Somatic Disorders

Ms. P, age 44, is concerned about her risk of osteoporosis after her 70-year-old mother is hospitalized for a hip fracture. Ms. P has been taking fluoxetine, 40 mg/d, for 10 years to treat recurrent major depressive episodes that began at age 25. She was diagnosed with anorexia nervosa as a teenager, but recovered after 2 years of psychotherapy. She is lactose intolerant, has mild asthma that does not require steroids, and has no history of thyroid disease or bone fracture. Ms. P smokes 10 cigarettes a day but denies using alcohol or illicit drugs. She does not exercise, and her menses occur every 28 to 30 days.

Osteoporosis is a skeletal disease characterized by low bone mineralization and deteriorating bone architecture that results in increased susceptibility to fracture. Approximately 1 in 2 women and 1 in 5 men in the United States will have an osteoporosis-related fracture.¹ Proximal femur and vertebral fractures are most common—1.5 million per year—but other bones may be involved.²

Osteoporosis-related fractures are associated with substantial morbidity and mortality. After a hip fracture, osteoporosis patients have a 10% to 20% risk of death within a year.³ Those who recover from hip fracture have a 2.5-fold increased risk of recurrent fracture and often struggle with chronic pain, disability, and loss of self-esteem and independence.^1,3–5

Evidence links osteoporosis and depression

Research has shown that patients with major depression are at higher risk of osteoporosis.⁶ In one study, bone mineral density among 70 depressed outpatients was 15% lower than among age-matched controls.⁷ In a cross-sectional study, Michelson et al⁸ found that compared with nondepressed controls, women with current or past major depression had a lower mean bone mineral density—6.5% lower at the spine and 13.6% lower at the femoral neck.

Fewer prospective studies exist; however, most found depression has some impact on bone health. Whooley et al⁹ prospectively evaluated changes in bone mineral density among 7,414 Caucasian women age ≥65 for 6 years. Depressed women—those who scored ≥6 on the Geriatric Depression Scale—had a 40% higher risk of nonvertebral fracture after adjusting for history of fracture, weight, physical activity level, smoking, alcohol use, nutritional status, and cognitive function. The depressed cohort also had an increased risk of vertebral fracture. In a prospective study of 21,441 Norwegian female and male subjects, women who reported being depressed at 2 of 3 time points—from 1980 until 1995—had 2.5 times the risk of sustaining a nonvertebral fracture compared with those who did not report depression.¹⁰

Depressed women also have greater bone loss over time. Mean hip bone mineral density decreased by 0.69% per year in nondepressed women vs 0.96% in depressed women in a study of 4,177 women age ≥69.¹¹ These findings were significant after adjusting for age, functional status, cognitive function, smoking, calcium intake, vitamin D supplement use, weight, antidepressant use, and bisphosphonate use. These findings have been replicated.¹²

Behavioral factors such as tobacco use and physical inactivity play a role in the risk of osteoporosis; however, emerging findings suggest a pathophysiologic link between depression and poor bone health. Depression is associated with lower estrogen and testosterone levels, which have been linked to decreased bone formation.⁶ Similarly, compared with matched controls, depressed women with low bone mineral density have higher urinary cortisol levels, suggesting that hypercortisolemia accelerates bone turnover.^6,9,13 Finally, evidence suggests that depression is a pro-inflammatory state associated with production of numerous cytokines. Interleukin-6 and tumor necrosis factor-alpha, for example, inhibit osteoclast apoptosis and accelerate bone turnover.⁶

Fracture risk and psychotropics

Many psychotropic medications—including anticonvulsants, barbiturates, narcotics, and neuroleptics^14–16—are associated with increased risk of falls, fractures, and osteoporosis. In this article we focus on selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) because little data is available on other antidepressants (Table 1).^17–22

SSRIs are associated with increased fracture risk. In a cohort of 5,995 men age ≥65, Haney et al²³ showed that men taking SSRIs have lower bone mineral density at the hip (3.9% lower) and spine (5.6% lower) compared with non-users after adjusting for age, weight, and race. Current SSRI use carries a greater risk than past use. In a prospective study of 7,983 men and women age ≥55, Ziere et al²⁴ reported that risk of nonvertebral fracture among current SSRI users was 28% higher than among past users over a mean follow-up of 8.4 years. In the same study, the risk ratio of nonvertebral fracture was 2.10 for patients using SSRIs within the previous 6 months and 2.98 for use >6 months.

Table 1

Psychotropic medications associated with osteoporosis risk

Increased fracture risk with SSRIs may be partially explained by the greater risk of osteoporosis in major depression.²⁵ SSRI use has been linked to higher risk of fracture in the absence of depressive symptoms, however.²⁶ Bolton et al¹⁷ revealed a trend of increasing fracture risk with higher SSRI dose. In this study, SSRI users had 45% greater likelihood of fracture than controls after adjusting for a diagnosis of depression.

Researchers are studying the mechanism by which SSRIs affect bone mineralization. Serotonin receptors—including 5-HT2A, 5-HT2B, and 5-HT2C—are present in bone.²⁷ Preliminary investigations suggest SSRIs are concentrated in bone and impact fibroblast formation and osteoblast activity. High bone marrow concentrations of fluoxetine inhibit human osteoblast proliferation. Osteoblasts contribute to bone production.²⁸ Fluoxetine concentrations in bone marrow can be up to 100-fold higher than serum levels, and the drug can be detected in bone up to 3 months after discontinuation.

TCAs. U.S. veterans with prior hip fracture are twice as likely to have received TCAs than age- and sex-matched controls.¹⁴In prospective studies, the risk of hip fracture among men and women age ≥65 is 50% higher in patients exposed to TCAs.³⁰ Other investigations have revealed a dose-response relationship between TCA use and risk of fracture.³¹ A direct comparison of TCAs and SSRIs has found an equivalent increase in fracture risk in these 2 classes.³⁰

A direct effect of TCAs on bone metabolism has not been elucidated. However, side effects of TCAs include orthostatic hypotension, impaired cognition, dizziness, and altered balance, all of which increase the risk of falls and fractures, particularly in elderly patients.³¹ Most studies of TCAs, however, do not account for depression’s role in fracture risk. Some patients in these studies may have received TCAs for disorders other than major depression, such as peripheral neuropathy or prophylaxis of migraine headaches.

Benzodiazepine use is associated with confusion, ataxia, and vertigo, which may increase the incidence of falls. Even low doses pose a risk. In one case-control study of 1,222 hip fracture patients age ≥65, use of >3 mg/d diazepam equivalents increased risk of hip fracture by 50% after adjusting for confounding factors.³⁰ Although the data are mixed, benzodiazepines with shorter half-lives (eg, lorazepam) might not be safer than those with longer half-lives (eg, clonazepam).^31,32

Other psychotropics. Some anticonvulsants may lead to bone demineralization via induction of the cytochrome P450 hepatic enzyme system, which accelerates conversion of vitamin D to an inactive metabolite that cannot adequately facilitate absorption of ingested calcium. The subsequent release of parathyroid hormone causes bone resorption.³³ Patients taking anticonvulsants have nearly double the serum parathyroid hormone level of matched controls.³⁴ Carbamazepine, oxcarbazepine, and valproate have been associated with increased risk of fracture.³² Although lamotrigine has not been widely studied, evidence suggests that its impact on bone metabolism is negligible.³⁵

Many antipsychotics, including risperidone and haloperidol, have been associated with osteoporosis. The mechanism by which antipsychotics accelerate bone turnover has not been described; hyperprolactinemia likely plays a role.³⁶

Screening and treatment

Effective pharmacotherapy for osteoporosis includes bisphosphonates (eg, alendronate), selective estrogen receptor modulators (eg, raloxifene), recombinant parathyroid hormone (eg, teriparatide), as well as calcium and vitamin D supplementation. Consider recommending bone density evaluation for depressed patients who have predisposing risk factors (Table 2)¹ and those with long-term exposure to psychotropic agents. Dual energy X-ray absorptiometry is the preferred screening method. Refer patients whose results indicate osteopenia or osteoporosis to primary care. Although pharmacotherapy for osteoporosis should be managed by primary care practitioners, psychiatrists can serve an important role by promoting healthy lifestyle behaviors—such as regular exercise and adequate dietary vitamin D and calcium intake (Table 3).¹

Table 2

Risk factors for osteoporosis-related fracture*

Table 3

Reducing osteoporosis risk: Recommendations for patients age >50

CASE CONTINUED: High risk can be lowered

Ms. P’s family history, antidepressant use, smoking, and low dietary calcium intake associated with lactose intolerance increase her risk for osteoporosis. Her history of anorexia nervosa also increases her risk if she experiences amenorrhea. You advise her that she can ameliorate some of these factors by quitting smoking, exercising regularly, and taking calcium and vitamin D supplements. You refer her to her primary care physician because she wishes to undergo bone mineral density screening.

Related resources

• National Osteoporosis Foundation. Clinician‘s guide to prevention and treatment of osteoporosis. www.nof.org/professionals/Clinicians_Guide.htm.
• World Health Organization Fracture Risk Assessment Tool. Calculates a 10-year probability of hip fracture using demographic data, family history, comorbid medication and predisposing medical conditions. www.shef.ac.uk/FRAX.

Drug brand names

• Alendronate • Fosamax
• Carbamazepine • Tegretol
• Clonazepam • Klonopin
• Diazepam • Valium
• Fluoxetine • Prozac
• Haloperidol • Haldol
• Lamotrigine • Lamictal
• Lithium • Eskalith, Lithobid
• Lorazepam • Ativan
• Oxcarbazepine • Trileptal
• Prednisone • Deltasone, Meticorten
• Raloxifene • Evista
• Risperidone • Risperdal
• Teriparatide • Forteo
• Valproate • Depakote

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Ms. P, age 44, is concerned about her risk of osteoporosis after her 70-year-old mother is hospitalized for a hip fracture. Ms. P has been taking fluoxetine, 40 mg/d, for 10 years to treat recurrent major depressive episodes that began at age 25. She was diagnosed with anorexia nervosa as a teenager, but recovered after 2 years of psychotherapy. She is lactose intolerant, has mild asthma that does not require steroids, and has no history of thyroid disease or bone fracture. Ms. P smokes 10 cigarettes a day but denies using alcohol or illicit drugs. She does not exercise, and her menses occur every 28 to 30 days.

Osteoporosis is a skeletal disease characterized by low bone mineralization and deteriorating bone architecture that results in increased susceptibility to fracture. Approximately 1 in 2 women and 1 in 5 men in the United States will have an osteoporosis-related fracture.¹ Proximal femur and vertebral fractures are most common—1.5 million per year—but other bones may be involved.²

Osteoporosis-related fractures are associated with substantial morbidity and mortality. After a hip fracture, osteoporosis patients have a 10% to 20% risk of death within a year.³ Those who recover from hip fracture have a 2.5-fold increased risk of recurrent fracture and often struggle with chronic pain, disability, and loss of self-esteem and independence.^1,3–5

Evidence links osteoporosis and depression

Research has shown that patients with major depression are at higher risk of osteoporosis.⁶ In one study, bone mineral density among 70 depressed outpatients was 15% lower than among age-matched controls.⁷ In a cross-sectional study, Michelson et al⁸ found that compared with nondepressed controls, women with current or past major depression had a lower mean bone mineral density—6.5% lower at the spine and 13.6% lower at the femoral neck.

Fewer prospective studies exist; however, most found depression has some impact on bone health. Whooley et al⁹ prospectively evaluated changes in bone mineral density among 7,414 Caucasian women age ≥65 for 6 years. Depressed women—those who scored ≥6 on the Geriatric Depression Scale—had a 40% higher risk of nonvertebral fracture after adjusting for history of fracture, weight, physical activity level, smoking, alcohol use, nutritional status, and cognitive function. The depressed cohort also had an increased risk of vertebral fracture. In a prospective study of 21,441 Norwegian female and male subjects, women who reported being depressed at 2 of 3 time points—from 1980 until 1995—had 2.5 times the risk of sustaining a nonvertebral fracture compared with those who did not report depression.¹⁰

Depressed women also have greater bone loss over time. Mean hip bone mineral density decreased by 0.69% per year in nondepressed women vs 0.96% in depressed women in a study of 4,177 women age ≥69.¹¹ These findings were significant after adjusting for age, functional status, cognitive function, smoking, calcium intake, vitamin D supplement use, weight, antidepressant use, and bisphosphonate use. These findings have been replicated.¹²

Behavioral factors such as tobacco use and physical inactivity play a role in the risk of osteoporosis; however, emerging findings suggest a pathophysiologic link between depression and poor bone health. Depression is associated with lower estrogen and testosterone levels, which have been linked to decreased bone formation.⁶ Similarly, compared with matched controls, depressed women with low bone mineral density have higher urinary cortisol levels, suggesting that hypercortisolemia accelerates bone turnover.^6,9,13 Finally, evidence suggests that depression is a pro-inflammatory state associated with production of numerous cytokines. Interleukin-6 and tumor necrosis factor-alpha, for example, inhibit osteoclast apoptosis and accelerate bone turnover.⁶

Fracture risk and psychotropics

Many psychotropic medications—including anticonvulsants, barbiturates, narcotics, and neuroleptics^14–16—are associated with increased risk of falls, fractures, and osteoporosis. In this article we focus on selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) because little data is available on other antidepressants (Table 1).^17–22

SSRIs are associated with increased fracture risk. In a cohort of 5,995 men age ≥65, Haney et al²³ showed that men taking SSRIs have lower bone mineral density at the hip (3.9% lower) and spine (5.6% lower) compared with non-users after adjusting for age, weight, and race. Current SSRI use carries a greater risk than past use. In a prospective study of 7,983 men and women age ≥55, Ziere et al²⁴ reported that risk of nonvertebral fracture among current SSRI users was 28% higher than among past users over a mean follow-up of 8.4 years. In the same study, the risk ratio of nonvertebral fracture was 2.10 for patients using SSRIs within the previous 6 months and 2.98 for use >6 months.

Table 1

Psychotropic medications associated with osteoporosis risk

Increased fracture risk with SSRIs may be partially explained by the greater risk of osteoporosis in major depression.²⁵ SSRI use has been linked to higher risk of fracture in the absence of depressive symptoms, however.²⁶ Bolton et al¹⁷ revealed a trend of increasing fracture risk with higher SSRI dose. In this study, SSRI users had 45% greater likelihood of fracture than controls after adjusting for a diagnosis of depression.

Researchers are studying the mechanism by which SSRIs affect bone mineralization. Serotonin receptors—including 5-HT2A, 5-HT2B, and 5-HT2C—are present in bone.²⁷ Preliminary investigations suggest SSRIs are concentrated in bone and impact fibroblast formation and osteoblast activity. High bone marrow concentrations of fluoxetine inhibit human osteoblast proliferation. Osteoblasts contribute to bone production.²⁸ Fluoxetine concentrations in bone marrow can be up to 100-fold higher than serum levels, and the drug can be detected in bone up to 3 months after discontinuation.

TCAs. U.S. veterans with prior hip fracture are twice as likely to have received TCAs than age- and sex-matched controls.¹⁴In prospective studies, the risk of hip fracture among men and women age ≥65 is 50% higher in patients exposed to TCAs.³⁰ Other investigations have revealed a dose-response relationship between TCA use and risk of fracture.³¹ A direct comparison of TCAs and SSRIs has found an equivalent increase in fracture risk in these 2 classes.³⁰

A direct effect of TCAs on bone metabolism has not been elucidated. However, side effects of TCAs include orthostatic hypotension, impaired cognition, dizziness, and altered balance, all of which increase the risk of falls and fractures, particularly in elderly patients.³¹ Most studies of TCAs, however, do not account for depression’s role in fracture risk. Some patients in these studies may have received TCAs for disorders other than major depression, such as peripheral neuropathy or prophylaxis of migraine headaches.

Benzodiazepine use is associated with confusion, ataxia, and vertigo, which may increase the incidence of falls. Even low doses pose a risk. In one case-control study of 1,222 hip fracture patients age ≥65, use of >3 mg/d diazepam equivalents increased risk of hip fracture by 50% after adjusting for confounding factors.³⁰ Although the data are mixed, benzodiazepines with shorter half-lives (eg, lorazepam) might not be safer than those with longer half-lives (eg, clonazepam).^31,32

Other psychotropics. Some anticonvulsants may lead to bone demineralization via induction of the cytochrome P450 hepatic enzyme system, which accelerates conversion of vitamin D to an inactive metabolite that cannot adequately facilitate absorption of ingested calcium. The subsequent release of parathyroid hormone causes bone resorption.³³ Patients taking anticonvulsants have nearly double the serum parathyroid hormone level of matched controls.³⁴ Carbamazepine, oxcarbazepine, and valproate have been associated with increased risk of fracture.³² Although lamotrigine has not been widely studied, evidence suggests that its impact on bone metabolism is negligible.³⁵

Many antipsychotics, including risperidone and haloperidol, have been associated with osteoporosis. The mechanism by which antipsychotics accelerate bone turnover has not been described; hyperprolactinemia likely plays a role.³⁶

Screening and treatment

Effective pharmacotherapy for osteoporosis includes bisphosphonates (eg, alendronate), selective estrogen receptor modulators (eg, raloxifene), recombinant parathyroid hormone (eg, teriparatide), as well as calcium and vitamin D supplementation. Consider recommending bone density evaluation for depressed patients who have predisposing risk factors (Table 2)¹ and those with long-term exposure to psychotropic agents. Dual energy X-ray absorptiometry is the preferred screening method. Refer patients whose results indicate osteopenia or osteoporosis to primary care. Although pharmacotherapy for osteoporosis should be managed by primary care practitioners, psychiatrists can serve an important role by promoting healthy lifestyle behaviors—such as regular exercise and adequate dietary vitamin D and calcium intake (Table 3).¹

Table 2

Risk factors for osteoporosis-related fracture*

Table 3

Reducing osteoporosis risk: Recommendations for patients age >50

CASE CONTINUED: High risk can be lowered

Ms. P’s family history, antidepressant use, smoking, and low dietary calcium intake associated with lactose intolerance increase her risk for osteoporosis. Her history of anorexia nervosa also increases her risk if she experiences amenorrhea. You advise her that she can ameliorate some of these factors by quitting smoking, exercising regularly, and taking calcium and vitamin D supplements. You refer her to her primary care physician because she wishes to undergo bone mineral density screening.

Related resources

• National Osteoporosis Foundation. Clinician‘s guide to prevention and treatment of osteoporosis. www.nof.org/professionals/Clinicians_Guide.htm.
• World Health Organization Fracture Risk Assessment Tool. Calculates a 10-year probability of hip fracture using demographic data, family history, comorbid medication and predisposing medical conditions. www.shef.ac.uk/FRAX.

