Somatic Disorders

A substantial proportion of psychiatric patients suffer from a somatic illness concomitantly with a mood, thought, or behavioral disorder. Some complicated patients may be afflicted by a combination of 4 or 5 different psychiatric or general medical disorders, requiring the use of multiple medications, which almost always increases the risk of adverse effects, pharmacokinetic interactions, and adherence gaps, and also escalates costs.

In addition, multiple medications may set off other iatrogenic consequences, such as exacerbation of psychiatric symptoms caused by a nonpsychotropic medication (such as an antihypertensive worsening depressive symptoms) or aggravation of a general medical condition by a psychotropic (such as prolongation of the QT interval or hyperglycemia secondary to an atypical antipsychotic).

Thus, it is quite pleasing when the use of a single medication can simultaneously relieve ≥2 unrelated medical disorders, preempting the need for multiple medications. This is the essence of parsimonious pharmacotherapy, a “2 birds with 1 stone” approach that evades polypharmacy and its side effect burden and added cost.

Consider the following examples of how a single psychotropic—by virtue of both its efficacy and what may be considered a side effect—can relieve 2 psychiatric disorders, or a psychiatric and a physical disorder, or even 2 physical disorders:

Depression with premature ejaculation. Delayed orgasm associated with selective serotonin reuptake inhibitors (SSRIs) administered for depression can simultaneously mitigate premature ejaculation as an added benefit.

Bipolar disorder with migraine. Valproate is a commonly used mood stabilizer that also is effective and indicated for migraines. Lithium, another widely used mood stabilizer, can relieve cluster headaches.

A mood or psychotic disorder with insomnia. Antidepressant medications with sedating properties can treat unipolar or bipolar depression and simultaneously allay the insomnia that often coexists with a mood disorder. Similarly, sedating antipsychotic medications administered at bedtime can relieve psychosis and its coexisting insomnia.

A mood or psychotic disorder with anxiety. Anxiety frequently accompanies unipolar or bipolar depression or schizophrenia. An SSRI can help both depression and anxiety, and some antipsychotics also can relieve both psychosis and anxiety.

Bipolar disorder or schizophrenia with obesity. Some metabolically neutral atypical agents (aripiprazole, lurasidone, ziprasidone) can control schizophrenia symptoms and/or bipolar mania while helping obese patients shed weight acquired during previous treatment with an obesogenic antipsychotic.

Depression and/or anxiety with thrombotic disease. SSRIs treat both depression and anxiety, and their anticoagulant side effect reduces the risk of thrombus formation in patients at risk for thrombotic disease.

Bipolar disorder with leukopenia. Lithium is a standard mood stabilizer that controls bipolar disorder, and its leukocytosis side effect helps increase white blood cell production and alleviate leukopenia.

Depression or anxiety with pain. This is a well-known parsimonious pharmacotherapy. Pain symptoms are a common feature or comorbidity of depression, and practically all antidepressants have analgesic effects.

Bipolar disorder with alcohol or cocaine addiction. The anticonvulsant/mood stabilizer valproate has been shown to significantly reduce both manic symptoms and comorbid heavy drinking in placebo- controlled studies. Another anticonvulsant/antimanic agent, carbamazepine, has been reported to reduce cocaine craving.

Migraine and obesity in a psychiatric patient. Topiramate is approved for migraines but its appetite-suppressing side effect can help decrease weight in patients with a high body mass index.

Posttraumatic stress disorder (PTSD) patients with depression, anxiety, obsessive-compulsive disorder, impulsivity, and insomnia. Here is a good example of how a sedating antidepressant agent—especially an SSRI—can help multiple symptom domains of PTSD.

Most psychiatric practitioners are aware of how to exploit side effects to help a coexisting medical disorder, or how to employ a multi-action drug to relieve a cluster of coexisting symptoms. Thus, psychiatric patients’ medical history can and should influence drug selection for the possible employment of parsimonious pharmacotherapy, which is gratifying for clinicians and a welcome antidote to polypharmacy in some patients with multiple medical disorders.

A substantial proportion of psychiatric patients suffer from a somatic illness concomitantly with a mood, thought, or behavioral disorder. Some complicated patients may be afflicted by a combination of 4 or 5 different psychiatric or general medical disorders, requiring the use of multiple medications, which almost always increases the risk of adverse effects, pharmacokinetic interactions, and adherence gaps, and also escalates costs.

In addition, multiple medications may set off other iatrogenic consequences, such as exacerbation of psychiatric symptoms caused by a nonpsychotropic medication (such as an antihypertensive worsening depressive symptoms) or aggravation of a general medical condition by a psychotropic (such as prolongation of the QT interval or hyperglycemia secondary to an atypical antipsychotic).

Thus, it is quite pleasing when the use of a single medication can simultaneously relieve ≥2 unrelated medical disorders, preempting the need for multiple medications. This is the essence of parsimonious pharmacotherapy, a “2 birds with 1 stone” approach that evades polypharmacy and its side effect burden and added cost.

Consider the following examples of how a single psychotropic—by virtue of both its efficacy and what may be considered a side effect—can relieve 2 psychiatric disorders, or a psychiatric and a physical disorder, or even 2 physical disorders:

Depression with premature ejaculation. Delayed orgasm associated with selective serotonin reuptake inhibitors (SSRIs) administered for depression can simultaneously mitigate premature ejaculation as an added benefit.

Bipolar disorder with migraine. Valproate is a commonly used mood stabilizer that also is effective and indicated for migraines. Lithium, another widely used mood stabilizer, can relieve cluster headaches.

A mood or psychotic disorder with insomnia. Antidepressant medications with sedating properties can treat unipolar or bipolar depression and simultaneously allay the insomnia that often coexists with a mood disorder. Similarly, sedating antipsychotic medications administered at bedtime can relieve psychosis and its coexisting insomnia.

A mood or psychotic disorder with anxiety. Anxiety frequently accompanies unipolar or bipolar depression or schizophrenia. An SSRI can help both depression and anxiety, and some antipsychotics also can relieve both psychosis and anxiety.

Bipolar disorder or schizophrenia with obesity. Some metabolically neutral atypical agents (aripiprazole, lurasidone, ziprasidone) can control schizophrenia symptoms and/or bipolar mania while helping obese patients shed weight acquired during previous treatment with an obesogenic antipsychotic.

Depression and/or anxiety with thrombotic disease. SSRIs treat both depression and anxiety, and their anticoagulant side effect reduces the risk of thrombus formation in patients at risk for thrombotic disease.

Bipolar disorder with leukopenia. Lithium is a standard mood stabilizer that controls bipolar disorder, and its leukocytosis side effect helps increase white blood cell production and alleviate leukopenia.

Depression or anxiety with pain. This is a well-known parsimonious pharmacotherapy. Pain symptoms are a common feature or comorbidity of depression, and practically all antidepressants have analgesic effects.

Bipolar disorder with alcohol or cocaine addiction. The anticonvulsant/mood stabilizer valproate has been shown to significantly reduce both manic symptoms and comorbid heavy drinking in placebo- controlled studies. Another anticonvulsant/antimanic agent, carbamazepine, has been reported to reduce cocaine craving.

Migraine and obesity in a psychiatric patient. Topiramate is approved for migraines but its appetite-suppressing side effect can help decrease weight in patients with a high body mass index.

Posttraumatic stress disorder (PTSD) patients with depression, anxiety, obsessive-compulsive disorder, impulsivity, and insomnia. Here is a good example of how a sedating antidepressant agent—especially an SSRI—can help multiple symptom domains of PTSD.

Most psychiatric practitioners are aware of how to exploit side effects to help a coexisting medical disorder, or how to employ a multi-action drug to relieve a cluster of coexisting symptoms. Thus, psychiatric patients’ medical history can and should influence drug selection for the possible employment of parsimonious pharmacotherapy, which is gratifying for clinicians and a welcome antidote to polypharmacy in some patients with multiple medical disorders.

A substantial proportion of psychiatric patients suffer from a somatic illness concomitantly with a mood, thought, or behavioral disorder. Some complicated patients may be afflicted by a combination of 4 or 5 different psychiatric or general medical disorders, requiring the use of multiple medications, which almost always increases the risk of adverse effects, pharmacokinetic interactions, and adherence gaps, and also escalates costs.

In addition, multiple medications may set off other iatrogenic consequences, such as exacerbation of psychiatric symptoms caused by a nonpsychotropic medication (such as an antihypertensive worsening depressive symptoms) or aggravation of a general medical condition by a psychotropic (such as prolongation of the QT interval or hyperglycemia secondary to an atypical antipsychotic).

Thus, it is quite pleasing when the use of a single medication can simultaneously relieve ≥2 unrelated medical disorders, preempting the need for multiple medications. This is the essence of parsimonious pharmacotherapy, a “2 birds with 1 stone” approach that evades polypharmacy and its side effect burden and added cost.

Consider the following examples of how a single psychotropic—by virtue of both its efficacy and what may be considered a side effect—can relieve 2 psychiatric disorders, or a psychiatric and a physical disorder, or even 2 physical disorders:

Depression with premature ejaculation. Delayed orgasm associated with selective serotonin reuptake inhibitors (SSRIs) administered for depression can simultaneously mitigate premature ejaculation as an added benefit.

Bipolar disorder with migraine. Valproate is a commonly used mood stabilizer that also is effective and indicated for migraines. Lithium, another widely used mood stabilizer, can relieve cluster headaches.

A mood or psychotic disorder with insomnia. Antidepressant medications with sedating properties can treat unipolar or bipolar depression and simultaneously allay the insomnia that often coexists with a mood disorder. Similarly, sedating antipsychotic medications administered at bedtime can relieve psychosis and its coexisting insomnia.

A mood or psychotic disorder with anxiety. Anxiety frequently accompanies unipolar or bipolar depression or schizophrenia. An SSRI can help both depression and anxiety, and some antipsychotics also can relieve both psychosis and anxiety.

Bipolar disorder or schizophrenia with obesity. Some metabolically neutral atypical agents (aripiprazole, lurasidone, ziprasidone) can control schizophrenia symptoms and/or bipolar mania while helping obese patients shed weight acquired during previous treatment with an obesogenic antipsychotic.

Depression and/or anxiety with thrombotic disease. SSRIs treat both depression and anxiety, and their anticoagulant side effect reduces the risk of thrombus formation in patients at risk for thrombotic disease.

Bipolar disorder with leukopenia. Lithium is a standard mood stabilizer that controls bipolar disorder, and its leukocytosis side effect helps increase white blood cell production and alleviate leukopenia.

Depression or anxiety with pain. This is a well-known parsimonious pharmacotherapy. Pain symptoms are a common feature or comorbidity of depression, and practically all antidepressants have analgesic effects.

Bipolar disorder with alcohol or cocaine addiction. The anticonvulsant/mood stabilizer valproate has been shown to significantly reduce both manic symptoms and comorbid heavy drinking in placebo- controlled studies. Another anticonvulsant/antimanic agent, carbamazepine, has been reported to reduce cocaine craving.

Migraine and obesity in a psychiatric patient. Topiramate is approved for migraines but its appetite-suppressing side effect can help decrease weight in patients with a high body mass index.

Posttraumatic stress disorder (PTSD) patients with depression, anxiety, obsessive-compulsive disorder, impulsivity, and insomnia. Here is a good example of how a sedating antidepressant agent—especially an SSRI—can help multiple symptom domains of PTSD.

Most psychiatric practitioners are aware of how to exploit side effects to help a coexisting medical disorder, or how to employ a multi-action drug to relieve a cluster of coexisting symptoms. Thus, psychiatric patients’ medical history can and should influence drug selection for the possible employment of parsimonious pharmacotherapy, which is gratifying for clinicians and a welcome antidote to polypharmacy in some patients with multiple medical disorders.

TUCSON – Can patients with generalized anxiety disorder get so anxious that they are literally scared to death?

Evidently so, according to findings from the large prospective Heart and Soul Study.

The cohort study involved 1,015 San Francisco Bay area outpatients with stable coronary heart disease prospectively followed for a mean of 5.6 years. A total of 371 acute myocardial infarctions, strokes, and other cardiovascular events occurred during 5,711 person-years of follow-up, Dr. Alan J. Gelenberg reported at the annual psychopharmacology review sponsored by the University of Arizona.

The age-adjusted cardiovascular event rate in the 106 Heart and Soul participants with baseline generalized anxiety disorder (GAD) was 9.9%, significantly greater than the 6.6% rate in those without GAD.

After adjustment for potential confounding variables, including major depression and other comorbid conditions, patient demographics, cardiac disease severity, and medication use, GAD remained independently associated with a highly significant 74% increased cardiovascular event rate (Arch. Gen. Psychiatry 2010;67:750-8).

The study serves as one example of the substantial morbidity and mortality associated with GAD.

Major depression, too, has been shown to be a strong predictor of cardiovascular mortality. Indeed, in a classic French Canadian study of 896 post-MI patients, the single greatest predictor of cardiac death over the next 5 years – stronger, for example, than left ventricular ejection fraction, diabetes, or a history of prior MI – was a patient’s score on the Beck Depression Inventory during the acute MI hospitalization (Circulation 2002;105:1049-53), noted Dr. Gelenberg, professor and chair of the department of psychiatry at Pennsylvania State University, Hershey.

Both GAD and depression kill in another way: suicide, the eighth-leading cause of death in the United States. GAD has been shown in several studies to increase suicide risk in adults, and in the Great Smoky Mountains Study, the combination of GAD and current depression was associated with a substantially increased risk of suicidality in teenagers, Dr. Gelenberg observed.

In various studies, 8%-19% of patients hospitalized for major depressive disorder eventually committed suicide, he added.

The Heart and Soul Study was funded by the Department of Veterans Affairs; the National Heart, Lung, and Blood Institute; and several foundations. Dr. Gelenberg said he had no relevant financial disclosures.

TUCSON – Can patients with generalized anxiety disorder get so anxious that they are literally scared to death?

Evidently so, according to findings from the large prospective Heart and Soul Study.

The cohort study involved 1,015 San Francisco Bay area outpatients with stable coronary heart disease prospectively followed for a mean of 5.6 years. A total of 371 acute myocardial infarctions, strokes, and other cardiovascular events occurred during 5,711 person-years of follow-up, Dr. Alan J. Gelenberg reported at the annual psychopharmacology review sponsored by the University of Arizona.

