with benzodiazepines for other anxiety disorders and a few reports in OCD
MAO inhibitor	60-90 mg/d	≥ 10 weeks	extrapolated from clinical practice with MAO inhibitors for major depression, panic disorder; tyramine diet must be adhered to; adequate washout of most antidepressants is required before initiating
Buspirone	up to 60 mg/d	≥ 6 weeks	reflecting protocols adopted in clinical trials for OCD

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

 

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

 

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

 

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Clomipramine	150-200 mg/d
Fluoxetine	40-80 mg/d
Sertraline	50-200 mg/d
Fluvoxamine	200-300 mg/d
Paroxetine	40-60 mg/d
Citalopram	40-60 mg/d
The higher end of the dosage ranges shown above is preferred if tolerated. All clinical trials with SRIs for OCD should last at least 10 weeks.

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

 

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Likely effective ♦♦	Possibly effective (insufficient data for adequate assessment of efficacy) ♦
Neuroleptics	Clonidine
Busipirone	Fenfluramine
Clonazepam	Nortriptyline
Lithium	Pindolol
	Trazodone
	Tryptophan
Dosage for these agents has not been adequately studied for augmentation of SRIs. Clinical trial length should be for 2 to 8 weeks.

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Drug	Dosage	Duration	Comments
Clonazepam	0.5-5 mg/d	≥ 4 weeks	extrapolated from experience with benzodiazepines for other anxiety disorders and a few reports in OCD
MAO inhibitor	60-90 mg/d	≥ 10 weeks	extrapolated from clinical practice with MAO inhibitors for major depression, panic disorder; tyramine diet must be adhered to; adequate washout of most antidepressants is required before initiating
Buspirone	up to 60 mg/d	≥ 6 weeks	reflecting protocols adopted in clinical trials for OCD

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

 

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

 

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

 

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Clomipramine	150-200 mg/d
Fluoxetine	40-80 mg/d
Sertraline	50-200 mg/d
Fluvoxamine	200-300 mg/d
Paroxetine	40-60 mg/d
Citalopram	40-60 mg/d
The higher end of the dosage ranges shown above is preferred if tolerated. All clinical trials with SRIs for OCD should last at least 10 weeks.

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

 

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Likely effective ♦♦	Possibly effective (insufficient data for adequate assessment of efficacy) ♦
Neuroleptics	Clonidine
Busipirone	Fenfluramine
Clonazepam	Nortriptyline
Lithium	Pindolol
	Trazodone
	Tryptophan
Dosage for these agents has not been adequately studied for augmentation of SRIs. Clinical trial length should be for 2 to 8 weeks.

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Drug	Dosage	Duration	Comments
Clonazepam	0.5-5 mg/d	≥ 4 weeks	extrapolated from experience with benzodiazepines for other anxiety disorders and a few reports in OCD
MAO inhibitor	60-90 mg/d	≥ 10 weeks	extrapolated from clinical practice with MAO inhibitors for major depression, panic disorder; tyramine diet must be adhered to; adequate washout of most antidepressants is required before initiating
Buspirone	up to 60 mg/d	≥ 6 weeks	reflecting protocols adopted in clinical trials for OCD

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

 

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

 

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

 

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Clomipramine	150-200 mg/d
Fluoxetine	40-80 mg/d
Sertraline	50-200 mg/d
Fluvoxamine	200-300 mg/d
Paroxetine	40-60 mg/d
Citalopram	40-60 mg/d
The higher end of the dosage ranges shown above is preferred if tolerated. All clinical trials with SRIs for OCD should last at least 10 weeks.

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

 

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Likely effective ♦♦	Possibly effective (insufficient data for adequate assessment of efficacy) ♦
Neuroleptics	Clonidine
Busipirone	Fenfluramine
Clonazepam	Nortriptyline
Lithium	Pindolol
	Trazodone
	Tryptophan
Dosage for these agents has not been adequately studied for augmentation of SRIs. Clinical trial length should be for 2 to 8 weeks.

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Drug	Dosage	Duration	Comments
Clonazepam	0.5-5 mg/d	≥ 4 weeks	extrapolated from experience with benzodiazepines for other anxiety disorders and a few reports in OCD
MAO inhibitor	60-90 mg/d	≥ 10 weeks	extrapolated from clinical practice with MAO inhibitors for major depression, panic disorder; tyramine diet must be adhered to; adequate washout of most antidepressants is required before initiating
Buspirone	up to 60 mg/d	≥ 6 weeks	reflecting protocols adopted in clinical trials for OCD

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

 

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

 

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

 

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Clomipramine	150-200 mg/d
Fluoxetine	40-80 mg/d
Sertraline	50-200 mg/d
Fluvoxamine	200-300 mg/d
Paroxetine	40-60 mg/d
Citalopram	40-60 mg/d
The higher end of the dosage ranges shown above is preferred if tolerated. All clinical trials with SRIs for OCD should last at least 10 weeks.

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

 

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Likely effective ♦♦	Possibly effective (insufficient data for adequate assessment of efficacy) ♦
Neuroleptics	Clonidine
Busipirone	Fenfluramine
Clonazepam	Nortriptyline
Lithium	Pindolol
	Trazodone
	Tryptophan
Dosage for these agents has not been adequately studied for augmentation of SRIs. Clinical trial length should be for 2 to 8 weeks.

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Drug	Dosage	Duration	Comments
Clonazepam	0.5-5 mg/d	≥ 4 weeks	extrapolated from experience with benzodiazepines for other anxiety disorders and a few reports in OCD
MAO inhibitor	60-90 mg/d	≥ 10 weeks	extrapolated from clinical practice with MAO inhibitors for major depression, panic disorder; tyramine diet must be adhered to; adequate washout of most antidepressants is required before initiating
Buspirone	up to 60 mg/d	≥ 6 weeks	reflecting protocols adopted in clinical trials for OCD

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

 

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

 

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

 

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Clomipramine	150-200 mg/d
Fluoxetine	40-80 mg/d
Sertraline	50-200 mg/d
Fluvoxamine	200-300 mg/d
Paroxetine	40-60 mg/d
Citalopram	40-60 mg/d
The higher end of the dosage ranges shown above is preferred if tolerated. All clinical trials with SRIs for OCD should last at least 10 weeks.

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

 

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Likely effective ♦♦	Possibly effective (insufficient data for adequate assessment of efficacy) ♦
Neuroleptics	Clonidine
Busipirone	Fenfluramine
Clonazepam	Nortriptyline
Lithium	Pindolol
	Trazodone
	Tryptophan
Dosage for these agents has not been adequately studied for augmentation of SRIs. Clinical trial length should be for 2 to 8 weeks.

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Drug	Dosage	Duration	Comments
Clonazepam	0.5-5 mg/d	≥ 4 weeks	extrapolated from experience with benzodiazepines for other anxiety disorders and a few reports in OCD
MAO inhibitor	60-90 mg/d	≥ 10 weeks	extrapolated from clinical practice with MAO inhibitors for major depression, panic disorder; tyramine diet must be adhered to; adequate washout of most antidepressants is required before initiating
Buspirone	up to 60 mg/d	≥ 6 weeks	reflecting protocols adopted in clinical trials for OCD

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

 

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

Since September 11, America has carried on under a cloud of fear. Though the cloud is lifting, it will not disappear for months or years. The terrorist attacks on New York City and Washington, DC, the resultant military action in Afghanistan, and the anthrax scare—combined with pervasive, nagging doubts about homeland security and the specter of another possible future terrorist attack—all are straining the nation’s collective emotional well-being.

Psychiatrists in America have reported new cases of terror-inspired acute stress disorder, anxiety, depression, and other illnesses, as well as recurrences of posttraumatic stress disorder (PTSD) in existing patients, in the weeks after the recent attacks and the anthrax scare. What will be the impact on psychiatric practice in the coming months and years?

“We are all at ground zero,” says Kenneth S. Thompson, MD, of Pittsburgh, an experienced disaster psychiatrist. But he and other subspecialists have identified four critical areas in which psychiatrists should be prepared:

1. Identifying how terrorist attacks and scares can exacerbate symptoms in patients now in your practice;
2. Diagnosing PTSD among comorbid conditions present in existing or new patients;
3. Treating—and avoiding over-treatment—of patients with acute stress disorder and PTSD;
4. Managing fear in your communities—in response to the Sept. 11 attacks, to the anthrax scare, or in anticipation of an impending catastrophe.

To bring you this special report, the editors of Current Psychiatry have reviewed the literature and interviewed psychiatrists nationwide and in countries such as Israel and Colombia, where terrorism has been a fact of life for years (see “PTSD lessons from Israel, Colombia,”).

Terror and your patients

Which symptoms are you most likely to see in existing patients subsequent to recent events? In the weeks following the Sept. 11 attacks, psychiatrists reported the most commonly seen symptoms as increased anxiety and worsened depression. Sleep disturbances, agoraphobia, suicidality, and severe reactions among patients with personality disorders also were reported.

Patients with previous PTSD or exposure to trauma face a high risk of new or recurrent PTSD in the wake of Sept. 11 than do those not previously exposed to trauma.¹ War veterans with prior posttraumatic symptoms have been particularly prone to recurrent PTSD after the attacks. James Allen, MD, of the Department of Psychiatry and Behavioral Sciences at the University of Oklahoma Health Sciences Center, calls this the “additive effect”: patients traumatized by military service in Vietnam experience a recurrence after seeing a major disaster or atrocity. Dr. Allen, who was extensively involved with Oklahoma City’s disaster psychiatry effort after the 1995 bombing there, recalls seeing patients who were traumatized in Vietnam suffer a recurrence after the Alfred P. Murrah Building attack, and then another relapse after Sept. 11.

“The Sept. 11 attacks were very similar to the war for them,” says Juan Corvalan, MD, of the PTSD Unit of the St. Louis Veterans Administration Medical Center, referring to the numerous war veterans he treated after the atrocities. “Seeing it on TV triggered many memories.” By early November, however, many who experienced recurrent PTSD had returned to their pre-Sept. 11 mental states.

Craig Katz, MD, director of emergency psychiatry services at New York’s Mount Sinai Medical Center, says that a patient’s psychiatric history is crucial to determining risk for PTSD or other terror-related sequelae:

“You can recognize that a given person is at high risk for PTSD post-trauma, based on any combination of these factors—having a psychiatric history, past trauma, high exposure to the event, psychosocial problems pre-disaster, or lack of supports post-disaster.”

The clinical interview is a vital tool in assessing patients with suspected PTSD or posttraumatic sequelae, says Arieh Shalev, MD, of the department of psychiatry at Hadassah University Hospital in Jerusalem, Israel. “It provides the opportunity to discuss the traumatic event with the patient, and to listen to his or her perceptions of the event and its effects” in order to carefully appraise the patient’s symptoms.²

The guidelines set forth in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) remain the gold standard for confirming a diagnosis of PTSD and discerning long-term posttraumatic sequelae from temporary acute stress disorder (Box 1). The guidelines have proved far from foolproof, however, and the existence of psychiatric comorbidities often clouds the picture.

Box 1

 

Differential diagnosis of PTSD

Patients with PTSD are more likely to have substantial psychiatric comorbidity than are those without the disorder.³ Possible reasons include suspected self-medication of PTSD symptoms, particularly among patients with substance abuse, and the possible overreporting of symptoms by patients. Psychiatrists should maintain a high level of suspicion for PTSD when managing a new or existing patient with psychopathology.