Drug brand names

• Alendronate • Fosamax
• Carbamazepine • Tegretol
• Clonazepam • Klonopin
• Diazepam • Valium
• Fluoxetine • Prozac
• Haloperidol • Haldol
• Lamotrigine • Lamictal
• Lithium • Eskalith, Lithobid
• Lorazepam • Ativan
• Oxcarbazepine • Trileptal
• Prednisone • Deltasone, Meticorten
• Raloxifene • Evista
• Risperidone • Risperdal
• Teriparatide • Forteo
• Valproate • Depakote

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Ms. P, age 44, is concerned about her risk of osteoporosis after her 70-year-old mother is hospitalized for a hip fracture. Ms. P has been taking fluoxetine, 40 mg/d, for 10 years to treat recurrent major depressive episodes that began at age 25. She was diagnosed with anorexia nervosa as a teenager, but recovered after 2 years of psychotherapy. She is lactose intolerant, has mild asthma that does not require steroids, and has no history of thyroid disease or bone fracture. Ms. P smokes 10 cigarettes a day but denies using alcohol or illicit drugs. She does not exercise, and her menses occur every 28 to 30 days.

Osteoporosis is a skeletal disease characterized by low bone mineralization and deteriorating bone architecture that results in increased susceptibility to fracture. Approximately 1 in 2 women and 1 in 5 men in the United States will have an osteoporosis-related fracture.¹ Proximal femur and vertebral fractures are most common—1.5 million per year—but other bones may be involved.²

Osteoporosis-related fractures are associated with substantial morbidity and mortality. After a hip fracture, osteoporosis patients have a 10% to 20% risk of death within a year.³ Those who recover from hip fracture have a 2.5-fold increased risk of recurrent fracture and often struggle with chronic pain, disability, and loss of self-esteem and independence.^1,3–5

Evidence links osteoporosis and depression

Research has shown that patients with major depression are at higher risk of osteoporosis.⁶ In one study, bone mineral density among 70 depressed outpatients was 15% lower than among age-matched controls.⁷ In a cross-sectional study, Michelson et al⁸ found that compared with nondepressed controls, women with current or past major depression had a lower mean bone mineral density—6.5% lower at the spine and 13.6% lower at the femoral neck.

Fewer prospective studies exist; however, most found depression has some impact on bone health. Whooley et al⁹ prospectively evaluated changes in bone mineral density among 7,414 Caucasian women age ≥65 for 6 years. Depressed women—those who scored ≥6 on the Geriatric Depression Scale—had a 40% higher risk of nonvertebral fracture after adjusting for history of fracture, weight, physical activity level, smoking, alcohol use, nutritional status, and cognitive function. The depressed cohort also had an increased risk of vertebral fracture. In a prospective study of 21,441 Norwegian female and male subjects, women who reported being depressed at 2 of 3 time points—from 1980 until 1995—had 2.5 times the risk of sustaining a nonvertebral fracture compared with those who did not report depression.¹⁰

Depressed women also have greater bone loss over time. Mean hip bone mineral density decreased by 0.69% per year in nondepressed women vs 0.96% in depressed women in a study of 4,177 women age ≥69.¹¹ These findings were significant after adjusting for age, functional status, cognitive function, smoking, calcium intake, vitamin D supplement use, weight, antidepressant use, and bisphosphonate use. These findings have been replicated.¹²

Behavioral factors such as tobacco use and physical inactivity play a role in the risk of osteoporosis; however, emerging findings suggest a pathophysiologic link between depression and poor bone health. Depression is associated with lower estrogen and testosterone levels, which have been linked to decreased bone formation.⁶ Similarly, compared with matched controls, depressed women with low bone mineral density have higher urinary cortisol levels, suggesting that hypercortisolemia accelerates bone turnover.^6,9,13 Finally, evidence suggests that depression is a pro-inflammatory state associated with production of numerous cytokines. Interleukin-6 and tumor necrosis factor-alpha, for example, inhibit osteoclast apoptosis and accelerate bone turnover.⁶

Fracture risk and psychotropics

Many psychotropic medications—including anticonvulsants, barbiturates, narcotics, and neuroleptics^14–16—are associated with increased risk of falls, fractures, and osteoporosis. In this article we focus on selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) because little data is available on other antidepressants (Table 1).^17–22

SSRIs are associated with increased fracture risk. In a cohort of 5,995 men age ≥65, Haney et al²³ showed that men taking SSRIs have lower bone mineral density at the hip (3.9% lower) and spine (5.6% lower) compared with non-users after adjusting for age, weight, and race. Current SSRI use carries a greater risk than past use. In a prospective study of 7,983 men and women age ≥55, Ziere et al²⁴ reported that risk of nonvertebral fracture among current SSRI users was 28% higher than among past users over a mean follow-up of 8.4 years. In the same study, the risk ratio of nonvertebral fracture was 2.10 for patients using SSRIs within the previous 6 months and 2.98 for use >6 months.

Table 1

Psychotropic medications associated with osteoporosis risk

Increased fracture risk with SSRIs may be partially explained by the greater risk of osteoporosis in major depression.²⁵ SSRI use has been linked to higher risk of fracture in the absence of depressive symptoms, however.²⁶ Bolton et al¹⁷ revealed a trend of increasing fracture risk with higher SSRI dose. In this study, SSRI users had 45% greater likelihood of fracture than controls after adjusting for a diagnosis of depression.

Researchers are studying the mechanism by which SSRIs affect bone mineralization. Serotonin receptors—including 5-HT2A, 5-HT2B, and 5-HT2C—are present in bone.²⁷ Preliminary investigations suggest SSRIs are concentrated in bone and impact fibroblast formation and osteoblast activity. High bone marrow concentrations of fluoxetine inhibit human osteoblast proliferation. Osteoblasts contribute to bone production.²⁸ Fluoxetine concentrations in bone marrow can be up to 100-fold higher than serum levels, and the drug can be detected in bone up to 3 months after discontinuation.

TCAs. U.S. veterans with prior hip fracture are twice as likely to have received TCAs than age- and sex-matched controls.¹⁴In prospective studies, the risk of hip fracture among men and women age ≥65 is 50% higher in patients exposed to TCAs.³⁰ Other investigations have revealed a dose-response relationship between TCA use and risk of fracture.³¹ A direct comparison of TCAs and SSRIs has found an equivalent increase in fracture risk in these 2 classes.³⁰

A direct effect of TCAs on bone metabolism has not been elucidated. However, side effects of TCAs include orthostatic hypotension, impaired cognition, dizziness, and altered balance, all of which increase the risk of falls and fractures, particularly in elderly patients.³¹ Most studies of TCAs, however, do not account for depression’s role in fracture risk. Some patients in these studies may have received TCAs for disorders other than major depression, such as peripheral neuropathy or prophylaxis of migraine headaches.

Benzodiazepine use is associated with confusion, ataxia, and vertigo, which may increase the incidence of falls. Even low doses pose a risk. In one case-control study of 1,222 hip fracture patients age ≥65, use of >3 mg/d diazepam equivalents increased risk of hip fracture by 50% after adjusting for confounding factors.³⁰ Although the data are mixed, benzodiazepines with shorter half-lives (eg, lorazepam) might not be safer than those with longer half-lives (eg, clonazepam).^31,32

Other psychotropics. Some anticonvulsants may lead to bone demineralization via induction of the cytochrome P450 hepatic enzyme system, which accelerates conversion of vitamin D to an inactive metabolite that cannot adequately facilitate absorption of ingested calcium. The subsequent release of parathyroid hormone causes bone resorption.³³ Patients taking anticonvulsants have nearly double the serum parathyroid hormone level of matched controls.³⁴ Carbamazepine, oxcarbazepine, and valproate have been associated with increased risk of fracture.³² Although lamotrigine has not been widely studied, evidence suggests that its impact on bone metabolism is negligible.³⁵

Many antipsychotics, including risperidone and haloperidol, have been associated with osteoporosis. The mechanism by which antipsychotics accelerate bone turnover has not been described; hyperprolactinemia likely plays a role.³⁶

Screening and treatment

Effective pharmacotherapy for osteoporosis includes bisphosphonates (eg, alendronate), selective estrogen receptor modulators (eg, raloxifene), recombinant parathyroid hormone (eg, teriparatide), as well as calcium and vitamin D supplementation. Consider recommending bone density evaluation for depressed patients who have predisposing risk factors (Table 2)¹ and those with long-term exposure to psychotropic agents. Dual energy X-ray absorptiometry is the preferred screening method. Refer patients whose results indicate osteopenia or osteoporosis to primary care. Although pharmacotherapy for osteoporosis should be managed by primary care practitioners, psychiatrists can serve an important role by promoting healthy lifestyle behaviors—such as regular exercise and adequate dietary vitamin D and calcium intake (Table 3).¹

Table 2

Risk factors for osteoporosis-related fracture*

Table 3

Reducing osteoporosis risk: Recommendations for patients age >50

CASE CONTINUED: High risk can be lowered

Ms. P’s family history, antidepressant use, smoking, and low dietary calcium intake associated with lactose intolerance increase her risk for osteoporosis. Her history of anorexia nervosa also increases her risk if she experiences amenorrhea. You advise her that she can ameliorate some of these factors by quitting smoking, exercising regularly, and taking calcium and vitamin D supplements. You refer her to her primary care physician because she wishes to undergo bone mineral density screening.

Related resources

• National Osteoporosis Foundation. Clinician‘s guide to prevention and treatment of osteoporosis. www.nof.org/professionals/Clinicians_Guide.htm.
• World Health Organization Fracture Risk Assessment Tool. Calculates a 10-year probability of hip fracture using demographic data, family history, comorbid medication and predisposing medical conditions. www.shef.ac.uk/FRAX.

Drug brand names

• Alendronate • Fosamax
• Carbamazepine • Tegretol
• Clonazepam • Klonopin
• Diazepam • Valium
• Fluoxetine • Prozac
• Haloperidol • Haldol
• Lamotrigine • Lamictal
• Lithium • Eskalith, Lithobid
• Lorazepam • Ativan
• Oxcarbazepine • Trileptal
• Prednisone • Deltasone, Meticorten
• Raloxifene • Evista
• Risperidone • Risperdal
• Teriparatide • Forteo
• Valproate • Depakote

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Overall cancer incidence and mortality are declining in the United States, according to a report issued by the National Cancer Institute.

These reductions are attributed mostly to decreases in both incidence and mortality for lung, prostate, and co-lorectal cancer in men, and breast and co-lorectal cancer in women. For all types of cancers combined, new diagnoses dropped an average of almost 1% per year from 1999 to 2006, and deaths from cancer declined an average of 1.6% per year from 2001 to 2006.

In terms of gender, cancer rates overall are still higher for men than for women, although cancer incidence and mortality decreased more in men. In particular, for colorectal cancer–the second-leading cause of cancer deaths in the United States–overall rates are declining, but the rising incidence in men and women under age 50 years is worrisome, the report said.

The researchers also found that incidence rates in men have declined for cancers of the oral cavity, stomach, and brain, but rose for kidney/renal, liver, and esophageal cancers, as well as for leukemia, myeloma, and melanoma. In women, incidence rates decreased for uterine, ovarian, cervical, and oral-cavity cancers, but increased for lung, thyroid, pancreatic, bladder, and kidney cancers, as well as for non-Hodgkin's lymphoma, melanoma, and leukemia.

Among racial and ethnic groups, cancer mortality was highest in blacks and lowest among Asian/Pacific Islanders. In addition, death rates from pancreatic cancer increased among whites but decreased among blacks.

The authors modeled projections of colorectal cancer rates and found that by getting more patients to adopt lifestyle changes such as quitting smoking and by increasing the use of colonoscopy and other screening techniques, overall co-lorectal cancer mortality could be cut in half by 2020.

The report was written by researchers from the NCI, the Centers for Disease Control and Prevention, the American Cancer Society, and the North American Association of Central Cancer Registries. (Cancer 2010;116:544-73).

Information on newly diagnosed invasive cancers was obtained from population-based cancer registries that participate in the NCI's Surveillance, Epidemiology, and End Results program and/or the CDC's National Program of Cancer Registries.

For most states, population estimates as of July 1 of each year were used to calculate annual incidence and death rates; these estimates are presumed to reflect the average population of a defined geographic area for a calendar year, the authors noted.

“The continued decline in overall cancer rates documents the success we have had with our aggressive efforts to reduce risk in large populations, to provide for early detection, and to develop new therapies that have been successfully applied in this past decade,” Dr. John E. Niederhuber, NCI director, said in a statement.

Overall cancer incidence and mortality are declining in the United States, according to a report issued by the National Cancer Institute.

These reductions are attributed mostly to decreases in both incidence and mortality for lung, prostate, and co-lorectal cancer in men, and breast and co-lorectal cancer in women. For all types of cancers combined, new diagnoses dropped an average of almost 1% per year from 1999 to 2006, and deaths from cancer declined an average of 1.6% per year from 2001 to 2006.

In terms of gender, cancer rates overall are still higher for men than for women, although cancer incidence and mortality decreased more in men. In particular, for colorectal cancer–the second-leading cause of cancer deaths in the United States–overall rates are declining, but the rising incidence in men and women under age 50 years is worrisome, the report said.

The researchers also found that incidence rates in men have declined for cancers of the oral cavity, stomach, and brain, but rose for kidney/renal, liver, and esophageal cancers, as well as for leukemia, myeloma, and melanoma. In women, incidence rates decreased for uterine, ovarian, cervical, and oral-cavity cancers, but increased for lung, thyroid, pancreatic, bladder, and kidney cancers, as well as for non-Hodgkin's lymphoma, melanoma, and leukemia.

Among racial and ethnic groups, cancer mortality was highest in blacks and lowest among Asian/Pacific Islanders. In addition, death rates from pancreatic cancer increased among whites but decreased among blacks.

The authors modeled projections of colorectal cancer rates and found that by getting more patients to adopt lifestyle changes such as quitting smoking and by increasing the use of colonoscopy and other screening techniques, overall co-lorectal cancer mortality could be cut in half by 2020.

The report was written by researchers from the NCI, the Centers for Disease Control and Prevention, the American Cancer Society, and the North American Association of Central Cancer Registries. (Cancer 2010;116:544-73).

Information on newly diagnosed invasive cancers was obtained from population-based cancer registries that participate in the NCI's Surveillance, Epidemiology, and End Results program and/or the CDC's National Program of Cancer Registries.

For most states, population estimates as of July 1 of each year were used to calculate annual incidence and death rates; these estimates are presumed to reflect the average population of a defined geographic area for a calendar year, the authors noted.

“The continued decline in overall cancer rates documents the success we have had with our aggressive efforts to reduce risk in large populations, to provide for early detection, and to develop new therapies that have been successfully applied in this past decade,” Dr. John E. Niederhuber, NCI director, said in a statement.

Overall cancer incidence and mortality are declining in the United States, according to a report issued by the National Cancer Institute.

These reductions are attributed mostly to decreases in both incidence and mortality for lung, prostate, and co-lorectal cancer in men, and breast and co-lorectal cancer in women. For all types of cancers combined, new diagnoses dropped an average of almost 1% per year from 1999 to 2006, and deaths from cancer declined an average of 1.6% per year from 2001 to 2006.

In terms of gender, cancer rates overall are still higher for men than for women, although cancer incidence and mortality decreased more in men. In particular, for colorectal cancer–the second-leading cause of cancer deaths in the United States–overall rates are declining, but the rising incidence in men and women under age 50 years is worrisome, the report said.

The researchers also found that incidence rates in men have declined for cancers of the oral cavity, stomach, and brain, but rose for kidney/renal, liver, and esophageal cancers, as well as for leukemia, myeloma, and melanoma. In women, incidence rates decreased for uterine, ovarian, cervical, and oral-cavity cancers, but increased for lung, thyroid, pancreatic, bladder, and kidney cancers, as well as for non-Hodgkin's lymphoma, melanoma, and leukemia.

Among racial and ethnic groups, cancer mortality was highest in blacks and lowest among Asian/Pacific Islanders. In addition, death rates from pancreatic cancer increased among whites but decreased among blacks.

The authors modeled projections of colorectal cancer rates and found that by getting more patients to adopt lifestyle changes such as quitting smoking and by increasing the use of colonoscopy and other screening techniques, overall co-lorectal cancer mortality could be cut in half by 2020.

The report was written by researchers from the NCI, the Centers for Disease Control and Prevention, the American Cancer Society, and the North American Association of Central Cancer Registries. (Cancer 2010;116:544-73).

Information on newly diagnosed invasive cancers was obtained from population-based cancer registries that participate in the NCI's Surveillance, Epidemiology, and End Results program and/or the CDC's National Program of Cancer Registries.

For most states, population estimates as of July 1 of each year were used to calculate annual incidence and death rates; these estimates are presumed to reflect the average population of a defined geographic area for a calendar year, the authors noted.

“The continued decline in overall cancer rates documents the success we have had with our aggressive efforts to reduce risk in large populations, to provide for early detection, and to develop new therapies that have been successfully applied in this past decade,” Dr. John E. Niederhuber, NCI director, said in a statement.

NEW ORLEANS – Psychiatrists and other mental health professionals often lack sufficient background in oncology to effectively provide psychosocial care to cancer patients.

The Henry Ford Health System (HFHS) in Detroit has designed a program to fill this need, resulting in improved access to specialized care for their large patient base.

The program was described by Wendy Goldberg, a nurse practitioner at the Josephine Ford Cancer Center (JFCC) of the HFHS, at the annual conference of the American Psychosocial Oncology Society.

A review of the literature showed that one-third to one-half of all cancer patients experience significant psychosocial distress, and that psychological interventions are effective in remediating distress (Psychooncology 2004;13:837-49), Ms. Goldberg and colleagues noted in their poster.

“We have 7,000 cancer patients in our health care system … in southeast Michigan. We know that providing psychosocial care to this cancer population is important, but our psycho-oncology program consists of only a psycho-oncology nurse practitioner (myself) and a health psychology fellow,” she said.

Because of the volume of this population, the patients' disease states, and issues of transportation, many patients requiring psychosocial services now see counselors within their communities who lack expertise in cancer care. The patients who were seen in the community have been highly dissatisfied with such care, Ms. Goldberg explained in an interview.

“Patients complained to their oncologists that their therapists did not understand their situation or were not helpful,” she noted.

Envisioning a program that would prepare psychotherapy generalists in the community to deliver specialized psycho-oncology services, Ms. Goldberg and colleagues designed an intensive, specialized, mastery-based training program that covered cancer “basics” as well as the psychological and behavioral dimensions of cancer. (See box.)

The program was attended by 91 mental health care providers, including psychiatrists, psychologists, social workers, and nurse practitioners from within the HFHS and the southeast Michigan region. Faculty included a psychologist, health psychology fellow, psychiatric nurse practitioner, psychiatric social worker, and oncology nurse practitioner, all with advanced training in the field.

The content for the 8-hour course included cancer biology and treatment issues, psychiatric comorbidity, psychological and psychopharmacologic interventions, ethics, and genetic testing in cancer populations. Interactive lectures, case presentations, and panel discussions with patients and family members focused on the mastery of essential knowledge, attitudes, and skill development in psycho-oncology care. Enrollees from the HFHS were invited to participate in the next two phases of the program, which entailed ongoing, small-group, peer supervision via telephone conferences and a 1-day clinical observation.

At the conclusion of the seminar, participants reported high satisfaction with the course. On a quality-rating scale of 0–5, mean ratings were 4.5 or higher on all content and organizational categories. Virtually all respondents said that the program was highly applicable to their profession and yielded information that would be professionally useful.

“The response was unbelievably positive,” Ms. Goldberg reported. “We were optimistic that the program would be appreciated, but many participants said it was the best course they had ever taken, and they did not realize how much they didn't know.”

Ms. Goldberg and her colleagues are now formalizing the course and training model for implementation by others.