The age-adjusted cardiovascular event rate in the 106 Heart and Soul participants with baseline generalized anxiety disorder (GAD) was 9.9%, significantly greater than the 6.6% rate in those without GAD.

After adjustment for potential confounding variables, including major depression and other comorbid conditions, patient demographics, cardiac disease severity, and medication use, GAD remained independently associated with a highly significant 74% increased cardiovascular event rate (Arch. Gen. Psychiatry 2010;67:750-8).

The study serves as one example of the substantial morbidity and mortality associated with GAD.

Major depression, too, has been shown to be a strong predictor of cardiovascular mortality. Indeed, in a classic French Canadian study of 896 post-MI patients, the single greatest predictor of cardiac death over the next 5 years – stronger, for example, than left ventricular ejection fraction, diabetes, or a history of prior MI – was a patient’s score on the Beck Depression Inventory during the acute MI hospitalization (Circulation 2002;105:1049-53), noted Dr. Gelenberg, professor and chair of the department of psychiatry at Pennsylvania State University, Hershey.

Both GAD and depression kill in another way: suicide, the eighth-leading cause of death in the United States. GAD has been shown in several studies to increase suicide risk in adults, and in the Great Smoky Mountains Study, the combination of GAD and current depression was associated with a substantially increased risk of suicidality in teenagers, Dr. Gelenberg observed.

In various studies, 8%-19% of patients hospitalized for major depressive disorder eventually committed suicide, he added.

The Heart and Soul Study was funded by the Department of Veterans Affairs; the National Heart, Lung, and Blood Institute; and several foundations. Dr. Gelenberg said he had no relevant financial disclosures.

TUCSON – Can patients with generalized anxiety disorder get so anxious that they are literally scared to death?

Evidently so, according to findings from the large prospective Heart and Soul Study.

The cohort study involved 1,015 San Francisco Bay area outpatients with stable coronary heart disease prospectively followed for a mean of 5.6 years. A total of 371 acute myocardial infarctions, strokes, and other cardiovascular events occurred during 5,711 person-years of follow-up, Dr. Alan J. Gelenberg reported at the annual psychopharmacology review sponsored by the University of Arizona.

The age-adjusted cardiovascular event rate in the 106 Heart and Soul participants with baseline generalized anxiety disorder (GAD) was 9.9%, significantly greater than the 6.6% rate in those without GAD.

After adjustment for potential confounding variables, including major depression and other comorbid conditions, patient demographics, cardiac disease severity, and medication use, GAD remained independently associated with a highly significant 74% increased cardiovascular event rate (Arch. Gen. Psychiatry 2010;67:750-8).

The study serves as one example of the substantial morbidity and mortality associated with GAD.

Major depression, too, has been shown to be a strong predictor of cardiovascular mortality. Indeed, in a classic French Canadian study of 896 post-MI patients, the single greatest predictor of cardiac death over the next 5 years – stronger, for example, than left ventricular ejection fraction, diabetes, or a history of prior MI – was a patient’s score on the Beck Depression Inventory during the acute MI hospitalization (Circulation 2002;105:1049-53), noted Dr. Gelenberg, professor and chair of the department of psychiatry at Pennsylvania State University, Hershey.

Both GAD and depression kill in another way: suicide, the eighth-leading cause of death in the United States. GAD has been shown in several studies to increase suicide risk in adults, and in the Great Smoky Mountains Study, the combination of GAD and current depression was associated with a substantially increased risk of suicidality in teenagers, Dr. Gelenberg observed.

In various studies, 8%-19% of patients hospitalized for major depressive disorder eventually committed suicide, he added.

The Heart and Soul Study was funded by the Department of Veterans Affairs; the National Heart, Lung, and Blood Institute; and several foundations. Dr. Gelenberg said he had no relevant financial disclosures.

Combining L-methylfolate with an SSRI or an SNRI proved more effective than monotherapy at treatment initiation in a study of 242 patients with major depressive disorder published in Innovations in Clinical Neuroscience.

When they added 7.5 mg or 15 mg of L-methylfolate to another antidepressant, Dr. Lawrence D. Ginsberg and his associates reported improvement in patients’ symptoms and a reduction in Clinical Global Impression-Severity (CGI-S) scores, in which 1 is "normal" and 7 is "extremely ill."

In the group of 95 patients on combination treatment, 18.5% saw at least a two-point reduction in CGI-S scores during a 60-day period. In contrast, only 7% saw the same reduction in the group of 147 patients on monotherapy of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI), reported Dr. Ginsberg, a Houston psychiatrist who is in private practice.

Patients on the L-methylfolate combo also improved more rapidly. Their median time to achieve at least a two-point reduction on the CGI-S scale was 177 days, compared with 231 days for those on the monotherapy group. The team did not find any side effects from the addition of L-methylfolate (Innov. Clin. Neurosci. 2011;8:19-28).

The patients were aged 18-70 years, and each one began with a CGI-S score of 4-5. Although the results built upon those of previous investigations on the effective use of folate when treating major depressive episodes, this single-site study limited itself to retrospective chart analysis. The team did not measure patients’ baseline folate levels.

In an interview, Dr. Ginsberg explained his reasoning in deciding who got the monotherapy and who received the L-methylfolate-antidepressant combination. "If I felt it was in the best interests of an individual patient, then I prescribed L-methylfolate," he said.

The use of L-methylfolate is part of a "paradigm shift" over the last 5 years toward initial combination therapy, said Dr. Stephen M. Stahl, adjunct psychiatry professor at the University of California, San Diego. He added, however, that psychiatrists have tried multiple therapies at treatment initiation for almost a decade now.

Dr. Stahl, whose work is cited in Dr. Ginsberg’s study, said that whereas the classical approach is to try adjunctive therapy after monotherapy fails, the norm in cancer and HIV/AIDS treatment is to begin with three or four drugs. "Depression is moving in that direction," he said in an interview. Dr. Stahl, who is also chairman of the Neuroscience Education Institute, expressed doubts about the Ginsberg study design. "This is more of an interesting hypothesis-generating study than a hypothesis-confirming study," he said. Because the study was neither randomized nor controlled, he said it was "not a completely objective comparison" of the test group and the control group.

Dr. Ginsberg’s study is by no means isolated. Dr. Maurizio Fava, psychiatry professor at Harvard Medical School, Boston, presented a similar study in a poster at the American College of Neuropsychopharmacology’s annual meeting in December, but these results have not yet been published in a peer-reviewed journal.

Dr. Stahl considers Dr. Fava’s results to be more convincing because of that study’s randomized controlled design. "Taken in the context of the Fava study, the Ginsberg study is more interesting," he said.

However, Dr. Stahl acknowledged that such a comparison is difficult because, although Dr. Fava tested the effectiveness of adding L-methylfolate to treatment with SSRIs, his study does not focus on treatment initiation.

The Ginsberg study received funding from Pamlab, which manufactures the medical food L-methylfolate under the brand name Deplin. Dr. Ginsberg also reported his work as a speaker for Pamlab and as a consultant for various other pharmaceutical companies. Dr. Stahl disclosed that he has done consulting for Pamlab. Dr. Fava also has consulted for and received funding from Pamlab.

Combining L-methylfolate with an SSRI or an SNRI proved more effective than monotherapy at treatment initiation in a study of 242 patients with major depressive disorder published in Innovations in Clinical Neuroscience.

When they added 7.5 mg or 15 mg of L-methylfolate to another antidepressant, Dr. Lawrence D. Ginsberg and his associates reported improvement in patients’ symptoms and a reduction in Clinical Global Impression-Severity (CGI-S) scores, in which 1 is "normal" and 7 is "extremely ill."

In the group of 95 patients on combination treatment, 18.5% saw at least a two-point reduction in CGI-S scores during a 60-day period. In contrast, only 7% saw the same reduction in the group of 147 patients on monotherapy of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI), reported Dr. Ginsberg, a Houston psychiatrist who is in private practice.

Patients on the L-methylfolate combo also improved more rapidly. Their median time to achieve at least a two-point reduction on the CGI-S scale was 177 days, compared with 231 days for those on the monotherapy group. The team did not find any side effects from the addition of L-methylfolate (Innov. Clin. Neurosci. 2011;8:19-28).

The patients were aged 18-70 years, and each one began with a CGI-S score of 4-5. Although the results built upon those of previous investigations on the effective use of folate when treating major depressive episodes, this single-site study limited itself to retrospective chart analysis. The team did not measure patients’ baseline folate levels.

In an interview, Dr. Ginsberg explained his reasoning in deciding who got the monotherapy and who received the L-methylfolate-antidepressant combination. "If I felt it was in the best interests of an individual patient, then I prescribed L-methylfolate," he said.

The use of L-methylfolate is part of a "paradigm shift" over the last 5 years toward initial combination therapy, said Dr. Stephen M. Stahl, adjunct psychiatry professor at the University of California, San Diego. He added, however, that psychiatrists have tried multiple therapies at treatment initiation for almost a decade now.

Dr. Stahl, whose work is cited in Dr. Ginsberg’s study, said that whereas the classical approach is to try adjunctive therapy after monotherapy fails, the norm in cancer and HIV/AIDS treatment is to begin with three or four drugs. "Depression is moving in that direction," he said in an interview. Dr. Stahl, who is also chairman of the Neuroscience Education Institute, expressed doubts about the Ginsberg study design. "This is more of an interesting hypothesis-generating study than a hypothesis-confirming study," he said. Because the study was neither randomized nor controlled, he said it was "not a completely objective comparison" of the test group and the control group.

Dr. Ginsberg’s study is by no means isolated. Dr. Maurizio Fava, psychiatry professor at Harvard Medical School, Boston, presented a similar study in a poster at the American College of Neuropsychopharmacology’s annual meeting in December, but these results have not yet been published in a peer-reviewed journal.

Dr. Stahl considers Dr. Fava’s results to be more convincing because of that study’s randomized controlled design. "Taken in the context of the Fava study, the Ginsberg study is more interesting," he said.

However, Dr. Stahl acknowledged that such a comparison is difficult because, although Dr. Fava tested the effectiveness of adding L-methylfolate to treatment with SSRIs, his study does not focus on treatment initiation.

The Ginsberg study received funding from Pamlab, which manufactures the medical food L-methylfolate under the brand name Deplin. Dr. Ginsberg also reported his work as a speaker for Pamlab and as a consultant for various other pharmaceutical companies. Dr. Stahl disclosed that he has done consulting for Pamlab. Dr. Fava also has consulted for and received funding from Pamlab.

Combining L-methylfolate with an SSRI or an SNRI proved more effective than monotherapy at treatment initiation in a study of 242 patients with major depressive disorder published in Innovations in Clinical Neuroscience.

When they added 7.5 mg or 15 mg of L-methylfolate to another antidepressant, Dr. Lawrence D. Ginsberg and his associates reported improvement in patients’ symptoms and a reduction in Clinical Global Impression-Severity (CGI-S) scores, in which 1 is "normal" and 7 is "extremely ill."

In the group of 95 patients on combination treatment, 18.5% saw at least a two-point reduction in CGI-S scores during a 60-day period. In contrast, only 7% saw the same reduction in the group of 147 patients on monotherapy of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI), reported Dr. Ginsberg, a Houston psychiatrist who is in private practice.

Patients on the L-methylfolate combo also improved more rapidly. Their median time to achieve at least a two-point reduction on the CGI-S scale was 177 days, compared with 231 days for those on the monotherapy group. The team did not find any side effects from the addition of L-methylfolate (Innov. Clin. Neurosci. 2011;8:19-28).

The patients were aged 18-70 years, and each one began with a CGI-S score of 4-5. Although the results built upon those of previous investigations on the effective use of folate when treating major depressive episodes, this single-site study limited itself to retrospective chart analysis. The team did not measure patients’ baseline folate levels.

In an interview, Dr. Ginsberg explained his reasoning in deciding who got the monotherapy and who received the L-methylfolate-antidepressant combination. "If I felt it was in the best interests of an individual patient, then I prescribed L-methylfolate," he said.

The use of L-methylfolate is part of a "paradigm shift" over the last 5 years toward initial combination therapy, said Dr. Stephen M. Stahl, adjunct psychiatry professor at the University of California, San Diego. He added, however, that psychiatrists have tried multiple therapies at treatment initiation for almost a decade now.

Dr. Stahl, whose work is cited in Dr. Ginsberg’s study, said that whereas the classical approach is to try adjunctive therapy after monotherapy fails, the norm in cancer and HIV/AIDS treatment is to begin with three or four drugs. "Depression is moving in that direction," he said in an interview. Dr. Stahl, who is also chairman of the Neuroscience Education Institute, expressed doubts about the Ginsberg study design. "This is more of an interesting hypothesis-generating study than a hypothesis-confirming study," he said. Because the study was neither randomized nor controlled, he said it was "not a completely objective comparison" of the test group and the control group.

Dr. Ginsberg’s study is by no means isolated. Dr. Maurizio Fava, psychiatry professor at Harvard Medical School, Boston, presented a similar study in a poster at the American College of Neuropsychopharmacology’s annual meeting in December, but these results have not yet been published in a peer-reviewed journal.

Dr. Stahl considers Dr. Fava’s results to be more convincing because of that study’s randomized controlled design. "Taken in the context of the Fava study, the Ginsberg study is more interesting," he said.

However, Dr. Stahl acknowledged that such a comparison is difficult because, although Dr. Fava tested the effectiveness of adding L-methylfolate to treatment with SSRIs, his study does not focus on treatment initiation.

The Ginsberg study received funding from Pamlab, which manufactures the medical food L-methylfolate under the brand name Deplin. Dr. Ginsberg also reported his work as a speaker for Pamlab and as a consultant for various other pharmaceutical companies. Dr. Stahl disclosed that he has done consulting for Pamlab. Dr. Fava also has consulted for and received funding from Pamlab.

Injectable long-acting risperidone was no better than was a psychiatrist’s choice of oral antipsychotic agents in forestalling hospitalization of patients with unstable schizophrenia and schizoaffective disorder, according to a report in the March 3 issue of the New England Journal of Medicine.

In a multicenter clinical trial comparing the two treatment approaches, the time to psychiatric hospitalization was no different between patients receiving risperidone injections approximately every 2 weeks and those receiving daily oral therapy. Results were the same on several standard measures of psychiatric symptoms and quality of life, and the use of other medical services also was the same.