Citing data from the National Comorbidity Study of the Institute for Social Research at the University of Michigan, Kessler and others in 1995 noted that more than 80 percent of individuals with PTSD meet criteria for at least one other psychiatric diagnosis. Roughly half of PTSD sufferers met criteria for three or more comorbidities.³

Kathleen Brady, MD, professor of psychiatry at the Medical University of South Carolina in Charleston, noted in a 1997 study that affective disorders, other anxiety disorders, somatization, substance abuse, and dissociative disorders are common comorbidities of PTSD.⁵ Dr. Shalev and colleagues in one study found that a history of major depressive disorder may increase the severity of posttraumatic morbidity.⁶ Dr. Brady and others also have found that PTSD patients with a comorbid substance abuse disorder experience severe PTSD symptoms while in a withdrawal state.⁷

Box 2

PTSD often is overlooked in the presence of other psychiatric diagnoses. Meuser et al in 1998 studied 275 patients with schizophrenia and bipolar disorder. As many as 98 percent of patients reported lifetime exposure to at least one traumatic event. The researchers found diagnosable PTSD in 119 (43 %) of the subjects, but only three (2%) had the diagnosis in their charts.⁸

In a later study, Dr. Brady and others cited substantial symptom overlap between PTSD and other psychiatric diagnoses, particularly major depressive disorder. This can contribute to underdiagnosis of PTSD, the researchers found.⁷ (Box 2).

Box 3

Dr. Brady recommends that psychiatrists and primary care physicians routinely screen patients for exposure to traumatic events. Ask patients specifically about their reaction to such events and encourage them to talk about it. Patients often feel either guilty or embarrassed about the traumatic event, or do not believe it affects their presenting complaints, she notes. Other approaches may be needed to identify the risk of PTSD in children (Box 3).

 

Identifying a traumatic event of an extreme nature, for example, a life-threatening experience, is key to diagnosing PTSD in the presence of comorbidities, Dr. Corvalan says. “Some of the symptoms—such as avoidance, numbing, and increased arousal—are present in other disorders and may have occurred before exposure to the traumatic event.” If they did, he says, PTSD is ruled out.

Gauging the extent of the patient’s exposure to the traumatic event is critical to determining the likelihood of PTSD onset. Dr. Allen, of Oklahoma City, points to studies that show that the closer and longer the patient has been exposed to a catastrophic event, the more likely he or she will develop PTSD.^9,10

Julia Frank, MD, associate professor and director of student education and psychiatry at George Washington University in Washington, DC, suggests screening for symptoms that are unique to PTSD as stated in the DSM-IV, such as nightmares, difficulty remembering the traumatic event, and extreme reactions to reminders of the trauma. She also proposes analyzing the past event and the patient’s reaction to it to confirm that it is a source of trauma.

Patients with PTSD symptoms are easily startled by loud or piercing noises. Dr. Shalev says this characteristic sets true PTSD cases apart from other psychopathology, particularly depression. In one study, Israeli combat veterans with PTSD exhibited a more pronounced heart rate and skin conductance when exposed to auditory stimuli than did combat veterans with no PTSD symptoms.¹¹

Drs. Allen and Frank note that patients who have anthrax-related fears and no prior PTSD symptoms are not likely to develop PTSD. They may, however, manifest symptoms of chronic fatigue, fibromyalgia, and generalized anxiety disorder. Patients may be jumpy, intense, or lethargic, with autonomic instability and rapid heart rate. They may feel alienated and mistrustful of the government. A nonspecific stress disorder and mixed anxiety depression are other possible effects.

Who to treat—and how

Psychiatrists nationwide have reported increased patient presentations after the Sept. 11 attacks and throughout the anthrax scare. Studies conducted after the Oklahoma City bombing also suggest that psychiatrists could be seeing more patients in the coming months.^12,13 As caseloads increase, so do the questions about who to treat, how, and how to avoid the possibility of overtreatment.

 

“In order to provide effective care to our patients it is necessary to have clear ideas on how to follow criteria for diagnosis and as a consequence for treatment,” Dr. Corvalan says. “The field at times is confusing; patients do not always follow the diagnostic criteria. The needs of the moment, limitations of recourses, intensity and variety of symptoms, urgency of the situation, etc., all conspire to make the job more difficult.”

Patients with anthrax-related anxiety should be encouraged to “try to function as normally as possible and keep an open communication with peers and those who they look to for information,” Dr. Frank notes. Dr. Allen adds that his patients with anthrax-inspired stress have responded well to breathing, meditation and other relaxation techniques.

Treatment of patients who are severely traumatized and exhibit true PTSD symptoms will vary based on severity of exposure, history of prior PTSD, and existence of comorbidities. A combination of pharmacological and psychosocial therapy is the common first-line treatment.

The selective serotonin reuptake inhibitor (SSRI) sertraline is specifically indicated for treating confirmed PTSD symptoms, and several studies have documented the agent’s effectiveness for this use.^14,15 Dr. Frank recommends dosages between 50 and 200 mg/d depending on the patient’s body weight or complaint of side effects (e.g., diarrhea, nausea, or sexual dysfunction). Other SSRIs, as well as tricyclics and MAO inhibitors, are alternatives. Fluoxetine, amitriptyline, phenelzine, and imipramine have all been found more effective than a placebo;^16-18 paroxetine also has been shown effective in specific populations.¹⁹

Box 4

Benzodiazapenes also may be prescribed to manage PTSD symptoms. Patients should be counseled against taking these sedating agents in the daytime, however, as they can lead to fogginess, detachment, and trouble functioning.

Assessing the patient’s available social support also is crucial to PTSD treatment. “Do patients talk to other people about the event?” Dr. Frank asks. “Are they trying to get back to a daily routine? Can they make sense of this experience? Are they incorporating the event into a world view?”

Dr. Thompson, the Pittsburgh disaster psychiatrist, agrees. Psychiatrists should encourage their patients to talk more about their trauma and how fear is affecting their lives. “We don’t discuss with our trauma patients as much as we might what the experience has been like for them,” he says.

Small-group therapy is the most conducive approach to psychotherapy for PTSD, according to Dr. Frank, although individual counseling can work in many cases. Several studies have found group therapy effective,^20,21 and 12-step group therapy has shown promise in PTSD patients with comorbid substance abuse disorder.²²

Managing fear

Just as people grieve and confront death in stages, Dr. Thompson, who helped coordinate Oklahoma City’s disaster psychiatry effort, has discovered that the public usually employs a similar subconscious process to cope with a traumatic event (Box 4).

 

But Americans have had no time to recover. As U.S. troops seek justice in Afghanistan, back home people grapple with the threat of anthrax contamination and the prospect of another terrorist attack. The ominously enhanced presence of security at airports, major bridges, sporting and entertainment events, and in other aspects of everyday life, has further fueled the sensation that all is not right.

“The September 11 tragedy brings trauma home,” adds Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. “The anthrax scare and the Nov. 12 plane crash of American Airlines Flight 587 only further remind people of their vulnerability and fears. If the anthrax scare were an accident, people would have been relieved. Since the plane crash was ruled an accident, it has offered people a chance to feel more in control. Accidents can be fixed with better maintenance. Terrorism cannot.”

Dr. Katz of New York City and other disaster psychiatrists are urging their colleagues to help manage public fear by reaching out through community efforts.

Dr. Katz is president of the volunteer group Disaster Psychiatry Outreach, which helped coordinate the city’s post-Sept. 11 trauma psychiatry effort. Visitors waiting at New York’s Family Assistance Center, a referral and help center for people who lost family and friends in the World Trade Center attack, were approached by Dr. Katz and other colleagues to let them know that psychiatric services were available if needed. By doing this, he says, Disaster Psychiatry Outreach clinicians have identified, treated, and referred scores of patients with terror-related stress who otherwise would have gone untreated.

Joseph Dorzab, MD, of the Holt-Krock Clinic in Fort Smith, Ark., also has offered his services. Members of his clinic’s psychiatry department have made several TV appearances, and have given and coordinated area lectures. Working with the local mental health association, the department also is starting a community forum called Mental Health Mondays, an open discussion group with coffee and cookies at a local coffee shop.

In Pittsburgh, Dr. Thompson is encouraging psychiatrists to educate their communities about how traumatic events affect the public. He proposes:

• Staging community meetings to brief religious and other leaders on how to manage traumatized people;
• Informing local news editors about the nature of psychiatric disorders;
• Instructing school administrators about detecting signs of distress in children;
• Contacting local government officials to offer input in devising the town’s emergency response plan.

Psychiatrists also can educate themselves about managing public trauma, thanks to scores of studies that have been done in recent years following major man-made and natural disasters, from Mount St. Helens and Hurricane Andrew, to Chernobyl and the Yom Kippur War. Dr. Thompson urges psychiatrists to seek out the papers of prominent leaders in trauma-related psychiatry, mentioning studies by Carol North, MD, Betty Pfefferbaum, MD, and Robert Ursano, MD, as examples. Other sources include the Web sites of the American Psychiatric Association and National Center for PTSD. (See Related Resources.)

In the end, psychiatrists have been well primed for dealing with public disaster—just by treating individual patients whose psychiatric disorders emanated from everyday life, Dr. Thompson says. “Psychiatrists know more about trauma than they recognize.”

Related resources

• National Center for PTSD Web site
• National Institute of Mental Health:
• Linenthal EJ. The Unfinished Bombing: Oklahoma City in American Memory. Oxford University Press, 2001.
• Norwood AE, Ursano RJ, Fullerton CS. Disaster psychiatry: principles of practice. Psychiatr Q. 2000; 71(3):207-226.
• American Psychiatric Association Web site:
• The Psychiatric Training Manual for Teachers and Mental Health Professionals

Drug brand names

• Amitriptyline • Elavil
• Bupropion • Wellbutrin
• Fluoxetine • Prozac
• Imipramine • Tofranil
• Paroxetine • Paxil
• Phenelzine • Nardil
• Sertraline • Zoloft

Since September 11, America has carried on under a cloud of fear. Though the cloud is lifting, it will not disappear for months or years. The terrorist attacks on New York City and Washington, DC, the resultant military action in Afghanistan, and the anthrax scare—combined with pervasive, nagging doubts about homeland security and the specter of another possible future terrorist attack—all are straining the nation’s collective emotional well-being.

Psychiatrists in America have reported new cases of terror-inspired acute stress disorder, anxiety, depression, and other illnesses, as well as recurrences of posttraumatic stress disorder (PTSD) in existing patients, in the weeks after the recent attacks and the anthrax scare. What will be the impact on psychiatric practice in the coming months and years?

“We are all at ground zero,” says Kenneth S. Thompson, MD, of Pittsburgh, an experienced disaster psychiatrist. But he and other subspecialists have identified four critical areas in which psychiatrists should be prepared:

1. Identifying how terrorist attacks and scares can exacerbate symptoms in patients now in your practice;
2. Diagnosing PTSD among comorbid conditions present in existing or new patients;
3. Treating—and avoiding over-treatment—of patients with acute stress disorder and PTSD;
4. Managing fear in your communities—in response to the Sept. 11 attacks, to the anthrax scare, or in anticipation of an impending catastrophe.

To bring you this special report, the editors of Current Psychiatry have reviewed the literature and interviewed psychiatrists nationwide and in countries such as Israel and Colombia, where terrorism has been a fact of life for years (see “PTSD lessons from Israel, Colombia,”).

Terror and your patients

Which symptoms are you most likely to see in existing patients subsequent to recent events? In the weeks following the Sept. 11 attacks, psychiatrists reported the most commonly seen symptoms as increased anxiety and worsened depression. Sleep disturbances, agoraphobia, suicidality, and severe reactions among patients with personality disorders also were reported.

Patients with previous PTSD or exposure to trauma face a high risk of new or recurrent PTSD in the wake of Sept. 11 than do those not previously exposed to trauma.¹ War veterans with prior posttraumatic symptoms have been particularly prone to recurrent PTSD after the attacks. James Allen, MD, of the Department of Psychiatry and Behavioral Sciences at the University of Oklahoma Health Sciences Center, calls this the “additive effect”: patients traumatized by military service in Vietnam experience a recurrence after seeing a major disaster or atrocity. Dr. Allen, who was extensively involved with Oklahoma City’s disaster psychiatry effort after the 1995 bombing there, recalls seeing patients who were traumatized in Vietnam suffer a recurrence after the Alfred P. Murrah Building attack, and then another relapse after Sept. 11.