Case Histories Show Impact of Program on Patients

Therapists reported a gain in knowledge that helped them counsel cancer patients. These are some of their “before and after” stories, as described by Teresa Lynch, Ph.D., a psychologist at the JFCC, and Ms. Goldberg.

▸ Case No. 1. The therapist could not understand why his very ill patient resisted discussions about end-of-life issues. But after reviewing the patient's clinical status, he learned the patient was midway through his initial treatment, was ill from the side effects of surgery and radiation rather than from disease, and–most importantly–had an excellent chance of cure. The therapist then understood that exploring fears about death and dying was not relevant, and he redirected the focus of therapy toward emotional resiliency during treatment.

▸ Case No. 2. The patient did not understand her oncologists' insistence that she needed both chemotherapy and radiation therapy. The therapist was able to use her fundamental knowledge of cancer biology to probe the patient's understanding of these issues. She combined psychoeducation techniques with anxiety management to help the patient face an unpleasant reality. This interaction increased the patient's confidence in the therapist, which ultimately helped the patient receive optimal care.

▸ Case No. 3. The patient approached the program's psychiatrist about her difficulty in proceeding with treatment recommendations until she could better manage her anxiety, attend to important personal business, and think more about her treatment options. The psychiatrist and nurse practitioner discussed the case together, and concluded that further delays in initiating cancer treatment could jeopardize the patient's chance for a good response, including cure. The team strategized ways to shift the focus of therapy to concerns about the risks of delay, rather than the patient's need to be “perfectly ready” before beginning treatment. The psychiatrist adjusted her treatment approach from reflective listening to a psychoeducational/problem-solving strategy that helped the patient overcome a dangerous state of paralysis and avoidance. The patient later directly expressed her gratitude for this intervention to the oncology team.

▸ Case No. 4. A therapist who was working with a breast cancer patient wanted a greater appreciation of what her patient would face after completing chemotherapy. The therapist had no knowledge of tumor biology, including the meaning of estrogen receptor positivity. Therapists do have access to patients' electronic medical records (EMRs) in the health care system–the aim being to promote integrated care–but most therapists do not know what information to look for or where to find it in the EMR. To address this need, the psychosocial educational program devoted a telephone supervisory session to teaching therapists how to navigate the relevant aspects of the patient's EMR. At the same time, the teaching team reinforced some of the didactic information presented during the psycho-oncology seminar.

NEW ORLEANS – Psychiatrists and other mental health professionals often lack sufficient background in oncology to effectively provide psychosocial care to cancer patients.

The Henry Ford Health System (HFHS) in Detroit has designed a program to fill this need, resulting in improved access to specialized care for their large patient base.

The program was described by Wendy Goldberg, a nurse practitioner at the Josephine Ford Cancer Center (JFCC) of the HFHS, at the annual conference of the American Psychosocial Oncology Society.

A review of the literature showed that one-third to one-half of all cancer patients experience significant psychosocial distress, and that psychological interventions are effective in remediating distress (Psychooncology 2004;13:837-49), Ms. Goldberg and colleagues noted in their poster.

“We have 7,000 cancer patients in our health care system … in southeast Michigan. We know that providing psychosocial care to this cancer population is important, but our psycho-oncology program consists of only a psycho-oncology nurse practitioner (myself) and a health psychology fellow,” she said.

Because of the volume of this population, the patients' disease states, and issues of transportation, many patients requiring psychosocial services now see counselors within their communities who lack expertise in cancer care. The patients who were seen in the community have been highly dissatisfied with such care, Ms. Goldberg explained in an interview.

“Patients complained to their oncologists that their therapists did not understand their situation or were not helpful,” she noted.

Envisioning a program that would prepare psychotherapy generalists in the community to deliver specialized psycho-oncology services, Ms. Goldberg and colleagues designed an intensive, specialized, mastery-based training program that covered cancer “basics” as well as the psychological and behavioral dimensions of cancer. (See box.)

The program was attended by 91 mental health care providers, including psychiatrists, psychologists, social workers, and nurse practitioners from within the HFHS and the southeast Michigan region. Faculty included a psychologist, health psychology fellow, psychiatric nurse practitioner, psychiatric social worker, and oncology nurse practitioner, all with advanced training in the field.

The content for the 8-hour course included cancer biology and treatment issues, psychiatric comorbidity, psychological and psychopharmacologic interventions, ethics, and genetic testing in cancer populations. Interactive lectures, case presentations, and panel discussions with patients and family members focused on the mastery of essential knowledge, attitudes, and skill development in psycho-oncology care. Enrollees from the HFHS were invited to participate in the next two phases of the program, which entailed ongoing, small-group, peer supervision via telephone conferences and a 1-day clinical observation.

At the conclusion of the seminar, participants reported high satisfaction with the course. On a quality-rating scale of 0–5, mean ratings were 4.5 or higher on all content and organizational categories. Virtually all respondents said that the program was highly applicable to their profession and yielded information that would be professionally useful.

“The response was unbelievably positive,” Ms. Goldberg reported. “We were optimistic that the program would be appreciated, but many participants said it was the best course they had ever taken, and they did not realize how much they didn't know.”

Ms. Goldberg and her colleagues are now formalizing the course and training model for implementation by others.

Case Histories Show Impact of Program on Patients

Therapists reported a gain in knowledge that helped them counsel cancer patients. These are some of their “before and after” stories, as described by Teresa Lynch, Ph.D., a psychologist at the JFCC, and Ms. Goldberg.

▸ Case No. 1. The therapist could not understand why his very ill patient resisted discussions about end-of-life issues. But after reviewing the patient's clinical status, he learned the patient was midway through his initial treatment, was ill from the side effects of surgery and radiation rather than from disease, and–most importantly–had an excellent chance of cure. The therapist then understood that exploring fears about death and dying was not relevant, and he redirected the focus of therapy toward emotional resiliency during treatment.

▸ Case No. 2. The patient did not understand her oncologists' insistence that she needed both chemotherapy and radiation therapy. The therapist was able to use her fundamental knowledge of cancer biology to probe the patient's understanding of these issues. She combined psychoeducation techniques with anxiety management to help the patient face an unpleasant reality. This interaction increased the patient's confidence in the therapist, which ultimately helped the patient receive optimal care.

▸ Case No. 3. The patient approached the program's psychiatrist about her difficulty in proceeding with treatment recommendations until she could better manage her anxiety, attend to important personal business, and think more about her treatment options. The psychiatrist and nurse practitioner discussed the case together, and concluded that further delays in initiating cancer treatment could jeopardize the patient's chance for a good response, including cure. The team strategized ways to shift the focus of therapy to concerns about the risks of delay, rather than the patient's need to be “perfectly ready” before beginning treatment. The psychiatrist adjusted her treatment approach from reflective listening to a psychoeducational/problem-solving strategy that helped the patient overcome a dangerous state of paralysis and avoidance. The patient later directly expressed her gratitude for this intervention to the oncology team.

▸ Case No. 4. A therapist who was working with a breast cancer patient wanted a greater appreciation of what her patient would face after completing chemotherapy. The therapist had no knowledge of tumor biology, including the meaning of estrogen receptor positivity. Therapists do have access to patients' electronic medical records (EMRs) in the health care system–the aim being to promote integrated care–but most therapists do not know what information to look for or where to find it in the EMR. To address this need, the psychosocial educational program devoted a telephone supervisory session to teaching therapists how to navigate the relevant aspects of the patient's EMR. At the same time, the teaching team reinforced some of the didactic information presented during the psycho-oncology seminar.

NEW ORLEANS – Psychiatrists and other mental health professionals often lack sufficient background in oncology to effectively provide psychosocial care to cancer patients.

The Henry Ford Health System (HFHS) in Detroit has designed a program to fill this need, resulting in improved access to specialized care for their large patient base.

The program was described by Wendy Goldberg, a nurse practitioner at the Josephine Ford Cancer Center (JFCC) of the HFHS, at the annual conference of the American Psychosocial Oncology Society.

A review of the literature showed that one-third to one-half of all cancer patients experience significant psychosocial distress, and that psychological interventions are effective in remediating distress (Psychooncology 2004;13:837-49), Ms. Goldberg and colleagues noted in their poster.

“We have 7,000 cancer patients in our health care system … in southeast Michigan. We know that providing psychosocial care to this cancer population is important, but our psycho-oncology program consists of only a psycho-oncology nurse practitioner (myself) and a health psychology fellow,” she said.

Because of the volume of this population, the patients' disease states, and issues of transportation, many patients requiring psychosocial services now see counselors within their communities who lack expertise in cancer care. The patients who were seen in the community have been highly dissatisfied with such care, Ms. Goldberg explained in an interview.

“Patients complained to their oncologists that their therapists did not understand their situation or were not helpful,” she noted.

Envisioning a program that would prepare psychotherapy generalists in the community to deliver specialized psycho-oncology services, Ms. Goldberg and colleagues designed an intensive, specialized, mastery-based training program that covered cancer “basics” as well as the psychological and behavioral dimensions of cancer. (See box.)

The program was attended by 91 mental health care providers, including psychiatrists, psychologists, social workers, and nurse practitioners from within the HFHS and the southeast Michigan region. Faculty included a psychologist, health psychology fellow, psychiatric nurse practitioner, psychiatric social worker, and oncology nurse practitioner, all with advanced training in the field.

The content for the 8-hour course included cancer biology and treatment issues, psychiatric comorbidity, psychological and psychopharmacologic interventions, ethics, and genetic testing in cancer populations. Interactive lectures, case presentations, and panel discussions with patients and family members focused on the mastery of essential knowledge, attitudes, and skill development in psycho-oncology care. Enrollees from the HFHS were invited to participate in the next two phases of the program, which entailed ongoing, small-group, peer supervision via telephone conferences and a 1-day clinical observation.

At the conclusion of the seminar, participants reported high satisfaction with the course. On a quality-rating scale of 0–5, mean ratings were 4.5 or higher on all content and organizational categories. Virtually all respondents said that the program was highly applicable to their profession and yielded information that would be professionally useful.

“The response was unbelievably positive,” Ms. Goldberg reported. “We were optimistic that the program would be appreciated, but many participants said it was the best course they had ever taken, and they did not realize how much they didn't know.”

Ms. Goldberg and her colleagues are now formalizing the course and training model for implementation by others.

Case Histories Show Impact of Program on Patients

Therapists reported a gain in knowledge that helped them counsel cancer patients. These are some of their “before and after” stories, as described by Teresa Lynch, Ph.D., a psychologist at the JFCC, and Ms. Goldberg.

▸ Case No. 1. The therapist could not understand why his very ill patient resisted discussions about end-of-life issues. But after reviewing the patient's clinical status, he learned the patient was midway through his initial treatment, was ill from the side effects of surgery and radiation rather than from disease, and–most importantly–had an excellent chance of cure. The therapist then understood that exploring fears about death and dying was not relevant, and he redirected the focus of therapy toward emotional resiliency during treatment.

▸ Case No. 2. The patient did not understand her oncologists' insistence that she needed both chemotherapy and radiation therapy. The therapist was able to use her fundamental knowledge of cancer biology to probe the patient's understanding of these issues. She combined psychoeducation techniques with anxiety management to help the patient face an unpleasant reality. This interaction increased the patient's confidence in the therapist, which ultimately helped the patient receive optimal care.

▸ Case No. 3. The patient approached the program's psychiatrist about her difficulty in proceeding with treatment recommendations until she could better manage her anxiety, attend to important personal business, and think more about her treatment options. The psychiatrist and nurse practitioner discussed the case together, and concluded that further delays in initiating cancer treatment could jeopardize the patient's chance for a good response, including cure. The team strategized ways to shift the focus of therapy to concerns about the risks of delay, rather than the patient's need to be “perfectly ready” before beginning treatment. The psychiatrist adjusted her treatment approach from reflective listening to a psychoeducational/problem-solving strategy that helped the patient overcome a dangerous state of paralysis and avoidance. The patient later directly expressed her gratitude for this intervention to the oncology team.

▸ Case No. 4. A therapist who was working with a breast cancer patient wanted a greater appreciation of what her patient would face after completing chemotherapy. The therapist had no knowledge of tumor biology, including the meaning of estrogen receptor positivity. Therapists do have access to patients' electronic medical records (EMRs) in the health care system–the aim being to promote integrated care–but most therapists do not know what information to look for or where to find it in the EMR. To address this need, the psychosocial educational program devoted a telephone supervisory session to teaching therapists how to navigate the relevant aspects of the patient's EMR. At the same time, the teaching team reinforced some of the didactic information presented during the psycho-oncology seminar.

CASE: Self-reported TBI

When charged with raping a 19-year-old woman, Mr. P, age 32, pleads not guilty by reason of insanity (NGRI). He has a self-reported history of traumatic brain injury (TBI) and claims that since suffering a blow to the head 8 years before the rape, he has experienced episodes of personality changes, psychosis, and violent behavior. Mr. P is adamant that any wrongdoing on his part was beyond his control, and he argues that consequences of the brain injury, such as hallucinations and aggressive behavior, had recently emerged. The court asks that a forensic psychiatrist evaluate Mr. P.

An only child, Mr. P was raised by his mother in an inner city area. His father was dependent on alcohol and cocaine and abandoned the family shortly after Mr. P’s birth. Mr. P abuses alcohol, as evidenced by previous driving under the influence charges, but denies illicit drug use. He graduated from high school with average grades and denies a history of disciplinary action at school or home. Although Mr. P was charged with misdemeanors in his late teens, the sexual assault is his first felony charge. Mr. P describes himself as a “charmer.”

After high school, Mr. P worked full-time in construction, where he claims he suffered a traumatic blow to the head. Despite this injury, he continued to work and socialize and never sought treatment at a mental health clinic.

The authors’ observations

Although defendants may legitimately suffer from TBI and resultant complications, many individuals capitalize on a history of minor head injury to support their NGRI defense.¹ Forensic psychiatrists must retain a healthy degree of clinical suspicion for malingering in defendants who claim NGRI as a result of complications from brain injury, especially when the injury and complications are not documented and simply patient-reported.

TBI is a CNS injury that occurs when an outside force traumatically injures the brain and can cause a variety of physical, cognitive, emotional, and behavioral effects ( Table 1 ).² Cognitive deficits include:

• impaired attention
• disrupted insight
• poor judgment
• thought disorders.

Reduced processing speed, distractibility, and deficits in executive functions such as abstract reasoning, planning, problem solving, and multitasking have been documented. Memory loss—the most common cognitive impairment among head-injured people—occurs in 20% to 79% of people with closed head trauma, depending on injury severity.³ People who have suffered TBI may have difficulty understanding or producing spoken or written language, or with more subtle aspects of communication, such as body language.

TBI may cause emotional or behavioral problems and personality changes. Mood and affect changes are common. TBI predisposes patients to obsessive-compulsive disorder, substance abuse, dysthymia, clinical depression, bipolar disorder, phobias, panic disorder, and schizophrenia.⁴ Frontal lobe injuries have been correlated with disinhibition and inappropriate or childish behavior, and temporal lobe injuries with irritability and aggression.⁵

Table 1

TBI symptoms correspond to area of injury

TBI and the insanity defense

The M’Naghten Rule of 1843 requires that for an insanity defense, the defendant must have a mental disease or defect that causes him not to know the nature and quality or the wrongfulness of his act.⁶ TBI is an abnormal condition of the mind leading to a mental disease that can substantially affect control of emotions and behaviors.

Nevertheless, TBI-induced criminality remains controversial.⁷ Theories on the etiology of impulse dyscontrol resulting from TBI have suggested structural damage to the brain and altered neurotransmitters. In TBI, the amygdala—which is located within the anterior temporal lobe and adjoins emotions to thoughts—often is injured. Damage to this structure leads to poor impulse control and violent behavior. Damage to specific neurotransmitter systems that causes elevated norepinephrine and dopamine levels and reduced serotonin levels have also been implicated as a cause of impulse dyscontrol in TBI patients.⁸

In theory, TBI patients potentially could have enough cognitive impairment to have a substantial lack of appreciation of the criminality or wrongfulness of an act. TBI-related impulsivity and cognitive impairment can lead to recklessness and negligence.⁹ The U.S. Supreme Court has acknowledged that CNS dysfunction affects judgment, reality testing, and self-control.¹⁰

EVALUATION: Vague answers

To determine whether Mr. P’s defense is plausible, the forensic psychiatrist must pay attention to the details of the patient’s presentation and history. During the interview, Mr. P quickly shifts from cooperative to obstinate and restricted. He ruminates on the head injury causing him to suffer auditory hallucinations, which he claims he always obeys. Mr. P refuses to provide details of the hallucinations, however, and answers most questions about the head injury or his defense with vague answers, including “I don’t know.”

Because of Mr. P’s reluctance to share information, his lack of psychiatric symptoms other than those he self-reports, and the presence of potential secondary gain from an NGRI defense, the psychiatrist begins to suspect malingering.

The authors’ observations

Malingering is a condition—not a diagnosis—characterized by intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives.¹¹ The presence of external incentives distinguishes malingering from psychiatric illnesses such as factitious and somatoform disorders, in which there is no apparent external incentive. Malingering of psychiatric symptoms occurs in up to 20% of forensic patients, 5% of military recruits, and 1% of mental health patients.⁵ Stimuli for malingering range from seeking food and shelter to avoiding criminal responsibility ( Table 2 ). Malingering is more common in individuals being evaluated for criminal responsibility than for competence to stand trial. The 3 categories of malingering are:

Table 2

Common external incentives for malingering

• pure malingering—feigning a nonexistent disorder
• partial malingering—consciously exaggerating real symptoms

• false imputation—ascribing real symptoms to a cause the individual knows is unrelated to the symptoms.¹²

Determining if a defendant with a history of TBI is malingering requires a multi-step approach that encompasses the clinical interview, a thorough review of collateral data, and focused psychological testing. In interviews, psychiatrists detect approximately 50% of lies, which is no better than would be discovered by chance.¹³ If you suspect a patient is malingering, combine a structured clinical interview with collateral sources such as old hospital records, treatment history, insurance records, police reports, and interviews with close family and friends.

TBI patients’ poor cognition, memory deficits, and inattention will prove challenging. Malingering patients who attempt to capitalize on a pre-existing TBI to evade responsibility for a current criminal charge may grossly exaggerate or even fake intellectual deficits. Be patient with such defendants and remain aware that such people will give vague or hedging answers to straightforward questions, often accompanied by “I don’t know.” Prolonging the interview may be helpful because it may fatigue a defendant who is faking.¹²

Some patients who malinger after sustaining a TBI will attempt to feign psychotic symptoms. Table 3 ¹⁴ illustrates criteria for assessing a patient suspected of malingering psychosis and Table 4 ¹⁴ highlights atypical psychotic symptoms that suggest feigning illness. Malingering of psychosis can be both assessed in the interview and through testing.

Table 3

Criteria for malingered psychosis

Table 4

Atypical psychotic symptoms that suggest malingering

Psychological testing

Several standardized diagnostic instruments can be used to help determine whether a patient is feigning or exaggerating psychotic symptoms or cognitive impairments ( Table 5 ). Testing for a patient such as Mr. P—who attributes any criminal wrongdoing to psychosis and also cites limited cognition as a reason for trouble in the interview—would include personality tests, tests to assess exaggerations of psychosis, and cognitive tests.