"Taken together, these findings are consistent with [those of] 3 efficacy trials that also showed no superiority of long-acting injectable risperidone over oral regimens in patients with stable schizophrenia," wrote Dr. Robert A. Rosenheck of the Veterans Affairs New England Mental Illness, Research Education, and Clinical Center, West Haven, Conn., and his associates.

It was hoped that long-acting injectable delivery would improve treatment adherence by ensuring sustained blood levels of the drug, which would in turn improve symptom control and reduce the rate of hospitalization for relapse. Dr. Rosenheck and his colleagues tested that hypothesis in what they described as the first long-term randomized clinical trial of this formulation involving patients with unstable disease.

The study included patients with unstable schizophrenia or schizoaffective disorder who were considered at risk for rehospitalization because they were currently hospitalized (40%), had been hospitalized during the preceding 2 years (55%), or had recently increased their use of psychiatric services (5%). Most had demonstrated difficulty with medication adherence.

The study population comprised 369 older, predominantly male veterans treated at 14 sites and followed for up to 2 years.

During a mean follow-up of approximately 11 months, 81 (45%) of the 182 patients who had been randomly assigned to receive oral medication required psychiatric hospitalization, compared with 72 (39%) of 187 patients randomly assigned to receive long-acting risperidone. This difference was not significant, the investigators said (N. Engl. J. Med. 2011;364:842-51).

The time interval until hospitalization and the hospital length of stay also were not significantly different between the two study groups. Changes since baseline in patients’ total scores and subscale scores on the Positive and Negative Syndrome Scale (PANSS) also were no different. Similarly, scores on three measures of quality of life, the Clinical Global Impressions scale, and the Addiction Severity Index were similar between the two study groups.

Long-acting injectable risperidone was associated with more "general disorders and administration site conditions" such as pain or induration at the injection site, as well as with more "nervous system disorders" such as headache and extrapyramidal signs and symptoms. This suggests that patients who take oral agents "may flexibly adjust their medication use to avoid such adverse effects," Dr. Rosenheck and his associates said.

This study was supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs, which also provided the injectable risperidone.

Injectable long-acting risperidone was no better than was a psychiatrist’s choice of oral antipsychotic agents in forestalling hospitalization of patients with unstable schizophrenia and schizoaffective disorder, according to a report in the March 3 issue of the New England Journal of Medicine.

In a multicenter clinical trial comparing the two treatment approaches, the time to psychiatric hospitalization was no different between patients receiving risperidone injections approximately every 2 weeks and those receiving daily oral therapy. Results were the same on several standard measures of psychiatric symptoms and quality of life, and the use of other medical services also was the same.

"Taken together, these findings are consistent with [those of] 3 efficacy trials that also showed no superiority of long-acting injectable risperidone over oral regimens in patients with stable schizophrenia," wrote Dr. Robert A. Rosenheck of the Veterans Affairs New England Mental Illness, Research Education, and Clinical Center, West Haven, Conn., and his associates.

It was hoped that long-acting injectable delivery would improve treatment adherence by ensuring sustained blood levels of the drug, which would in turn improve symptom control and reduce the rate of hospitalization for relapse. Dr. Rosenheck and his colleagues tested that hypothesis in what they described as the first long-term randomized clinical trial of this formulation involving patients with unstable disease.

The study included patients with unstable schizophrenia or schizoaffective disorder who were considered at risk for rehospitalization because they were currently hospitalized (40%), had been hospitalized during the preceding 2 years (55%), or had recently increased their use of psychiatric services (5%). Most had demonstrated difficulty with medication adherence.

The study population comprised 369 older, predominantly male veterans treated at 14 sites and followed for up to 2 years.

During a mean follow-up of approximately 11 months, 81 (45%) of the 182 patients who had been randomly assigned to receive oral medication required psychiatric hospitalization, compared with 72 (39%) of 187 patients randomly assigned to receive long-acting risperidone. This difference was not significant, the investigators said (N. Engl. J. Med. 2011;364:842-51).

The time interval until hospitalization and the hospital length of stay also were not significantly different between the two study groups. Changes since baseline in patients’ total scores and subscale scores on the Positive and Negative Syndrome Scale (PANSS) also were no different. Similarly, scores on three measures of quality of life, the Clinical Global Impressions scale, and the Addiction Severity Index were similar between the two study groups.

Long-acting injectable risperidone was associated with more "general disorders and administration site conditions" such as pain or induration at the injection site, as well as with more "nervous system disorders" such as headache and extrapyramidal signs and symptoms. This suggests that patients who take oral agents "may flexibly adjust their medication use to avoid such adverse effects," Dr. Rosenheck and his associates said.

This study was supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs, which also provided the injectable risperidone.

Injectable long-acting risperidone was no better than was a psychiatrist’s choice of oral antipsychotic agents in forestalling hospitalization of patients with unstable schizophrenia and schizoaffective disorder, according to a report in the March 3 issue of the New England Journal of Medicine.

In a multicenter clinical trial comparing the two treatment approaches, the time to psychiatric hospitalization was no different between patients receiving risperidone injections approximately every 2 weeks and those receiving daily oral therapy. Results were the same on several standard measures of psychiatric symptoms and quality of life, and the use of other medical services also was the same.

"Taken together, these findings are consistent with [those of] 3 efficacy trials that also showed no superiority of long-acting injectable risperidone over oral regimens in patients with stable schizophrenia," wrote Dr. Robert A. Rosenheck of the Veterans Affairs New England Mental Illness, Research Education, and Clinical Center, West Haven, Conn., and his associates.

It was hoped that long-acting injectable delivery would improve treatment adherence by ensuring sustained blood levels of the drug, which would in turn improve symptom control and reduce the rate of hospitalization for relapse. Dr. Rosenheck and his colleagues tested that hypothesis in what they described as the first long-term randomized clinical trial of this formulation involving patients with unstable disease.

The study included patients with unstable schizophrenia or schizoaffective disorder who were considered at risk for rehospitalization because they were currently hospitalized (40%), had been hospitalized during the preceding 2 years (55%), or had recently increased their use of psychiatric services (5%). Most had demonstrated difficulty with medication adherence.

The study population comprised 369 older, predominantly male veterans treated at 14 sites and followed for up to 2 years.

During a mean follow-up of approximately 11 months, 81 (45%) of the 182 patients who had been randomly assigned to receive oral medication required psychiatric hospitalization, compared with 72 (39%) of 187 patients randomly assigned to receive long-acting risperidone. This difference was not significant, the investigators said (N. Engl. J. Med. 2011;364:842-51).

The time interval until hospitalization and the hospital length of stay also were not significantly different between the two study groups. Changes since baseline in patients’ total scores and subscale scores on the Positive and Negative Syndrome Scale (PANSS) also were no different. Similarly, scores on three measures of quality of life, the Clinical Global Impressions scale, and the Addiction Severity Index were similar between the two study groups.

Long-acting injectable risperidone was associated with more "general disorders and administration site conditions" such as pain or induration at the injection site, as well as with more "nervous system disorders" such as headache and extrapyramidal signs and symptoms. This suggests that patients who take oral agents "may flexibly adjust their medication use to avoid such adverse effects," Dr. Rosenheck and his associates said.

This study was supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs, which also provided the injectable risperidone.

TUCSON – New British guidelines on the management of generalized anxiety disorder advocate a stepped-care approach to this common psychiatric condition that one U.S. expert considers thoughtful and highly reasonable.

The U.K. National Institute for Health and Clinical Excellence (NICE) guidelines recommend as a first step in generalized anxiety disorder (GAD) simple, low-cost self-help and guided self-help educational and coaching interventions that can be provided in pamphlets or on the Internet.

"I like this a lot, because as we hope to get universal health coverage and yet not break the bank, online therapies that can be done essentially for free – you and your computer, sitting in your bedroom – can be a good first step in treating common conditions such as insomnia or anxiety," Dr. Alan J. Gelenberg said at the annual psychopharmacology review, sponsored by the University of Arizona.

Photo credit: ©absolut/Fotolia.com

The next step under the NICE guidelines is low-intensity group therapy. But if a patient continues to have marked functional impairment despite group sessions, it’s time to offer the choice of either pharmacotherapy or high-intensity, manual-based psychotherapy in the form of applied relaxation or cognitive-behavioral therapy.

The recently published guidelines (BMJ 2011;342 [doi:10.1135/bmj.c7460]) recommend selective serotonin reuptake inhibitors (SSRIs) as the first-line class of medications, with sertraline singled out as the drug of first choice. Interestingly, sertraline is not approved for treatment of GAD in the United Kingdom or the United States. The guideline writing group stated that, while NICE does not ordinarily recommend the use of a drug for an unlicensed application, an exception was made for sertraline, because the generic version is particularly cost effective.

"The NICE guidelines tend to be more cost conscious than other international guidelines in psychiatry," Dr. Gelenberg observed. "I prefer some of the off-patent generics as first line; I’ll go along with the Brits and the NICE guidelines."

There is persuasive published clinical trials evidence for sertraline’s effectiveness in GAD. Its manufacturer made a business decision not to pursue regulatory approval for the indication, because the drug was scheduled to lose its patent protection soon.

Although very few head-to-head clinical trials exist, all of the antidepressants in the various classes studied for GAD appear to have comparable efficacy. They are significantly more effective than placebo. However, there is a consistently large placebo effect in the studies, and the effect size of the medication compared to placebo is actually rather modest, according to Dr. Gelenberg, professor and chair of the department of psychiatry at Pennsylvania State University, Hershey.

One of the factors he likes best about the new NICE guidelines is the emphatic statement that benzodiazepines should not be offered in the treatment of GAD except short term during acute crises. This recommendation is at odds with current prescribing trends both in the United Kingdom and the United States, where benzodiazepines are prescribed for GAD more often than antidepressants, and the most frequently prescribed benzodiazepine is alprazolam (Xanax). This is a sore point for Dr. Gelenberg. He dislikes alprazolam, which he views as an often-abused drug with a "very nasty" withdrawal syndrome.

A consistent finding in numerous head-to-head studies of benzodiazepines vs. antidepressants over the past 2 decades is that the benzodiazepines bring faster improvement in the somatic symptoms of anxiety but, in the end, the antidepressant is always the clear winner in terms of efficacy. On this basis, a case can be made for a few weeks of concomitant therapy with a long-half-life benzodiazepine in selected patients as a lead in while waiting for the antidepressant to achieve full effect, he continued.

The NICE guidelines recommend that if sertraline is ineffective, offer another SSRI or a serotonin–norepinephrine reuptake inhibitor (SNRI). If the SSRIs and SNRIs are not tolerated, the guidelines recommend turning to pregabalin (Lyrica), which is approved for GAD in the United Kingdom but not in the United States. The clinical trials evidence shows pregabalin works as fast as alprazolam or lorazepam while achieving symptom improvement scores comparable with antidepressants, making it a particularly attractive back-up option in antidepressant nonresponders, Dr. Gelenberg said.

The Food and Drug Administration–approved drugs for GAD are the SNRIs venlafaxine and duloxetine, the SSRIs paroxetine and escitalopram, alprazolam, and buspirone. However, escitalopram and alprazolam are approved for acute treatment only, and buspirone is approved as maintenance therapy only. There is a widespread impression that buspirone is less effective than antidepressants in GAD, and most experts don’t use it much, he continued.

NICE advises against using antipsychotic agents for treatment of GAD in primary care, because the evidence of clinical efficacy is weak and the risk of serious side effects is well established.

In psychiatrists’ hands, however, Dr. Gelenberg considers second-generation antipsychotic agents a reasonable next step in treatment nonresponders. The evidence of efficacy for quetiapine (Seroquel) in GAD is "quite impressive," he said, citing a recent Cochrane analysis of four placebo-controlled clinical trials of quetiapine monotherapy for GAD totaling 2,265 patients. The Cochrane report concluded that quetiapine’s efficacy is comparable to that of antidepressants, although the dropout rate attributable to side effects – mostly sedation and weight gain – is higher (Cochrane Database Syst. Rev.;12:CD008120).

The NICE guidelines do not address the question of how long effective therapy should be continued. Dr. Gelenberg pointed to a recent enlightening study on this score by Dr. Karl E. Rickels and his colleagues at the University of Pennsylvania, Philadelphia, which concluded that treatment should continue for at least 12 months.

The study involved 268 GAD patients treated for 6 months with open-label extended-release venlafaxine. The 51% who were significantly improved at that point were then randomized double-blind to an additional 6 months of extended-release venlafaxine or placebo. Among patients still in the study at the 12-month mark, those on placebo were placed on another 6 months of placebo, while those on venlafaxine XR were randomized to a double-blind test for an additional 6 months of the drug or placebo.

During months 6-12, patients still on venlafaxine XR had a 10% relapse rate, compared with 54% in those switched to placebo. Among patients who’d been on venlafaxine XR during the first 12 months, those assigned to the antidepressant in months 12-18 had a 7% relapse rate during that final period, compared with 32% for those switched to placebo. Reassuringly, most patients who relapsed when taken off the antidepressant responded to a second course of therapy. The take-home message, according to the investigators, is that successful treatment should be maintained for at least a year (Arch. Gen. Psychiatry 2010;67:1274-81).

"GAD is a chronic disorder, and probably most patients need much longer therapy, but I don’t get as upset when a patient wants to stop as I do when it’s someone with severe major depressive disorder or bipolar disorder. I’m more inclined to say, ‘Try it. We’ll work together, and if you feel the anxiety start to return we’ll put you back on therapy,’ " Dr. Gelenberg said.

He disclosed that he serves as a consultant to Eli Lilly, Best Practice, AstraZeneca, Wyeth, GlaxoSmithKline, ZARS Pharma, Jazz Pharmaceuticals, H. Lundbeck A/S, Takeda, eResearch Technology, Dey Pharma, PGxHealth, and Myriad Genetics.

TUCSON – New British guidelines on the management of generalized anxiety disorder advocate a stepped-care approach to this common psychiatric condition that one U.S. expert considers thoughtful and highly reasonable.

The U.K. National Institute for Health and Clinical Excellence (NICE) guidelines recommend as a first step in generalized anxiety disorder (GAD) simple, low-cost self-help and guided self-help educational and coaching interventions that can be provided in pamphlets or on the Internet.

"I like this a lot, because as we hope to get universal health coverage and yet not break the bank, online therapies that can be done essentially for free – you and your computer, sitting in your bedroom – can be a good first step in treating common conditions such as insomnia or anxiety," Dr. Alan J. Gelenberg said at the annual psychopharmacology review, sponsored by the University of Arizona.