“The Sept. 11 attacks were very similar to the war for them,” says Juan Corvalan, MD, of the PTSD Unit of the St. Louis Veterans Administration Medical Center, referring to the numerous war veterans he treated after the atrocities. “Seeing it on TV triggered many memories.” By early November, however, many who experienced recurrent PTSD had returned to their pre-Sept. 11 mental states.

Craig Katz, MD, director of emergency psychiatry services at New York’s Mount Sinai Medical Center, says that a patient’s psychiatric history is crucial to determining risk for PTSD or other terror-related sequelae:

“You can recognize that a given person is at high risk for PTSD post-trauma, based on any combination of these factors—having a psychiatric history, past trauma, high exposure to the event, psychosocial problems pre-disaster, or lack of supports post-disaster.”

The clinical interview is a vital tool in assessing patients with suspected PTSD or posttraumatic sequelae, says Arieh Shalev, MD, of the department of psychiatry at Hadassah University Hospital in Jerusalem, Israel. “It provides the opportunity to discuss the traumatic event with the patient, and to listen to his or her perceptions of the event and its effects” in order to carefully appraise the patient’s symptoms.²

The guidelines set forth in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) remain the gold standard for confirming a diagnosis of PTSD and discerning long-term posttraumatic sequelae from temporary acute stress disorder (Box 1). The guidelines have proved far from foolproof, however, and the existence of psychiatric comorbidities often clouds the picture.

Box 1

 

Differential diagnosis of PTSD

Patients with PTSD are more likely to have substantial psychiatric comorbidity than are those without the disorder.³ Possible reasons include suspected self-medication of PTSD symptoms, particularly among patients with substance abuse, and the possible overreporting of symptoms by patients. Psychiatrists should maintain a high level of suspicion for PTSD when managing a new or existing patient with psychopathology.

Citing data from the National Comorbidity Study of the Institute for Social Research at the University of Michigan, Kessler and others in 1995 noted that more than 80 percent of individuals with PTSD meet criteria for at least one other psychiatric diagnosis. Roughly half of PTSD sufferers met criteria for three or more comorbidities.³

Kathleen Brady, MD, professor of psychiatry at the Medical University of South Carolina in Charleston, noted in a 1997 study that affective disorders, other anxiety disorders, somatization, substance abuse, and dissociative disorders are common comorbidities of PTSD.⁵ Dr. Shalev and colleagues in one study found that a history of major depressive disorder may increase the severity of posttraumatic morbidity.⁶ Dr. Brady and others also have found that PTSD patients with a comorbid substance abuse disorder experience severe PTSD symptoms while in a withdrawal state.⁷

Box 2

PTSD often is overlooked in the presence of other psychiatric diagnoses. Meuser et al in 1998 studied 275 patients with schizophrenia and bipolar disorder. As many as 98 percent of patients reported lifetime exposure to at least one traumatic event. The researchers found diagnosable PTSD in 119 (43 %) of the subjects, but only three (2%) had the diagnosis in their charts.⁸

In a later study, Dr. Brady and others cited substantial symptom overlap between PTSD and other psychiatric diagnoses, particularly major depressive disorder. This can contribute to underdiagnosis of PTSD, the researchers found.⁷ (Box 2).

Box 3

Dr. Brady recommends that psychiatrists and primary care physicians routinely screen patients for exposure to traumatic events. Ask patients specifically about their reaction to such events and encourage them to talk about it. Patients often feel either guilty or embarrassed about the traumatic event, or do not believe it affects their presenting complaints, she notes. Other approaches may be needed to identify the risk of PTSD in children (Box 3).

 

Identifying a traumatic event of an extreme nature, for example, a life-threatening experience, is key to diagnosing PTSD in the presence of comorbidities, Dr. Corvalan says. “Some of the symptoms—such as avoidance, numbing, and increased arousal—are present in other disorders and may have occurred before exposure to the traumatic event.” If they did, he says, PTSD is ruled out.

Gauging the extent of the patient’s exposure to the traumatic event is critical to determining the likelihood of PTSD onset. Dr. Allen, of Oklahoma City, points to studies that show that the closer and longer the patient has been exposed to a catastrophic event, the more likely he or she will develop PTSD.^9,10

Julia Frank, MD, associate professor and director of student education and psychiatry at George Washington University in Washington, DC, suggests screening for symptoms that are unique to PTSD as stated in the DSM-IV, such as nightmares, difficulty remembering the traumatic event, and extreme reactions to reminders of the trauma. She also proposes analyzing the past event and the patient’s reaction to it to confirm that it is a source of trauma.

Patients with PTSD symptoms are easily startled by loud or piercing noises. Dr. Shalev says this characteristic sets true PTSD cases apart from other psychopathology, particularly depression. In one study, Israeli combat veterans with PTSD exhibited a more pronounced heart rate and skin conductance when exposed to auditory stimuli than did combat veterans with no PTSD symptoms.¹¹

Drs. Allen and Frank note that patients who have anthrax-related fears and no prior PTSD symptoms are not likely to develop PTSD. They may, however, manifest symptoms of chronic fatigue, fibromyalgia, and generalized anxiety disorder. Patients may be jumpy, intense, or lethargic, with autonomic instability and rapid heart rate. They may feel alienated and mistrustful of the government. A nonspecific stress disorder and mixed anxiety depression are other possible effects.

Who to treat—and how

Psychiatrists nationwide have reported increased patient presentations after the Sept. 11 attacks and throughout the anthrax scare. Studies conducted after the Oklahoma City bombing also suggest that psychiatrists could be seeing more patients in the coming months.^12,13 As caseloads increase, so do the questions about who to treat, how, and how to avoid the possibility of overtreatment.

 

“In order to provide effective care to our patients it is necessary to have clear ideas on how to follow criteria for diagnosis and as a consequence for treatment,” Dr. Corvalan says. “The field at times is confusing; patients do not always follow the diagnostic criteria. The needs of the moment, limitations of recourses, intensity and variety of symptoms, urgency of the situation, etc., all conspire to make the job more difficult.”

Patients with anthrax-related anxiety should be encouraged to “try to function as normally as possible and keep an open communication with peers and those who they look to for information,” Dr. Frank notes. Dr. Allen adds that his patients with anthrax-inspired stress have responded well to breathing, meditation and other relaxation techniques.

Treatment of patients who are severely traumatized and exhibit true PTSD symptoms will vary based on severity of exposure, history of prior PTSD, and existence of comorbidities. A combination of pharmacological and psychosocial therapy is the common first-line treatment.

The selective serotonin reuptake inhibitor (SSRI) sertraline is specifically indicated for treating confirmed PTSD symptoms, and several studies have documented the agent’s effectiveness for this use.^14,15 Dr. Frank recommends dosages between 50 and 200 mg/d depending on the patient’s body weight or complaint of side effects (e.g., diarrhea, nausea, or sexual dysfunction). Other SSRIs, as well as tricyclics and MAO inhibitors, are alternatives. Fluoxetine, amitriptyline, phenelzine, and imipramine have all been found more effective than a placebo;^16-18 paroxetine also has been shown effective in specific populations.¹⁹

Box 4

Benzodiazapenes also may be prescribed to manage PTSD symptoms. Patients should be counseled against taking these sedating agents in the daytime, however, as they can lead to fogginess, detachment, and trouble functioning.

Assessing the patient’s available social support also is crucial to PTSD treatment. “Do patients talk to other people about the event?” Dr. Frank asks. “Are they trying to get back to a daily routine? Can they make sense of this experience? Are they incorporating the event into a world view?”

Dr. Thompson, the Pittsburgh disaster psychiatrist, agrees. Psychiatrists should encourage their patients to talk more about their trauma and how fear is affecting their lives. “We don’t discuss with our trauma patients as much as we might what the experience has been like for them,” he says.

Small-group therapy is the most conducive approach to psychotherapy for PTSD, according to Dr. Frank, although individual counseling can work in many cases. Several studies have found group therapy effective,^20,21 and 12-step group therapy has shown promise in PTSD patients with comorbid substance abuse disorder.²²

Managing fear

Just as people grieve and confront death in stages, Dr. Thompson, who helped coordinate Oklahoma City’s disaster psychiatry effort, has discovered that the public usually employs a similar subconscious process to cope with a traumatic event (Box 4).

 

But Americans have had no time to recover. As U.S. troops seek justice in Afghanistan, back home people grapple with the threat of anthrax contamination and the prospect of another terrorist attack. The ominously enhanced presence of security at airports, major bridges, sporting and entertainment events, and in other aspects of everyday life, has further fueled the sensation that all is not right.

“The September 11 tragedy brings trauma home,” adds Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. “The anthrax scare and the Nov. 12 plane crash of American Airlines Flight 587 only further remind people of their vulnerability and fears. If the anthrax scare were an accident, people would have been relieved. Since the plane crash was ruled an accident, it has offered people a chance to feel more in control. Accidents can be fixed with better maintenance. Terrorism cannot.”

Dr. Katz of New York City and other disaster psychiatrists are urging their colleagues to help manage public fear by reaching out through community efforts.

Dr. Katz is president of the volunteer group Disaster Psychiatry Outreach, which helped coordinate the city’s post-Sept. 11 trauma psychiatry effort. Visitors waiting at New York’s Family Assistance Center, a referral and help center for people who lost family and friends in the World Trade Center attack, were approached by Dr. Katz and other colleagues to let them know that psychiatric services were available if needed. By doing this, he says, Disaster Psychiatry Outreach clinicians have identified, treated, and referred scores of patients with terror-related stress who otherwise would have gone untreated.

Joseph Dorzab, MD, of the Holt-Krock Clinic in Fort Smith, Ark., also has offered his services. Members of his clinic’s psychiatry department have made several TV appearances, and have given and coordinated area lectures. Working with the local mental health association, the department also is starting a community forum called Mental Health Mondays, an open discussion group with coffee and cookies at a local coffee shop.

In Pittsburgh, Dr. Thompson is encouraging psychiatrists to educate their communities about how traumatic events affect the public. He proposes:

• Staging community meetings to brief religious and other leaders on how to manage traumatized people;
• Informing local news editors about the nature of psychiatric disorders;
• Instructing school administrators about detecting signs of distress in children;
• Contacting local government officials to offer input in devising the town’s emergency response plan.

Psychiatrists also can educate themselves about managing public trauma, thanks to scores of studies that have been done in recent years following major man-made and natural disasters, from Mount St. Helens and Hurricane Andrew, to Chernobyl and the Yom Kippur War. Dr. Thompson urges psychiatrists to seek out the papers of prominent leaders in trauma-related psychiatry, mentioning studies by Carol North, MD, Betty Pfefferbaum, MD, and Robert Ursano, MD, as examples. Other sources include the Web sites of the American Psychiatric Association and National Center for PTSD. (See Related Resources.)

In the end, psychiatrists have been well primed for dealing with public disaster—just by treating individual patients whose psychiatric disorders emanated from everyday life, Dr. Thompson says. “Psychiatrists know more about trauma than they recognize.”

Related resources

• National Center for PTSD Web site
• National Institute of Mental Health:
• Linenthal EJ. The Unfinished Bombing: Oklahoma City in American Memory. Oxford University Press, 2001.
• Norwood AE, Ursano RJ, Fullerton CS. Disaster psychiatry: principles of practice. Psychiatr Q. 2000; 71(3):207-226.
• American Psychiatric Association Web site:
• The Psychiatric Training Manual for Teachers and Mental Health Professionals

Drug brand names

• Amitriptyline • Elavil
• Bupropion • Wellbutrin
• Fluoxetine • Prozac
• Imipramine • Tofranil
• Paroxetine • Paxil
• Phenelzine • Nardil
• Sertraline • Zoloft

Since September 11, America has carried on under a cloud of fear. Though the cloud is lifting, it will not disappear for months or years. The terrorist attacks on New York City and Washington, DC, the resultant military action in Afghanistan, and the anthrax scare—combined with pervasive, nagging doubts about homeland security and the specter of another possible future terrorist attack—all are straining the nation’s collective emotional well-being.