In the forensic setting, the preferred personality test is the MMPI-2.¹⁵ It consists of 567 items, with 10 clinical scales and several validity scales. The F scale, “faking good” or “faking bad,” detects people who are answering questions with the goal of appearing better or worse than they actually are. The Personal Assessment Inventory (PAI)¹⁶ is a 344-item test with a 4-point response format. The 22 scales cover a range of important axis I and II psychopathology.

SIRS¹⁷ is the gold standard in detecting malingered psychiatric illness; it includes questions about rare symptoms and uncommon symptom pairing. M-FAST¹⁸ was developed to provide a brief, reliable screen for malingered mental illness. It has shown good validity and high correlation with the SIRS and MMPI-2.

Tests of exaggerated cognitive impairment are extremely important in evaluating patients who claim to suffer from complications following TBI. TOMM¹⁹ —a 50-item recognition test designed to discriminate between true memory-impaired patients and malingerers—is the most studied and valid of such tests. Defendants’ scores that meet the recommended criteria for detecting malingering—≥5 errors on the retention trial—were found to also report a history of head injury.¹

Although not as well validated, the Portland Digit Recognition Test (PDRT)²⁰ is an alternative to the TOMM. This test is a forced-choice measure of recognition designed for assessing the possibility of malingering in individuals claiming mental illness because of head injury. The Victoria Symptoms Validity Test (VSVT)²¹ is used in outpatient and inpatient settings and also uses a forced-choice model to assess possible exaggeration or feigning of cognitive impairments. Finally, the Word Memory Test (WMT)²² is a neuropsychological assessment that evaluates the effort participants put forth.

Table 5

Standardized diagnostic instruments for detecting malingering

OUTCOME: Unsupported claims

Mr. P’s hospital records reveal a very minor head trauma that resulted in no structural brain abnormalities on imaging tests. Collateral interviews with Mr. P’s family and close friends fail to support the defendant’s claim that after the accident he began to experience behavioral changes and periods of psychosis. Mr. P’s SIRS and TOMM scores indicate malingering, and the psychiatrist did not support his NGRI defense.

Related resource

• Williamson DJ. Neurocognitive impairment: feigned, exaggerated, or real? Current Psychiatry. 2007;6(8):19-37.

Disclosure

Dr. Nasrallah receives research grant/research support from Forest Pharmaceuticals, GlaxoSmithKline, Janssen, Otsuka America Pharmaceuticals, Pfizer Inc., Roche, sanofi-aventis, and Shire, is on the advisory board of Abbott Laboratories, AstraZeneca, Janssen, Novartis, Pfizer Inc., and Merck, and is on the speakers’ bureau for Abbott Laboratories, AstraZeneca, Janssen, Novartis, Pfizer Inc., and Merck.

Dr. Farrell reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Self-reported TBI

When charged with raping a 19-year-old woman, Mr. P, age 32, pleads not guilty by reason of insanity (NGRI). He has a self-reported history of traumatic brain injury (TBI) and claims that since suffering a blow to the head 8 years before the rape, he has experienced episodes of personality changes, psychosis, and violent behavior. Mr. P is adamant that any wrongdoing on his part was beyond his control, and he argues that consequences of the brain injury, such as hallucinations and aggressive behavior, had recently emerged. The court asks that a forensic psychiatrist evaluate Mr. P.

An only child, Mr. P was raised by his mother in an inner city area. His father was dependent on alcohol and cocaine and abandoned the family shortly after Mr. P’s birth. Mr. P abuses alcohol, as evidenced by previous driving under the influence charges, but denies illicit drug use. He graduated from high school with average grades and denies a history of disciplinary action at school or home. Although Mr. P was charged with misdemeanors in his late teens, the sexual assault is his first felony charge. Mr. P describes himself as a “charmer.”

After high school, Mr. P worked full-time in construction, where he claims he suffered a traumatic blow to the head. Despite this injury, he continued to work and socialize and never sought treatment at a mental health clinic.

The authors’ observations

Although defendants may legitimately suffer from TBI and resultant complications, many individuals capitalize on a history of minor head injury to support their NGRI defense.¹ Forensic psychiatrists must retain a healthy degree of clinical suspicion for malingering in defendants who claim NGRI as a result of complications from brain injury, especially when the injury and complications are not documented and simply patient-reported.

TBI is a CNS injury that occurs when an outside force traumatically injures the brain and can cause a variety of physical, cognitive, emotional, and behavioral effects ( Table 1 ).² Cognitive deficits include:

• impaired attention
• disrupted insight
• poor judgment
• thought disorders.

Reduced processing speed, distractibility, and deficits in executive functions such as abstract reasoning, planning, problem solving, and multitasking have been documented. Memory loss—the most common cognitive impairment among head-injured people—occurs in 20% to 79% of people with closed head trauma, depending on injury severity.³ People who have suffered TBI may have difficulty understanding or producing spoken or written language, or with more subtle aspects of communication, such as body language.

TBI may cause emotional or behavioral problems and personality changes. Mood and affect changes are common. TBI predisposes patients to obsessive-compulsive disorder, substance abuse, dysthymia, clinical depression, bipolar disorder, phobias, panic disorder, and schizophrenia.⁴ Frontal lobe injuries have been correlated with disinhibition and inappropriate or childish behavior, and temporal lobe injuries with irritability and aggression.⁵

Table 1

TBI symptoms correspond to area of injury

TBI and the insanity defense

The M’Naghten Rule of 1843 requires that for an insanity defense, the defendant must have a mental disease or defect that causes him not to know the nature and quality or the wrongfulness of his act.⁶ TBI is an abnormal condition of the mind leading to a mental disease that can substantially affect control of emotions and behaviors.

Nevertheless, TBI-induced criminality remains controversial.⁷ Theories on the etiology of impulse dyscontrol resulting from TBI have suggested structural damage to the brain and altered neurotransmitters. In TBI, the amygdala—which is located within the anterior temporal lobe and adjoins emotions to thoughts—often is injured. Damage to this structure leads to poor impulse control and violent behavior. Damage to specific neurotransmitter systems that causes elevated norepinephrine and dopamine levels and reduced serotonin levels have also been implicated as a cause of impulse dyscontrol in TBI patients.⁸

In theory, TBI patients potentially could have enough cognitive impairment to have a substantial lack of appreciation of the criminality or wrongfulness of an act. TBI-related impulsivity and cognitive impairment can lead to recklessness and negligence.⁹ The U.S. Supreme Court has acknowledged that CNS dysfunction affects judgment, reality testing, and self-control.¹⁰

EVALUATION: Vague answers

To determine whether Mr. P’s defense is plausible, the forensic psychiatrist must pay attention to the details of the patient’s presentation and history. During the interview, Mr. P quickly shifts from cooperative to obstinate and restricted. He ruminates on the head injury causing him to suffer auditory hallucinations, which he claims he always obeys. Mr. P refuses to provide details of the hallucinations, however, and answers most questions about the head injury or his defense with vague answers, including “I don’t know.”

Because of Mr. P’s reluctance to share information, his lack of psychiatric symptoms other than those he self-reports, and the presence of potential secondary gain from an NGRI defense, the psychiatrist begins to suspect malingering.

The authors’ observations

Malingering is a condition—not a diagnosis—characterized by intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives.¹¹ The presence of external incentives distinguishes malingering from psychiatric illnesses such as factitious and somatoform disorders, in which there is no apparent external incentive. Malingering of psychiatric symptoms occurs in up to 20% of forensic patients, 5% of military recruits, and 1% of mental health patients.⁵ Stimuli for malingering range from seeking food and shelter to avoiding criminal responsibility ( Table 2 ). Malingering is more common in individuals being evaluated for criminal responsibility than for competence to stand trial. The 3 categories of malingering are:

Table 2

Common external incentives for malingering

• pure malingering—feigning a nonexistent disorder
• partial malingering—consciously exaggerating real symptoms

• false imputation—ascribing real symptoms to a cause the individual knows is unrelated to the symptoms.¹²

Determining if a defendant with a history of TBI is malingering requires a multi-step approach that encompasses the clinical interview, a thorough review of collateral data, and focused psychological testing. In interviews, psychiatrists detect approximately 50% of lies, which is no better than would be discovered by chance.¹³ If you suspect a patient is malingering, combine a structured clinical interview with collateral sources such as old hospital records, treatment history, insurance records, police reports, and interviews with close family and friends.

TBI patients’ poor cognition, memory deficits, and inattention will prove challenging. Malingering patients who attempt to capitalize on a pre-existing TBI to evade responsibility for a current criminal charge may grossly exaggerate or even fake intellectual deficits. Be patient with such defendants and remain aware that such people will give vague or hedging answers to straightforward questions, often accompanied by “I don’t know.” Prolonging the interview may be helpful because it may fatigue a defendant who is faking.¹²

Some patients who malinger after sustaining a TBI will attempt to feign psychotic symptoms. Table 3 ¹⁴ illustrates criteria for assessing a patient suspected of malingering psychosis and Table 4 ¹⁴ highlights atypical psychotic symptoms that suggest feigning illness. Malingering of psychosis can be both assessed in the interview and through testing.

Table 3

Criteria for malingered psychosis

Table 4

Atypical psychotic symptoms that suggest malingering

Psychological testing

Several standardized diagnostic instruments can be used to help determine whether a patient is feigning or exaggerating psychotic symptoms or cognitive impairments ( Table 5 ). Testing for a patient such as Mr. P—who attributes any criminal wrongdoing to psychosis and also cites limited cognition as a reason for trouble in the interview—would include personality tests, tests to assess exaggerations of psychosis, and cognitive tests.

In the forensic setting, the preferred personality test is the MMPI-2.¹⁵ It consists of 567 items, with 10 clinical scales and several validity scales. The F scale, “faking good” or “faking bad,” detects people who are answering questions with the goal of appearing better or worse than they actually are. The Personal Assessment Inventory (PAI)¹⁶ is a 344-item test with a 4-point response format. The 22 scales cover a range of important axis I and II psychopathology.

SIRS¹⁷ is the gold standard in detecting malingered psychiatric illness; it includes questions about rare symptoms and uncommon symptom pairing. M-FAST¹⁸ was developed to provide a brief, reliable screen for malingered mental illness. It has shown good validity and high correlation with the SIRS and MMPI-2.

Tests of exaggerated cognitive impairment are extremely important in evaluating patients who claim to suffer from complications following TBI. TOMM¹⁹ —a 50-item recognition test designed to discriminate between true memory-impaired patients and malingerers—is the most studied and valid of such tests. Defendants’ scores that meet the recommended criteria for detecting malingering—≥5 errors on the retention trial—were found to also report a history of head injury.¹

Although not as well validated, the Portland Digit Recognition Test (PDRT)²⁰ is an alternative to the TOMM. This test is a forced-choice measure of recognition designed for assessing the possibility of malingering in individuals claiming mental illness because of head injury. The Victoria Symptoms Validity Test (VSVT)²¹ is used in outpatient and inpatient settings and also uses a forced-choice model to assess possible exaggeration or feigning of cognitive impairments. Finally, the Word Memory Test (WMT)²² is a neuropsychological assessment that evaluates the effort participants put forth.

Table 5

Standardized diagnostic instruments for detecting malingering

OUTCOME: Unsupported claims

Mr. P’s hospital records reveal a very minor head trauma that resulted in no structural brain abnormalities on imaging tests. Collateral interviews with Mr. P’s family and close friends fail to support the defendant’s claim that after the accident he began to experience behavioral changes and periods of psychosis. Mr. P’s SIRS and TOMM scores indicate malingering, and the psychiatrist did not support his NGRI defense.

Related resource

• Williamson DJ. Neurocognitive impairment: feigned, exaggerated, or real? Current Psychiatry. 2007;6(8):19-37.

Disclosure

Dr. Nasrallah receives research grant/research support from Forest Pharmaceuticals, GlaxoSmithKline, Janssen, Otsuka America Pharmaceuticals, Pfizer Inc., Roche, sanofi-aventis, and Shire, is on the advisory board of Abbott Laboratories, AstraZeneca, Janssen, Novartis, Pfizer Inc., and Merck, and is on the speakers’ bureau for Abbott Laboratories, AstraZeneca, Janssen, Novartis, Pfizer Inc., and Merck.

Dr. Farrell reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Self-reported TBI

When charged with raping a 19-year-old woman, Mr. P, age 32, pleads not guilty by reason of insanity (NGRI). He has a self-reported history of traumatic brain injury (TBI) and claims that since suffering a blow to the head 8 years before the rape, he has experienced episodes of personality changes, psychosis, and violent behavior. Mr. P is adamant that any wrongdoing on his part was beyond his control, and he argues that consequences of the brain injury, such as hallucinations and aggressive behavior, had recently emerged. The court asks that a forensic psychiatrist evaluate Mr. P.

An only child, Mr. P was raised by his mother in an inner city area. His father was dependent on alcohol and cocaine and abandoned the family shortly after Mr. P’s birth. Mr. P abuses alcohol, as evidenced by previous driving under the influence charges, but denies illicit drug use. He graduated from high school with average grades and denies a history of disciplinary action at school or home. Although Mr. P was charged with misdemeanors in his late teens, the sexual assault is his first felony charge. Mr. P describes himself as a “charmer.”

After high school, Mr. P worked full-time in construction, where he claims he suffered a traumatic blow to the head. Despite this injury, he continued to work and socialize and never sought treatment at a mental health clinic.

The authors’ observations

Although defendants may legitimately suffer from TBI and resultant complications, many individuals capitalize on a history of minor head injury to support their NGRI defense.¹ Forensic psychiatrists must retain a healthy degree of clinical suspicion for malingering in defendants who claim NGRI as a result of complications from brain injury, especially when the injury and complications are not documented and simply patient-reported.

TBI is a CNS injury that occurs when an outside force traumatically injures the brain and can cause a variety of physical, cognitive, emotional, and behavioral effects ( Table 1 ).² Cognitive deficits include:

• impaired attention
• disrupted insight
• poor judgment
• thought disorders.

Reduced processing speed, distractibility, and deficits in executive functions such as abstract reasoning, planning, problem solving, and multitasking have been documented. Memory loss—the most common cognitive impairment among head-injured people—occurs in 20% to 79% of people with closed head trauma, depending on injury severity.³ People who have suffered TBI may have difficulty understanding or producing spoken or written language, or with more subtle aspects of communication, such as body language.

TBI may cause emotional or behavioral problems and personality changes. Mood and affect changes are common. TBI predisposes patients to obsessive-compulsive disorder, substance abuse, dysthymia, clinical depression, bipolar disorder, phobias, panic disorder, and schizophrenia.⁴ Frontal lobe injuries have been correlated with disinhibition and inappropriate or childish behavior, and temporal lobe injuries with irritability and aggression.⁵

Table 1

TBI symptoms correspond to area of injury

TBI and the insanity defense

The M’Naghten Rule of 1843 requires that for an insanity defense, the defendant must have a mental disease or defect that causes him not to know the nature and quality or the wrongfulness of his act.⁶ TBI is an abnormal condition of the mind leading to a mental disease that can substantially affect control of emotions and behaviors.

Nevertheless, TBI-induced criminality remains controversial.⁷ Theories on the etiology of impulse dyscontrol resulting from TBI have suggested structural damage to the brain and altered neurotransmitters. In TBI, the amygdala—which is located within the anterior temporal lobe and adjoins emotions to thoughts—often is injured. Damage to this structure leads to poor impulse control and violent behavior. Damage to specific neurotransmitter systems that causes elevated norepinephrine and dopamine levels and reduced serotonin levels have also been implicated as a cause of impulse dyscontrol in TBI patients.⁸

In theory, TBI patients potentially could have enough cognitive impairment to have a substantial lack of appreciation of the criminality or wrongfulness of an act. TBI-related impulsivity and cognitive impairment can lead to recklessness and negligence.⁹ The U.S. Supreme Court has acknowledged that CNS dysfunction affects judgment, reality testing, and self-control.¹⁰

EVALUATION: Vague answers

To determine whether Mr. P’s defense is plausible, the forensic psychiatrist must pay attention to the details of the patient’s presentation and history. During the interview, Mr. P quickly shifts from cooperative to obstinate and restricted. He ruminates on the head injury causing him to suffer auditory hallucinations, which he claims he always obeys. Mr. P refuses to provide details of the hallucinations, however, and answers most questions about the head injury or his defense with vague answers, including “I don’t know.”

Because of Mr. P’s reluctance to share information, his lack of psychiatric symptoms other than those he self-reports, and the presence of potential secondary gain from an NGRI defense, the psychiatrist begins to suspect malingering.

The authors’ observations

Malingering is a condition—not a diagnosis—characterized by intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives.¹¹ The presence of external incentives distinguishes malingering from psychiatric illnesses such as factitious and somatoform disorders, in which there is no apparent external incentive. Malingering of psychiatric symptoms occurs in up to 20% of forensic patients, 5% of military recruits, and 1% of mental health patients.⁵ Stimuli for malingering range from seeking food and shelter to avoiding criminal responsibility ( Table 2 ). Malingering is more common in individuals being evaluated for criminal responsibility than for competence to stand trial. The 3 categories of malingering are:

Table 2

Common external incentives for malingering

• pure malingering—feigning a nonexistent disorder
• partial malingering—consciously exaggerating real symptoms

• false imputation—ascribing real symptoms to a cause the individual knows is unrelated to the symptoms.¹²

Determining if a defendant with a history of TBI is malingering requires a multi-step approach that encompasses the clinical interview, a thorough review of collateral data, and focused psychological testing. In interviews, psychiatrists detect approximately 50% of lies, which is no better than would be discovered by chance.¹³ If you suspect a patient is malingering, combine a structured clinical interview with collateral sources such as old hospital records, treatment history, insurance records, police reports, and interviews with close family and friends.

TBI patients’ poor cognition, memory deficits, and inattention will prove challenging. Malingering patients who attempt to capitalize on a pre-existing TBI to evade responsibility for a current criminal charge may grossly exaggerate or even fake intellectual deficits. Be patient with such defendants and remain aware that such people will give vague or hedging answers to straightforward questions, often accompanied by “I don’t know.” Prolonging the interview may be helpful because it may fatigue a defendant who is faking.¹²

Some patients who malinger after sustaining a TBI will attempt to feign psychotic symptoms. Table 3 ¹⁴ illustrates criteria for assessing a patient suspected of malingering psychosis and Table 4 ¹⁴ highlights atypical psychotic symptoms that suggest feigning illness. Malingering of psychosis can be both assessed in the interview and through testing.

Table 3

Criteria for malingered psychosis

Table 4

Atypical psychotic symptoms that suggest malingering

Psychological testing

Several standardized diagnostic instruments can be used to help determine whether a patient is feigning or exaggerating psychotic symptoms or cognitive impairments ( Table 5 ). Testing for a patient such as Mr. P—who attributes any criminal wrongdoing to psychosis and also cites limited cognition as a reason for trouble in the interview—would include personality tests, tests to assess exaggerations of psychosis, and cognitive tests.

In the forensic setting, the preferred personality test is the MMPI-2.¹⁵ It consists of 567 items, with 10 clinical scales and several validity scales. The F scale, “faking good” or “faking bad,” detects people who are answering questions with the goal of appearing better or worse than they actually are. The Personal Assessment Inventory (PAI)¹⁶ is a 344-item test with a 4-point response format. The 22 scales cover a range of important axis I and II psychopathology.