Photo credit: ©absolut/Fotolia.com

The next step under the NICE guidelines is low-intensity group therapy. But if a patient continues to have marked functional impairment despite group sessions, it’s time to offer the choice of either pharmacotherapy or high-intensity, manual-based psychotherapy in the form of applied relaxation or cognitive-behavioral therapy.

The recently published guidelines (BMJ 2011;342 [doi:10.1135/bmj.c7460]) recommend selective serotonin reuptake inhibitors (SSRIs) as the first-line class of medications, with sertraline singled out as the drug of first choice. Interestingly, sertraline is not approved for treatment of GAD in the United Kingdom or the United States. The guideline writing group stated that, while NICE does not ordinarily recommend the use of a drug for an unlicensed application, an exception was made for sertraline, because the generic version is particularly cost effective.

"The NICE guidelines tend to be more cost conscious than other international guidelines in psychiatry," Dr. Gelenberg observed. "I prefer some of the off-patent generics as first line; I’ll go along with the Brits and the NICE guidelines."

There is persuasive published clinical trials evidence for sertraline’s effectiveness in GAD. Its manufacturer made a business decision not to pursue regulatory approval for the indication, because the drug was scheduled to lose its patent protection soon.

Although very few head-to-head clinical trials exist, all of the antidepressants in the various classes studied for GAD appear to have comparable efficacy. They are significantly more effective than placebo. However, there is a consistently large placebo effect in the studies, and the effect size of the medication compared to placebo is actually rather modest, according to Dr. Gelenberg, professor and chair of the department of psychiatry at Pennsylvania State University, Hershey.

One of the factors he likes best about the new NICE guidelines is the emphatic statement that benzodiazepines should not be offered in the treatment of GAD except short term during acute crises. This recommendation is at odds with current prescribing trends both in the United Kingdom and the United States, where benzodiazepines are prescribed for GAD more often than antidepressants, and the most frequently prescribed benzodiazepine is alprazolam (Xanax). This is a sore point for Dr. Gelenberg. He dislikes alprazolam, which he views as an often-abused drug with a "very nasty" withdrawal syndrome.

A consistent finding in numerous head-to-head studies of benzodiazepines vs. antidepressants over the past 2 decades is that the benzodiazepines bring faster improvement in the somatic symptoms of anxiety but, in the end, the antidepressant is always the clear winner in terms of efficacy. On this basis, a case can be made for a few weeks of concomitant therapy with a long-half-life benzodiazepine in selected patients as a lead in while waiting for the antidepressant to achieve full effect, he continued.

The NICE guidelines recommend that if sertraline is ineffective, offer another SSRI or a serotonin–norepinephrine reuptake inhibitor (SNRI). If the SSRIs and SNRIs are not tolerated, the guidelines recommend turning to pregabalin (Lyrica), which is approved for GAD in the United Kingdom but not in the United States. The clinical trials evidence shows pregabalin works as fast as alprazolam or lorazepam while achieving symptom improvement scores comparable with antidepressants, making it a particularly attractive back-up option in antidepressant nonresponders, Dr. Gelenberg said.

The Food and Drug Administration–approved drugs for GAD are the SNRIs venlafaxine and duloxetine, the SSRIs paroxetine and escitalopram, alprazolam, and buspirone. However, escitalopram and alprazolam are approved for acute treatment only, and buspirone is approved as maintenance therapy only. There is a widespread impression that buspirone is less effective than antidepressants in GAD, and most experts don’t use it much, he continued.

NICE advises against using antipsychotic agents for treatment of GAD in primary care, because the evidence of clinical efficacy is weak and the risk of serious side effects is well established.

In psychiatrists’ hands, however, Dr. Gelenberg considers second-generation antipsychotic agents a reasonable next step in treatment nonresponders. The evidence of efficacy for quetiapine (Seroquel) in GAD is "quite impressive," he said, citing a recent Cochrane analysis of four placebo-controlled clinical trials of quetiapine monotherapy for GAD totaling 2,265 patients. The Cochrane report concluded that quetiapine’s efficacy is comparable to that of antidepressants, although the dropout rate attributable to side effects – mostly sedation and weight gain – is higher (Cochrane Database Syst. Rev.;12:CD008120).

The NICE guidelines do not address the question of how long effective therapy should be continued. Dr. Gelenberg pointed to a recent enlightening study on this score by Dr. Karl E. Rickels and his colleagues at the University of Pennsylvania, Philadelphia, which concluded that treatment should continue for at least 12 months.

The study involved 268 GAD patients treated for 6 months with open-label extended-release venlafaxine. The 51% who were significantly improved at that point were then randomized double-blind to an additional 6 months of extended-release venlafaxine or placebo. Among patients still in the study at the 12-month mark, those on placebo were placed on another 6 months of placebo, while those on venlafaxine XR were randomized to a double-blind test for an additional 6 months of the drug or placebo.

During months 6-12, patients still on venlafaxine XR had a 10% relapse rate, compared with 54% in those switched to placebo. Among patients who’d been on venlafaxine XR during the first 12 months, those assigned to the antidepressant in months 12-18 had a 7% relapse rate during that final period, compared with 32% for those switched to placebo. Reassuringly, most patients who relapsed when taken off the antidepressant responded to a second course of therapy. The take-home message, according to the investigators, is that successful treatment should be maintained for at least a year (Arch. Gen. Psychiatry 2010;67:1274-81).

"GAD is a chronic disorder, and probably most patients need much longer therapy, but I don’t get as upset when a patient wants to stop as I do when it’s someone with severe major depressive disorder or bipolar disorder. I’m more inclined to say, ‘Try it. We’ll work together, and if you feel the anxiety start to return we’ll put you back on therapy,’ " Dr. Gelenberg said.

He disclosed that he serves as a consultant to Eli Lilly, Best Practice, AstraZeneca, Wyeth, GlaxoSmithKline, ZARS Pharma, Jazz Pharmaceuticals, H. Lundbeck A/S, Takeda, eResearch Technology, Dey Pharma, PGxHealth, and Myriad Genetics.

TUCSON – New British guidelines on the management of generalized anxiety disorder advocate a stepped-care approach to this common psychiatric condition that one U.S. expert considers thoughtful and highly reasonable.

The U.K. National Institute for Health and Clinical Excellence (NICE) guidelines recommend as a first step in generalized anxiety disorder (GAD) simple, low-cost self-help and guided self-help educational and coaching interventions that can be provided in pamphlets or on the Internet.

"I like this a lot, because as we hope to get universal health coverage and yet not break the bank, online therapies that can be done essentially for free – you and your computer, sitting in your bedroom – can be a good first step in treating common conditions such as insomnia or anxiety," Dr. Alan J. Gelenberg said at the annual psychopharmacology review, sponsored by the University of Arizona.

Photo credit: ©absolut/Fotolia.com

The next step under the NICE guidelines is low-intensity group therapy. But if a patient continues to have marked functional impairment despite group sessions, it’s time to offer the choice of either pharmacotherapy or high-intensity, manual-based psychotherapy in the form of applied relaxation or cognitive-behavioral therapy.

The recently published guidelines (BMJ 2011;342 [doi:10.1135/bmj.c7460]) recommend selective serotonin reuptake inhibitors (SSRIs) as the first-line class of medications, with sertraline singled out as the drug of first choice. Interestingly, sertraline is not approved for treatment of GAD in the United Kingdom or the United States. The guideline writing group stated that, while NICE does not ordinarily recommend the use of a drug for an unlicensed application, an exception was made for sertraline, because the generic version is particularly cost effective.

"The NICE guidelines tend to be more cost conscious than other international guidelines in psychiatry," Dr. Gelenberg observed. "I prefer some of the off-patent generics as first line; I’ll go along with the Brits and the NICE guidelines."

There is persuasive published clinical trials evidence for sertraline’s effectiveness in GAD. Its manufacturer made a business decision not to pursue regulatory approval for the indication, because the drug was scheduled to lose its patent protection soon.

Although very few head-to-head clinical trials exist, all of the antidepressants in the various classes studied for GAD appear to have comparable efficacy. They are significantly more effective than placebo. However, there is a consistently large placebo effect in the studies, and the effect size of the medication compared to placebo is actually rather modest, according to Dr. Gelenberg, professor and chair of the department of psychiatry at Pennsylvania State University, Hershey.

One of the factors he likes best about the new NICE guidelines is the emphatic statement that benzodiazepines should not be offered in the treatment of GAD except short term during acute crises. This recommendation is at odds with current prescribing trends both in the United Kingdom and the United States, where benzodiazepines are prescribed for GAD more often than antidepressants, and the most frequently prescribed benzodiazepine is alprazolam (Xanax). This is a sore point for Dr. Gelenberg. He dislikes alprazolam, which he views as an often-abused drug with a "very nasty" withdrawal syndrome.

A consistent finding in numerous head-to-head studies of benzodiazepines vs. antidepressants over the past 2 decades is that the benzodiazepines bring faster improvement in the somatic symptoms of anxiety but, in the end, the antidepressant is always the clear winner in terms of efficacy. On this basis, a case can be made for a few weeks of concomitant therapy with a long-half-life benzodiazepine in selected patients as a lead in while waiting for the antidepressant to achieve full effect, he continued.

The NICE guidelines recommend that if sertraline is ineffective, offer another SSRI or a serotonin–norepinephrine reuptake inhibitor (SNRI). If the SSRIs and SNRIs are not tolerated, the guidelines recommend turning to pregabalin (Lyrica), which is approved for GAD in the United Kingdom but not in the United States. The clinical trials evidence shows pregabalin works as fast as alprazolam or lorazepam while achieving symptom improvement scores comparable with antidepressants, making it a particularly attractive back-up option in antidepressant nonresponders, Dr. Gelenberg said.

The Food and Drug Administration–approved drugs for GAD are the SNRIs venlafaxine and duloxetine, the SSRIs paroxetine and escitalopram, alprazolam, and buspirone. However, escitalopram and alprazolam are approved for acute treatment only, and buspirone is approved as maintenance therapy only. There is a widespread impression that buspirone is less effective than antidepressants in GAD, and most experts don’t use it much, he continued.

NICE advises against using antipsychotic agents for treatment of GAD in primary care, because the evidence of clinical efficacy is weak and the risk of serious side effects is well established.

In psychiatrists’ hands, however, Dr. Gelenberg considers second-generation antipsychotic agents a reasonable next step in treatment nonresponders. The evidence of efficacy for quetiapine (Seroquel) in GAD is "quite impressive," he said, citing a recent Cochrane analysis of four placebo-controlled clinical trials of quetiapine monotherapy for GAD totaling 2,265 patients. The Cochrane report concluded that quetiapine’s efficacy is comparable to that of antidepressants, although the dropout rate attributable to side effects – mostly sedation and weight gain – is higher (Cochrane Database Syst. Rev.;12:CD008120).

The NICE guidelines do not address the question of how long effective therapy should be continued. Dr. Gelenberg pointed to a recent enlightening study on this score by Dr. Karl E. Rickels and his colleagues at the University of Pennsylvania, Philadelphia, which concluded that treatment should continue for at least 12 months.

The study involved 268 GAD patients treated for 6 months with open-label extended-release venlafaxine. The 51% who were significantly improved at that point were then randomized double-blind to an additional 6 months of extended-release venlafaxine or placebo. Among patients still in the study at the 12-month mark, those on placebo were placed on another 6 months of placebo, while those on venlafaxine XR were randomized to a double-blind test for an additional 6 months of the drug or placebo.

During months 6-12, patients still on venlafaxine XR had a 10% relapse rate, compared with 54% in those switched to placebo. Among patients who’d been on venlafaxine XR during the first 12 months, those assigned to the antidepressant in months 12-18 had a 7% relapse rate during that final period, compared with 32% for those switched to placebo. Reassuringly, most patients who relapsed when taken off the antidepressant responded to a second course of therapy. The take-home message, according to the investigators, is that successful treatment should be maintained for at least a year (Arch. Gen. Psychiatry 2010;67:1274-81).

"GAD is a chronic disorder, and probably most patients need much longer therapy, but I don’t get as upset when a patient wants to stop as I do when it’s someone with severe major depressive disorder or bipolar disorder. I’m more inclined to say, ‘Try it. We’ll work together, and if you feel the anxiety start to return we’ll put you back on therapy,’ " Dr. Gelenberg said.

He disclosed that he serves as a consultant to Eli Lilly, Best Practice, AstraZeneca, Wyeth, GlaxoSmithKline, ZARS Pharma, Jazz Pharmaceuticals, H. Lundbeck A/S, Takeda, eResearch Technology, Dey Pharma, PGxHealth, and Myriad Genetics.

LONDON – Cognitive behavioral therapy and graded exercise therapy are both safe and effective to use in combination with specialist medical care for chronic fatigue syndrome, according to the results of a large randomized, controlled trial.

In contrast, adapted pacing therapy (APT), which several patient organizations have advocated as the preferred treatment choice together with specialist medical care, offers no real benefit – leading some experts to suggest that perhaps APT should no longer be used.

The findings were reported online Feb. 17 in the Lancet.

Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) – but not APT – significantly lowered fatigue and raised physical function scores when compared with specialist medical care (SMC) alone.

At 1-year follow-up, the respective changes in fatigue and physical function scores versus SMC alone were –3.4 and +7.1 for CBT, and –3.2 and +9.4 for GET, all of which were statistically significant differences. In contrast, the changes in those scores for APT were –0.7 and –3.4, respectively, differences that weren’t statistically significant.

Although the effects of CBT and GET on chronic fatigue syndrome (CFS) are still rather moderate, "the bottom line is that patients given CBT and GET showed more improvement than the other two groups," said Trudie Chalder, Ph.D., one of the study’s authors and a professor of cognitive behavioral psychotherapy at King’s College London (Lancet 2011 Feb. 17 [doi:10.1016/S0140-6736(11)60096-2]).

CFS affects around a quarter of a million people in the United Kingdom. Symptoms include severe fatigue, poor concentration and memory, disturbed sleep, and muscle and joint pain. Effective treatments for the condition are limited, with debate over the use of CBT and GET versus the more frequently used APT.

CBT and GET offer a more hopeful approach to CFS treatment than APT, because they focus on patients’ abilities rather than their disabilities, the investigators noted. APT is based on a more nihilistic premise, focusing on coming to terms with the illness and optimizing activities accordingly, they added.