Psychiatrists in America have reported new cases of terror-inspired acute stress disorder, anxiety, depression, and other illnesses, as well as recurrences of posttraumatic stress disorder (PTSD) in existing patients, in the weeks after the recent attacks and the anthrax scare. What will be the impact on psychiatric practice in the coming months and years?

“We are all at ground zero,” says Kenneth S. Thompson, MD, of Pittsburgh, an experienced disaster psychiatrist. But he and other subspecialists have identified four critical areas in which psychiatrists should be prepared:

1. Identifying how terrorist attacks and scares can exacerbate symptoms in patients now in your practice;
2. Diagnosing PTSD among comorbid conditions present in existing or new patients;
3. Treating—and avoiding over-treatment—of patients with acute stress disorder and PTSD;
4. Managing fear in your communities—in response to the Sept. 11 attacks, to the anthrax scare, or in anticipation of an impending catastrophe.

To bring you this special report, the editors of Current Psychiatry have reviewed the literature and interviewed psychiatrists nationwide and in countries such as Israel and Colombia, where terrorism has been a fact of life for years (see “PTSD lessons from Israel, Colombia,”).

Terror and your patients

Which symptoms are you most likely to see in existing patients subsequent to recent events? In the weeks following the Sept. 11 attacks, psychiatrists reported the most commonly seen symptoms as increased anxiety and worsened depression. Sleep disturbances, agoraphobia, suicidality, and severe reactions among patients with personality disorders also were reported.

Patients with previous PTSD or exposure to trauma face a high risk of new or recurrent PTSD in the wake of Sept. 11 than do those not previously exposed to trauma.¹ War veterans with prior posttraumatic symptoms have been particularly prone to recurrent PTSD after the attacks. James Allen, MD, of the Department of Psychiatry and Behavioral Sciences at the University of Oklahoma Health Sciences Center, calls this the “additive effect”: patients traumatized by military service in Vietnam experience a recurrence after seeing a major disaster or atrocity. Dr. Allen, who was extensively involved with Oklahoma City’s disaster psychiatry effort after the 1995 bombing there, recalls seeing patients who were traumatized in Vietnam suffer a recurrence after the Alfred P. Murrah Building attack, and then another relapse after Sept. 11.

“The Sept. 11 attacks were very similar to the war for them,” says Juan Corvalan, MD, of the PTSD Unit of the St. Louis Veterans Administration Medical Center, referring to the numerous war veterans he treated after the atrocities. “Seeing it on TV triggered many memories.” By early November, however, many who experienced recurrent PTSD had returned to their pre-Sept. 11 mental states.

Craig Katz, MD, director of emergency psychiatry services at New York’s Mount Sinai Medical Center, says that a patient’s psychiatric history is crucial to determining risk for PTSD or other terror-related sequelae:

“You can recognize that a given person is at high risk for PTSD post-trauma, based on any combination of these factors—having a psychiatric history, past trauma, high exposure to the event, psychosocial problems pre-disaster, or lack of supports post-disaster.”

The clinical interview is a vital tool in assessing patients with suspected PTSD or posttraumatic sequelae, says Arieh Shalev, MD, of the department of psychiatry at Hadassah University Hospital in Jerusalem, Israel. “It provides the opportunity to discuss the traumatic event with the patient, and to listen to his or her perceptions of the event and its effects” in order to carefully appraise the patient’s symptoms.²

The guidelines set forth in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) remain the gold standard for confirming a diagnosis of PTSD and discerning long-term posttraumatic sequelae from temporary acute stress disorder (Box 1). The guidelines have proved far from foolproof, however, and the existence of psychiatric comorbidities often clouds the picture.

Box 1

 

Differential diagnosis of PTSD

Patients with PTSD are more likely to have substantial psychiatric comorbidity than are those without the disorder.³ Possible reasons include suspected self-medication of PTSD symptoms, particularly among patients with substance abuse, and the possible overreporting of symptoms by patients. Psychiatrists should maintain a high level of suspicion for PTSD when managing a new or existing patient with psychopathology.

Citing data from the National Comorbidity Study of the Institute for Social Research at the University of Michigan, Kessler and others in 1995 noted that more than 80 percent of individuals with PTSD meet criteria for at least one other psychiatric diagnosis. Roughly half of PTSD sufferers met criteria for three or more comorbidities.³

Kathleen Brady, MD, professor of psychiatry at the Medical University of South Carolina in Charleston, noted in a 1997 study that affective disorders, other anxiety disorders, somatization, substance abuse, and dissociative disorders are common comorbidities of PTSD.⁵ Dr. Shalev and colleagues in one study found that a history of major depressive disorder may increase the severity of posttraumatic morbidity.⁶ Dr. Brady and others also have found that PTSD patients with a comorbid substance abuse disorder experience severe PTSD symptoms while in a withdrawal state.⁷

Box 2

PTSD often is overlooked in the presence of other psychiatric diagnoses. Meuser et al in 1998 studied 275 patients with schizophrenia and bipolar disorder. As many as 98 percent of patients reported lifetime exposure to at least one traumatic event. The researchers found diagnosable PTSD in 119 (43 %) of the subjects, but only three (2%) had the diagnosis in their charts.⁸

In a later study, Dr. Brady and others cited substantial symptom overlap between PTSD and other psychiatric diagnoses, particularly major depressive disorder. This can contribute to underdiagnosis of PTSD, the researchers found.⁷ (Box 2).

Box 3

Dr. Brady recommends that psychiatrists and primary care physicians routinely screen patients for exposure to traumatic events. Ask patients specifically about their reaction to such events and encourage them to talk about it. Patients often feel either guilty or embarrassed about the traumatic event, or do not believe it affects their presenting complaints, she notes. Other approaches may be needed to identify the risk of PTSD in children (Box 3).

 

Identifying a traumatic event of an extreme nature, for example, a life-threatening experience, is key to diagnosing PTSD in the presence of comorbidities, Dr. Corvalan says. “Some of the symptoms—such as avoidance, numbing, and increased arousal—are present in other disorders and may have occurred before exposure to the traumatic event.” If they did, he says, PTSD is ruled out.

Gauging the extent of the patient’s exposure to the traumatic event is critical to determining the likelihood of PTSD onset. Dr. Allen, of Oklahoma City, points to studies that show that the closer and longer the patient has been exposed to a catastrophic event, the more likely he or she will develop PTSD.^9,10

Julia Frank, MD, associate professor and director of student education and psychiatry at George Washington University in Washington, DC, suggests screening for symptoms that are unique to PTSD as stated in the DSM-IV, such as nightmares, difficulty remembering the traumatic event, and extreme reactions to reminders of the trauma. She also proposes analyzing the past event and the patient’s reaction to it to confirm that it is a source of trauma.

Patients with PTSD symptoms are easily startled by loud or piercing noises. Dr. Shalev says this characteristic sets true PTSD cases apart from other psychopathology, particularly depression. In one study, Israeli combat veterans with PTSD exhibited a more pronounced heart rate and skin conductance when exposed to auditory stimuli than did combat veterans with no PTSD symptoms.¹¹

Drs. Allen and Frank note that patients who have anthrax-related fears and no prior PTSD symptoms are not likely to develop PTSD. They may, however, manifest symptoms of chronic fatigue, fibromyalgia, and generalized anxiety disorder. Patients may be jumpy, intense, or lethargic, with autonomic instability and rapid heart rate. They may feel alienated and mistrustful of the government. A nonspecific stress disorder and mixed anxiety depression are other possible effects.

Who to treat—and how

Psychiatrists nationwide have reported increased patient presentations after the Sept. 11 attacks and throughout the anthrax scare. Studies conducted after the Oklahoma City bombing also suggest that psychiatrists could be seeing more patients in the coming months.^12,13 As caseloads increase, so do the questions about who to treat, how, and how to avoid the possibility of overtreatment.

 

“In order to provide effective care to our patients it is necessary to have clear ideas on how to follow criteria for diagnosis and as a consequence for treatment,” Dr. Corvalan says. “The field at times is confusing; patients do not always follow the diagnostic criteria. The needs of the moment, limitations of recourses, intensity and variety of symptoms, urgency of the situation, etc., all conspire to make the job more difficult.”

Patients with anthrax-related anxiety should be encouraged to “try to function as normally as possible and keep an open communication with peers and those who they look to for information,” Dr. Frank notes. Dr. Allen adds that his patients with anthrax-inspired stress have responded well to breathing, meditation and other relaxation techniques.

Treatment of patients who are severely traumatized and exhibit true PTSD symptoms will vary based on severity of exposure, history of prior PTSD, and existence of comorbidities. A combination of pharmacological and psychosocial therapy is the common first-line treatment.

The selective serotonin reuptake inhibitor (SSRI) sertraline is specifically indicated for treating confirmed PTSD symptoms, and several studies have documented the agent’s effectiveness for this use.^14,15 Dr. Frank recommends dosages between 50 and 200 mg/d depending on the patient’s body weight or complaint of side effects (e.g., diarrhea, nausea, or sexual dysfunction). Other SSRIs, as well as tricyclics and MAO inhibitors, are alternatives. Fluoxetine, amitriptyline, phenelzine, and imipramine have all been found more effective than a placebo;^16-18 paroxetine also has been shown effective in specific populations.¹⁹

Box 4

Benzodiazapenes also may be prescribed to manage PTSD symptoms. Patients should be counseled against taking these sedating agents in the daytime, however, as they can lead to fogginess, detachment, and trouble functioning.

Assessing the patient’s available social support also is crucial to PTSD treatment. “Do patients talk to other people about the event?” Dr. Frank asks. “Are they trying to get back to a daily routine? Can they make sense of this experience? Are they incorporating the event into a world view?”

Dr. Thompson, the Pittsburgh disaster psychiatrist, agrees. Psychiatrists should encourage their patients to talk more about their trauma and how fear is affecting their lives. “We don’t discuss with our trauma patients as much as we might what the experience has been like for them,” he says.

Small-group therapy is the most conducive approach to psychotherapy for PTSD, according to Dr. Frank, although individual counseling can work in many cases. Several studies have found group therapy effective,^20,21 and 12-step group therapy has shown promise in PTSD patients with comorbid substance abuse disorder.²²

Managing fear

Just as people grieve and confront death in stages, Dr. Thompson, who helped coordinate Oklahoma City’s disaster psychiatry effort, has discovered that the public usually employs a similar subconscious process to cope with a traumatic event (Box 4).

 

But Americans have had no time to recover. As U.S. troops seek justice in Afghanistan, back home people grapple with the threat of anthrax contamination and the prospect of another terrorist attack. The ominously enhanced presence of security at airports, major bridges, sporting and entertainment events, and in other aspects of everyday life, has further fueled the sensation that all is not right.

“The September 11 tragedy brings trauma home,” adds Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. “The anthrax scare and the Nov. 12 plane crash of American Airlines Flight 587 only further remind people of their vulnerability and fears. If the anthrax scare were an accident, people would have been relieved. Since the plane crash was ruled an accident, it has offered people a chance to feel more in control. Accidents can be fixed with better maintenance. Terrorism cannot.”

Dr. Katz of New York City and other disaster psychiatrists are urging their colleagues to help manage public fear by reaching out through community efforts.

Dr. Katz is president of the volunteer group Disaster Psychiatry Outreach, which helped coordinate the city’s post-Sept. 11 trauma psychiatry effort. Visitors waiting at New York’s Family Assistance Center, a referral and help center for people who lost family and friends in the World Trade Center attack, were approached by Dr. Katz and other colleagues to let them know that psychiatric services were available if needed. By doing this, he says, Disaster Psychiatry Outreach clinicians have identified, treated, and referred scores of patients with terror-related stress who otherwise would have gone untreated.

