Evidence-Based Reviews

Prescribing thyroid hormones with antidepressants—whether to augment the antidepressant effect or accelerate patient response—is a well-researched strategy for treatment-resistant major depressive disorder (MDD). Thyroid hormones are known to boost response to tricyclics, and preliminary evidence shows they may be useful adjuvants to selective serotonin reuptake inhibitors (SSRIs) as well.

Thyroid hormones enter the brain slowly across the blood-brain barrier and choroid plexus. They accumulate in the locus ceruleus and other structures and are distributed widely along noradrenergic pathways.

Effective treatments are available for MDD, although 30% to 40% of patients do not respond to one or more antidepressant trials (Box).^1-4 This article offers:

• new information about why triiodothyronine (T3) and thyroxine (T4) can “super-charge” antidepressant response
• tips on how to use thyroid hormones in patients with MDD, including effective dosages, patient monitoring, and treatment durations.

Box

Why thyroid hormones?

Thyroid hormones enter the brain slowly across the blood-brain barrier and the choroid plexus—cerebrospinal fluid barriers. T4 is the main source of brain T3—after attack by 5’deiodinase—but circulating T3 also crosses the blood-brain barrier through active transport.

Thyroid hormones accumulate in the locus ceruleus and other central noradrenergic structures and are distributed widely in the brain along noradrenergic pathways.^5-7 The mechanism of their therapeutic effect for MDD is not well understood, and various hypotheses have been proposed.

Subclinical hypothyroidism. Early studies such as by Howland⁸ of treatment-refractory MDD suggested that thyroid hormone augmentation might correct a hypothyroid state. However, blood thyroid hormone levels are not associated with resistance to antidepressant treatment, according to studies of MDD populations.^9-10 Also, thyroid hormones’ therapeutic action in MDD appears unlikely to be related to treating subclinical hypothyroidism because patients’ euthyroid status was verified in all adjuvant studies since 1980.

Joffe et al¹¹ proposed that MDD is characterized by a relative excess of T4 versus T3—probably related to a deficit in converting T4 to T3 in the periphery—and administering T3 would therefore correct this imbalance. They offered no strong evidence for an increased T4 level, however, and later studies failed to detect the postulated blood T3 abnormalities in MDD.^9-10 Also—as suggested by studies with high-dose T4 augmentation^12,13—the adjuvant antidepressant effect of thyroid hormones is not restricted to T3, although T3 may be more efficacious than T4.¹⁴

Neurotransmitter effects. Thyroid hormones’ role in increasing serotonin (5-HT) release could partially explain the benefit of adjuvant thyroid hormone therapy in MDD. Researchers found:

• T3 increased cortical 5-HT levels, probably by reducing the autoinhibitory effect of the presynaptic 5-HT_1A receptor¹⁵
• adding T3 to clomipramine therapy increased 5-HT levels to a greater extent than T3 or clomipramine used alone¹⁶
• Low 5-HT activity, shown in hypothyroid patients, increased after T4 replacement.¹⁷

This 5-HT release theory cannot explain why thyroid hormones have a rapid clinical effect in MDD. Most studies report the hormones have clinical efficacy in MDD within 4 weeks.¹⁸ Similarly, selective serotonin reuptake inhibitors (SSRIs) increase 5-HT levels within hours of treatment onset, but the clinical effect occurs 4 to 6 weeks later.¹⁹ Therefore, increased 5-HT levels cannot fully explain thyroid hormones’ early effect.

Close interaction between thyroid hormones and the noradrenergic system also has been examined. Brain T3 is primarily localized in the central noradrenergic systems, with axonal anterograde transport of T3 from the locus ceruleus. T3 is processed and accumulated in the noradrenergic system, carried via axonal transport, then delivered from nerve cell bodies to its neuronal targets.^5,7 T3 thus functions as a coneurotransmitter with norepinephrine.

Cellular energy metabolism. We recently reported that thyroid hormones’ antidepressant effect may be related to brain cellular energy metabolism. Thyroid hormones increase cellular levels of adenosine triphosphate (ATP) and phosphocreatine (PCr) in the hypothyroid brain.²⁰ Brain imaging—phosphorus-31 nuclear magnetic resonance spectroscopy (31P-MRS)—of subjects with MDD shows decreased brain levels of ATP and increased PCr.²¹

Our group showed that the antidepressant effect of T3 augmentation of SSRIs is correlated with significant increases in ATP levels and decreases in PCr. This effect—which appears to represent re-normalization of brain bioenergetics in treatment responders—did not occur in nonresponders (Iosifescu et al, presented at APA, 2004).

The effect of thyroid hormones on bioenergetic metabolism is compatible with the hypothesized effects on noradrenergic and serotonergic systems.^5,7 These mechanisms may represent different links in the same chain of events.