The Pacing, Graded Activity, and Cognitive Behaviour Therapy: a Randomised Evaluation (PACE) trial was a prospective, multicenter, randomized trial of 640 outpatients with CFS comparing four parallel treatment arms: SMC alone, SMC plus APT, SMC plus CBT, and SMC plus GET. Patients were given individual therapy sessions once a month and group interventions every 3 months. Interventions were given for up to 24 weeks, with follow-up assessments at 1 year.

More than 3,100 patients were originally screened for the trial, but only those who met the Oxford criteria for CFS were enrolled. Those criteria require fatigue to be the predominant symptom, accompanied by significant physical disability in the absence of any other psychiatric or organic brain disorder.

Approximately 75% of the study participants were women, and the majority (93%) of patients was white. The mean age was 38 years, and the mean duration of illness was 32 months. The coprimary end points of fatigue and physical functioning were measured using the patient-reported Chalder fatigue questionnaire and the Short Form-36 physical function subscale.

"The take-home message is that we now have robust evidence of the effectiveness, and importantly for patients, the safety of CBT and GET, as long as they are given by properly trained people," said Dr. Michael Sharp, a study coauthor who is a professor of psychological medicine and director of psychological medicine research at the University of Edinburgh, Scotland.

Funding for the PACE trial was provided by the U.K. Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, and Department for Work and Pensions. Dr. Chalder and Dr. Sharp reported no relevant conflicts of interest.

"Although the PACE trial shows that recovery from chronic fatigue syndrome is possible, there is clearly room for improvement with both interventions (cognitive behaviour therapy and graded exercise therapy)," noted Dr. Gijs Bleijenberg and Dr. Hans Knoop of Radboud University Nijmegen (Netherlands) Medical Centre in an accompanying editorial (Lancet 2011 Feb. 17 [doi:10.1016/S0140-6736(11)60172-4]).

"Both interventions could be improved if more was known about the mechanisms of change," they added. "Future studies into mechanisms of change are urgently needed and could help to improve the efficacy of the interventions, by focusing on the elements that are crucial for change."

Other independent experts welcomed the findings of the PACE study, commending the trial for finally answering a long-held dilemma.

"This study matters – it matters a lot," said Dr. Willie Hamilton, a primary care practitioner and professor of primary care diagnostics at the Peninsula College of Medicine and Dentistry in Exeter, England.

"Until now, we have known that only CBT and GET work for some people. We didn’t know if pacing worked," Dr. Hamilton said. "This caused a real dilemma – especially for those in primary care. We didn’t know whether to recommend pacing or to refer for CBT or GET. This study should solve that."

His words were echoed by Dr. Derick Wade, a consultant in neurological rehabilitation and clinical director at the Oxford Center for Enablement. "The trial design in this study was very good, and it means that the conclusions drawn can be drawn with confidence," Dr. Wade said.

While the study’s findings confirm the safety and effectiveness of CBT and GET, Dr. Wade noted, the findings on the use of APT show that "one commonly used intervention is not effective and therefore should not be used."

Dr. Fergus Macbeth, director of the Centre for Clinical Practice at the National Institute for Health and Clinical Excellence, London, said, "We welcome the findings of the PACE trial, which further support cognitive behavioural therapy and graded exercise therapy as safe and effective treatment options for people who have mild/moderate chronic fatigue syndrome or myalgic encephalomyelitis. These findings are in line with our current recommendations on the management of this condition.

"We will now analyze the results of this important trial in more detail before making a final decision on whether there is a clinical need to update our guideline," Dr. Macbeth said.

LONDON – Cognitive behavioral therapy and graded exercise therapy are both safe and effective to use in combination with specialist medical care for chronic fatigue syndrome, according to the results of a large randomized, controlled trial.

In contrast, adapted pacing therapy (APT), which several patient organizations have advocated as the preferred treatment choice together with specialist medical care, offers no real benefit – leading some experts to suggest that perhaps APT should no longer be used.

The findings were reported online Feb. 17 in the Lancet.

Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) – but not APT – significantly lowered fatigue and raised physical function scores when compared with specialist medical care (SMC) alone.

At 1-year follow-up, the respective changes in fatigue and physical function scores versus SMC alone were –3.4 and +7.1 for CBT, and –3.2 and +9.4 for GET, all of which were statistically significant differences. In contrast, the changes in those scores for APT were –0.7 and –3.4, respectively, differences that weren’t statistically significant.

Although the effects of CBT and GET on chronic fatigue syndrome (CFS) are still rather moderate, "the bottom line is that patients given CBT and GET showed more improvement than the other two groups," said Trudie Chalder, Ph.D., one of the study’s authors and a professor of cognitive behavioral psychotherapy at King’s College London (Lancet 2011 Feb. 17 [doi:10.1016/S0140-6736(11)60096-2]).

CFS affects around a quarter of a million people in the United Kingdom. Symptoms include severe fatigue, poor concentration and memory, disturbed sleep, and muscle and joint pain. Effective treatments for the condition are limited, with debate over the use of CBT and GET versus the more frequently used APT.

CBT and GET offer a more hopeful approach to CFS treatment than APT, because they focus on patients’ abilities rather than their disabilities, the investigators noted. APT is based on a more nihilistic premise, focusing on coming to terms with the illness and optimizing activities accordingly, they added.

The Pacing, Graded Activity, and Cognitive Behaviour Therapy: a Randomised Evaluation (PACE) trial was a prospective, multicenter, randomized trial of 640 outpatients with CFS comparing four parallel treatment arms: SMC alone, SMC plus APT, SMC plus CBT, and SMC plus GET. Patients were given individual therapy sessions once a month and group interventions every 3 months. Interventions were given for up to 24 weeks, with follow-up assessments at 1 year.

More than 3,100 patients were originally screened for the trial, but only those who met the Oxford criteria for CFS were enrolled. Those criteria require fatigue to be the predominant symptom, accompanied by significant physical disability in the absence of any other psychiatric or organic brain disorder.

Approximately 75% of the study participants were women, and the majority (93%) of patients was white. The mean age was 38 years, and the mean duration of illness was 32 months. The coprimary end points of fatigue and physical functioning were measured using the patient-reported Chalder fatigue questionnaire and the Short Form-36 physical function subscale.

"The take-home message is that we now have robust evidence of the effectiveness, and importantly for patients, the safety of CBT and GET, as long as they are given by properly trained people," said Dr. Michael Sharp, a study coauthor who is a professor of psychological medicine and director of psychological medicine research at the University of Edinburgh, Scotland.

Funding for the PACE trial was provided by the U.K. Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, and Department for Work and Pensions. Dr. Chalder and Dr. Sharp reported no relevant conflicts of interest.

"Although the PACE trial shows that recovery from chronic fatigue syndrome is possible, there is clearly room for improvement with both interventions (cognitive behaviour therapy and graded exercise therapy)," noted Dr. Gijs Bleijenberg and Dr. Hans Knoop of Radboud University Nijmegen (Netherlands) Medical Centre in an accompanying editorial (Lancet 2011 Feb. 17 [doi:10.1016/S0140-6736(11)60172-4]).

"Both interventions could be improved if more was known about the mechanisms of change," they added. "Future studies into mechanisms of change are urgently needed and could help to improve the efficacy of the interventions, by focusing on the elements that are crucial for change."

Other independent experts welcomed the findings of the PACE study, commending the trial for finally answering a long-held dilemma.

"This study matters – it matters a lot," said Dr. Willie Hamilton, a primary care practitioner and professor of primary care diagnostics at the Peninsula College of Medicine and Dentistry in Exeter, England.

"Until now, we have known that only CBT and GET work for some people. We didn’t know if pacing worked," Dr. Hamilton said. "This caused a real dilemma – especially for those in primary care. We didn’t know whether to recommend pacing or to refer for CBT or GET. This study should solve that."

His words were echoed by Dr. Derick Wade, a consultant in neurological rehabilitation and clinical director at the Oxford Center for Enablement. "The trial design in this study was very good, and it means that the conclusions drawn can be drawn with confidence," Dr. Wade said.

While the study’s findings confirm the safety and effectiveness of CBT and GET, Dr. Wade noted, the findings on the use of APT show that "one commonly used intervention is not effective and therefore should not be used."

Dr. Fergus Macbeth, director of the Centre for Clinical Practice at the National Institute for Health and Clinical Excellence, London, said, "We welcome the findings of the PACE trial, which further support cognitive behavioural therapy and graded exercise therapy as safe and effective treatment options for people who have mild/moderate chronic fatigue syndrome or myalgic encephalomyelitis. These findings are in line with our current recommendations on the management of this condition.

"We will now analyze the results of this important trial in more detail before making a final decision on whether there is a clinical need to update our guideline," Dr. Macbeth said.

LONDON – Cognitive behavioral therapy and graded exercise therapy are both safe and effective to use in combination with specialist medical care for chronic fatigue syndrome, according to the results of a large randomized, controlled trial.

In contrast, adapted pacing therapy (APT), which several patient organizations have advocated as the preferred treatment choice together with specialist medical care, offers no real benefit – leading some experts to suggest that perhaps APT should no longer be used.

The findings were reported online Feb. 17 in the Lancet.

Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) – but not APT – significantly lowered fatigue and raised physical function scores when compared with specialist medical care (SMC) alone.

At 1-year follow-up, the respective changes in fatigue and physical function scores versus SMC alone were –3.4 and +7.1 for CBT, and –3.2 and +9.4 for GET, all of which were statistically significant differences. In contrast, the changes in those scores for APT were –0.7 and –3.4, respectively, differences that weren’t statistically significant.

Although the effects of CBT and GET on chronic fatigue syndrome (CFS) are still rather moderate, "the bottom line is that patients given CBT and GET showed more improvement than the other two groups," said Trudie Chalder, Ph.D., one of the study’s authors and a professor of cognitive behavioral psychotherapy at King’s College London (Lancet 2011 Feb. 17 [doi:10.1016/S0140-6736(11)60096-2]).

CFS affects around a quarter of a million people in the United Kingdom. Symptoms include severe fatigue, poor concentration and memory, disturbed sleep, and muscle and joint pain. Effective treatments for the condition are limited, with debate over the use of CBT and GET versus the more frequently used APT.

CBT and GET offer a more hopeful approach to CFS treatment than APT, because they focus on patients’ abilities rather than their disabilities, the investigators noted. APT is based on a more nihilistic premise, focusing on coming to terms with the illness and optimizing activities accordingly, they added.

The Pacing, Graded Activity, and Cognitive Behaviour Therapy: a Randomised Evaluation (PACE) trial was a prospective, multicenter, randomized trial of 640 outpatients with CFS comparing four parallel treatment arms: SMC alone, SMC plus APT, SMC plus CBT, and SMC plus GET. Patients were given individual therapy sessions once a month and group interventions every 3 months. Interventions were given for up to 24 weeks, with follow-up assessments at 1 year.

More than 3,100 patients were originally screened for the trial, but only those who met the Oxford criteria for CFS were enrolled. Those criteria require fatigue to be the predominant symptom, accompanied by significant physical disability in the absence of any other psychiatric or organic brain disorder.

Approximately 75% of the study participants were women, and the majority (93%) of patients was white. The mean age was 38 years, and the mean duration of illness was 32 months. The coprimary end points of fatigue and physical functioning were measured using the patient-reported Chalder fatigue questionnaire and the Short Form-36 physical function subscale.

"The take-home message is that we now have robust evidence of the effectiveness, and importantly for patients, the safety of CBT and GET, as long as they are given by properly trained people," said Dr. Michael Sharp, a study coauthor who is a professor of psychological medicine and director of psychological medicine research at the University of Edinburgh, Scotland.

Funding for the PACE trial was provided by the U.K. Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, and Department for Work and Pensions. Dr. Chalder and Dr. Sharp reported no relevant conflicts of interest.

"Although the PACE trial shows that recovery from chronic fatigue syndrome is possible, there is clearly room for improvement with both interventions (cognitive behaviour therapy and graded exercise therapy)," noted Dr. Gijs Bleijenberg and Dr. Hans Knoop of Radboud University Nijmegen (Netherlands) Medical Centre in an accompanying editorial (Lancet 2011 Feb. 17 [doi:10.1016/S0140-6736(11)60172-4]).

"Both interventions could be improved if more was known about the mechanisms of change," they added. "Future studies into mechanisms of change are urgently needed and could help to improve the efficacy of the interventions, by focusing on the elements that are crucial for change."

Other independent experts welcomed the findings of the PACE study, commending the trial for finally answering a long-held dilemma.

"This study matters – it matters a lot," said Dr. Willie Hamilton, a primary care practitioner and professor of primary care diagnostics at the Peninsula College of Medicine and Dentistry in Exeter, England.

"Until now, we have known that only CBT and GET work for some people. We didn’t know if pacing worked," Dr. Hamilton said. "This caused a real dilemma – especially for those in primary care. We didn’t know whether to recommend pacing or to refer for CBT or GET. This study should solve that."

His words were echoed by Dr. Derick Wade, a consultant in neurological rehabilitation and clinical director at the Oxford Center for Enablement. "The trial design in this study was very good, and it means that the conclusions drawn can be drawn with confidence," Dr. Wade said.

While the study’s findings confirm the safety and effectiveness of CBT and GET, Dr. Wade noted, the findings on the use of APT show that "one commonly used intervention is not effective and therefore should not be used."

Dr. Fergus Macbeth, director of the Centre for Clinical Practice at the National Institute for Health and Clinical Excellence, London, said, "We welcome the findings of the PACE trial, which further support cognitive behavioural therapy and graded exercise therapy as safe and effective treatment options for people who have mild/moderate chronic fatigue syndrome or myalgic encephalomyelitis. These findings are in line with our current recommendations on the management of this condition.

"We will now analyze the results of this important trial in more detail before making a final decision on whether there is a clinical need to update our guideline," Dr. Macbeth said.

HUNTINGTON BEACH, CALIF. – Three things have been found to be strong predictors of whether a patient will develop post-traumatic stress disorder following physical trauma, Medical College of Wisconsin, Milwaukee, researchers reported.

Patients are more likely to develop PTSD if they were victims of violence; if they perceive they were grievously injured, regardless of their injury severity score; and if they think they were almost killed, whether that’s true or not.

The researchers used surveys to determine what factors predict PTSD in trauma patients, fourth-year medical student Jessica Anderson said when she presented the findings at the Academic Surgical Conference, which was sponsored by the Association for Academic Surgery and the Society of University Surgeons.