Joseph Dorzab, MD, of the Holt-Krock Clinic in Fort Smith, Ark., also has offered his services. Members of his clinic’s psychiatry department have made several TV appearances, and have given and coordinated area lectures. Working with the local mental health association, the department also is starting a community forum called Mental Health Mondays, an open discussion group with coffee and cookies at a local coffee shop.

In Pittsburgh, Dr. Thompson is encouraging psychiatrists to educate their communities about how traumatic events affect the public. He proposes:

• Staging community meetings to brief religious and other leaders on how to manage traumatized people;
• Informing local news editors about the nature of psychiatric disorders;
• Instructing school administrators about detecting signs of distress in children;
• Contacting local government officials to offer input in devising the town’s emergency response plan.

Psychiatrists also can educate themselves about managing public trauma, thanks to scores of studies that have been done in recent years following major man-made and natural disasters, from Mount St. Helens and Hurricane Andrew, to Chernobyl and the Yom Kippur War. Dr. Thompson urges psychiatrists to seek out the papers of prominent leaders in trauma-related psychiatry, mentioning studies by Carol North, MD, Betty Pfefferbaum, MD, and Robert Ursano, MD, as examples. Other sources include the Web sites of the American Psychiatric Association and National Center for PTSD. (See Related Resources.)

In the end, psychiatrists have been well primed for dealing with public disaster—just by treating individual patients whose psychiatric disorders emanated from everyday life, Dr. Thompson says. “Psychiatrists know more about trauma than they recognize.”

Related resources

• National Center for PTSD Web site
• National Institute of Mental Health:
• Linenthal EJ. The Unfinished Bombing: Oklahoma City in American Memory. Oxford University Press, 2001.
• Norwood AE, Ursano RJ, Fullerton CS. Disaster psychiatry: principles of practice. Psychiatr Q. 2000; 71(3):207-226.
• American Psychiatric Association Web site:
• The Psychiatric Training Manual for Teachers and Mental Health Professionals

Drug brand names

• Amitriptyline • Elavil
• Bupropion • Wellbutrin
• Fluoxetine • Prozac
• Imipramine • Tofranil
• Paroxetine • Paxil
• Phenelzine • Nardil
• Sertraline • Zoloft

Untreated excessive daytime sleepiness (EDS) results in compromised quality of life, reduced productivity, and public safety concerns.¹ Obstructive sleep apnea (OSA), restless legs syndrome, circadian rhythm disorders, and narcolepsy are frequently underdiagnosed sleep disorders that can cause EDS. These conditions commonly go undetected and untreated for several reasons:

• Patients may not recognize sleepiness as a legitimate medical concern.
• Physicians, with few exceptions, typically have little training in sleep disorders and limited time to diagnose them.² Screening questions regarding sleep are typically absent.
• Definitive diagnostic tests are costly.

As a result, many patients go without appropriate sleep evaluations. Instead a depressive or other psychiatric disorder may be suspected because of the sleepy patient’s poor energy, hypersomnia, amotivation, irritability, and frustration. Because of ongoing behavioral symptoms, patients with an undiagnosed primary sleep disorder are often referred to psychiatrists. Thus, a clear understanding of the differential diagnosis of EDS is crucial.

Patients with sleep issues fall into three major categories:

1. Patients with EDS.
2. Individuals with insomnia, another large group often seen by psychiatrists. Generally, these patients are less hesitant than patients with EDS to seek help because of the marked distress they suffer nightly when trying to sleep. Insomniacs typically experience minimal EDS.
3. Patients with unusual behaviors at night that range from arm waving to violent behaviors.

Assessing the sleepy patient

When evaluating a patient with sleep complaints, several valuable sources of data come into play.

Initially, observe the patient in the waiting room or office before starting the interview. Did the patient nod off while waiting for his or her appointment? Pay attention to any patient who appears sleepy—even if he or she denies having trouble staying awake. Over time, sleepy patients may have lost their perspective on alertness. Some patients have had EDS for so many years that they no longer recall what it is like to feel fully awake.

Collateral history is often important because family members generally observe the sleeping patient. The bed partner often provides valuable information about snoring, irregular breathing leg kicks, unplanned naps, and strained interpersonal relationships due to EDS. For the patient who does not have a bed partner, ask his or her travel companion, with whom the patient may have shared accommodations.

Unfortunately, few useful screening tests exist. Most questionnaires about sleepiness are neither very reliable nor valid. One of the better questionnaires, the Epworth Sleepiness Scale, helps confirm the presence of sleepiness with a score <8, differentiating the inability to stay awake from fatigue. (Box 1 can be cut out, copied, and handed to patients). This brief questionnaire also provides a useful measure of severity.³

The value of the Epworth scale is limited, however, because patient answers often are based on a specific time and context that may not be representative. Additional validated surveys include the Pittsburgh Sleep Quality Inventory and several that focus on OSA.⁴

Box 1

Electroencephalographic (EEG) monitoring can accurately measure the patient’s degree of sleep disruption. This information is critical in understanding if a patient’s EDS is caused by a physiologic condition that prevents quality nocturnal sleep. At this time, however, no portable devices that employ EEG technology are used in clinical settings.

Additionally, none of the widely used screening devices that assess leg kicks indicate the presence of possible periodic limb movements.

Even though overnight pulse oximetry has been used to screen for sleep-disordered breathing,⁵ the technology has limitations. For one, most pulse oximeters do not provide information about sleep stage or body position. Some patients with significant sleep-disordered breathing lack adequate oxygen desaturations but have frequent EEG arousals due to sleep issues. In this case, pulse oximetry would generate a false negative result because EEG data is not collected. The inadequate sensitivity is most likely to occur with females and thin patients.

 

Oximetry provides only one or two types of data (oxygen saturation plus possibly heart rate), while other physiologic processes, e.g., body movement or sleep architecture, can repetitively be disrupted during sleep.

The most critical steps in detecting sleep disorders do not require technology or specialized expertise, but rather intuition and common sense. The psychiatrist should consider the possibility of a sleep disorder and incorporate pertinent questions into the clinical interview. Figure 1 lists sequential questions that might uncover specific sleep disorders. Once suspected, the decision whether to refer the patient to a sleep disorder center for diagnostic testing depends on the type of sleep disorder detected.

Diagnosing and treating OSA

Recent epidemiologic studies show that OSA affects at least 4% of men and 2% of women in the United States.⁶ Psychiatrists are virtually assured of seeing patients with undiagnosed OSA. The condition is caused by repeated collapse of the soft tissues surrounding the upper airway, decreasing airflow that is restored when the patient briefly awakens. Patients develop EDS because of sleep fragmented by frequent arousals.

Figure 1 THE SLEEPY PATIENT: Possible medical and psychiatric explanations

Obese patients are at higher risk than are patients at normal weight because of their body habitus. Alcohol or sedative medication use close to bedtime can aggravate OSA. These substances promote muscle relaxation and increase the arousal threshold, meaning that patients do not wake readily when apneas occur.

Long-term complications of untreated OSA include sleepiness leading to accidents, hypertension, cerebrovascular disease, and progressive obesity. New data associate OSA with multiple potential cardiovascular complications (arrhythmias, congestive heart failure, and myocardial infarction).⁷ Therefore, recognition and treatment are paramount.

The physical examination should focus on detecting nasal obstruction (having the patient sniff separately through each nostril can be helpful), big neck, crowded oropharynx (a low-hanging palate, reddened uvula, enlarged tonsils, large tongue size relative to oropharynx diameter) and jaw structure (particularly a small retrognathic mandible).

Referral for nocturnal polysomnography might be the next step. During a comprehensive sleep study, data is collected about respiratory, cardiovascular, and muscle activity at night, as well as the sounds the patient makes (e.g., snoring, coughing) when asleep. EEG monitoring also is performed. OSA may be diagnosed if repeated episodes of reduced airflow and oxygen desaturation are observed; these typically result in brief shifts in EEG frequency called arousals.

First-line interventions for OSA include avoidance of alcohol within 1 to 2 hours of bedtime, sleeping on the side instead of the back, weight loss (ideally with a regular exercise program), and nasal sprays for allergies.

If the first-line treatments for OSA are ineffective, nasal continuous positive airway pressure (CPAP) works well for almost all patients who adhere to the regimen.⁸ CPAP requires the patient to wear a nasal mask that delivers room air, splinting open the nasopharynx and the upper airway (Box 2). Some patients benefit from a brief trial of a sleeping medication, e.g., zolpidem or trazodone, for the first 1 to 2 weeks of nasal CPAP usage.

Box 2

 

Surgical options exist for OSA. The most common procedures are uvulopalatopharyngoplasty (UPPP) and laser-assisted uvulopalatoplasty (LAUP). Other procedures in use include tongue reduction and mandibular advancement.

The response rate to OSA surgery averages around 50% but varies on the patient’s characteristics and procedure selected.⁹ Positive outcomes are most likely for thin patients with obvious upper airway obstruction, including a deviated nasal septum, large tonsils, a low-hanging palate, and large uvula. Potential complications include nasal regurgitation, voice change, postoperative pain, bleeding, infection, tongue numbness, and snoring without apnea (silent apnea).

Oral appliances have a vital niche in OSA treatment. Multiple devices have been developed that open the oropharynx by moving the mandible and tongue out of way. A growing body of data shows that oral appliances improve sleep and reduce EDS and promote patient satisfaction more effectively than nasal CPAP.¹⁰ Several studies also show that patients with mild to moderate OSA accept these devices well.

Oral devices do have drawbacks, however. In most settings, effectiveness cannot be observed during a “split-night” laboratory sleep study because the patient has not yet purchased the device. Also, multiple visits sometimes are required to custom fit the oral appliance; this can pose a hardship to patients who live a distance from the provider.

Restless legs syndrome, periodic limb movement disorder

The patient with restless legs syndrome typically reports a restless painful feeling in the limbs that occurs in the evening and at night, disrupting sleep. This condition, which affects 10% of the population, is associated with aging, blood loss, anemia, peripheral neuropathies, and pregnancy.¹¹ Patients can have childhood onset and in some cases there is a familial tendency.

Most patients with restless legs syndrome have periodic limb movements (repetitive leg jerks or twitches). The clinical significance of periodic limb movements with no subjective disagreeable feelings in the limbs is controversial. Typically, treatment is not instituted in these cases.

The history usually confirms the diagnosis without a sleep study. Sleep studies are used only if a co-existing sleep problem is suspected or if the diagnosis is not clear-cut.

One suspected mechanism of restless legs syndrome is a dopamine-deficient state. A serum ferritin level can help detect a relative iron deficiency, iron being a cofactor for dopamine synthesis.¹²

Treatment can include iron repletion when indicated. Medications include dopaminergic agents, most notably pramipexole and levodopa/carbidopa. Other options include gabapentin, benzodiazepines, and narcotics. Antidepressants have been suspected to worsen this condition but definitive studies are lacking.¹³

Identifying, correcting circadian rhythm disorders

Instead of compromising the quality or quantity of sleep, circadian rhythm disorders cause sleep to occur at inappropriate times. Adolescents or young adults are most likely to confront these disorders.

The delayed sleep phase disorder—that is, a persistent pattern of staying up late and “sleeping in” the next morning—is the most common example. A careful assessment will reveal that the patient is getting a satisfactory amount of sleep that occurs at a socially unacceptable time, sometimes to the extreme that his or her nights and days are reversed.

Patients can be reluctant to acknowledge the severity of their problem, which can lead to both inaccurate sleep diaries and interviews. A portable device called a wrist actigraph provides data about limb movement, thus more objectively measuring the patient’s sleep schedule.