Antidepressant boosters

Thyroid hormones have been used extensively to treat MDD since the 1950s, when researchers reported that T3 monotherapy was efficacious for treating depression. These early studies had important methodologic limitations, including open designs and poorly defined diagnostic criteria and response.

For MDD, the most extensively researched uses of thyroid hormones are to augment therapy for antidepressant nonresponders and to accelerate partial response to antidepressants.

Tricyclics. Open studies primarily among outpatients in the 1970s and ‘80s suggested that thyroid hormones are a valid augmentation strategy for nonresponders to tricyclic antidepressants. Most—but not all—reported response rates >50% with T3 dosages of 20 to 50 mcg/d.^22,23

Compared with outpatient studies, however, an open trial of T3 augmentation by Birkenhager et al²⁴ found no evidence of efficacy in 14 severely depressed inpatients who had not responded to 6 weeks of tricyclics. These patients—mainly with melancholic and/or psychotic depression—showed greater response to a monoamine oxidase inhibitor (MAOI) or electroconvulsive therapy than to thyroid hormone.

Three of five double-blind controlled studies of thyroid hormone augmentation of tricyclics reported response rates of 50 to 65% (Table).^14,18,25 Earlier controlled studies, including two negative studies^26,27 had important methodologic limitations: all included few subjects (≤16), and two studies included both unipolar and bipolar patients. Joffe et al partially addressed these problems with two randomized, double-blind studies that were controlled with placebo or T4:

• In a 3-week trial, T3 was more effective than T4 when added to imipramine or desipramine.¹⁴
• In a 2-week trial, T3 was significantly more effective than placebo when added to imipramine or desipramine.²⁵

In the latter study, T3 and lithium augmentation appeared equally effective. Conversely, T4 was more effective than lithium as the first augmentation strategy in a double-blind, crossover study by Spoov and Lahdelma.²⁸

In conclusion, depressed patients given T3 with tricyclic antidepressants may be twice as likely as controls to respond to treatment, according to a meta-analysis of eight studies totaling 292 patients. This analysis by Aronson et al²⁹ supports T3 augmentation while addressing the surveyed studies’ limitations.

Table

Treatment-resistant MDD: Controlled studies of thyroid hormone augmentation

MAO inhibitors. One small report has addressed the efficacy of thyroid hormones as adjuvants to MAOIs.³⁰ In two patients, adding T3 to phenelzine enhanced the antidepressant response.

High-dose T4. Two open studies of patients with treatment-resistant bipolar or unipolar depression^12,13 have examined the efficacy of high-dose T4 augmentation. These patients were taking a variety of antidepressants, including TCAs and SSRIs.

• In the study by Baurer et al,¹² clinical remission (Hamilton Depression Scale [HAM-D] score ≤10) occurred in 4 of 5 patients with severe treatment-resistant unipolar depression who received adjunctive T4, mean 482±72 mcg/d, with antidepressants.
• In the study by Rudas et al,¹³ clinical remission (HAM-D ≤9) occurred in 7 of 9 patients with treatment-resistant MDD after T4, 150 to 300 mcg/d, was added to their antidepressant therapy. Side effects may limit this high-dose strategy, however, because 2 of the patients dropped out with thyrotoxicosis symptoms.

SSRIs. Three open trials to date have investigated using thyroid hormones to augment SSRIs in treatment-resistant MDD. In a prospective study by Agid and Lerer,³¹ 10 of 25 (40%) patients who did not respond to SSRI treatment did so after T3 was added. No men improved, however, which led the authors to suggest that men and women might respond differently to T3 augmentation of SSRIs.

In our study, 7 of 20 patients (35%) with MDD who did not respond to 8 weeks of SSRI therapy did so when we added T3, 50 mcg/d, for 4 weeks (Figure). Response rates were high (5/5, 100%) in patients with atypical features by DSMIV criteria and low (1/8, 12.5%) in those with melancholic features.³²

Abraham et al³³ added T3, 50 mcg/d, to the regimens of 12 patients with MDD who did not respond to SSRIs alone. One patient dropped out with side effects. After 4 weeks of T3 augmentation, 5 patients (42%) showed 50% or greater improvement in HAM-D scores from baseline.

Figure T3 augmentation of SSRIs in 20 patients with resistant major depressive disorder

Open T3 augmentation, 50 mcg/d, given to 20 nonresponders to 8 weeks of selective serotonin reuptake inhibitors (SSRIs) improved baseline CGI-S scores significantly (P=0.006) at 4 weeks in those with atypical depression and modestly (P>0.05) in those with melancholic depression.

Source: Reference 32Antidepressant accelerators. Five of seven early double-blind, controlled studies indicated that adding small doses of thyroid hormones at the beginning of antidepressant treatment accelerated treatment response. All were limited by small sample sizes and other methodologic problems. A more-recent meta-analysis of six studies totalling 125 patients by Altshuler et al³⁴ found:

• T3 was significantly more effective than placebo in accelerating clinical response to tricyclics
• the acceleration effect was more pronounced for women than for men.