Within about 72 hours of admission, 403 trauma patients completed the 17-question Post-Traumatic Stress Disorder checklist (pdf) and the Short Form-36 – a quality of life survey that assesses mental and physical function; 129 filled out the forms when requested to do so 6 months later.

A previous study found severe PTSD symptoms in 22.5% of patients admitted to the trauma service; in the new study, 18.6% of the 6-month respondents had checklist scores above 44, indicating PTSD.

Victims of violence – shootings, stabbings, or assaults – had mean 6-month checklist scores of 45.79; mean score for accident victims was 32.27 (P = .005).

Higher PTSD scores correlated with lower quality-of-life scores. Assault victims also scored lower on mental functioning at 6 months (P = .001).

"The variables that were statistically significant in predicting PTSD severity at 6 months included assaultive type of mechanism, scene heart rate, perceived injury severity score, and perceived life threat," Ms. Anderson said.

Age and gender were not predictive. On multiple regression analysis, scene heart rate was no longer significant.

Such studies of PTSD in trauma patients are relatively new, said Dr. Karen Brasel, a surgery professor at the college and a trauma surgeon at its associated Froedtert Memorial Lutheran Hospital, also in Milwaukee.

These three factors have been identified before among military personnel and domestic violence victims, but they appear to apply to other trauma victims, as well, she said.

"People don’t really think about PTSD in relation to garden-variety car crashes or getting stabbed in a gang fight," said Dr. Brasel, who is helping to lead efforts at the hospital to address PTSD in trauma patients.

Although nothing can be done about the injury mechanism, the other two contributing factors – the perceptions about injury severity and death risk – may be amenable to cognitive-behavioral therapy (CBT).

Patients admitted to the hospital’s level 1 trauma center are screened as soon as possible for PTSD symptoms with the civilian version of the PTSD Checklist.

Those who score above 44, indicating severe PTSD symptoms, are referred to psychologist Terri deRoon Cassini, Ph.D., who begins to work with them to mitigate PTSD symptoms, and continues to do so after they are discharged.

Since joining the trauma team in September 2008, Dr. deRoon Cassini has used CBT to halt possible PTSD for several hundred assault victims and survivors of car crashes and other accidents. The CBT approach involves disengaging the memory of the event from the autonomic response to it, as it’s the hyperactivated fight-or-flight response that creates and maintains the panic attacks, nightmares, flashbacks, and other PTSD symptoms that make return to a normal quality of life difficult.

Patients tell Dr. deRoon Cassini their stories over and over again; with each retelling, the autonomic response fades. Eventually, the trauma becomes just another memory, not something the body relives 24 hours a day.

"A lot of times people will say, ‘I’m having flashbacks, I’m having nightmares, I’m going crazy. I keep seeing the car flipping over and over and over again. I keep hearing the gun go off,’ " she said.

After the conditioned response is broken through CBT, she helps patients "process what happened and restructure their cognitive perceptions," she said. Eventually they realize "that was really scary, but it’s over," said Dr. deRoon Cassini.

A randomized trial is planned to measure the success of that approach, Dr. Brasel said. In the planned trial, half of newly admitted high scorers on the PTSD checklist will be randomized to CBT, half to no treatment.

They’ll be followed to assess rates of PTSD development, a diagnosis that requires symptoms be present at least 1 month, with the goal of finding out if early intervention helps.

The trial will include salivary cortisol measurements and possibly functional MRI, Dr. Brasel said.

Dr. Brasel, Dr. deRoon Cassini, and Ms. Anderson said they have no conflicts of interest.

The PTSD risk factor study was funded in part by a Centers for Disease Control and Prevention grant to the college’s Injury Research Center. The study was done not only to figure out how to best help patients after physical trauma, but also "to provide evidence to the funding agencies that this is truly an important thing to investigate," Dr. Brasel said.

The researchers said they had no conflicts of interest.

HUNTINGTON BEACH, CALIF. – Three things have been found to be strong predictors of whether a patient will develop post-traumatic stress disorder following physical trauma, Medical College of Wisconsin, Milwaukee, researchers reported.

Patients are more likely to develop PTSD if they were victims of violence; if they perceive they were grievously injured, regardless of their injury severity score; and if they think they were almost killed, whether that’s true or not.

The researchers used surveys to determine what factors predict PTSD in trauma patients, fourth-year medical student Jessica Anderson said when she presented the findings at the Academic Surgical Conference, which was sponsored by the Association for Academic Surgery and the Society of University Surgeons.

Within about 72 hours of admission, 403 trauma patients completed the 17-question Post-Traumatic Stress Disorder checklist (pdf) and the Short Form-36 – a quality of life survey that assesses mental and physical function; 129 filled out the forms when requested to do so 6 months later.

A previous study found severe PTSD symptoms in 22.5% of patients admitted to the trauma service; in the new study, 18.6% of the 6-month respondents had checklist scores above 44, indicating PTSD.

Victims of violence – shootings, stabbings, or assaults – had mean 6-month checklist scores of 45.79; mean score for accident victims was 32.27 (P = .005).

Higher PTSD scores correlated with lower quality-of-life scores. Assault victims also scored lower on mental functioning at 6 months (P = .001).

"The variables that were statistically significant in predicting PTSD severity at 6 months included assaultive type of mechanism, scene heart rate, perceived injury severity score, and perceived life threat," Ms. Anderson said.

Age and gender were not predictive. On multiple regression analysis, scene heart rate was no longer significant.

Such studies of PTSD in trauma patients are relatively new, said Dr. Karen Brasel, a surgery professor at the college and a trauma surgeon at its associated Froedtert Memorial Lutheran Hospital, also in Milwaukee.

These three factors have been identified before among military personnel and domestic violence victims, but they appear to apply to other trauma victims, as well, she said.

"People don’t really think about PTSD in relation to garden-variety car crashes or getting stabbed in a gang fight," said Dr. Brasel, who is helping to lead efforts at the hospital to address PTSD in trauma patients.

Although nothing can be done about the injury mechanism, the other two contributing factors – the perceptions about injury severity and death risk – may be amenable to cognitive-behavioral therapy (CBT).

Patients admitted to the hospital’s level 1 trauma center are screened as soon as possible for PTSD symptoms with the civilian version of the PTSD Checklist.

Those who score above 44, indicating severe PTSD symptoms, are referred to psychologist Terri deRoon Cassini, Ph.D., who begins to work with them to mitigate PTSD symptoms, and continues to do so after they are discharged.

Since joining the trauma team in September 2008, Dr. deRoon Cassini has used CBT to halt possible PTSD for several hundred assault victims and survivors of car crashes and other accidents. The CBT approach involves disengaging the memory of the event from the autonomic response to it, as it’s the hyperactivated fight-or-flight response that creates and maintains the panic attacks, nightmares, flashbacks, and other PTSD symptoms that make return to a normal quality of life difficult.

Patients tell Dr. deRoon Cassini their stories over and over again; with each retelling, the autonomic response fades. Eventually, the trauma becomes just another memory, not something the body relives 24 hours a day.

"A lot of times people will say, ‘I’m having flashbacks, I’m having nightmares, I’m going crazy. I keep seeing the car flipping over and over and over again. I keep hearing the gun go off,’ " she said.

After the conditioned response is broken through CBT, she helps patients "process what happened and restructure their cognitive perceptions," she said. Eventually they realize "that was really scary, but it’s over," said Dr. deRoon Cassini.

A randomized trial is planned to measure the success of that approach, Dr. Brasel said. In the planned trial, half of newly admitted high scorers on the PTSD checklist will be randomized to CBT, half to no treatment.

They’ll be followed to assess rates of PTSD development, a diagnosis that requires symptoms be present at least 1 month, with the goal of finding out if early intervention helps.

The trial will include salivary cortisol measurements and possibly functional MRI, Dr. Brasel said.

Dr. Brasel, Dr. deRoon Cassini, and Ms. Anderson said they have no conflicts of interest.

The PTSD risk factor study was funded in part by a Centers for Disease Control and Prevention grant to the college’s Injury Research Center. The study was done not only to figure out how to best help patients after physical trauma, but also "to provide evidence to the funding agencies that this is truly an important thing to investigate," Dr. Brasel said.

The researchers said they had no conflicts of interest.

HUNTINGTON BEACH, CALIF. – Three things have been found to be strong predictors of whether a patient will develop post-traumatic stress disorder following physical trauma, Medical College of Wisconsin, Milwaukee, researchers reported.

Patients are more likely to develop PTSD if they were victims of violence; if they perceive they were grievously injured, regardless of their injury severity score; and if they think they were almost killed, whether that’s true or not.

The researchers used surveys to determine what factors predict PTSD in trauma patients, fourth-year medical student Jessica Anderson said when she presented the findings at the Academic Surgical Conference, which was sponsored by the Association for Academic Surgery and the Society of University Surgeons.

Within about 72 hours of admission, 403 trauma patients completed the 17-question Post-Traumatic Stress Disorder checklist (pdf) and the Short Form-36 – a quality of life survey that assesses mental and physical function; 129 filled out the forms when requested to do so 6 months later.

A previous study found severe PTSD symptoms in 22.5% of patients admitted to the trauma service; in the new study, 18.6% of the 6-month respondents had checklist scores above 44, indicating PTSD.

Victims of violence – shootings, stabbings, or assaults – had mean 6-month checklist scores of 45.79; mean score for accident victims was 32.27 (P = .005).

Higher PTSD scores correlated with lower quality-of-life scores. Assault victims also scored lower on mental functioning at 6 months (P = .001).

"The variables that were statistically significant in predicting PTSD severity at 6 months included assaultive type of mechanism, scene heart rate, perceived injury severity score, and perceived life threat," Ms. Anderson said.

Age and gender were not predictive. On multiple regression analysis, scene heart rate was no longer significant.

Such studies of PTSD in trauma patients are relatively new, said Dr. Karen Brasel, a surgery professor at the college and a trauma surgeon at its associated Froedtert Memorial Lutheran Hospital, also in Milwaukee.

These three factors have been identified before among military personnel and domestic violence victims, but they appear to apply to other trauma victims, as well, she said.

"People don’t really think about PTSD in relation to garden-variety car crashes or getting stabbed in a gang fight," said Dr. Brasel, who is helping to lead efforts at the hospital to address PTSD in trauma patients.

Although nothing can be done about the injury mechanism, the other two contributing factors – the perceptions about injury severity and death risk – may be amenable to cognitive-behavioral therapy (CBT).

Patients admitted to the hospital’s level 1 trauma center are screened as soon as possible for PTSD symptoms with the civilian version of the PTSD Checklist.

Those who score above 44, indicating severe PTSD symptoms, are referred to psychologist Terri deRoon Cassini, Ph.D., who begins to work with them to mitigate PTSD symptoms, and continues to do so after they are discharged.

Since joining the trauma team in September 2008, Dr. deRoon Cassini has used CBT to halt possible PTSD for several hundred assault victims and survivors of car crashes and other accidents. The CBT approach involves disengaging the memory of the event from the autonomic response to it, as it’s the hyperactivated fight-or-flight response that creates and maintains the panic attacks, nightmares, flashbacks, and other PTSD symptoms that make return to a normal quality of life difficult.

Patients tell Dr. deRoon Cassini their stories over and over again; with each retelling, the autonomic response fades. Eventually, the trauma becomes just another memory, not something the body relives 24 hours a day.

"A lot of times people will say, ‘I’m having flashbacks, I’m having nightmares, I’m going crazy. I keep seeing the car flipping over and over and over again. I keep hearing the gun go off,’ " she said.

After the conditioned response is broken through CBT, she helps patients "process what happened and restructure their cognitive perceptions," she said. Eventually they realize "that was really scary, but it’s over," said Dr. deRoon Cassini.

A randomized trial is planned to measure the success of that approach, Dr. Brasel said. In the planned trial, half of newly admitted high scorers on the PTSD checklist will be randomized to CBT, half to no treatment.

They’ll be followed to assess rates of PTSD development, a diagnosis that requires symptoms be present at least 1 month, with the goal of finding out if early intervention helps.

The trial will include salivary cortisol measurements and possibly functional MRI, Dr. Brasel said.

Dr. Brasel, Dr. deRoon Cassini, and Ms. Anderson said they have no conflicts of interest.

The PTSD risk factor study was funded in part by a Centers for Disease Control and Prevention grant to the college’s Injury Research Center. The study was done not only to figure out how to best help patients after physical trauma, but also "to provide evidence to the funding agencies that this is truly an important thing to investigate," Dr. Brasel said.

The researchers said they had no conflicts of interest.

Edinburgh, Scotland – Newer screening tools for depression and anxiety in persons with epilepsy have been developed that are much faster and easier to use than anything previously available.

The tools long favored by psychiatrists, including the Hospital Anxiety and Depression Scale and the Beck Depression Inventory, are too lengthy, cumbersome, and hard to score for use as routine screening instruments by busy primary care physicians, neurologists, and epilepsy nurses. Also, these are verbal tests, and patients with epilepsy often have difficulty in concentrating and completing them, Dr. Niruj Agrawal said at the congress.

Depression and anxiety are far more common in patients with epilepsy than in the general population. These conditions are underdiagnosed in patients with epilepsy and adversely affect their quality of life. Routine screening is warranted. The newer, brief instruments, such as the Emotional Thermometer-7 (ET-7) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), make this much more practical, said Dr. Agrawal, a psychiatrist at St. George’s Hospital, London.

Multiple studies conducted in various parts of the world show that roughly one-third of patients with epilepsy seen in primary care settings are depressed. The prevalence rises to about 50% among patients seen in specialty neurologic settings for more resistant epilepsy. A large U.S. study has shown that patients with epilepsy and comorbid depression are heavier users of health care services, with more visits to primary care clinics and emergency departments than patients with epilepsy alone (Epilepsy Behav. 2007;10:539-46).

One of the most compelling arguments for routine screening for anxiety and depression in persons with epilepsy is that these comorbidities massively increase suicide risk. A large national Danish study showed that individuals with epilepsy alone had a suicide rate 2.4-fold greater than controls, while those with epilepsy plus an anxiety disorder had a suicide rate 11.4-fold greater than controls, and patients with epilepsy and depression had a stunning 32-fold increase in suicide (Lancet Neurol. 2007;6:693-8).

Quality of life scores in the two-thirds of patients with epilepsy who become seizure-free with treatment are similar to scores in the general population, but patients with refractory epilepsy tend to score poorly on such measures. A prospective study at New York University showed that depression was present in 54% of a series of patients hospitalized for refractory epilepsy, of whom only 17% were on antidepressants. Depression was a powerful predictor of quality of life scores in this study, whereas seizure frequency was not (Neurology 2004;62:258-61).