Psychiatrists frequently encounter patients with delayed sleep phase disorder because of a high degree of comorbidity with depressive disorders.¹⁴ The cause of this syndrome is unclear, but environmental factors including light exposure, social patterns, psychological issues, and possibly a genetic substrate, are known to contribute.

A less common circadian rhythm disorder, advanced sleep phase disorder, can also cause EDS. Patients have an inappropriately early time of sleep onset and then are fully awake in the middle of the night. A recent report describes a large family with a severe form of this disorder that is linked to an abnormality on chromosome two.¹⁵

Relatively few effective treatments have been identified for circadian rhythm disorders. Some patients elect not to pursue therapy, instead selecting activities that fit around their unconventional sleep schedules. Sometimes individuals with delayed sleep phase cannot arrange their education or work hours around their atypical sleep schedules. These patients experience poor early morning academic or work performance due to sleepiness.

The internal circadian clock can be gradually readjusted with either phototherapy or gradual shifting of the major sleep period (Box 4). Stimulant or hypnotic medications generally are not utilized.

Insufficient sleep syndrome

Studies indicate that more people are attempting to burn the candle at both ends and are consequently developing a newly identified condition, insufficient sleep syndrome.¹⁶ In our 24-hour society, people often are trying to make do with less than the required 7-1/2 hours sleep per day. This may have adverse consequences to their health. When people are required to perform shift work, the problem is compounded because of the difficulty in obtaining sufficient quality sleep during daylight hours.

 

Many patients do not seek out treatment for fatigue or sleepiness because they are aware of the lifestyle choices that they have made. Still, they might develop psychologic symptoms like irritability, mood swings, and strained interpersonal relationships. These symptoms often will prompt patients to request treatment.

Box 4

Psychiatrists should take a careful history that includes a discussion of the patient’s daily and weekly schedule. Avoid psychostimulant medications. Instead, address the non-negotiable need to get adequate sleep and challenge the patients to prioritize his or her activities around a full night’s sleep.

When to consider narcolepsy

Narcolepsy, a less common sleep disorder, can lead to severe occupational, educational, and family disruption. Narcolepsy, which affects 0.05% of the population, is a potentially debilitating disease of the central nervous system that involves abnormal regulation of REM sleep. EDS is the cardinal symptom, often associated with cataplexy (75%), sleep paralysis (50%), vivid dreams, and insomnia, all of which can represent inappropriate intrusion of REM phenomena.

After obtaining a history suggestive of narcolepsy, the psychiatrist should employ either the history, a sleep diary, or wrist actigraphy to document whether the patient is getting adequate sleep with a consistent sleep/wake cycle. Next, consider referring the patient for polysomnography, primarily to rule out other causes of EDS like sleep disorder breathing. In some cases, the REM latency on the overnight sleep study will be less than 20 minutes after sleep onset, which supports the diagnosis of narcolepsy. A multiple sleep latency test (MSLT), a diagnostic test that consists of the patient taking four to five daytime naps, is performed the following day.

Narcolepsy is confirmed if the patient has a mean initial sleep latency of less than 10 minutes during these naps plus at least two REM episodes occurring within 15 minutes after sleep onset.

Recent research shows that most patients who have narcolepsy with cataplexy have undetectable levels of a specific neuropeptide (which is called either hypocretin or orexin) in the cerebrospinal fluid.¹⁷ Hypocretin/orexin replacement therapy is a theoretical future possibility, but for now treatment includes a combination of optimal sleep hygiene, psychostimulants, antidepressants, and hypnotics.

Other causes of EDS

Other causes of EDS include unrecognized alcohol dependence, inappropriate or excessive medication use, and depressive disorders. Overnight sleep studies are seldom indicated unless patients endorse the symptoms in Figure 1.

Before pursuing sleep studies (polysomnography or an MSLT), eliminate medications that might confound the results. Such agents include antidepressants, which alter the timing and duration of REM sleep, and sedating medications, which modify initial sleep latency and sleep efficiency and potentially aggravate sleep disordered breathing. Although initial REM latency provides a potential biologic marker of major depression, this measurement is more often used in research studies than in clinical psychiatry.

Primary insomnia is a distressing inability to sleep at night or nap during the day. This suggests a hyperarousal state in several ways, and is the opposite of EDS.¹⁸ In rare cases, however, patients who cannot sleep at night also do have EDS. When evaluated, these patients typically endorse at least one of the symptoms in Figure 1. Overnight sleep studies occasionally demonstrate that the insomnia is a symptom of another underlying specific sleep disorder, such as OSA or restless legs syndrome.

 

Psychiatrists treating a patient with chronic insomnia may appropriately undertake several trials of behavioral interventions or sedating medications before making a referral to a sleep disorder center. Patients can struggle with unrecognized primary sleep disorders for years, and many are evaluated by psychiatrists who institute an empiric trial of stimulating antidepressant medications. Use of antidepressants in these situations is unlikely to cause harm, but they might complicate diagnostic testing. When coexisting depression and a primary sleep disorder are confirmed, management of the sleepy patient optimally entails specific treatments that separately target each condition.

Related resources

• National Sleep Foundation www.sleepfoundation.org
• American Academy of Sleep Medicine www.asda.org
• American Sleep Apnea Association www.sleepapnea.org
• Restless Legs Syndrome Foundation www.rls.org
• Association for the Study of Light Therapy and Biological Rhythms www.sltbr.org

Disclosure

The author reports no affiliation or financial arrangements with any of the companies whose products are mentioned in this article.

Drug brand names

• Carbidopa/levodopa • Sinemet
• Gabapentin • Neurontin
• Pramipexole • Mirapex
• Trazodone • Desyrel
• Zolpidem • Ambien

Untreated excessive daytime sleepiness (EDS) results in compromised quality of life, reduced productivity, and public safety concerns.¹ Obstructive sleep apnea (OSA), restless legs syndrome, circadian rhythm disorders, and narcolepsy are frequently underdiagnosed sleep disorders that can cause EDS. These conditions commonly go undetected and untreated for several reasons:

• Patients may not recognize sleepiness as a legitimate medical concern.
• Physicians, with few exceptions, typically have little training in sleep disorders and limited time to diagnose them.² Screening questions regarding sleep are typically absent.
• Definitive diagnostic tests are costly.

As a result, many patients go without appropriate sleep evaluations. Instead a depressive or other psychiatric disorder may be suspected because of the sleepy patient’s poor energy, hypersomnia, amotivation, irritability, and frustration. Because of ongoing behavioral symptoms, patients with an undiagnosed primary sleep disorder are often referred to psychiatrists. Thus, a clear understanding of the differential diagnosis of EDS is crucial.

Patients with sleep issues fall into three major categories:

1. Patients with EDS.
2. Individuals with insomnia, another large group often seen by psychiatrists. Generally, these patients are less hesitant than patients with EDS to seek help because of the marked distress they suffer nightly when trying to sleep. Insomniacs typically experience minimal EDS.
3. Patients with unusual behaviors at night that range from arm waving to violent behaviors.

Assessing the sleepy patient

When evaluating a patient with sleep complaints, several valuable sources of data come into play.

Initially, observe the patient in the waiting room or office before starting the interview. Did the patient nod off while waiting for his or her appointment? Pay attention to any patient who appears sleepy—even if he or she denies having trouble staying awake. Over time, sleepy patients may have lost their perspective on alertness. Some patients have had EDS for so many years that they no longer recall what it is like to feel fully awake.

Collateral history is often important because family members generally observe the sleeping patient. The bed partner often provides valuable information about snoring, irregular breathing leg kicks, unplanned naps, and strained interpersonal relationships due to EDS. For the patient who does not have a bed partner, ask his or her travel companion, with whom the patient may have shared accommodations.

Unfortunately, few useful screening tests exist. Most questionnaires about sleepiness are neither very reliable nor valid. One of the better questionnaires, the Epworth Sleepiness Scale, helps confirm the presence of sleepiness with a score <8, differentiating the inability to stay awake from fatigue. (Box 1 can be cut out, copied, and handed to patients). This brief questionnaire also provides a useful measure of severity.³

The value of the Epworth scale is limited, however, because patient answers often are based on a specific time and context that may not be representative. Additional validated surveys include the Pittsburgh Sleep Quality Inventory and several that focus on OSA.⁴

Box 1

Electroencephalographic (EEG) monitoring can accurately measure the patient’s degree of sleep disruption. This information is critical in understanding if a patient’s EDS is caused by a physiologic condition that prevents quality nocturnal sleep. At this time, however, no portable devices that employ EEG technology are used in clinical settings.

Additionally, none of the widely used screening devices that assess leg kicks indicate the presence of possible periodic limb movements.

Even though overnight pulse oximetry has been used to screen for sleep-disordered breathing,⁵ the technology has limitations. For one, most pulse oximeters do not provide information about sleep stage or body position. Some patients with significant sleep-disordered breathing lack adequate oxygen desaturations but have frequent EEG arousals due to sleep issues. In this case, pulse oximetry would generate a false negative result because EEG data is not collected. The inadequate sensitivity is most likely to occur with females and thin patients.

 

Oximetry provides only one or two types of data (oxygen saturation plus possibly heart rate), while other physiologic processes, e.g., body movement or sleep architecture, can repetitively be disrupted during sleep.

The most critical steps in detecting sleep disorders do not require technology or specialized expertise, but rather intuition and common sense. The psychiatrist should consider the possibility of a sleep disorder and incorporate pertinent questions into the clinical interview. Figure 1 lists sequential questions that might uncover specific sleep disorders. Once suspected, the decision whether to refer the patient to a sleep disorder center for diagnostic testing depends on the type of sleep disorder detected.

Diagnosing and treating OSA

Recent epidemiologic studies show that OSA affects at least 4% of men and 2% of women in the United States.⁶ Psychiatrists are virtually assured of seeing patients with undiagnosed OSA. The condition is caused by repeated collapse of the soft tissues surrounding the upper airway, decreasing airflow that is restored when the patient briefly awakens. Patients develop EDS because of sleep fragmented by frequent arousals.

Figure 1 THE SLEEPY PATIENT: Possible medical and psychiatric explanations

Obese patients are at higher risk than are patients at normal weight because of their body habitus. Alcohol or sedative medication use close to bedtime can aggravate OSA. These substances promote muscle relaxation and increase the arousal threshold, meaning that patients do not wake readily when apneas occur.

Long-term complications of untreated OSA include sleepiness leading to accidents, hypertension, cerebrovascular disease, and progressive obesity. New data associate OSA with multiple potential cardiovascular complications (arrhythmias, congestive heart failure, and myocardial infarction).⁷ Therefore, recognition and treatment are paramount.

The physical examination should focus on detecting nasal obstruction (having the patient sniff separately through each nostril can be helpful), big neck, crowded oropharynx (a low-hanging palate, reddened uvula, enlarged tonsils, large tongue size relative to oropharynx diameter) and jaw structure (particularly a small retrognathic mandible).

Referral for nocturnal polysomnography might be the next step. During a comprehensive sleep study, data is collected about respiratory, cardiovascular, and muscle activity at night, as well as the sounds the patient makes (e.g., snoring, coughing) when asleep. EEG monitoring also is performed. OSA may be diagnosed if repeated episodes of reduced airflow and oxygen desaturation are observed; these typically result in brief shifts in EEG frequency called arousals.

First-line interventions for OSA include avoidance of alcohol within 1 to 2 hours of bedtime, sleeping on the side instead of the back, weight loss (ideally with a regular exercise program), and nasal sprays for allergies.

If the first-line treatments for OSA are ineffective, nasal continuous positive airway pressure (CPAP) works well for almost all patients who adhere to the regimen.⁸ CPAP requires the patient to wear a nasal mask that delivers room air, splinting open the nasopharynx and the upper airway (Box 2). Some patients benefit from a brief trial of a sleeping medication, e.g., zolpidem or trazodone, for the first 1 to 2 weeks of nasal CPAP usage.