SIRS¹⁷ is the gold standard in detecting malingered psychiatric illness; it includes questions about rare symptoms and uncommon symptom pairing. M-FAST¹⁸ was developed to provide a brief, reliable screen for malingered mental illness. It has shown good validity and high correlation with the SIRS and MMPI-2.

Tests of exaggerated cognitive impairment are extremely important in evaluating patients who claim to suffer from complications following TBI. TOMM¹⁹ —a 50-item recognition test designed to discriminate between true memory-impaired patients and malingerers—is the most studied and valid of such tests. Defendants’ scores that meet the recommended criteria for detecting malingering—≥5 errors on the retention trial—were found to also report a history of head injury.¹

Although not as well validated, the Portland Digit Recognition Test (PDRT)²⁰ is an alternative to the TOMM. This test is a forced-choice measure of recognition designed for assessing the possibility of malingering in individuals claiming mental illness because of head injury. The Victoria Symptoms Validity Test (VSVT)²¹ is used in outpatient and inpatient settings and also uses a forced-choice model to assess possible exaggeration or feigning of cognitive impairments. Finally, the Word Memory Test (WMT)²² is a neuropsychological assessment that evaluates the effort participants put forth.

Table 5

Standardized diagnostic instruments for detecting malingering

OUTCOME: Unsupported claims

Mr. P’s hospital records reveal a very minor head trauma that resulted in no structural brain abnormalities on imaging tests. Collateral interviews with Mr. P’s family and close friends fail to support the defendant’s claim that after the accident he began to experience behavioral changes and periods of psychosis. Mr. P’s SIRS and TOMM scores indicate malingering, and the psychiatrist did not support his NGRI defense.

Related resource

• Williamson DJ. Neurocognitive impairment: feigned, exaggerated, or real? Current Psychiatry. 2007;6(8):19-37.

Disclosure

Dr. Nasrallah receives research grant/research support from Forest Pharmaceuticals, GlaxoSmithKline, Janssen, Otsuka America Pharmaceuticals, Pfizer Inc., Roche, sanofi-aventis, and Shire, is on the advisory board of Abbott Laboratories, AstraZeneca, Janssen, Novartis, Pfizer Inc., and Merck, and is on the speakers’ bureau for Abbott Laboratories, AstraZeneca, Janssen, Novartis, Pfizer Inc., and Merck.

Dr. Farrell reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article

Sammy, age 7, is referred to you by his pediatrician because of a 4-week history of frequent eye blinking. His parents say he blinks a lot when bored but very little when playing baseball. They recall that he also has intermittently sniffed and nodded his head over the last 12 months. Neither Sammy nor his friends seem to be bothered by the blinking. Except for the tics, Sammy’s physical and mental status exams are normal.

Since preschool, Sammy’s teachers have complained that his backpack and desk are always a mess. Sammy is well-meaning but forgetful in his chores at home. A paternal uncle has head-turning movements, counts his steps, and becomes distressed if books on his shelf are not in alphabetical order.

Tics, such as strong eye blinks or repetitive shoulder shrugs, can distress a child or his/her parents, but the conditions associated with tic disorders often are more problematic than the tic disorder itself. High rates of comorbid conditions are recognized in persons with Tourette syndrome, including:

• obsessive-compulsive disorder (OCD) in >80%¹
• attention-deficit/hyperactivity disorder (ADHD) in ≤70%²
• anxiety disorders in 30%³
• rage, aggression, learning disabilities, and autism less commonly.

The strategy we recommend for managing tic disorders includes assessing tic severity, educating the family about the illness, determining whether a comorbid condition is present, and managing these conditions appropriately. Above all, we emphasize a risk-benefit analysis guided by the Hippocratic principle of “do no harm.”

Characteristics of tic disorders

You diagnose Sammy with Tourette syndrome because he meets DSM-IV-TR criteria of at least 2 motor tics and 1 vocal tic that have persisted for 1 year without more than a 3-month hiatus, with tic onset before age 18. Because tics may resemble other movement disorders, you rule out stereotypies, dystonia, chorea, ballism, and myoclonus (Table 1). You explain to his parents that Sammy’s condition is a heritable, neurobehavioral disorder that typically begins in childhood and is associated in families with OCD, ADHD, and autism spectrum disorders.

His parents ask about the difference between tics and other movements. You explain that eye-blinking tics—like other motor tics—appear as sudden, repetitive, stereotyped, nonrhythmic movements that involve discrete muscle groups. (View a video of a patient with tics.) Simple motor tics are focal movements involving 1 group of muscles, whereas complex tics are sequential patterns of movement that involve >1 muscle group or resemble purposeful movements (Table 2).

Table 1

Features of 5 movement disorders that may resemble tics

Table 2

Characteristics of simple and complex motor and vocal tics*

Older children frequently describe a premonitory urge prior to the tic. Patients typically can suppress tics for a transient period of time, although during tic suppression they usually feel restless and anticipate performing their tic. The ultimate performance of the tic brings relief. Tic suppression also occurs during focused activity. Emotional stress, fatigue, illness, or boredom can exacerbate tics.

To begin monitoring Sammy’s clinical course, you administer 3 assessment tools described inTable 3. You explain to Sammy’s parents that these tests will be repeated yearly or when tics worsen. However, you tell his parents that these scores alone will not determine present or future clinical decisions, including treatments. You also recommend that they connect with support groups on the Tourette Syndrome Association (TSA) Web site.

CASE CONTINUED: Changes over time

Sammy’s parents appreciate your explanation and say they will share information from the TSA Web site with Sammy’s principal, teachers, and classmates. The family agrees to return in 6 months or sooner if the tics worsen.

By age 8, Sammy develops multiple tics: facial grimacing, looking upwards, punching movements, whistling, and throat clearing. He is slightly bothered by these tics, and his friends have asked him about them. He tells them he has Tourette syndrome, and that usually ends the questioning. He returns for a follow-up visit because his parents notice a dramatic increase in his tics after Sammy’s father loses his job.

Treatment options

When deciding to treat a child’s tics, the first step is to determine whether to pursue a nonpharmacologic or pharmacologic approach (Algorithm). To tailor an approach most suited for an individual child, discuss with the family their feelings about therapy and medications. This information—along with tic severity—will help determine a treatment plan.

Behavior therapy and medication are management strategies; neither can cure a tic disorder. The most conservative approach to tic treatment is to:

• provide the child and family with basic guidelines for managing tics
• help alleviate environmental stress and other potential triggers.

Algorithm: Recommended treatment of tics in children and adolescents

CASE CONTINUED: A first intervention

You discuss treatment options with Sammy’s family, and they view medication as a last resort. Sammy does not seem to be bothered by his tics, and his parents do not wish to start him on daily medications. Given this situation, habit reversal therapy (HRT) is appropriate for Sammy because he is old enough to participate in HRT to reduce his tics.

HRT is an effective nonpharmacologic approach to help children with tics.⁴ Its 3 components are:

• awareness training
• competing response training
• social support.⁵

This simplified version of the original HRT can be completed in eight 1-hour sessions. Good candidates are patients who are cognitively mature enough to understand the therapy’s goals and compliant with frequent clinic visits. They also must practice the strategies at home.

It should not be difficult for psychiatrists to learn HRT—or refer to therapists who are willing to learn it—with the available instructional manual.

CASE CONTINUED: Practicing alternatives

You ask Sammy to imitate his tics. After helping him become more aware of his tics, you encourage him to develop a more socially appropriate movement to engage in whenever he feels the urge to punch. Sammy chooses to clench his fist in his pocket. He also learns to breathe in whenever he has an urge to whistle. you advise Sammy’s parents to reward his efforts to suppress the tics. He practices the strategies daily.

At age 12, Sammy returns to your office. He has begun to have frequent neck-jerking tics, which cause neck pain and daily headaches. He also is slapping his thigh and having frequent vocal tics characterized by loud shrieking. The vocal tics are disruptive in class, even though Sammy sits toward the back of the room. Sammy’s classmates tease him, and he is very frustrated.

Medication approach

The decision to start a medication for tics is complex. Scores from the YGTSS, PUTS, and GTS-QOL scales (Table 3) provide only a partial clinical picture. This decision should be reached after a detailed discussion with the family about benefits and risks of medications and ensuring that everyone’s expectations are reasonable.

A variety of medications are available to treat patients with tics (Table 4). No medication can completely eliminate tics, however, and many have substantial side effects. Before initiating medical treatment, consider 3 questions:

• Is moderate or severe pain involved?
• Is there significant functional interference?
• Is there significant social disruption despite efforts to optimize the social environment for the child?

Sammy’s frequent neck-jerking tics now cause chronic daily headaches, and his shrieking vocal tics are interfering with classroom activities, so we recommended a 3-month trial of guanfacine following the dosing schedule in Table 4.

Table 3

3 scales for assessing tic severity and impact on functioning

Table 4

Medications with evidence of tic-suppressing effects*

The first-line pharmacologic agent for tic suppression generally is an alpha-adrenergic medication, unless the tics are severe.⁶

Clonidine and guanfacine usually are started at low doses and increased gradually. Although not as effective as neuroleptics, alpha-adrenergics have a lower potential for side effects and are easier to use because no laboratory tests need to be monitored. Adverse effects associated with alpha-adrenergic medications include sedation, dry mouth, dizziness, headache, and rebound hypertension if discontinued abruptly.

If tics are causing pain, some clinicians prefer conservative measures such as heat or ice, massage, analgesics, relaxation therapy, and reassurance.

Second-line agents include typical and atypical antipsychotics. Haloperidol and pimozide have shown efficacy in reducing tics in placebo- controlled studies,^7,8 as have risperidone (in 4 randomized controlled trials [RCTs]) and ziprasidone (in 1 RCT).^9,10 The emergence of serious side effects is a risk for both typical and atypical antipsychotics (Table 5).

Table 5

Potential adverse effects of antipsychotic treatment in children*

As part of your informed consent discussion, weigh the risk of side effects against the benefits of treatment. Point out to patients and their families that they can expect to see a decrease in tic frequency, but symptoms will not necessarily disappear with any medication. We tell our patients that with antipsychotics the best we can hope for is to reduce tic frequency by approximately one-half.⁶

When treating tics, start with 1 medication. However, if the tics are severe enough to require more than 1 medication, check for drug interactions.

Third-line agents. Agents that have not been tested in placebo-controlled trials can be considered third line; these are listed as category C (supported by open-label studies) in Table 4. Botulinum toxin injection has been found to be effective for motor and vocal tics.^11,12 Botulinum toxin and implantation of deep brain stimulators¹³ are invasive options and generally are reserved for severe, treatment-resistant tics.

CASE CONTINUED: Managing antipsychotics

After trying guanfacine for 12 weeks, Sammy notices no tic reduction. His parents consent to a low dose of risperidone. you review with them the American Psychiatric Association (APA)/American Diabetes Association (ADA) guidelines¹⁴ for managing metabolic problems in patients treated with atypical antipsychotics.

As instructed in the APA/ADA guidelines, obtain baseline measurements and monitor for metabolic effects of antipsychotic therapy over time (Table 6). Sammy starts risperidone at 0.5 mg once daily. After 2 weeks, he notices a decrease in his tics. At the 3-month visit after starting risperidone, he is happy with his risperidone dose and does not want to increase it. He has gained 3 pounds, and you instruct him to eat a well-balanced diet and exercise routinely. At the 6-month visit, his tics are minimal and his weight has stabilized.

Table 6

Children receiving antipsychotics: monitoring recommendations

You recommend that Sammy remain on risperidone for another 3 months of stability and then begin to taper this medication. You review the risks and benefits of long-term treatment with risperidone, pointing out that it may lead to abnormal movements upon withdrawal, and explain that you typically do not treat children with antipsychotics for more than one year continuously.

CASE CONTINUED: Comorbid symptoms

Since starting 7th grade, Sammy has worried excessively about making mistakes. He spends 6 hours each night on homework, which he often does not turn in because of anxiety about not getting answers perfectly right. Classmates notice that Sammy taps the door 3 times when he comes into the classroom and that he steps over the black tiles in the hallway.

Consider the presence and impact of comorbid OCD or ADHD, which can impair children’s quality of life more than tics themselves.¹⁵ Assessment scales can help you make a diagnosis and monitor treatment.

If you suspect OCD, the clinician-rated Children’s Yale Brown Obsessive Compulsive Scale is the gold standard for describing the phenomenology and measuring symptom severity. Additional scales to measure symptoms’ impact on family life include the Leyton Obsessional Inventory—child version, Family Accommodation Scale for OCD, and Child OCD Impact Scale.

ADHD scales include the Conners Parent Rating Scale—Revised, Conners Teacher Rating Scale—Revised, Swanson, Nolan, and Pelham, or the Vanderbilt ADHD Diagnostic Parent and Teacher Rating Scales. Because ADHD symptoms must be present in more than 1 environment to meet diagnostic criteria, ask parents and teachers to complete the Conners or Vanderbilt scales.

In children who present with a tic disorder plus a comorbid condition, prioritize treatment by determining which symptoms interfere with the child’s ability to function at school, at home, and in the social arena. Children who require treatment for >1 disorder often are referred initially for cognitive-behavioral therapy for OCD symptoms while receiving pharmacologic treatment for ADHD and/or Tourette syndrome. When necessary, it is usually safe to combine antipsychotics, stimulants, and selective serotonin reuptake inhibitors, although medication interactions should be reviewed in each specific case.

Related resources

• Woods DW. Managing Tourette syndrome: a behavioral intervention for children and adults. Therapist guide. New York, NY: Oxford University Press; 2008.
• Tourette Syndrome Association. www.tsa-usa.org.
• International OCD Foundation. www.ocfoundation.org.

Drug brand names

• Baclofen • Lioresal
• Botulinum toxin • Botox, Myobloc
• Clomipramine • Anafranil
• Clonidine • Catapres
• Guanfacine • Tenex
• Fluphenazine • Prolixin
• Flutamide • Eulexin
• Haloperidol • Haldol
• Mecamylamine • Inversine
• Nicotine patch • NicoDerm
• Olanzapine • Zyprexa
• Pimozide • Orap
• Risperidone • Risperdal
• Tetrabenazine • Xenazine
• Ziprasidone • Geodon

Disclosures

Dr. Harris has received research support from the Translational Research Initiative at Cincinnati Children’s Hospital Medical Center.

Dr. Wu reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article

Sammy, age 7, is referred to you by his pediatrician because of a 4-week history of frequent eye blinking. His parents say he blinks a lot when bored but very little when playing baseball. They recall that he also has intermittently sniffed and nodded his head over the last 12 months. Neither Sammy nor his friends seem to be bothered by the blinking. Except for the tics, Sammy’s physical and mental status exams are normal.

Since preschool, Sammy’s teachers have complained that his backpack and desk are always a mess. Sammy is well-meaning but forgetful in his chores at home. A paternal uncle has head-turning movements, counts his steps, and becomes distressed if books on his shelf are not in alphabetical order.

Tics, such as strong eye blinks or repetitive shoulder shrugs, can distress a child or his/her parents, but the conditions associated with tic disorders often are more problematic than the tic disorder itself. High rates of comorbid conditions are recognized in persons with Tourette syndrome, including:

• obsessive-compulsive disorder (OCD) in >80%¹
• attention-deficit/hyperactivity disorder (ADHD) in ≤70%²
• anxiety disorders in 30%³
• rage, aggression, learning disabilities, and autism less commonly.

The strategy we recommend for managing tic disorders includes assessing tic severity, educating the family about the illness, determining whether a comorbid condition is present, and managing these conditions appropriately. Above all, we emphasize a risk-benefit analysis guided by the Hippocratic principle of “do no harm.”

Characteristics of tic disorders

You diagnose Sammy with Tourette syndrome because he meets DSM-IV-TR criteria of at least 2 motor tics and 1 vocal tic that have persisted for 1 year without more than a 3-month hiatus, with tic onset before age 18. Because tics may resemble other movement disorders, you rule out stereotypies, dystonia, chorea, ballism, and myoclonus (Table 1). You explain to his parents that Sammy’s condition is a heritable, neurobehavioral disorder that typically begins in childhood and is associated in families with OCD, ADHD, and autism spectrum disorders.

His parents ask about the difference between tics and other movements. You explain that eye-blinking tics—like other motor tics—appear as sudden, repetitive, stereotyped, nonrhythmic movements that involve discrete muscle groups. (View a video of a patient with tics.) Simple motor tics are focal movements involving 1 group of muscles, whereas complex tics are sequential patterns of movement that involve >1 muscle group or resemble purposeful movements (Table 2).

Table 1

Features of 5 movement disorders that may resemble tics

Table 2

Characteristics of simple and complex motor and vocal tics*

Older children frequently describe a premonitory urge prior to the tic. Patients typically can suppress tics for a transient period of time, although during tic suppression they usually feel restless and anticipate performing their tic. The ultimate performance of the tic brings relief. Tic suppression also occurs during focused activity. Emotional stress, fatigue, illness, or boredom can exacerbate tics.

To begin monitoring Sammy’s clinical course, you administer 3 assessment tools described inTable 3. You explain to Sammy’s parents that these tests will be repeated yearly or when tics worsen. However, you tell his parents that these scores alone will not determine present or future clinical decisions, including treatments. You also recommend that they connect with support groups on the Tourette Syndrome Association (TSA) Web site.

CASE CONTINUED: Changes over time

Sammy’s parents appreciate your explanation and say they will share information from the TSA Web site with Sammy’s principal, teachers, and classmates. The family agrees to return in 6 months or sooner if the tics worsen.

By age 8, Sammy develops multiple tics: facial grimacing, looking upwards, punching movements, whistling, and throat clearing. He is slightly bothered by these tics, and his friends have asked him about them. He tells them he has Tourette syndrome, and that usually ends the questioning. He returns for a follow-up visit because his parents notice a dramatic increase in his tics after Sammy’s father loses his job.

Treatment options

When deciding to treat a child’s tics, the first step is to determine whether to pursue a nonpharmacologic or pharmacologic approach (Algorithm). To tailor an approach most suited for an individual child, discuss with the family their feelings about therapy and medications. This information—along with tic severity—will help determine a treatment plan.

Behavior therapy and medication are management strategies; neither can cure a tic disorder. The most conservative approach to tic treatment is to:

• provide the child and family with basic guidelines for managing tics
• help alleviate environmental stress and other potential triggers.

Algorithm: Recommended treatment of tics in children and adolescents

CASE CONTINUED: A first intervention

You discuss treatment options with Sammy’s family, and they view medication as a last resort. Sammy does not seem to be bothered by his tics, and his parents do not wish to start him on daily medications. Given this situation, habit reversal therapy (HRT) is appropriate for Sammy because he is old enough to participate in HRT to reduce his tics.

HRT is an effective nonpharmacologic approach to help children with tics.⁴ Its 3 components are:

• awareness training
• competing response training
• social support.⁵

This simplified version of the original HRT can be completed in eight 1-hour sessions. Good candidates are patients who are cognitively mature enough to understand the therapy’s goals and compliant with frequent clinic visits. They also must practice the strategies at home.

It should not be difficult for psychiatrists to learn HRT—or refer to therapists who are willing to learn it—with the available instructional manual.