These findings have been replicated elsewhere. The message is that alleviating depression in patients with treatment-resistant epilepsy will do more to improve their quality of life than reducing their seizure frequency, unless the seizures can be eliminated altogether, Dr. Agrawal said.

Turning to the brief instruments designed for rapid detection of depression in epilepsy, he noted that the NDDI-E had a negative predictive value of 96%, a positive predictive value of 62%, sensitivity of 81%, and specificity of 90% in a study of 205 adult outpatients with epilepsy (Lancet Neurol. 2006;5:399-405).

The NDDI-E was developed by neurologists at Columbia University in New York who were seeking a simple means of differentiating true depression from the common adverse effects of antiepileptic drugs, which can mask some symptoms of depression or cause symptoms that can be mistaken for depression, such as disturbances in sleep, concentration, and appetite.

Patients taking the NDDI-E assign scores of 1-4 on each of 6 items: everything is a struggle; nothing I do is right; I feel guilty; I’d be better off dead; I feel frustrated; and I have difficulty finding pleasure. The scores range from 1 point if the patient never experiences a particular symptom to 4 points if they always or often do. The investigators found that a score of 15 is the best cutoff point.

Dr. Agrawal has been working with the ET-7, a series of patient-rated visual analog scales originally developed by Dr. Alex J. Mitchell of the Leicester (U.K.) Royal Infirmary for use in screening cancer patients for depression and anxiety (Psychooncology 2010;19:125-33; Psychooncology 2010;19:134-40).

Dr. Agrawal recently performed a comparative study of five screening tools in a series of 250 epilepsy patients. The five instruments were the ET-7, the NDDI-E, the BDI-II, the HADS, and the Major Depression Inventory. Using the ICD-10 diagnostic criteria as the gold standard, the most accurate test was the BDI-II, which Dr. Agrawal considers impractical for use by busy non-psychiatrists. He was able to confirm the reliability of the NDDI-E, which in this population had a sensitivity of 87% and specificity of 81%. The ET-7, a brief nonverbal instrument, had a sensitivity of 74% and specificity of 86%.

This study underscored the high degree of overlap between depression and anxiety. Half of the 250 epilepsy patients had significant anxiety symptoms and 37% were depressed. But only 5% of patients with depression did not have anxiety, and only 10% of patients who had anxiety did not have depression, the psychiatrist noted.

He declared no conflicts of interest.

Edinburgh, Scotland – Newer screening tools for depression and anxiety in persons with epilepsy have been developed that are much faster and easier to use than anything previously available.

The tools long favored by psychiatrists, including the Hospital Anxiety and Depression Scale and the Beck Depression Inventory, are too lengthy, cumbersome, and hard to score for use as routine screening instruments by busy primary care physicians, neurologists, and epilepsy nurses. Also, these are verbal tests, and patients with epilepsy often have difficulty in concentrating and completing them, Dr. Niruj Agrawal said at the congress.

Depression and anxiety are far more common in patients with epilepsy than in the general population. These conditions are underdiagnosed in patients with epilepsy and adversely affect their quality of life. Routine screening is warranted. The newer, brief instruments, such as the Emotional Thermometer-7 (ET-7) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), make this much more practical, said Dr. Agrawal, a psychiatrist at St. George’s Hospital, London.

Multiple studies conducted in various parts of the world show that roughly one-third of patients with epilepsy seen in primary care settings are depressed. The prevalence rises to about 50% among patients seen in specialty neurologic settings for more resistant epilepsy. A large U.S. study has shown that patients with epilepsy and comorbid depression are heavier users of health care services, with more visits to primary care clinics and emergency departments than patients with epilepsy alone (Epilepsy Behav. 2007;10:539-46).

One of the most compelling arguments for routine screening for anxiety and depression in persons with epilepsy is that these comorbidities massively increase suicide risk. A large national Danish study showed that individuals with epilepsy alone had a suicide rate 2.4-fold greater than controls, while those with epilepsy plus an anxiety disorder had a suicide rate 11.4-fold greater than controls, and patients with epilepsy and depression had a stunning 32-fold increase in suicide (Lancet Neurol. 2007;6:693-8).

Quality of life scores in the two-thirds of patients with epilepsy who become seizure-free with treatment are similar to scores in the general population, but patients with refractory epilepsy tend to score poorly on such measures. A prospective study at New York University showed that depression was present in 54% of a series of patients hospitalized for refractory epilepsy, of whom only 17% were on antidepressants. Depression was a powerful predictor of quality of life scores in this study, whereas seizure frequency was not (Neurology 2004;62:258-61).

These findings have been replicated elsewhere. The message is that alleviating depression in patients with treatment-resistant epilepsy will do more to improve their quality of life than reducing their seizure frequency, unless the seizures can be eliminated altogether, Dr. Agrawal said.

Turning to the brief instruments designed for rapid detection of depression in epilepsy, he noted that the NDDI-E had a negative predictive value of 96%, a positive predictive value of 62%, sensitivity of 81%, and specificity of 90% in a study of 205 adult outpatients with epilepsy (Lancet Neurol. 2006;5:399-405).

The NDDI-E was developed by neurologists at Columbia University in New York who were seeking a simple means of differentiating true depression from the common adverse effects of antiepileptic drugs, which can mask some symptoms of depression or cause symptoms that can be mistaken for depression, such as disturbances in sleep, concentration, and appetite.

Patients taking the NDDI-E assign scores of 1-4 on each of 6 items: everything is a struggle; nothing I do is right; I feel guilty; I’d be better off dead; I feel frustrated; and I have difficulty finding pleasure. The scores range from 1 point if the patient never experiences a particular symptom to 4 points if they always or often do. The investigators found that a score of 15 is the best cutoff point.

Dr. Agrawal has been working with the ET-7, a series of patient-rated visual analog scales originally developed by Dr. Alex J. Mitchell of the Leicester (U.K.) Royal Infirmary for use in screening cancer patients for depression and anxiety (Psychooncology 2010;19:125-33; Psychooncology 2010;19:134-40).

Dr. Agrawal recently performed a comparative study of five screening tools in a series of 250 epilepsy patients. The five instruments were the ET-7, the NDDI-E, the BDI-II, the HADS, and the Major Depression Inventory. Using the ICD-10 diagnostic criteria as the gold standard, the most accurate test was the BDI-II, which Dr. Agrawal considers impractical for use by busy non-psychiatrists. He was able to confirm the reliability of the NDDI-E, which in this population had a sensitivity of 87% and specificity of 81%. The ET-7, a brief nonverbal instrument, had a sensitivity of 74% and specificity of 86%.

This study underscored the high degree of overlap between depression and anxiety. Half of the 250 epilepsy patients had significant anxiety symptoms and 37% were depressed. But only 5% of patients with depression did not have anxiety, and only 10% of patients who had anxiety did not have depression, the psychiatrist noted.

He declared no conflicts of interest.

Edinburgh, Scotland – Newer screening tools for depression and anxiety in persons with epilepsy have been developed that are much faster and easier to use than anything previously available.

The tools long favored by psychiatrists, including the Hospital Anxiety and Depression Scale and the Beck Depression Inventory, are too lengthy, cumbersome, and hard to score for use as routine screening instruments by busy primary care physicians, neurologists, and epilepsy nurses. Also, these are verbal tests, and patients with epilepsy often have difficulty in concentrating and completing them, Dr. Niruj Agrawal said at the congress.

Depression and anxiety are far more common in patients with epilepsy than in the general population. These conditions are underdiagnosed in patients with epilepsy and adversely affect their quality of life. Routine screening is warranted. The newer, brief instruments, such as the Emotional Thermometer-7 (ET-7) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), make this much more practical, said Dr. Agrawal, a psychiatrist at St. George’s Hospital, London.

Multiple studies conducted in various parts of the world show that roughly one-third of patients with epilepsy seen in primary care settings are depressed. The prevalence rises to about 50% among patients seen in specialty neurologic settings for more resistant epilepsy. A large U.S. study has shown that patients with epilepsy and comorbid depression are heavier users of health care services, with more visits to primary care clinics and emergency departments than patients with epilepsy alone (Epilepsy Behav. 2007;10:539-46).

One of the most compelling arguments for routine screening for anxiety and depression in persons with epilepsy is that these comorbidities massively increase suicide risk. A large national Danish study showed that individuals with epilepsy alone had a suicide rate 2.4-fold greater than controls, while those with epilepsy plus an anxiety disorder had a suicide rate 11.4-fold greater than controls, and patients with epilepsy and depression had a stunning 32-fold increase in suicide (Lancet Neurol. 2007;6:693-8).

Quality of life scores in the two-thirds of patients with epilepsy who become seizure-free with treatment are similar to scores in the general population, but patients with refractory epilepsy tend to score poorly on such measures. A prospective study at New York University showed that depression was present in 54% of a series of patients hospitalized for refractory epilepsy, of whom only 17% were on antidepressants. Depression was a powerful predictor of quality of life scores in this study, whereas seizure frequency was not (Neurology 2004;62:258-61).

These findings have been replicated elsewhere. The message is that alleviating depression in patients with treatment-resistant epilepsy will do more to improve their quality of life than reducing their seizure frequency, unless the seizures can be eliminated altogether, Dr. Agrawal said.

Turning to the brief instruments designed for rapid detection of depression in epilepsy, he noted that the NDDI-E had a negative predictive value of 96%, a positive predictive value of 62%, sensitivity of 81%, and specificity of 90% in a study of 205 adult outpatients with epilepsy (Lancet Neurol. 2006;5:399-405).

The NDDI-E was developed by neurologists at Columbia University in New York who were seeking a simple means of differentiating true depression from the common adverse effects of antiepileptic drugs, which can mask some symptoms of depression or cause symptoms that can be mistaken for depression, such as disturbances in sleep, concentration, and appetite.

Patients taking the NDDI-E assign scores of 1-4 on each of 6 items: everything is a struggle; nothing I do is right; I feel guilty; I’d be better off dead; I feel frustrated; and I have difficulty finding pleasure. The scores range from 1 point if the patient never experiences a particular symptom to 4 points if they always or often do. The investigators found that a score of 15 is the best cutoff point.

Dr. Agrawal has been working with the ET-7, a series of patient-rated visual analog scales originally developed by Dr. Alex J. Mitchell of the Leicester (U.K.) Royal Infirmary for use in screening cancer patients for depression and anxiety (Psychooncology 2010;19:125-33; Psychooncology 2010;19:134-40).

Dr. Agrawal recently performed a comparative study of five screening tools in a series of 250 epilepsy patients. The five instruments were the ET-7, the NDDI-E, the BDI-II, the HADS, and the Major Depression Inventory. Using the ICD-10 diagnostic criteria as the gold standard, the most accurate test was the BDI-II, which Dr. Agrawal considers impractical for use by busy non-psychiatrists. He was able to confirm the reliability of the NDDI-E, which in this population had a sensitivity of 87% and specificity of 81%. The ET-7, a brief nonverbal instrument, had a sensitivity of 74% and specificity of 86%.

This study underscored the high degree of overlap between depression and anxiety. Half of the 250 epilepsy patients had significant anxiety symptoms and 37% were depressed. But only 5% of patients with depression did not have anxiety, and only 10% of patients who had anxiety did not have depression, the psychiatrist noted.

He declared no conflicts of interest.

EDINBURGH – Depression is common, underdiagnosed, and undertreated in patients with psoriatic arthritis.

Psychiatric evaluation of 50 consecutive patients at the University of Glasgow psoriatic arthritis clinic indicated that 15 patients, or 30%, were depressed. Three were rated as severely depressed based on their scores on the Hospital Anxiety and Depression Scale (HADS), while 12 others had moderate depression, Dr. Rajeev Krishnadas reported at the International Congress of the Royal College of Psychiatrists.

This high prevalence of depression in psoriatic arthritis patients is consistent with reports in the dermatologic literature (Br. J. Dermatol. 2008;159:704-10).

Of note, none of the depressed Scottish psoriatic arthritis patients was on a therapeutic dose of an antidepressant, added Dr. Krishnadas of the Sackler Institute of Psychobiological Research, Southern General Hospital, Glasgow.

This study is part of a larger ongoing investigation looking at the relationship between systemic inflammation and depression in patients with rheumatoid arthritis or psoriatic arthritis. In this portion of the study, a positive association was noted between HADS scores and C-reactive protein levels in the psoriatic arthritis cohort, although it must be noted that CRP scores accounted for only 7% of the overall variance in HADS scores.

Not surprisingly, higher HADS scores were associated with worse quality of life as assessed by the Dermatology Quality of Life Questionnaire as well as with higher scores on a self-rated pain scale.

Of greater interest psychodynamically, a negative correlation was found between HADS scores and emotional intelligence as measured by the Trait Emotional Intelligence Questionnaire – Short Form. High trait emotional intelligence reflects greater awareness of one’s own feelings as well as the feelings of others’. Individuals with high emotional intelligence are far better able to regulate their emotions than are those with lower trait emotional intelligence.

Patients who scored high in trait emotional intelligence had higher quality of life scores, lower CRP levels, and lower scores on the pain scale.

These findings are consistent with the hypothesis that a poor ability to be aware of and regulate one’s emotions predisposes to depression in the presence of a chronic medical condition or other major stressor, according to Dr. Krishnadas.

He declared having no conflicts of interest.

EDINBURGH – Depression is common, underdiagnosed, and undertreated in patients with psoriatic arthritis.

Psychiatric evaluation of 50 consecutive patients at the University of Glasgow psoriatic arthritis clinic indicated that 15 patients, or 30%, were depressed. Three were rated as severely depressed based on their scores on the Hospital Anxiety and Depression Scale (HADS), while 12 others had moderate depression, Dr. Rajeev Krishnadas reported at the International Congress of the Royal College of Psychiatrists.

This high prevalence of depression in psoriatic arthritis patients is consistent with reports in the dermatologic literature (Br. J. Dermatol. 2008;159:704-10).

Of note, none of the depressed Scottish psoriatic arthritis patients was on a therapeutic dose of an antidepressant, added Dr. Krishnadas of the Sackler Institute of Psychobiological Research, Southern General Hospital, Glasgow.