Box 2

 

Surgical options exist for OSA. The most common procedures are uvulopalatopharyngoplasty (UPPP) and laser-assisted uvulopalatoplasty (LAUP). Other procedures in use include tongue reduction and mandibular advancement.

The response rate to OSA surgery averages around 50% but varies on the patient’s characteristics and procedure selected.⁹ Positive outcomes are most likely for thin patients with obvious upper airway obstruction, including a deviated nasal septum, large tonsils, a low-hanging palate, and large uvula. Potential complications include nasal regurgitation, voice change, postoperative pain, bleeding, infection, tongue numbness, and snoring without apnea (silent apnea).

Oral appliances have a vital niche in OSA treatment. Multiple devices have been developed that open the oropharynx by moving the mandible and tongue out of way. A growing body of data shows that oral appliances improve sleep and reduce EDS and promote patient satisfaction more effectively than nasal CPAP.¹⁰ Several studies also show that patients with mild to moderate OSA accept these devices well.

Oral devices do have drawbacks, however. In most settings, effectiveness cannot be observed during a “split-night” laboratory sleep study because the patient has not yet purchased the device. Also, multiple visits sometimes are required to custom fit the oral appliance; this can pose a hardship to patients who live a distance from the provider.

Restless legs syndrome, periodic limb movement disorder

The patient with restless legs syndrome typically reports a restless painful feeling in the limbs that occurs in the evening and at night, disrupting sleep. This condition, which affects 10% of the population, is associated with aging, blood loss, anemia, peripheral neuropathies, and pregnancy.¹¹ Patients can have childhood onset and in some cases there is a familial tendency.

Most patients with restless legs syndrome have periodic limb movements (repetitive leg jerks or twitches). The clinical significance of periodic limb movements with no subjective disagreeable feelings in the limbs is controversial. Typically, treatment is not instituted in these cases.

The history usually confirms the diagnosis without a sleep study. Sleep studies are used only if a co-existing sleep problem is suspected or if the diagnosis is not clear-cut.

One suspected mechanism of restless legs syndrome is a dopamine-deficient state. A serum ferritin level can help detect a relative iron deficiency, iron being a cofactor for dopamine synthesis.¹²

Treatment can include iron repletion when indicated. Medications include dopaminergic agents, most notably pramipexole and levodopa/carbidopa. Other options include gabapentin, benzodiazepines, and narcotics. Antidepressants have been suspected to worsen this condition but definitive studies are lacking.¹³

Identifying, correcting circadian rhythm disorders

Instead of compromising the quality or quantity of sleep, circadian rhythm disorders cause sleep to occur at inappropriate times. Adolescents or young adults are most likely to confront these disorders.

The delayed sleep phase disorder—that is, a persistent pattern of staying up late and “sleeping in” the next morning—is the most common example. A careful assessment will reveal that the patient is getting a satisfactory amount of sleep that occurs at a socially unacceptable time, sometimes to the extreme that his or her nights and days are reversed.

Patients can be reluctant to acknowledge the severity of their problem, which can lead to both inaccurate sleep diaries and interviews. A portable device called a wrist actigraph provides data about limb movement, thus more objectively measuring the patient’s sleep schedule.

Psychiatrists frequently encounter patients with delayed sleep phase disorder because of a high degree of comorbidity with depressive disorders.¹⁴ The cause of this syndrome is unclear, but environmental factors including light exposure, social patterns, psychological issues, and possibly a genetic substrate, are known to contribute.

A less common circadian rhythm disorder, advanced sleep phase disorder, can also cause EDS. Patients have an inappropriately early time of sleep onset and then are fully awake in the middle of the night. A recent report describes a large family with a severe form of this disorder that is linked to an abnormality on chromosome two.¹⁵

Relatively few effective treatments have been identified for circadian rhythm disorders. Some patients elect not to pursue therapy, instead selecting activities that fit around their unconventional sleep schedules. Sometimes individuals with delayed sleep phase cannot arrange their education or work hours around their atypical sleep schedules. These patients experience poor early morning academic or work performance due to sleepiness.

The internal circadian clock can be gradually readjusted with either phototherapy or gradual shifting of the major sleep period (Box 4). Stimulant or hypnotic medications generally are not utilized.

Insufficient sleep syndrome

Studies indicate that more people are attempting to burn the candle at both ends and are consequently developing a newly identified condition, insufficient sleep syndrome.¹⁶ In our 24-hour society, people often are trying to make do with less than the required 7-1/2 hours sleep per day. This may have adverse consequences to their health. When people are required to perform shift work, the problem is compounded because of the difficulty in obtaining sufficient quality sleep during daylight hours.

 

Many patients do not seek out treatment for fatigue or sleepiness because they are aware of the lifestyle choices that they have made. Still, they might develop psychologic symptoms like irritability, mood swings, and strained interpersonal relationships. These symptoms often will prompt patients to request treatment.

Box 4

Psychiatrists should take a careful history that includes a discussion of the patient’s daily and weekly schedule. Avoid psychostimulant medications. Instead, address the non-negotiable need to get adequate sleep and challenge the patients to prioritize his or her activities around a full night’s sleep.

When to consider narcolepsy

Narcolepsy, a less common sleep disorder, can lead to severe occupational, educational, and family disruption. Narcolepsy, which affects 0.05% of the population, is a potentially debilitating disease of the central nervous system that involves abnormal regulation of REM sleep. EDS is the cardinal symptom, often associated with cataplexy (75%), sleep paralysis (50%), vivid dreams, and insomnia, all of which can represent inappropriate intrusion of REM phenomena.

After obtaining a history suggestive of narcolepsy, the psychiatrist should employ either the history, a sleep diary, or wrist actigraphy to document whether the patient is getting adequate sleep with a consistent sleep/wake cycle. Next, consider referring the patient for polysomnography, primarily to rule out other causes of EDS like sleep disorder breathing. In some cases, the REM latency on the overnight sleep study will be less than 20 minutes after sleep onset, which supports the diagnosis of narcolepsy. A multiple sleep latency test (MSLT), a diagnostic test that consists of the patient taking four to five daytime naps, is performed the following day.

Narcolepsy is confirmed if the patient has a mean initial sleep latency of less than 10 minutes during these naps plus at least two REM episodes occurring within 15 minutes after sleep onset.

Recent research shows that most patients who have narcolepsy with cataplexy have undetectable levels of a specific neuropeptide (which is called either hypocretin or orexin) in the cerebrospinal fluid.¹⁷ Hypocretin/orexin replacement therapy is a theoretical future possibility, but for now treatment includes a combination of optimal sleep hygiene, psychostimulants, antidepressants, and hypnotics.

Other causes of EDS

Other causes of EDS include unrecognized alcohol dependence, inappropriate or excessive medication use, and depressive disorders. Overnight sleep studies are seldom indicated unless patients endorse the symptoms in Figure 1.

Before pursuing sleep studies (polysomnography or an MSLT), eliminate medications that might confound the results. Such agents include antidepressants, which alter the timing and duration of REM sleep, and sedating medications, which modify initial sleep latency and sleep efficiency and potentially aggravate sleep disordered breathing. Although initial REM latency provides a potential biologic marker of major depression, this measurement is more often used in research studies than in clinical psychiatry.

Primary insomnia is a distressing inability to sleep at night or nap during the day. This suggests a hyperarousal state in several ways, and is the opposite of EDS.¹⁸ In rare cases, however, patients who cannot sleep at night also do have EDS. When evaluated, these patients typically endorse at least one of the symptoms in Figure 1. Overnight sleep studies occasionally demonstrate that the insomnia is a symptom of another underlying specific sleep disorder, such as OSA or restless legs syndrome.

 

Psychiatrists treating a patient with chronic insomnia may appropriately undertake several trials of behavioral interventions or sedating medications before making a referral to a sleep disorder center. Patients can struggle with unrecognized primary sleep disorders for years, and many are evaluated by psychiatrists who institute an empiric trial of stimulating antidepressant medications. Use of antidepressants in these situations is unlikely to cause harm, but they might complicate diagnostic testing. When coexisting depression and a primary sleep disorder are confirmed, management of the sleepy patient optimally entails specific treatments that separately target each condition.

Related resources

• National Sleep Foundation www.sleepfoundation.org
• American Academy of Sleep Medicine www.asda.org
• American Sleep Apnea Association www.sleepapnea.org
• Restless Legs Syndrome Foundation www.rls.org
• Association for the Study of Light Therapy and Biological Rhythms www.sltbr.org

Disclosure

The author reports no affiliation or financial arrangements with any of the companies whose products are mentioned in this article.

Drug brand names

• Carbidopa/levodopa • Sinemet
• Gabapentin • Neurontin
• Pramipexole • Mirapex
• Trazodone • Desyrel
• Zolpidem • Ambien

Untreated excessive daytime sleepiness (EDS) results in compromised quality of life, reduced productivity, and public safety concerns.¹ Obstructive sleep apnea (OSA), restless legs syndrome, circadian rhythm disorders, and narcolepsy are frequently underdiagnosed sleep disorders that can cause EDS. These conditions commonly go undetected and untreated for several reasons:

• Patients may not recognize sleepiness as a legitimate medical concern.
• Physicians, with few exceptions, typically have little training in sleep disorders and limited time to diagnose them.² Screening questions regarding sleep are typically absent.
• Definitive diagnostic tests are costly.

As a result, many patients go without appropriate sleep evaluations. Instead a depressive or other psychiatric disorder may be suspected because of the sleepy patient’s poor energy, hypersomnia, amotivation, irritability, and frustration. Because of ongoing behavioral symptoms, patients with an undiagnosed primary sleep disorder are often referred to psychiatrists. Thus, a clear understanding of the differential diagnosis of EDS is crucial.

Patients with sleep issues fall into three major categories:

1. Patients with EDS.
2. Individuals with insomnia, another large group often seen by psychiatrists. Generally, these patients are less hesitant than patients with EDS to seek help because of the marked distress they suffer nightly when trying to sleep. Insomniacs typically experience minimal EDS.
3. Patients with unusual behaviors at night that range from arm waving to violent behaviors.

Assessing the sleepy patient

When evaluating a patient with sleep complaints, several valuable sources of data come into play.

Initially, observe the patient in the waiting room or office before starting the interview. Did the patient nod off while waiting for his or her appointment? Pay attention to any patient who appears sleepy—even if he or she denies having trouble staying awake. Over time, sleepy patients may have lost their perspective on alertness. Some patients have had EDS for so many years that they no longer recall what it is like to feel fully awake.

Collateral history is often important because family members generally observe the sleeping patient. The bed partner often provides valuable information about snoring, irregular breathing leg kicks, unplanned naps, and strained interpersonal relationships due to EDS. For the patient who does not have a bed partner, ask his or her travel companion, with whom the patient may have shared accommodations.

Unfortunately, few useful screening tests exist. Most questionnaires about sleepiness are neither very reliable nor valid. One of the better questionnaires, the Epworth Sleepiness Scale, helps confirm the presence of sleepiness with a score <8, differentiating the inability to stay awake from fatigue. (Box 1 can be cut out, copied, and handed to patients). This brief questionnaire also provides a useful measure of severity.³

The value of the Epworth scale is limited, however, because patient answers often are based on a specific time and context that may not be representative. Additional validated surveys include the Pittsburgh Sleep Quality Inventory and several that focus on OSA.⁴

Box 1

Electroencephalographic (EEG) monitoring can accurately measure the patient’s degree of sleep disruption. This information is critical in understanding if a patient’s EDS is caused by a physiologic condition that prevents quality nocturnal sleep. At this time, however, no portable devices that employ EEG technology are used in clinical settings.

Additionally, none of the widely used screening devices that assess leg kicks indicate the presence of possible periodic limb movements.