CASE CONTINUED: Practicing alternatives

You ask Sammy to imitate his tics. After helping him become more aware of his tics, you encourage him to develop a more socially appropriate movement to engage in whenever he feels the urge to punch. Sammy chooses to clench his fist in his pocket. He also learns to breathe in whenever he has an urge to whistle. you advise Sammy’s parents to reward his efforts to suppress the tics. He practices the strategies daily.

At age 12, Sammy returns to your office. He has begun to have frequent neck-jerking tics, which cause neck pain and daily headaches. He also is slapping his thigh and having frequent vocal tics characterized by loud shrieking. The vocal tics are disruptive in class, even though Sammy sits toward the back of the room. Sammy’s classmates tease him, and he is very frustrated.

Medication approach

The decision to start a medication for tics is complex. Scores from the YGTSS, PUTS, and GTS-QOL scales (Table 3) provide only a partial clinical picture. This decision should be reached after a detailed discussion with the family about benefits and risks of medications and ensuring that everyone’s expectations are reasonable.

A variety of medications are available to treat patients with tics (Table 4). No medication can completely eliminate tics, however, and many have substantial side effects. Before initiating medical treatment, consider 3 questions:

• Is moderate or severe pain involved?
• Is there significant functional interference?
• Is there significant social disruption despite efforts to optimize the social environment for the child?

Sammy’s frequent neck-jerking tics now cause chronic daily headaches, and his shrieking vocal tics are interfering with classroom activities, so we recommended a 3-month trial of guanfacine following the dosing schedule in Table 4.

Table 3

3 scales for assessing tic severity and impact on functioning

Table 4

Medications with evidence of tic-suppressing effects*

The first-line pharmacologic agent for tic suppression generally is an alpha-adrenergic medication, unless the tics are severe.⁶

Clonidine and guanfacine usually are started at low doses and increased gradually. Although not as effective as neuroleptics, alpha-adrenergics have a lower potential for side effects and are easier to use because no laboratory tests need to be monitored. Adverse effects associated with alpha-adrenergic medications include sedation, dry mouth, dizziness, headache, and rebound hypertension if discontinued abruptly.

If tics are causing pain, some clinicians prefer conservative measures such as heat or ice, massage, analgesics, relaxation therapy, and reassurance.

Second-line agents include typical and atypical antipsychotics. Haloperidol and pimozide have shown efficacy in reducing tics in placebo- controlled studies,^7,8 as have risperidone (in 4 randomized controlled trials [RCTs]) and ziprasidone (in 1 RCT).^9,10 The emergence of serious side effects is a risk for both typical and atypical antipsychotics (Table 5).

Table 5

Potential adverse effects of antipsychotic treatment in children*

As part of your informed consent discussion, weigh the risk of side effects against the benefits of treatment. Point out to patients and their families that they can expect to see a decrease in tic frequency, but symptoms will not necessarily disappear with any medication. We tell our patients that with antipsychotics the best we can hope for is to reduce tic frequency by approximately one-half.⁶

When treating tics, start with 1 medication. However, if the tics are severe enough to require more than 1 medication, check for drug interactions.

Third-line agents. Agents that have not been tested in placebo-controlled trials can be considered third line; these are listed as category C (supported by open-label studies) in Table 4. Botulinum toxin injection has been found to be effective for motor and vocal tics.^11,12 Botulinum toxin and implantation of deep brain stimulators¹³ are invasive options and generally are reserved for severe, treatment-resistant tics.

CASE CONTINUED: Managing antipsychotics

After trying guanfacine for 12 weeks, Sammy notices no tic reduction. His parents consent to a low dose of risperidone. you review with them the American Psychiatric Association (APA)/American Diabetes Association (ADA) guidelines¹⁴ for managing metabolic problems in patients treated with atypical antipsychotics.

As instructed in the APA/ADA guidelines, obtain baseline measurements and monitor for metabolic effects of antipsychotic therapy over time (Table 6). Sammy starts risperidone at 0.5 mg once daily. After 2 weeks, he notices a decrease in his tics. At the 3-month visit after starting risperidone, he is happy with his risperidone dose and does not want to increase it. He has gained 3 pounds, and you instruct him to eat a well-balanced diet and exercise routinely. At the 6-month visit, his tics are minimal and his weight has stabilized.

Table 6

Children receiving antipsychotics: monitoring recommendations

You recommend that Sammy remain on risperidone for another 3 months of stability and then begin to taper this medication. You review the risks and benefits of long-term treatment with risperidone, pointing out that it may lead to abnormal movements upon withdrawal, and explain that you typically do not treat children with antipsychotics for more than one year continuously.

CASE CONTINUED: Comorbid symptoms

Since starting 7th grade, Sammy has worried excessively about making mistakes. He spends 6 hours each night on homework, which he often does not turn in because of anxiety about not getting answers perfectly right. Classmates notice that Sammy taps the door 3 times when he comes into the classroom and that he steps over the black tiles in the hallway.

Consider the presence and impact of comorbid OCD or ADHD, which can impair children’s quality of life more than tics themselves.¹⁵ Assessment scales can help you make a diagnosis and monitor treatment.

If you suspect OCD, the clinician-rated Children’s Yale Brown Obsessive Compulsive Scale is the gold standard for describing the phenomenology and measuring symptom severity. Additional scales to measure symptoms’ impact on family life include the Leyton Obsessional Inventory—child version, Family Accommodation Scale for OCD, and Child OCD Impact Scale.

ADHD scales include the Conners Parent Rating Scale—Revised, Conners Teacher Rating Scale—Revised, Swanson, Nolan, and Pelham, or the Vanderbilt ADHD Diagnostic Parent and Teacher Rating Scales. Because ADHD symptoms must be present in more than 1 environment to meet diagnostic criteria, ask parents and teachers to complete the Conners or Vanderbilt scales.

In children who present with a tic disorder plus a comorbid condition, prioritize treatment by determining which symptoms interfere with the child’s ability to function at school, at home, and in the social arena. Children who require treatment for >1 disorder often are referred initially for cognitive-behavioral therapy for OCD symptoms while receiving pharmacologic treatment for ADHD and/or Tourette syndrome. When necessary, it is usually safe to combine antipsychotics, stimulants, and selective serotonin reuptake inhibitors, although medication interactions should be reviewed in each specific case.

Related resources

• Woods DW. Managing Tourette syndrome: a behavioral intervention for children and adults. Therapist guide. New York, NY: Oxford University Press; 2008.
• Tourette Syndrome Association. www.tsa-usa.org.
• International OCD Foundation. www.ocfoundation.org.

Drug brand names

• Baclofen • Lioresal
• Botulinum toxin • Botox, Myobloc
• Clomipramine • Anafranil
• Clonidine • Catapres
• Guanfacine • Tenex
• Fluphenazine • Prolixin
• Flutamide • Eulexin
• Haloperidol • Haldol
• Mecamylamine • Inversine
• Nicotine patch • NicoDerm
• Olanzapine • Zyprexa
• Pimozide • Orap
• Risperidone • Risperdal
• Tetrabenazine • Xenazine
• Ziprasidone • Geodon

Disclosures

Dr. Harris has received research support from the Translational Research Initiative at Cincinnati Children’s Hospital Medical Center.

Dr. Wu reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article

Sammy, age 7, is referred to you by his pediatrician because of a 4-week history of frequent eye blinking. His parents say he blinks a lot when bored but very little when playing baseball. They recall that he also has intermittently sniffed and nodded his head over the last 12 months. Neither Sammy nor his friends seem to be bothered by the blinking. Except for the tics, Sammy’s physical and mental status exams are normal.

Since preschool, Sammy’s teachers have complained that his backpack and desk are always a mess. Sammy is well-meaning but forgetful in his chores at home. A paternal uncle has head-turning movements, counts his steps, and becomes distressed if books on his shelf are not in alphabetical order.

Tics, such as strong eye blinks or repetitive shoulder shrugs, can distress a child or his/her parents, but the conditions associated with tic disorders often are more problematic than the tic disorder itself. High rates of comorbid conditions are recognized in persons with Tourette syndrome, including:

• obsessive-compulsive disorder (OCD) in >80%¹
• attention-deficit/hyperactivity disorder (ADHD) in ≤70%²
• anxiety disorders in 30%³
• rage, aggression, learning disabilities, and autism less commonly.

The strategy we recommend for managing tic disorders includes assessing tic severity, educating the family about the illness, determining whether a comorbid condition is present, and managing these conditions appropriately. Above all, we emphasize a risk-benefit analysis guided by the Hippocratic principle of “do no harm.”

Characteristics of tic disorders

You diagnose Sammy with Tourette syndrome because he meets DSM-IV-TR criteria of at least 2 motor tics and 1 vocal tic that have persisted for 1 year without more than a 3-month hiatus, with tic onset before age 18. Because tics may resemble other movement disorders, you rule out stereotypies, dystonia, chorea, ballism, and myoclonus (Table 1). You explain to his parents that Sammy’s condition is a heritable, neurobehavioral disorder that typically begins in childhood and is associated in families with OCD, ADHD, and autism spectrum disorders.

His parents ask about the difference between tics and other movements. You explain that eye-blinking tics—like other motor tics—appear as sudden, repetitive, stereotyped, nonrhythmic movements that involve discrete muscle groups. (View a video of a patient with tics.) Simple motor tics are focal movements involving 1 group of muscles, whereas complex tics are sequential patterns of movement that involve >1 muscle group or resemble purposeful movements (Table 2).

Table 1

Features of 5 movement disorders that may resemble tics

Table 2

Characteristics of simple and complex motor and vocal tics*

Older children frequently describe a premonitory urge prior to the tic. Patients typically can suppress tics for a transient period of time, although during tic suppression they usually feel restless and anticipate performing their tic. The ultimate performance of the tic brings relief. Tic suppression also occurs during focused activity. Emotional stress, fatigue, illness, or boredom can exacerbate tics.

To begin monitoring Sammy’s clinical course, you administer 3 assessment tools described inTable 3. You explain to Sammy’s parents that these tests will be repeated yearly or when tics worsen. However, you tell his parents that these scores alone will not determine present or future clinical decisions, including treatments. You also recommend that they connect with support groups on the Tourette Syndrome Association (TSA) Web site.

CASE CONTINUED: Changes over time

Sammy’s parents appreciate your explanation and say they will share information from the TSA Web site with Sammy’s principal, teachers, and classmates. The family agrees to return in 6 months or sooner if the tics worsen.

By age 8, Sammy develops multiple tics: facial grimacing, looking upwards, punching movements, whistling, and throat clearing. He is slightly bothered by these tics, and his friends have asked him about them. He tells them he has Tourette syndrome, and that usually ends the questioning. He returns for a follow-up visit because his parents notice a dramatic increase in his tics after Sammy’s father loses his job.

Treatment options

When deciding to treat a child’s tics, the first step is to determine whether to pursue a nonpharmacologic or pharmacologic approach (Algorithm). To tailor an approach most suited for an individual child, discuss with the family their feelings about therapy and medications. This information—along with tic severity—will help determine a treatment plan.

Behavior therapy and medication are management strategies; neither can cure a tic disorder. The most conservative approach to tic treatment is to:

• provide the child and family with basic guidelines for managing tics
• help alleviate environmental stress and other potential triggers.

Algorithm: Recommended treatment of tics in children and adolescents

CASE CONTINUED: A first intervention

You discuss treatment options with Sammy’s family, and they view medication as a last resort. Sammy does not seem to be bothered by his tics, and his parents do not wish to start him on daily medications. Given this situation, habit reversal therapy (HRT) is appropriate for Sammy because he is old enough to participate in HRT to reduce his tics.

HRT is an effective nonpharmacologic approach to help children with tics.⁴ Its 3 components are:

• awareness training
• competing response training
• social support.⁵

This simplified version of the original HRT can be completed in eight 1-hour sessions. Good candidates are patients who are cognitively mature enough to understand the therapy’s goals and compliant with frequent clinic visits. They also must practice the strategies at home.

It should not be difficult for psychiatrists to learn HRT—or refer to therapists who are willing to learn it—with the available instructional manual.

CASE CONTINUED: Practicing alternatives

You ask Sammy to imitate his tics. After helping him become more aware of his tics, you encourage him to develop a more socially appropriate movement to engage in whenever he feels the urge to punch. Sammy chooses to clench his fist in his pocket. He also learns to breathe in whenever he has an urge to whistle. you advise Sammy’s parents to reward his efforts to suppress the tics. He practices the strategies daily.

At age 12, Sammy returns to your office. He has begun to have frequent neck-jerking tics, which cause neck pain and daily headaches. He also is slapping his thigh and having frequent vocal tics characterized by loud shrieking. The vocal tics are disruptive in class, even though Sammy sits toward the back of the room. Sammy’s classmates tease him, and he is very frustrated.

Medication approach

The decision to start a medication for tics is complex. Scores from the YGTSS, PUTS, and GTS-QOL scales (Table 3) provide only a partial clinical picture. This decision should be reached after a detailed discussion with the family about benefits and risks of medications and ensuring that everyone’s expectations are reasonable.

A variety of medications are available to treat patients with tics (Table 4). No medication can completely eliminate tics, however, and many have substantial side effects. Before initiating medical treatment, consider 3 questions:

• Is moderate or severe pain involved?
• Is there significant functional interference?
• Is there significant social disruption despite efforts to optimize the social environment for the child?

Sammy’s frequent neck-jerking tics now cause chronic daily headaches, and his shrieking vocal tics are interfering with classroom activities, so we recommended a 3-month trial of guanfacine following the dosing schedule in Table 4.

Table 3

3 scales for assessing tic severity and impact on functioning

Table 4

Medications with evidence of tic-suppressing effects*

The first-line pharmacologic agent for tic suppression generally is an alpha-adrenergic medication, unless the tics are severe.⁶

Clonidine and guanfacine usually are started at low doses and increased gradually. Although not as effective as neuroleptics, alpha-adrenergics have a lower potential for side effects and are easier to use because no laboratory tests need to be monitored. Adverse effects associated with alpha-adrenergic medications include sedation, dry mouth, dizziness, headache, and rebound hypertension if discontinued abruptly.

If tics are causing pain, some clinicians prefer conservative measures such as heat or ice, massage, analgesics, relaxation therapy, and reassurance.

Second-line agents include typical and atypical antipsychotics. Haloperidol and pimozide have shown efficacy in reducing tics in placebo- controlled studies,^7,8 as have risperidone (in 4 randomized controlled trials [RCTs]) and ziprasidone (in 1 RCT).^9,10 The emergence of serious side effects is a risk for both typical and atypical antipsychotics (Table 5).

Table 5

Potential adverse effects of antipsychotic treatment in children*

As part of your informed consent discussion, weigh the risk of side effects against the benefits of treatment. Point out to patients and their families that they can expect to see a decrease in tic frequency, but symptoms will not necessarily disappear with any medication. We tell our patients that with antipsychotics the best we can hope for is to reduce tic frequency by approximately one-half.⁶

When treating tics, start with 1 medication. However, if the tics are severe enough to require more than 1 medication, check for drug interactions.

Third-line agents. Agents that have not been tested in placebo-controlled trials can be considered third line; these are listed as category C (supported by open-label studies) in Table 4. Botulinum toxin injection has been found to be effective for motor and vocal tics.^11,12 Botulinum toxin and implantation of deep brain stimulators¹³ are invasive options and generally are reserved for severe, treatment-resistant tics.

CASE CONTINUED: Managing antipsychotics

After trying guanfacine for 12 weeks, Sammy notices no tic reduction. His parents consent to a low dose of risperidone. you review with them the American Psychiatric Association (APA)/American Diabetes Association (ADA) guidelines¹⁴ for managing metabolic problems in patients treated with atypical antipsychotics.

As instructed in the APA/ADA guidelines, obtain baseline measurements and monitor for metabolic effects of antipsychotic therapy over time (Table 6). Sammy starts risperidone at 0.5 mg once daily. After 2 weeks, he notices a decrease in his tics. At the 3-month visit after starting risperidone, he is happy with his risperidone dose and does not want to increase it. He has gained 3 pounds, and you instruct him to eat a well-balanced diet and exercise routinely. At the 6-month visit, his tics are minimal and his weight has stabilized.

Table 6

Children receiving antipsychotics: monitoring recommendations

You recommend that Sammy remain on risperidone for another 3 months of stability and then begin to taper this medication. You review the risks and benefits of long-term treatment with risperidone, pointing out that it may lead to abnormal movements upon withdrawal, and explain that you typically do not treat children with antipsychotics for more than one year continuously.

CASE CONTINUED: Comorbid symptoms

Since starting 7th grade, Sammy has worried excessively about making mistakes. He spends 6 hours each night on homework, which he often does not turn in because of anxiety about not getting answers perfectly right. Classmates notice that Sammy taps the door 3 times when he comes into the classroom and that he steps over the black tiles in the hallway.

Consider the presence and impact of comorbid OCD or ADHD, which can impair children’s quality of life more than tics themselves.¹⁵ Assessment scales can help you make a diagnosis and monitor treatment.

If you suspect OCD, the clinician-rated Children’s Yale Brown Obsessive Compulsive Scale is the gold standard for describing the phenomenology and measuring symptom severity. Additional scales to measure symptoms’ impact on family life include the Leyton Obsessional Inventory—child version, Family Accommodation Scale for OCD, and Child OCD Impact Scale.

ADHD scales include the Conners Parent Rating Scale—Revised, Conners Teacher Rating Scale—Revised, Swanson, Nolan, and Pelham, or the Vanderbilt ADHD Diagnostic Parent and Teacher Rating Scales. Because ADHD symptoms must be present in more than 1 environment to meet diagnostic criteria, ask parents and teachers to complete the Conners or Vanderbilt scales.

In children who present with a tic disorder plus a comorbid condition, prioritize treatment by determining which symptoms interfere with the child’s ability to function at school, at home, and in the social arena. Children who require treatment for >1 disorder often are referred initially for cognitive-behavioral therapy for OCD symptoms while receiving pharmacologic treatment for ADHD and/or Tourette syndrome. When necessary, it is usually safe to combine antipsychotics, stimulants, and selective serotonin reuptake inhibitors, although medication interactions should be reviewed in each specific case.

Related resources

• Woods DW. Managing Tourette syndrome: a behavioral intervention for children and adults. Therapist guide. New York, NY: Oxford University Press; 2008.
• Tourette Syndrome Association. www.tsa-usa.org.
• International OCD Foundation. www.ocfoundation.org.

Drug brand names

• Baclofen • Lioresal
• Botulinum toxin • Botox, Myobloc
• Clomipramine • Anafranil
• Clonidine • Catapres
• Guanfacine • Tenex
• Fluphenazine • Prolixin
• Flutamide • Eulexin
• Haloperidol • Haldol
• Mecamylamine • Inversine
• Nicotine patch • NicoDerm
• Olanzapine • Zyprexa
• Pimozide • Orap
• Risperidone • Risperdal
• Tetrabenazine • Xenazine
• Ziprasidone • Geodon

Disclosures

Dr. Harris has received research support from the Translational Research Initiative at Cincinnati Children’s Hospital Medical Center.

Dr. Wu reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

NEW ORLEANS – Persistent comorbid anxiety and depression are common in patients with coronary heart disease, and they carry a greater mortality risk than either mood disturbance alone.