This study is part of a larger ongoing investigation looking at the relationship between systemic inflammation and depression in patients with rheumatoid arthritis or psoriatic arthritis. In this portion of the study, a positive association was noted between HADS scores and C-reactive protein levels in the psoriatic arthritis cohort, although it must be noted that CRP scores accounted for only 7% of the overall variance in HADS scores.

Not surprisingly, higher HADS scores were associated with worse quality of life as assessed by the Dermatology Quality of Life Questionnaire as well as with higher scores on a self-rated pain scale.

Of greater interest psychodynamically, a negative correlation was found between HADS scores and emotional intelligence as measured by the Trait Emotional Intelligence Questionnaire – Short Form. High trait emotional intelligence reflects greater awareness of one’s own feelings as well as the feelings of others’. Individuals with high emotional intelligence are far better able to regulate their emotions than are those with lower trait emotional intelligence.

Patients who scored high in trait emotional intelligence had higher quality of life scores, lower CRP levels, and lower scores on the pain scale.

These findings are consistent with the hypothesis that a poor ability to be aware of and regulate one’s emotions predisposes to depression in the presence of a chronic medical condition or other major stressor, according to Dr. Krishnadas.

He declared having no conflicts of interest.

EDINBURGH – Depression is common, underdiagnosed, and undertreated in patients with psoriatic arthritis.

Psychiatric evaluation of 50 consecutive patients at the University of Glasgow psoriatic arthritis clinic indicated that 15 patients, or 30%, were depressed. Three were rated as severely depressed based on their scores on the Hospital Anxiety and Depression Scale (HADS), while 12 others had moderate depression, Dr. Rajeev Krishnadas reported at the International Congress of the Royal College of Psychiatrists.

This high prevalence of depression in psoriatic arthritis patients is consistent with reports in the dermatologic literature (Br. J. Dermatol. 2008;159:704-10).

Of note, none of the depressed Scottish psoriatic arthritis patients was on a therapeutic dose of an antidepressant, added Dr. Krishnadas of the Sackler Institute of Psychobiological Research, Southern General Hospital, Glasgow.

This study is part of a larger ongoing investigation looking at the relationship between systemic inflammation and depression in patients with rheumatoid arthritis or psoriatic arthritis. In this portion of the study, a positive association was noted between HADS scores and C-reactive protein levels in the psoriatic arthritis cohort, although it must be noted that CRP scores accounted for only 7% of the overall variance in HADS scores.

Not surprisingly, higher HADS scores were associated with worse quality of life as assessed by the Dermatology Quality of Life Questionnaire as well as with higher scores on a self-rated pain scale.

Of greater interest psychodynamically, a negative correlation was found between HADS scores and emotional intelligence as measured by the Trait Emotional Intelligence Questionnaire – Short Form. High trait emotional intelligence reflects greater awareness of one’s own feelings as well as the feelings of others’. Individuals with high emotional intelligence are far better able to regulate their emotions than are those with lower trait emotional intelligence.

Patients who scored high in trait emotional intelligence had higher quality of life scores, lower CRP levels, and lower scores on the pain scale.

These findings are consistent with the hypothesis that a poor ability to be aware of and regulate one’s emotions predisposes to depression in the presence of a chronic medical condition or other major stressor, according to Dr. Krishnadas.

He declared having no conflicts of interest.

Anorexia and bulimia can do measurable and likely irreversible damage to women’s eyes, researchers in Greece have found.

In a small study whose results were published online in the British Journal of Ophthalmology, Marilita M. Moschos, Ph.D., and her colleagues at the University of Athens reported finding "a significant anatomical and functional impairment, marked by a decrease in macular and retinal nerve fiber layer thickness as well as a decrease in electrical activity in the macula," among women with a history of anorexia or bulimia.

"The good thing is that the [anorexic and bulimic subjects] still had good vision," Dr. Moschos said in an interview. "But there is a crucial moment where if they lose more photoreceptors – for example, with untreated disease – "this will cause an irreversible vision loss."

For their research, Dr. Moschos and her colleagues evaluated macular and retinal nerve fiber layer thickness, as well as the electrical activity of the macula, in 13 female patients (mean age 28.6 years) with a diagnosis of anorexia nervosa (AN) – either of the calorie-restricting (n = 6) or binge-purge (n = 7) type, along with 20 healthy controls matched for age. Anorexic and bulimic patients had been diagnosed at least 8 years prior to the study and were in treatment at the time of the study, without current marked vitamin deficiencies [Br. J. Ophthalmol. 2010 [doi 10.1136/bjo.2009.177899]).

None of the anorexic or control patients had evidence of any visual failure; visual acuity for all remained normal. What the researchers found was subclinical damage to the structure of the anorexic women’s eyes. The anorexic women saw a mean foveal thickness of 140.04 mcm, compared with 150.85 in the control group. Retinal nerve fiber layers were also thinner – 116.42 mcm – in the superior area (vs. 123.15 in the control group) and 121.08 mcm in the inferior area (compared with 137.6 in the control group) around the optic nerve. With patients who self-induced vomiting, the damage was worse: in the left eye only, the calorie-restricting anorexics had a better foveal thickness (median 142 mcm) than did bulimics (median 134 mcm).

"Our results show that the retinal thickness of the macula is higher in restrictive-type anorectic patients than in binge-purge type patients, which means that the anatomical impairment of the fovea is greater in the AN binge-purge type, Dr. Moschos and colleagues wrote."

The possible reason for this, said Dr. Moschos in an interview, is that while calorie-restricting anorexics manage to obtain some vitamins, women who purge absorb fewer. "My opinion is that there is a correlation to vitamin deficiencies" over prolonged periods, she said.

Dr. Moschos and her colleagues noted that deficiencies of vitamin A in particular, a presumed culprit in one case study they cited of an anorexic with retinal lesions (J. Fr. Ophtalmol. 2007;30:15), were not seen among their subjects, whose own ocular changes, they speculated, were either caused by deficiencies of other nutrients or occurred in relation to dopamine, "an important neurotransmitter in the visual pathway."

The resxearchers mentioned several previous studies examining dopamine and physical changes to the retina. In people with Parkinson’s disease, "where there is a reduction in dopamine in the retina," they wrote, changes to retinal structure and function have been observed (Invest. Ophthalmol. Vis. Sci. 1990;31:2473-5).

And documented instances of impairment in visual discrimination learning among anorexics (Appetite 2003;40:85e9) "may be related to decreased appetitive function, possibly resulting from impaired dopaminergic neurotransmission, either as a result of food restriction or, more intriguingly, related to the underlying pathophysiology of AN itself," Dr. Moschos and her colleagues wrote.

The investigators acknowledged the limitations posed by the small size of their study, which is ongoing. Now, the group is extending the study to seek longer-term evidence of decline or even recovery in the young women’s maculae following treatment for their anorexia or bulimia. Currently, Dr. Moschos said, the wisdom that macular damage is irreversible stems from the fact that "what we know about maculae concerns much older people," than the anorexics in the study.

The study was funded by the University of Athens. Dr. Moschos and her colleagues reported no conflicts of interest.

Anorexia and bulimia can do measurable and likely irreversible damage to women’s eyes, researchers in Greece have found.

In a small study whose results were published online in the British Journal of Ophthalmology, Marilita M. Moschos, Ph.D., and her colleagues at the University of Athens reported finding "a significant anatomical and functional impairment, marked by a decrease in macular and retinal nerve fiber layer thickness as well as a decrease in electrical activity in the macula," among women with a history of anorexia or bulimia.

"The good thing is that the [anorexic and bulimic subjects] still had good vision," Dr. Moschos said in an interview. "But there is a crucial moment where if they lose more photoreceptors – for example, with untreated disease – "this will cause an irreversible vision loss."

For their research, Dr. Moschos and her colleagues evaluated macular and retinal nerve fiber layer thickness, as well as the electrical activity of the macula, in 13 female patients (mean age 28.6 years) with a diagnosis of anorexia nervosa (AN) – either of the calorie-restricting (n = 6) or binge-purge (n = 7) type, along with 20 healthy controls matched for age. Anorexic and bulimic patients had been diagnosed at least 8 years prior to the study and were in treatment at the time of the study, without current marked vitamin deficiencies [Br. J. Ophthalmol. 2010 [doi 10.1136/bjo.2009.177899]).

None of the anorexic or control patients had evidence of any visual failure; visual acuity for all remained normal. What the researchers found was subclinical damage to the structure of the anorexic women’s eyes. The anorexic women saw a mean foveal thickness of 140.04 mcm, compared with 150.85 in the control group. Retinal nerve fiber layers were also thinner – 116.42 mcm – in the superior area (vs. 123.15 in the control group) and 121.08 mcm in the inferior area (compared with 137.6 in the control group) around the optic nerve. With patients who self-induced vomiting, the damage was worse: in the left eye only, the calorie-restricting anorexics had a better foveal thickness (median 142 mcm) than did bulimics (median 134 mcm).

"Our results show that the retinal thickness of the macula is higher in restrictive-type anorectic patients than in binge-purge type patients, which means that the anatomical impairment of the fovea is greater in the AN binge-purge type, Dr. Moschos and colleagues wrote."

The possible reason for this, said Dr. Moschos in an interview, is that while calorie-restricting anorexics manage to obtain some vitamins, women who purge absorb fewer. "My opinion is that there is a correlation to vitamin deficiencies" over prolonged periods, she said.

Dr. Moschos and her colleagues noted that deficiencies of vitamin A in particular, a presumed culprit in one case study they cited of an anorexic with retinal lesions (J. Fr. Ophtalmol. 2007;30:15), were not seen among their subjects, whose own ocular changes, they speculated, were either caused by deficiencies of other nutrients or occurred in relation to dopamine, "an important neurotransmitter in the visual pathway."

The resxearchers mentioned several previous studies examining dopamine and physical changes to the retina. In people with Parkinson’s disease, "where there is a reduction in dopamine in the retina," they wrote, changes to retinal structure and function have been observed (Invest. Ophthalmol. Vis. Sci. 1990;31:2473-5).

And documented instances of impairment in visual discrimination learning among anorexics (Appetite 2003;40:85e9) "may be related to decreased appetitive function, possibly resulting from impaired dopaminergic neurotransmission, either as a result of food restriction or, more intriguingly, related to the underlying pathophysiology of AN itself," Dr. Moschos and her colleagues wrote.

The investigators acknowledged the limitations posed by the small size of their study, which is ongoing. Now, the group is extending the study to seek longer-term evidence of decline or even recovery in the young women’s maculae following treatment for their anorexia or bulimia. Currently, Dr. Moschos said, the wisdom that macular damage is irreversible stems from the fact that "what we know about maculae concerns much older people," than the anorexics in the study.

The study was funded by the University of Athens. Dr. Moschos and her colleagues reported no conflicts of interest.

Anorexia and bulimia can do measurable and likely irreversible damage to women’s eyes, researchers in Greece have found.

In a small study whose results were published online in the British Journal of Ophthalmology, Marilita M. Moschos, Ph.D., and her colleagues at the University of Athens reported finding "a significant anatomical and functional impairment, marked by a decrease in macular and retinal nerve fiber layer thickness as well as a decrease in electrical activity in the macula," among women with a history of anorexia or bulimia.

"The good thing is that the [anorexic and bulimic subjects] still had good vision," Dr. Moschos said in an interview. "But there is a crucial moment where if they lose more photoreceptors – for example, with untreated disease – "this will cause an irreversible vision loss."

For their research, Dr. Moschos and her colleagues evaluated macular and retinal nerve fiber layer thickness, as well as the electrical activity of the macula, in 13 female patients (mean age 28.6 years) with a diagnosis of anorexia nervosa (AN) – either of the calorie-restricting (n = 6) or binge-purge (n = 7) type, along with 20 healthy controls matched for age. Anorexic and bulimic patients had been diagnosed at least 8 years prior to the study and were in treatment at the time of the study, without current marked vitamin deficiencies [Br. J. Ophthalmol. 2010 [doi 10.1136/bjo.2009.177899]).

None of the anorexic or control patients had evidence of any visual failure; visual acuity for all remained normal. What the researchers found was subclinical damage to the structure of the anorexic women’s eyes. The anorexic women saw a mean foveal thickness of 140.04 mcm, compared with 150.85 in the control group. Retinal nerve fiber layers were also thinner – 116.42 mcm – in the superior area (vs. 123.15 in the control group) and 121.08 mcm in the inferior area (compared with 137.6 in the control group) around the optic nerve. With patients who self-induced vomiting, the damage was worse: in the left eye only, the calorie-restricting anorexics had a better foveal thickness (median 142 mcm) than did bulimics (median 134 mcm).

"Our results show that the retinal thickness of the macula is higher in restrictive-type anorectic patients than in binge-purge type patients, which means that the anatomical impairment of the fovea is greater in the AN binge-purge type, Dr. Moschos and colleagues wrote."

The possible reason for this, said Dr. Moschos in an interview, is that while calorie-restricting anorexics manage to obtain some vitamins, women who purge absorb fewer. "My opinion is that there is a correlation to vitamin deficiencies" over prolonged periods, she said.

Dr. Moschos and her colleagues noted that deficiencies of vitamin A in particular, a presumed culprit in one case study they cited of an anorexic with retinal lesions (J. Fr. Ophtalmol. 2007;30:15), were not seen among their subjects, whose own ocular changes, they speculated, were either caused by deficiencies of other nutrients or occurred in relation to dopamine, "an important neurotransmitter in the visual pathway."

The resxearchers mentioned several previous studies examining dopamine and physical changes to the retina. In people with Parkinson’s disease, "where there is a reduction in dopamine in the retina," they wrote, changes to retinal structure and function have been observed (Invest. Ophthalmol. Vis. Sci. 1990;31:2473-5).

And documented instances of impairment in visual discrimination learning among anorexics (Appetite 2003;40:85e9) "may be related to decreased appetitive function, possibly resulting from impaired dopaminergic neurotransmission, either as a result of food restriction or, more intriguingly, related to the underlying pathophysiology of AN itself," Dr. Moschos and her colleagues wrote.

The investigators acknowledged the limitations posed by the small size of their study, which is ongoing. Now, the group is extending the study to seek longer-term evidence of decline or even recovery in the young women’s maculae following treatment for their anorexia or bulimia. Currently, Dr. Moschos said, the wisdom that macular damage is irreversible stems from the fact that "what we know about maculae concerns much older people," than the anorexics in the study.

The study was funded by the University of Athens. Dr. Moschos and her colleagues reported no conflicts of interest.