Even though overnight pulse oximetry has been used to screen for sleep-disordered breathing,⁵ the technology has limitations. For one, most pulse oximeters do not provide information about sleep stage or body position. Some patients with significant sleep-disordered breathing lack adequate oxygen desaturations but have frequent EEG arousals due to sleep issues. In this case, pulse oximetry would generate a false negative result because EEG data is not collected. The inadequate sensitivity is most likely to occur with females and thin patients.

 

Oximetry provides only one or two types of data (oxygen saturation plus possibly heart rate), while other physiologic processes, e.g., body movement or sleep architecture, can repetitively be disrupted during sleep.

The most critical steps in detecting sleep disorders do not require technology or specialized expertise, but rather intuition and common sense. The psychiatrist should consider the possibility of a sleep disorder and incorporate pertinent questions into the clinical interview. Figure 1 lists sequential questions that might uncover specific sleep disorders. Once suspected, the decision whether to refer the patient to a sleep disorder center for diagnostic testing depends on the type of sleep disorder detected.

Diagnosing and treating OSA

Recent epidemiologic studies show that OSA affects at least 4% of men and 2% of women in the United States.⁶ Psychiatrists are virtually assured of seeing patients with undiagnosed OSA. The condition is caused by repeated collapse of the soft tissues surrounding the upper airway, decreasing airflow that is restored when the patient briefly awakens. Patients develop EDS because of sleep fragmented by frequent arousals.

Figure 1 THE SLEEPY PATIENT: Possible medical and psychiatric explanations

Obese patients are at higher risk than are patients at normal weight because of their body habitus. Alcohol or sedative medication use close to bedtime can aggravate OSA. These substances promote muscle relaxation and increase the arousal threshold, meaning that patients do not wake readily when apneas occur.

Long-term complications of untreated OSA include sleepiness leading to accidents, hypertension, cerebrovascular disease, and progressive obesity. New data associate OSA with multiple potential cardiovascular complications (arrhythmias, congestive heart failure, and myocardial infarction).⁷ Therefore, recognition and treatment are paramount.

The physical examination should focus on detecting nasal obstruction (having the patient sniff separately through each nostril can be helpful), big neck, crowded oropharynx (a low-hanging palate, reddened uvula, enlarged tonsils, large tongue size relative to oropharynx diameter) and jaw structure (particularly a small retrognathic mandible).

Referral for nocturnal polysomnography might be the next step. During a comprehensive sleep study, data is collected about respiratory, cardiovascular, and muscle activity at night, as well as the sounds the patient makes (e.g., snoring, coughing) when asleep. EEG monitoring also is performed. OSA may be diagnosed if repeated episodes of reduced airflow and oxygen desaturation are observed; these typically result in brief shifts in EEG frequency called arousals.

First-line interventions for OSA include avoidance of alcohol within 1 to 2 hours of bedtime, sleeping on the side instead of the back, weight loss (ideally with a regular exercise program), and nasal sprays for allergies.

If the first-line treatments for OSA are ineffective, nasal continuous positive airway pressure (CPAP) works well for almost all patients who adhere to the regimen.⁸ CPAP requires the patient to wear a nasal mask that delivers room air, splinting open the nasopharynx and the upper airway (Box 2). Some patients benefit from a brief trial of a sleeping medication, e.g., zolpidem or trazodone, for the first 1 to 2 weeks of nasal CPAP usage.

Box 2

 

Surgical options exist for OSA. The most common procedures are uvulopalatopharyngoplasty (UPPP) and laser-assisted uvulopalatoplasty (LAUP). Other procedures in use include tongue reduction and mandibular advancement.

The response rate to OSA surgery averages around 50% but varies on the patient’s characteristics and procedure selected.⁹ Positive outcomes are most likely for thin patients with obvious upper airway obstruction, including a deviated nasal septum, large tonsils, a low-hanging palate, and large uvula. Potential complications include nasal regurgitation, voice change, postoperative pain, bleeding, infection, tongue numbness, and snoring without apnea (silent apnea).

Oral appliances have a vital niche in OSA treatment. Multiple devices have been developed that open the oropharynx by moving the mandible and tongue out of way. A growing body of data shows that oral appliances improve sleep and reduce EDS and promote patient satisfaction more effectively than nasal CPAP.¹⁰ Several studies also show that patients with mild to moderate OSA accept these devices well.

Oral devices do have drawbacks, however. In most settings, effectiveness cannot be observed during a “split-night” laboratory sleep study because the patient has not yet purchased the device. Also, multiple visits sometimes are required to custom fit the oral appliance; this can pose a hardship to patients who live a distance from the provider.

Restless legs syndrome, periodic limb movement disorder

The patient with restless legs syndrome typically reports a restless painful feeling in the limbs that occurs in the evening and at night, disrupting sleep. This condition, which affects 10% of the population, is associated with aging, blood loss, anemia, peripheral neuropathies, and pregnancy.¹¹ Patients can have childhood onset and in some cases there is a familial tendency.

Most patients with restless legs syndrome have periodic limb movements (repetitive leg jerks or twitches). The clinical significance of periodic limb movements with no subjective disagreeable feelings in the limbs is controversial. Typically, treatment is not instituted in these cases.

The history usually confirms the diagnosis without a sleep study. Sleep studies are used only if a co-existing sleep problem is suspected or if the diagnosis is not clear-cut.

One suspected mechanism of restless legs syndrome is a dopamine-deficient state. A serum ferritin level can help detect a relative iron deficiency, iron being a cofactor for dopamine synthesis.¹²

Treatment can include iron repletion when indicated. Medications include dopaminergic agents, most notably pramipexole and levodopa/carbidopa. Other options include gabapentin, benzodiazepines, and narcotics. Antidepressants have been suspected to worsen this condition but definitive studies are lacking.¹³

Identifying, correcting circadian rhythm disorders

Instead of compromising the quality or quantity of sleep, circadian rhythm disorders cause sleep to occur at inappropriate times. Adolescents or young adults are most likely to confront these disorders.

The delayed sleep phase disorder—that is, a persistent pattern of staying up late and “sleeping in” the next morning—is the most common example. A careful assessment will reveal that the patient is getting a satisfactory amount of sleep that occurs at a socially unacceptable time, sometimes to the extreme that his or her nights and days are reversed.

Patients can be reluctant to acknowledge the severity of their problem, which can lead to both inaccurate sleep diaries and interviews. A portable device called a wrist actigraph provides data about limb movement, thus more objectively measuring the patient’s sleep schedule.

Psychiatrists frequently encounter patients with delayed sleep phase disorder because of a high degree of comorbidity with depressive disorders.¹⁴ The cause of this syndrome is unclear, but environmental factors including light exposure, social patterns, psychological issues, and possibly a genetic substrate, are known to contribute.

A less common circadian rhythm disorder, advanced sleep phase disorder, can also cause EDS. Patients have an inappropriately early time of sleep onset and then are fully awake in the middle of the night. A recent report describes a large family with a severe form of this disorder that is linked to an abnormality on chromosome two.¹⁵

Relatively few effective treatments have been identified for circadian rhythm disorders. Some patients elect not to pursue therapy, instead selecting activities that fit around their unconventional sleep schedules. Sometimes individuals with delayed sleep phase cannot arrange their education or work hours around their atypical sleep schedules. These patients experience poor early morning academic or work performance due to sleepiness.

The internal circadian clock can be gradually readjusted with either phototherapy or gradual shifting of the major sleep period (Box 4). Stimulant or hypnotic medications generally are not utilized.

Insufficient sleep syndrome

Studies indicate that more people are attempting to burn the candle at both ends and are consequently developing a newly identified condition, insufficient sleep syndrome.¹⁶ In our 24-hour society, people often are trying to make do with less than the required 7-1/2 hours sleep per day. This may have adverse consequences to their health. When people are required to perform shift work, the problem is compounded because of the difficulty in obtaining sufficient quality sleep during daylight hours.

 

Many patients do not seek out treatment for fatigue or sleepiness because they are aware of the lifestyle choices that they have made. Still, they might develop psychologic symptoms like irritability, mood swings, and strained interpersonal relationships. These symptoms often will prompt patients to request treatment.

Box 4

Psychiatrists should take a careful history that includes a discussion of the patient’s daily and weekly schedule. Avoid psychostimulant medications. Instead, address the non-negotiable need to get adequate sleep and challenge the patients to prioritize his or her activities around a full night’s sleep.

When to consider narcolepsy

Narcolepsy, a less common sleep disorder, can lead to severe occupational, educational, and family disruption. Narcolepsy, which affects 0.05% of the population, is a potentially debilitating disease of the central nervous system that involves abnormal regulation of REM sleep. EDS is the cardinal symptom, often associated with cataplexy (75%), sleep paralysis (50%), vivid dreams, and insomnia, all of which can represent inappropriate intrusion of REM phenomena.

After obtaining a history suggestive of narcolepsy, the psychiatrist should employ either the history, a sleep diary, or wrist actigraphy to document whether the patient is getting adequate sleep with a consistent sleep/wake cycle. Next, consider referring the patient for polysomnography, primarily to rule out other causes of EDS like sleep disorder breathing. In some cases, the REM latency on the overnight sleep study will be less than 20 minutes after sleep onset, which supports the diagnosis of narcolepsy. A multiple sleep latency test (MSLT), a diagnostic test that consists of the patient taking four to five daytime naps, is performed the following day.

Narcolepsy is confirmed if the patient has a mean initial sleep latency of less than 10 minutes during these naps plus at least two REM episodes occurring within 15 minutes after sleep onset.

Recent research shows that most patients who have narcolepsy with cataplexy have undetectable levels of a specific neuropeptide (which is called either hypocretin or orexin) in the cerebrospinal fluid.¹⁷ Hypocretin/orexin replacement therapy is a theoretical future possibility, but for now treatment includes a combination of optimal sleep hygiene, psychostimulants, antidepressants, and hypnotics.

Other causes of EDS

Other causes of EDS include unrecognized alcohol dependence, inappropriate or excessive medication use, and depressive disorders. Overnight sleep studies are seldom indicated unless patients endorse the symptoms in Figure 1.

Before pursuing sleep studies (polysomnography or an MSLT), eliminate medications that might confound the results. Such agents include antidepressants, which alter the timing and duration of REM sleep, and sedating medications, which modify initial sleep latency and sleep efficiency and potentially aggravate sleep disordered breathing. Although initial REM latency provides a potential biologic marker of major depression, this measurement is more often used in research studies than in clinical psychiatry.

Primary insomnia is a distressing inability to sleep at night or nap during the day. This suggests a hyperarousal state in several ways, and is the opposite of EDS.¹⁸ In rare cases, however, patients who cannot sleep at night also do have EDS. When evaluated, these patients typically endorse at least one of the symptoms in Figure 1. Overnight sleep studies occasionally demonstrate that the insomnia is a symptom of another underlying specific sleep disorder, such as OSA or restless legs syndrome.

 

Psychiatrists treating a patient with chronic insomnia may appropriately undertake several trials of behavioral interventions or sedating medications before making a referral to a sleep disorder center. Patients can struggle with unrecognized primary sleep disorders for years, and many are evaluated by psychiatrists who institute an empiric trial of stimulating antidepressant medications. Use of antidepressants in these situations is unlikely to cause harm, but they might complicate diagnostic testing. When coexisting depression and a primary sleep disorder are confirmed, management of the sleepy patient optimally entails specific treatments that separately target each condition.

Related resources

• National Sleep Foundation www.sleepfoundation.org
• American Academy of Sleep Medicine www.asda.org
• American Sleep Apnea Association www.sleepapnea.org
• Restless Legs Syndrome Foundation www.rls.org
• Association for the Study of Light Therapy and Biological Rhythms www.sltbr.org

Disclosure

The author reports no affiliation or financial arrangements with any of the companies whose products are mentioned in this article.

Drug brand names

• Carbidopa/levodopa • Sinemet
• Gabapentin • Neurontin
• Pramipexole • Mirapex
• Trazodone • Desyrel
• Zolpidem • Ambien