“It's important to look for both anxiety and depression and really home in on patients who have symptoms of both,” Lynn V. Doering, D.N.Sci., stressed in presenting the study results at the annual scientific sessions of the American Heart Association.

Persistence of the dual comorbid forms of dysphoria in patients with coronary heart disease (CHD) appears to be a key factor in the associated increased risk of all-cause mortality, added Dr. Doering of the University of California, Los Angeles. “Anxiety and depression must be assessed periodically in patients with CHD. While it is important to identify and treat new symptoms, it is perhaps even more important to attend to persistent symptoms that are unremittent, especially with treatment.”

She presented a secondary analysis of data from the PROMOTION trial, a multicenter randomized study of an educational nursing intervention designed to reduce prehospital delay to treatment of acute coronary syndrome in patients with known CHD. Her substudy focused on the 2,325 PROMOTION participants who completed mood evaluations at baseline and at 3 months, after which they were followed for a median of 22 months. Their mean age was 67 years, and 31% were women.

The brief mood assessment tools used were the Multiple Affect Adjective Checklist (MAACL) for depression and the six-item anxiety subscale of the Brief Symptom Inventory. Both are well validated, reliable instruments, Dr. Doering said.

Nineteen percent of participants were classified as persistently depressed on the basis of MAACL scores of 11 or more at both time points. Another 16% were deemed persistently anxious, with Brief Symptom Inventory scores below 0.33 at baseline and again at 3 months. Persistent comorbid anxiety and depression were more common than either condition alone, affecting 26% of subjects. Only 39% of the CHD patients were free of persistent anxiety and/or depression.

“In other words, almost two-thirds of the sample had a persistent mood disorder,” Dr. Doering observed.

A total of 63 deaths occurred during follow-up, for a 2.7% mortality rate, including 23 deaths that were cardiac-related.

Persistently distressed CHD patients tended to be younger, female, sedentary, and current smokers. They also were more likely to have diabetes, angina, a history of MI, and to not have attended cardiac rehabilitation.

In a multivariate Cox regression analysis adjusted for clinical and demographic variables and assignment to the intervention or control arm in the parent study, only three variables emerged as independent predictors of all-cause mortality: age, a history of MI, and the presence of persistent comorbid anxiety and depression.

Persistent comorbid anxiety and depression was the strongest predictor of mortality, with a 2.35-fold increased risk, even greater than that conferred by a prior MI. Neither persistent anxiety nor persistent depression alone was associated with increased mortality.

Dr. Doering received an award for presenting what was judged the outstanding study in the cardiovascular nursing section of the AHA meeting.

Future studies, she said, will focus on such key issues as the biobehavioral mechanisms involved in the link between persistent anxiety/depression and mortality, identification of subgroups at particularly high risk, optimal treatment options, and how to make treatments more acceptable to patients.

NEW ORLEANS – Persistent comorbid anxiety and depression are common in patients with coronary heart disease, and they carry a greater mortality risk than either mood disturbance alone.

“It's important to look for both anxiety and depression and really home in on patients who have symptoms of both,” Lynn V. Doering, D.N.Sci., stressed in presenting the study results at the annual scientific sessions of the American Heart Association.

Persistence of the dual comorbid forms of dysphoria in patients with coronary heart disease (CHD) appears to be a key factor in the associated increased risk of all-cause mortality, added Dr. Doering of the University of California, Los Angeles. “Anxiety and depression must be assessed periodically in patients with CHD. While it is important to identify and treat new symptoms, it is perhaps even more important to attend to persistent symptoms that are unremittent, especially with treatment.”

She presented a secondary analysis of data from the PROMOTION trial, a multicenter randomized study of an educational nursing intervention designed to reduce prehospital delay to treatment of acute coronary syndrome in patients with known CHD. Her substudy focused on the 2,325 PROMOTION participants who completed mood evaluations at baseline and at 3 months, after which they were followed for a median of 22 months. Their mean age was 67 years, and 31% were women.

The brief mood assessment tools used were the Multiple Affect Adjective Checklist (MAACL) for depression and the six-item anxiety subscale of the Brief Symptom Inventory. Both are well validated, reliable instruments, Dr. Doering said.

Nineteen percent of participants were classified as persistently depressed on the basis of MAACL scores of 11 or more at both time points. Another 16% were deemed persistently anxious, with Brief Symptom Inventory scores below 0.33 at baseline and again at 3 months. Persistent comorbid anxiety and depression were more common than either condition alone, affecting 26% of subjects. Only 39% of the CHD patients were free of persistent anxiety and/or depression.

“In other words, almost two-thirds of the sample had a persistent mood disorder,” Dr. Doering observed.

A total of 63 deaths occurred during follow-up, for a 2.7% mortality rate, including 23 deaths that were cardiac-related.

Persistently distressed CHD patients tended to be younger, female, sedentary, and current smokers. They also were more likely to have diabetes, angina, a history of MI, and to not have attended cardiac rehabilitation.

In a multivariate Cox regression analysis adjusted for clinical and demographic variables and assignment to the intervention or control arm in the parent study, only three variables emerged as independent predictors of all-cause mortality: age, a history of MI, and the presence of persistent comorbid anxiety and depression.

Persistent comorbid anxiety and depression was the strongest predictor of mortality, with a 2.35-fold increased risk, even greater than that conferred by a prior MI. Neither persistent anxiety nor persistent depression alone was associated with increased mortality.

Dr. Doering received an award for presenting what was judged the outstanding study in the cardiovascular nursing section of the AHA meeting.

Future studies, she said, will focus on such key issues as the biobehavioral mechanisms involved in the link between persistent anxiety/depression and mortality, identification of subgroups at particularly high risk, optimal treatment options, and how to make treatments more acceptable to patients.

NEW ORLEANS – Persistent comorbid anxiety and depression are common in patients with coronary heart disease, and they carry a greater mortality risk than either mood disturbance alone.

“It's important to look for both anxiety and depression and really home in on patients who have symptoms of both,” Lynn V. Doering, D.N.Sci., stressed in presenting the study results at the annual scientific sessions of the American Heart Association.

Persistence of the dual comorbid forms of dysphoria in patients with coronary heart disease (CHD) appears to be a key factor in the associated increased risk of all-cause mortality, added Dr. Doering of the University of California, Los Angeles. “Anxiety and depression must be assessed periodically in patients with CHD. While it is important to identify and treat new symptoms, it is perhaps even more important to attend to persistent symptoms that are unremittent, especially with treatment.”

She presented a secondary analysis of data from the PROMOTION trial, a multicenter randomized study of an educational nursing intervention designed to reduce prehospital delay to treatment of acute coronary syndrome in patients with known CHD. Her substudy focused on the 2,325 PROMOTION participants who completed mood evaluations at baseline and at 3 months, after which they were followed for a median of 22 months. Their mean age was 67 years, and 31% were women.

The brief mood assessment tools used were the Multiple Affect Adjective Checklist (MAACL) for depression and the six-item anxiety subscale of the Brief Symptom Inventory. Both are well validated, reliable instruments, Dr. Doering said.

Nineteen percent of participants were classified as persistently depressed on the basis of MAACL scores of 11 or more at both time points. Another 16% were deemed persistently anxious, with Brief Symptom Inventory scores below 0.33 at baseline and again at 3 months. Persistent comorbid anxiety and depression were more common than either condition alone, affecting 26% of subjects. Only 39% of the CHD patients were free of persistent anxiety and/or depression.

“In other words, almost two-thirds of the sample had a persistent mood disorder,” Dr. Doering observed.

A total of 63 deaths occurred during follow-up, for a 2.7% mortality rate, including 23 deaths that were cardiac-related.

Persistently distressed CHD patients tended to be younger, female, sedentary, and current smokers. They also were more likely to have diabetes, angina, a history of MI, and to not have attended cardiac rehabilitation.

In a multivariate Cox regression analysis adjusted for clinical and demographic variables and assignment to the intervention or control arm in the parent study, only three variables emerged as independent predictors of all-cause mortality: age, a history of MI, and the presence of persistent comorbid anxiety and depression.

Persistent comorbid anxiety and depression was the strongest predictor of mortality, with a 2.35-fold increased risk, even greater than that conferred by a prior MI. Neither persistent anxiety nor persistent depression alone was associated with increased mortality.

Dr. Doering received an award for presenting what was judged the outstanding study in the cardiovascular nursing section of the AHA meeting.

Future studies, she said, will focus on such key issues as the biobehavioral mechanisms involved in the link between persistent anxiety/depression and mortality, identification of subgroups at particularly high risk, optimal treatment options, and how to make treatments more acceptable to patients.

PHILADELPHIA – Patients with systemic lupus erythematosus who are also diagnosed with depression were nearly four times more likely to have subclinical atherosclerosis than were lupus patients without depression in a cross-sectional study with 161 women with lupus.

“Depression may be a component of the 'lupus factor' that increases risk for cardiovascular disease,” Carol M. Greco, Ph.D., said at the annual meeting of the American College of Rheumatology. “Depressive symptoms may add to the inflammatory burden” of systemic lupus erythematosus, said Dr. Greco, a clinical psychologist at the lupus center of the University of Pittsburgh.

Finding evidence of a role for depression in causing atherosclerosis in patients with SLE is important because depression is a modifiable risk factor that can be targeted for intervention, she added. Her group's next step is to follow these interactions in a longitudinal clinical study.

To examine correlates of preclinical atherosclerosis in women with SLE, Dr. Greco and her associates studied 161 lupus patients with no history of a cardiovascular event. The women had enrolled in the HEARTS (Heart Effects on Atherosclerosis and Risk of Thrombosis in SLE) study at the University of Pittsburgh. At their baseline examination in 2001-2005, their average age was 50 years; 88% were white. Their average waist:hip ratio (a measure of adiposity) was 0.85, 55% were hypertensive, and 36% had a history of smoking. Their average duration of SLE was 16 years, with an average SLE disease activity index of 2.0. Two-thirds of the women received steroid treatment, and among these patients the median duration on a steroid was 10 years.

The researchers assessed depression with the 20-item CES-D (Centers for Epidemiologic Study–Depression) scale. In Dr. Greco's analysis, patients who scored 16 or higher on the CES-D were diagnosed with depression, and among the 161 patients in the study 27% met this criterion.

Depression might be relatively common among patients with SLE as a manifestation of central nervous system involvement of the disease, or because medications used to treat SLE may contribute to mood symptoms, Dr. Greco said.

The researchers diagnosed atherosclerosis by two measures: coronary artery calcium detected by electron beam CT, and carotid artery plaque visualized with ultrasound. Patients with either a coronary artery calcium Agatston score greater than zero or a carotid plaque index score of at least 1, or both, were considered to have atherosclerosis. In the study, 63% of the patients met this standard for having atherosclerosis.

Depression was among the strongest factors. Lupus patients with a CES-D score of 16 or higher had a significant and independent 3.85-fold greater risk for atherosclerosis, compared with patients without depression.

PHILADELPHIA – Patients with systemic lupus erythematosus who are also diagnosed with depression were nearly four times more likely to have subclinical atherosclerosis than were lupus patients without depression in a cross-sectional study with 161 women with lupus.

“Depression may be a component of the 'lupus factor' that increases risk for cardiovascular disease,” Carol M. Greco, Ph.D., said at the annual meeting of the American College of Rheumatology. “Depressive symptoms may add to the inflammatory burden” of systemic lupus erythematosus, said Dr. Greco, a clinical psychologist at the lupus center of the University of Pittsburgh.

Finding evidence of a role for depression in causing atherosclerosis in patients with SLE is important because depression is a modifiable risk factor that can be targeted for intervention, she added. Her group's next step is to follow these interactions in a longitudinal clinical study.

To examine correlates of preclinical atherosclerosis in women with SLE, Dr. Greco and her associates studied 161 lupus patients with no history of a cardiovascular event. The women had enrolled in the HEARTS (Heart Effects on Atherosclerosis and Risk of Thrombosis in SLE) study at the University of Pittsburgh. At their baseline examination in 2001-2005, their average age was 50 years; 88% were white. Their average waist:hip ratio (a measure of adiposity) was 0.85, 55% were hypertensive, and 36% had a history of smoking. Their average duration of SLE was 16 years, with an average SLE disease activity index of 2.0. Two-thirds of the women received steroid treatment, and among these patients the median duration on a steroid was 10 years.

The researchers assessed depression with the 20-item CES-D (Centers for Epidemiologic Study–Depression) scale. In Dr. Greco's analysis, patients who scored 16 or higher on the CES-D were diagnosed with depression, and among the 161 patients in the study 27% met this criterion.

Depression might be relatively common among patients with SLE as a manifestation of central nervous system involvement of the disease, or because medications used to treat SLE may contribute to mood symptoms, Dr. Greco said.

The researchers diagnosed atherosclerosis by two measures: coronary artery calcium detected by electron beam CT, and carotid artery plaque visualized with ultrasound. Patients with either a coronary artery calcium Agatston score greater than zero or a carotid plaque index score of at least 1, or both, were considered to have atherosclerosis. In the study, 63% of the patients met this standard for having atherosclerosis.

Depression was among the strongest factors. Lupus patients with a CES-D score of 16 or higher had a significant and independent 3.85-fold greater risk for atherosclerosis, compared with patients without depression.

PHILADELPHIA – Patients with systemic lupus erythematosus who are also diagnosed with depression were nearly four times more likely to have subclinical atherosclerosis than were lupus patients without depression in a cross-sectional study with 161 women with lupus.

“Depression may be a component of the 'lupus factor' that increases risk for cardiovascular disease,” Carol M. Greco, Ph.D., said at the annual meeting of the American College of Rheumatology. “Depressive symptoms may add to the inflammatory burden” of systemic lupus erythematosus, said Dr. Greco, a clinical psychologist at the lupus center of the University of Pittsburgh.

Finding evidence of a role for depression in causing atherosclerosis in patients with SLE is important because depression is a modifiable risk factor that can be targeted for intervention, she added. Her group's next step is to follow these interactions in a longitudinal clinical study.

To examine correlates of preclinical atherosclerosis in women with SLE, Dr. Greco and her associates studied 161 lupus patients with no history of a cardiovascular event. The women had enrolled in the HEARTS (Heart Effects on Atherosclerosis and Risk of Thrombosis in SLE) study at the University of Pittsburgh. At their baseline examination in 2001-2005, their average age was 50 years; 88% were white. Their average waist:hip ratio (a measure of adiposity) was 0.85, 55% were hypertensive, and 36% had a history of smoking. Their average duration of SLE was 16 years, with an average SLE disease activity index of 2.0. Two-thirds of the women received steroid treatment, and among these patients the median duration on a steroid was 10 years.

The researchers assessed depression with the 20-item CES-D (Centers for Epidemiologic Study–Depression) scale. In Dr. Greco's analysis, patients who scored 16 or higher on the CES-D were diagnosed with depression, and among the 161 patients in the study 27% met this criterion.

Depression might be relatively common among patients with SLE as a manifestation of central nervous system involvement of the disease, or because medications used to treat SLE may contribute to mood symptoms, Dr. Greco said.

The researchers diagnosed atherosclerosis by two measures: coronary artery calcium detected by electron beam CT, and carotid artery plaque visualized with ultrasound. Patients with either a coronary artery calcium Agatston score greater than zero or a carotid plaque index score of at least 1, or both, were considered to have atherosclerosis. In the study, 63% of the patients met this standard for having atherosclerosis.

Depression was among the strongest factors. Lupus patients with a CES-D score of 16 or higher had a significant and independent 3.85-fold greater risk for atherosclerosis, compared with patients without depression.

ISTANBUL, TURKEY – The antidepressant trazodone showed objective polysomnographic evidence of efficacy for primary insomnia in a small double-blind, randomized trial.

This is the first objective evidence of a sleep-promoting effect for trazodone (Desyrel) in patients with primary insomnia–that is, unaccompanied by depression or anxiety, Dr. Louise M. Paterson told the annual congress of the European College of Neuropsychopharmacology.

It's an important observation, because trazodone is widely prescribed for this purpose despite the previous absence of supporting data. The drug is said to be the second most often prescribed for primary insomnia in the United States (J. Clin. Psychiatry 2005;66:469-76), though this is an off-label use for an agent licensed as an antidepressant, noted Dr. Paterson of the University of Bristol (England).

There is still an unmet clinical need for sleep-promoting agents that address poor sleep quality and treat middle insomnia–awakening in the middle of the night and difficulty falling back asleep–without causing dependence. The polysomnographic study suggests trazodone might have value toward that end.

Dr. Paterson reported on 12 adults, average age 43 years, with primary chronic insomnia of more than 1 year's duration. All had baseline normal-range anxiety and depression scores. None were on psychotropic or hypnotic medication. They were randomized double blind to 1 night of 100 mg of trazodone or placebo 2 hours before their usual bedtime, after which they underwent home polysomnography. At least 1 week later, they crossed over to the other study arm.

The 433-minute mean total sleep time on trazodone represented a 38-minute increase over placebo. The mean 129 minutes spent in slow wave sleep during the trazodone night was 33 minutes longer than with placebo. Time spent awake after sleep onset decreased from 77 minutes on placebo to 57 minutes on trazodone.

Trazodone also significantly reduced the number of awakenings while decreasing spindle density, with no change in REM sleep, overall sleep efficiency, or sleep onset, compared with placebo.

Results on the Leeds Sleep Evaluation Questionnaire and the St. Mary's Hospital Sleep Questionnaire showed significant improvements in subjective sleep factors (quality, satisfaction), compared with placebo. Yet there was no difference between trazodone and placebo in terms of “awakening from sleep” or “behavior following awake,” indicating the drug was not associated with a significant morning hangover effect, said Dr. Paterson.

There were 11 adverse events associated with the single dose of trazodone, compared with 3 with placebo. In patients on trazodone, two complained of dizziness; one had a fall; and one each reported clumsiness, nausea, attentional disturbance, or “feeling abnormal.” No one had any such complaints while on placebo.

The Avon and Wiltshire Mental Health Partnership NHS Trust funded the study. Dr. Paterson reported no financial conflicts of interest.

ISTANBUL, TURKEY – The antidepressant trazodone showed objective polysomnographic evidence of efficacy for primary insomnia in a small double-blind, randomized trial.

This is the first objective evidence of a sleep-promoting effect for trazodone (Desyrel) in patients with primary insomnia–that is, unaccompanied by depression or anxiety, Dr. Louise M. Paterson told the annual congress of the European College of Neuropsychopharmacology.

It's an important observation, because trazodone is widely prescribed for this purpose despite the previous absence of supporting data. The drug is said to be the second most often prescribed for primary insomnia in the United States (J. Clin. Psychiatry 2005;66:469-76), though this is an off-label use for an agent licensed as an antidepressant, noted Dr. Paterson of the University of Bristol (England).

There is still an unmet clinical need for sleep-promoting agents that address poor sleep quality and treat middle insomnia–awakening in the middle of the night and difficulty falling back asleep–without causing dependence. The polysomnographic study suggests trazodone might have value toward that end.

Dr. Paterson reported on 12 adults, average age 43 years, with primary chronic insomnia of more than 1 year's duration. All had baseline normal-range anxiety and depression scores. None were on psychotropic or hypnotic medication. They were randomized double blind to 1 night of 100 mg of trazodone or placebo 2 hours before their usual bedtime, after which they underwent home polysomnography. At least 1 week later, they crossed over to the other study arm.

The 433-minute mean total sleep time on trazodone represented a 38-minute increase over placebo. The mean 129 minutes spent in slow wave sleep during the trazodone night was 33 minutes longer than with placebo. Time spent awake after sleep onset decreased from 77 minutes on placebo to 57 minutes on trazodone.

Trazodone also significantly reduced the number of awakenings while decreasing spindle density, with no change in REM sleep, overall sleep efficiency, or sleep onset, compared with placebo.

Results on the Leeds Sleep Evaluation Questionnaire and the St. Mary's Hospital Sleep Questionnaire showed significant improvements in subjective sleep factors (quality, satisfaction), compared with placebo. Yet there was no difference between trazodone and placebo in terms of “awakening from sleep” or “behavior following awake,” indicating the drug was not associated with a significant morning hangover effect, said Dr. Paterson.

There were 11 adverse events associated with the single dose of trazodone, compared with 3 with placebo. In patients on trazodone, two complained of dizziness; one had a fall; and one each reported clumsiness, nausea, attentional disturbance, or “feeling abnormal.” No one had any such complaints while on placebo.

The Avon and Wiltshire Mental Health Partnership NHS Trust funded the study. Dr. Paterson reported no financial conflicts of interest.

ISTANBUL, TURKEY – The antidepressant trazodone showed objective polysomnographic evidence of efficacy for primary insomnia in a small double-blind, randomized trial.

This is the first objective evidence of a sleep-promoting effect for trazodone (Desyrel) in patients with primary insomnia–that is, unaccompanied by depression or anxiety, Dr. Louise M. Paterson told the annual congress of the European College of Neuropsychopharmacology.

It's an important observation, because trazodone is widely prescribed for this purpose despite the previous absence of supporting data. The drug is said to be the second most often prescribed for primary insomnia in the United States (J. Clin. Psychiatry 2005;66:469-76), though this is an off-label use for an agent licensed as an antidepressant, noted Dr. Paterson of the University of Bristol (England).

There is still an unmet clinical need for sleep-promoting agents that address poor sleep quality and treat middle insomnia–awakening in the middle of the night and difficulty falling back asleep–without causing dependence. The polysomnographic study suggests trazodone might have value toward that end.

Dr. Paterson reported on 12 adults, average age 43 years, with primary chronic insomnia of more than 1 year's duration. All had baseline normal-range anxiety and depression scores. None were on psychotropic or hypnotic medication. They were randomized double blind to 1 night of 100 mg of trazodone or placebo 2 hours before their usual bedtime, after which they underwent home polysomnography. At least 1 week later, they crossed over to the other study arm.

The 433-minute mean total sleep time on trazodone represented a 38-minute increase over placebo. The mean 129 minutes spent in slow wave sleep during the trazodone night was 33 minutes longer than with placebo. Time spent awake after sleep onset decreased from 77 minutes on placebo to 57 minutes on trazodone.

Trazodone also significantly reduced the number of awakenings while decreasing spindle density, with no change in REM sleep, overall sleep efficiency, or sleep onset, compared with placebo.

Results on the Leeds Sleep Evaluation Questionnaire and the St. Mary's Hospital Sleep Questionnaire showed significant improvements in subjective sleep factors (quality, satisfaction), compared with placebo. Yet there was no difference between trazodone and placebo in terms of “awakening from sleep” or “behavior following awake,” indicating the drug was not associated with a significant morning hangover effect, said Dr. Paterson.

There were 11 adverse events associated with the single dose of trazodone, compared with 3 with placebo. In patients on trazodone, two complained of dizziness; one had a fall; and one each reported clumsiness, nausea, attentional disturbance, or “feeling abnormal.” No one had any such complaints while on placebo.

The Avon and Wiltshire Mental Health Partnership NHS Trust funded the study. Dr. Paterson reported no financial conflicts of interest.

ATLANTA – Personal injury from a rocket attack, sleep difficulties, alcohol use, and nontraumatic major events in the past year significantly predicted functional impairment associated with symptoms of posttraumatic stress disorder in a large study of Israeli civilians exposed to pervasive war and terrorism.

Researchers surveyed 1,001 Israeli residents via telephone during the summer of 2008. A total of 500 respondents who lived close to the town of Sderot near the Gaza Strip and along the northern border of Gaza, an area subjected to frequent rocket attacks over several years, composed a higher-exposure group. Their reports of posttraumatic stress disorder (PTSD) symptoms and impairment were compared with those of 501 respondents who lived in lower-exposure regions of the country.

PTSD severity was similar between groups, but the level of symptom-related impairment was higher in those living in areas struck by rocket attacks.

A large proportion of people interviewed were distressed but did not necessarily meet the full criteria for PTSD, Katie J. Horsey, said in an interview at her poster during the annual meeting of the International Society for Trauma Stress Studies. “Only about 5.5% met full DSM-IV criteria for PTSD, but 29% reported impairment by those symptoms,” she said, adding that this subclinical impairment after exposure to pervasive trauma suggests reliance on a full PTSD diagnosis may be insufficient to identify those most in need of intervention.

The findings in the current study support previous findings that even people with subthreshold symptoms might significantly suffer from PTSD (Behav. Ther. 2009;40:39-49; J. Nerv. Ment. Dis. 2007;195:48-53). Psychosocial resource loss–defined as a loss of hope, of closeness to family, of a sense that one is of value to others, and of feelings of control over one's life–was “very significantly” associated with impairment, according to logistic regression analysis. People who reported a slight degree of loss were more than twice as likely to be impaired (odds ratio, 2.53), for example, and risk increased with a higher degree of loss (OR, 4.59), compared with those with no such loss.

“It may be that people who have more resources are better able to cope with their PTSD,” Ms. Horsey said.

In addition, poor or fair health quality and sleep difficulty each significantly predicted greater risk for functional impairment (OR, 1.71 and 1.73, respectively). “When you are not sleeping well, you cannot cope as well,” said Ms. Horsey, a doctoral student in the Clinical Psychology Program at Kent State University in Akron, Ohio.

Respondents who reported injury to themselves or a close other were at higher risk for impairment (OR, 2.8), compared with those who reported no such injuries (OR, 1.0).

It might be worthwhile to assess PTSD-related impairment–and not just symptoms–even in populations with a low level of symptoms, Ms. Horsey said. Some respondents reporting a high level of symptoms, including some who met all three DSM-IV clusters, did not report impairment. In contrast, some could not function well at a low level of symptoms.

All of the telephone interviews were conducted in Hebrew. The interviewers used the PTSD Symptom Scale–Self-Report Version, a measure previously validated in Hebrew-speaking populations. Impairment was based on a single question about whether posttraumatic symptoms interfered with functioning.

The researchers may explore more specifics, including which symptoms of PTSD are most associated with functional impairment and which areas of life are most impaired by exposure to trauma.

Ms. Horsey had no relevant disclosures. The study was supported by a National Institutes of Health grant.

Only about 5.5% of respondents met full DSM-IV criteria for PTSD, but 29% reported impairment by those symptoms.

Source MS. HORSEY

ATLANTA – Personal injury from a rocket attack, sleep difficulties, alcohol use, and nontraumatic major events in the past year significantly predicted functional impairment associated with symptoms of posttraumatic stress disorder in a large study of Israeli civilians exposed to pervasive war and terrorism.

Researchers surveyed 1,001 Israeli residents via telephone during the summer of 2008. A total of 500 respondents who lived close to the town of Sderot near the Gaza Strip and along the northern border of Gaza, an area subjected to frequent rocket attacks over several years, composed a higher-exposure group. Their reports of posttraumatic stress disorder (PTSD) symptoms and impairment were compared with those of 501 respondents who lived in lower-exposure regions of the country.

PTSD severity was similar between groups, but the level of symptom-related impairment was higher in those living in areas struck by rocket attacks.

A large proportion of people interviewed were distressed but did not necessarily meet the full criteria for PTSD, Katie J. Horsey, said in an interview at her poster during the annual meeting of the International Society for Trauma Stress Studies. “Only about 5.5% met full DSM-IV criteria for PTSD, but 29% reported impairment by those symptoms,” she said, adding that this subclinical impairment after exposure to pervasive trauma suggests reliance on a full PTSD diagnosis may be insufficient to identify those most in need of intervention.

The findings in the current study support previous findings that even people with subthreshold symptoms might significantly suffer from PTSD (Behav. Ther. 2009;40:39-49; J. Nerv. Ment. Dis. 2007;195:48-53). Psychosocial resource loss–defined as a loss of hope, of closeness to family, of a sense that one is of value to others, and of feelings of control over one's life–was “very significantly” associated with impairment, according to logistic regression analysis. People who reported a slight degree of loss were more than twice as likely to be impaired (odds ratio, 2.53), for example, and risk increased with a higher degree of loss (OR, 4.59), compared with those with no such loss.

“It may be that people who have more resources are better able to cope with their PTSD,” Ms. Horsey said.

In addition, poor or fair health quality and sleep difficulty each significantly predicted greater risk for functional impairment (OR, 1.71 and 1.73, respectively). “When you are not sleeping well, you cannot cope as well,” said Ms. Horsey, a doctoral student in the Clinical Psychology Program at Kent State University in Akron, Ohio.

Respondents who reported injury to themselves or a close other were at higher risk for impairment (OR, 2.8), compared with those who reported no such injuries (OR, 1.0).

It might be worthwhile to assess PTSD-related impairment–and not just symptoms–even in populations with a low level of symptoms, Ms. Horsey said. Some respondents reporting a high level of symptoms, including some who met all three DSM-IV clusters, did not report impairment. In contrast, some could not function well at a low level of symptoms.

All of the telephone interviews were conducted in Hebrew. The interviewers used the PTSD Symptom Scale–Self-Report Version, a measure previously validated in Hebrew-speaking populations. Impairment was based on a single question about whether posttraumatic symptoms interfered with functioning.

The researchers may explore more specifics, including which symptoms of PTSD are most associated with functional impairment and which areas of life are most impaired by exposure to trauma.

Ms. Horsey had no relevant disclosures. The study was supported by a National Institutes of Health grant.

Only about 5.5% of respondents met full DSM-IV criteria for PTSD, but 29% reported impairment by those symptoms.

Source MS. HORSEY

ATLANTA – Personal injury from a rocket attack, sleep difficulties, alcohol use, and nontraumatic major events in the past year significantly predicted functional impairment associated with symptoms of posttraumatic stress disorder in a large study of Israeli civilians exposed to pervasive war and terrorism.

Researchers surveyed 1,001 Israeli residents via telephone during the summer of 2008. A total of 500 respondents who lived close to the town of Sderot near the Gaza Strip and along the northern border of Gaza, an area subjected to frequent rocket attacks over several years, composed a higher-exposure group. Their reports of posttraumatic stress disorder (PTSD) symptoms and impairment were compared with those of 501 respondents who lived in lower-exposure regions of the country.

PTSD severity was similar between groups, but the level of symptom-related impairment was higher in those living in areas struck by rocket attacks.

A large proportion of people interviewed were distressed but did not necessarily meet the full criteria for PTSD, Katie J. Horsey, said in an interview at her poster during the annual meeting of the International Society for Trauma Stress Studies. “Only about 5.5% met full DSM-IV criteria for PTSD, but 29% reported impairment by those symptoms,” she said, adding that this subclinical impairment after exposure to pervasive trauma suggests reliance on a full PTSD diagnosis may be insufficient to identify those most in need of intervention.

The findings in the current study support previous findings that even people with subthreshold symptoms might significantly suffer from PTSD (Behav. Ther. 2009;40:39-49; J. Nerv. Ment. Dis. 2007;195:48-53). Psychosocial resource loss–defined as a loss of hope, of closeness to family, of a sense that one is of value to others, and of feelings of control over one's life–was “very significantly” associated with impairment, according to logistic regression analysis. People who reported a slight degree of loss were more than twice as likely to be impaired (odds ratio, 2.53), for example, and risk increased with a higher degree of loss (OR, 4.59), compared with those with no such loss.

“It may be that people who have more resources are better able to cope with their PTSD,” Ms. Horsey said.

In addition, poor or fair health quality and sleep difficulty each significantly predicted greater risk for functional impairment (OR, 1.71 and 1.73, respectively). “When you are not sleeping well, you cannot cope as well,” said Ms. Horsey, a doctoral student in the Clinical Psychology Program at Kent State University in Akron, Ohio.

Respondents who reported injury to themselves or a close other were at higher risk for impairment (OR, 2.8), compared with those who reported no such injuries (OR, 1.0).

It might be worthwhile to assess PTSD-related impairment–and not just symptoms–even in populations with a low level of symptoms, Ms. Horsey said. Some respondents reporting a high level of symptoms, including some who met all three DSM-IV clusters, did not report impairment. In contrast, some could not function well at a low level of symptoms.

All of the telephone interviews were conducted in Hebrew. The interviewers used the PTSD Symptom Scale–Self-Report Version, a measure previously validated in Hebrew-speaking populations. Impairment was based on a single question about whether posttraumatic symptoms interfered with functioning.

The researchers may explore more specifics, including which symptoms of PTSD are most associated with functional impairment and which areas of life are most impaired by exposure to trauma.

Ms. Horsey had no relevant disclosures. The study was supported by a National Institutes of Health grant.

Only about 5.5% of respondents met full DSM-IV criteria for PTSD, but 29% reported impairment by those symptoms.

Source MS. HORSEY

Symptoms of serotonin syndrome and neuroleptic malignant syndrome (NMS) are similar—mental status changes, autonomic dysfunction, and neuromuscular abnormalities—making the syndromes difficult to differentiate. However, therapeutic interventions and the mortality rates associated with these syndromes are widely divergent.

Because many medication regimens for treatment-resistant mood disorders modulate both serotonin and dopamine systems, psychiatrists must be prepared at any time to recognize either syndrome and quickly initiate appropriate treatment. For this, we rely on disease course, lab findings and vital signs, and the physical exam.

Clinical course

Serotonin syndrome symptoms can develop within minutes to hours after the administration of an agent that increases central serotonergic tone, such as a selective serotonin reuptake inhibitor. After rapid onset, serotonin syndrome symptoms may improve or even resolve within <24 hours. NMS, on the other hand, can develop days to weeks after the administration of a dopamine antagonist—such as an antipsychotic—and may take 3 to 14 days to resolve.

Labs and vital signs

The triad of fever, leukocytosis, and increased creatine kinase (CK) are associated with NMS. Hyperthermia is present in at least 90% of cases,¹ although, some definitions of NMS list fever as a sine qua non. Leukocytosis and elevated hepatic transaminases are reported in at least 75% of NMS cases and increased CK in >90% of cases.^1,2 These signs may be present in serotonin syndrome but are less common.

Although the pathophysiology of NMS is unclear and literature is limited, some case series report iron deficiency in >95% of cases.³ If this finding were replicated on a larger scale, iron deficiency might be a sensitive, rapid, and inexpensive test to help diagnose atypical NMS presentations. Larger studies are needed before clinicians can rely on this laboratory finding to diagnose NMS.

Physical exam findings

Neuromuscular manifestations also can help distinguish serotonin syndrome from NMS. Physicians often and rightly associate muscle rigidity with NMS. This finding also is present in approximately one-half of serotonin syndrome cases, however. Hyperreflexia and myoclonus, if present, may suggest serotonin syndrome.

Symptoms of serotonin syndrome and neuroleptic malignant syndrome (NMS) are similar—mental status changes, autonomic dysfunction, and neuromuscular abnormalities—making the syndromes difficult to differentiate. However, therapeutic interventions and the mortality rates associated with these syndromes are widely divergent.

Because many medication regimens for treatment-resistant mood disorders modulate both serotonin and dopamine systems, psychiatrists must be prepared at any time to recognize either syndrome and quickly initiate appropriate treatment. For this, we rely on disease course, lab findings and vital signs, and the physical exam.

Clinical course

Serotonin syndrome symptoms can develop within minutes to hours after the administration of an agent that increases central serotonergic tone, such as a selective serotonin reuptake inhibitor. After rapid onset, serotonin syndrome symptoms may improve or even resolve within <24 hours. NMS, on the other hand, can develop days to weeks after the administration of a dopamine antagonist—such as an antipsychotic—and may take 3 to 14 days to resolve.

Labs and vital signs

The triad of fever, leukocytosis, and increased creatine kinase (CK) are associated with NMS. Hyperthermia is present in at least 90% of cases,¹ although, some definitions of NMS list fever as a sine qua non. Leukocytosis and elevated hepatic transaminases are reported in at least 75% of NMS cases and increased CK in >90% of cases.^1,2 These signs may be present in serotonin syndrome but are less common.

Although the pathophysiology of NMS is unclear and literature is limited, some case series report iron deficiency in >95% of cases.³ If this finding were replicated on a larger scale, iron deficiency might be a sensitive, rapid, and inexpensive test to help diagnose atypical NMS presentations. Larger studies are needed before clinicians can rely on this laboratory finding to diagnose NMS.

Physical exam findings

Neuromuscular manifestations also can help distinguish serotonin syndrome from NMS. Physicians often and rightly associate muscle rigidity with NMS. This finding also is present in approximately one-half of serotonin syndrome cases, however. Hyperreflexia and myoclonus, if present, may suggest serotonin syndrome.

Symptoms of serotonin syndrome and neuroleptic malignant syndrome (NMS) are similar—mental status changes, autonomic dysfunction, and neuromuscular abnormalities—making the syndromes difficult to differentiate. However, therapeutic interventions and the mortality rates associated with these syndromes are widely divergent.

Because many medication regimens for treatment-resistant mood disorders modulate both serotonin and dopamine systems, psychiatrists must be prepared at any time to recognize either syndrome and quickly initiate appropriate treatment. For this, we rely on disease course, lab findings and vital signs, and the physical exam.

Clinical course

Serotonin syndrome symptoms can develop within minutes to hours after the administration of an agent that increases central serotonergic tone, such as a selective serotonin reuptake inhibitor. After rapid onset, serotonin syndrome symptoms may improve or even resolve within <24 hours. NMS, on the other hand, can develop days to weeks after the administration of a dopamine antagonist—such as an antipsychotic—and may take 3 to 14 days to resolve.

Labs and vital signs

The triad of fever, leukocytosis, and increased creatine kinase (CK) are associated with NMS. Hyperthermia is present in at least 90% of cases,¹ although, some definitions of NMS list fever as a sine qua non. Leukocytosis and elevated hepatic transaminases are reported in at least 75% of NMS cases and increased CK in >90% of cases.^1,2 These signs may be present in serotonin syndrome but are less common.

Although the pathophysiology of NMS is unclear and literature is limited, some case series report iron deficiency in >95% of cases.³ If this finding were replicated on a larger scale, iron deficiency might be a sensitive, rapid, and inexpensive test to help diagnose atypical NMS presentations. Larger studies are needed before clinicians can rely on this laboratory finding to diagnose NMS.

Physical exam findings

Neuromuscular manifestations also can help distinguish serotonin syndrome from NMS. Physicians often and rightly associate muscle rigidity with NMS. This finding also is present in approximately one-half of serotonin syndrome cases, however. Hyperreflexia and myoclonus, if present, may suggest serotonin syndrome.