Clinical recommendations

Thyroid hormones can be useful to augment and accelerate treatment of MDD. Evidence strongly supports their use with tricyclic antidepressants and suggests they also can be effective adjuvants for patients who do not respond to SSRIs.

Either T3 (up to 50 mcg/d) or T4 (up to 150 mcg/d) can be used as augmentation. T3’s antidepressant properties are considered more effective than those of T4, but the only head-to-head study supporting this conclusion was small (38 patients).¹⁴ Some T4 augmentation studies used very high dosages (300 to 600 mcg/d),¹² which increase the risk of acute overdose.

Start T3 augmentation at 25 mcg/d and increase, if tolerated, to 50 mcg/d after 1 week. Measure baseline serum thyroid-stimulating hormone (TSH), and do not treat patients with TSH <0.5 mIU/L). Baseline TSH, T4, or T3 levels do not predict response to T3 augmentation in euthyroid MDD patients.³²

Common side effects. Adjuvant T3, 25 to 50 mcg/d, was well-tolerated in our study of 20 patients also taking SSRIs:

• 2 (10%) experienced fatigue and diaphoresis
• 1 each (5%) had tremor, dry mouth, headaches, muscle aches, and vivid dreams.³²

We saw no significant changes in blood pressure, but heart rates increased significantly in our 4-week study—from 76±12 bpm (range 60 to 96) to 82±9 bpm (range 66 to 96). Thus, T3 augmentation may not be indicated for patients with coronary artery disease or chronic heart failure. Patients’ weight decreased an average 2.5±6.6 lbs (range –20 to +7).

Thyroid hormones may cause hypoglycemia and change insulin requirements in patients with diabetes. High doses of T3 or T4 may be associated with hyperthyroidism, weight loss, nervousness, sweating, tachycardia, insomnia, heat intolerance, menstrual irregularities, palpitations, psychosis, or fever. Discontinue treatment if these symptoms develop.

Onset of antidepressant effect. Assess patient response in 4 to 6 weeks, whether using augmentation to address antidepressant nonresponse^14,25 or to accelerate response.³³ If you detect only partial improvement, studies support continuing treatment up to 8 weeks.

Treatment duration. No guidelines exist on how long to continue thyroid hormones after the initial antidepressant response. TSH levels become suppressed (TSH <0.1 mIU/L) after 4 weeks of T3, 50 mcg/d, in patients with normal baseline thyroid function.³² This suggests thyroid hormone’s booster effect is self limited, and augmentation may not need to continue after 2 to 3 months—even in responders.

T3 augmentation at 25 mcg/d can be discontinued immediately. For 50 to 75 mcg/d, taper across 1 to 2 weeks. The hypothalamic-pituitary-thyroid axis returns to normal function 6 to 8 weeks after T3 augmentation is stopped.

In this model, thyroid hormone augmentation can be used to boost antidepressant efficacy several months at a time. If effective, the same strategy could be tried again for subsequent MDD episodes.

Related resources

• DeBattista C. Augmentation and combination strategies for depression. J Psychopharmacol 2006;20(3):11-18.
• Massachusetts General Hospital Psychiatric Academy (including web-casts on treatment-resistant depression. www.mghcme.com

Drug brand names

• Desipramine • Norpramin
• Imipramine • Tofranil
• Levothyroxine (T4) • Levoxyl, Levothroid, Synthroid, others
• Liothyronine (synthetic T3) • Cytomel

Disclosures

The author receives research support from Aspect Medical Systems, Forest Laboratories, and Janssen Pharmaceutica; is a consultant to Pfizer, Inc., and Forest Laboratories; and a speaker for Eli Lilly and Co., Pfizer, Inc., and Cephalon.

Prescribing thyroid hormones with antidepressants—whether to augment the antidepressant effect or accelerate patient response—is a well-researched strategy for treatment-resistant major depressive disorder (MDD). Thyroid hormones are known to boost response to tricyclics, and preliminary evidence shows they may be useful adjuvants to selective serotonin reuptake inhibitors (SSRIs) as well.

Thyroid hormones enter the brain slowly across the blood-brain barrier and choroid plexus. They accumulate in the locus ceruleus and other structures and are distributed widely along noradrenergic pathways.

Effective treatments are available for MDD, although 30% to 40% of patients do not respond to one or more antidepressant trials (Box).^1-4 This article offers:

• new information about why triiodothyronine (T3) and thyroxine (T4) can “super-charge” antidepressant response
• tips on how to use thyroid hormones in patients with MDD, including effective dosages, patient monitoring, and treatment durations.

Box

Why thyroid hormones?

Thyroid hormones enter the brain slowly across the blood-brain barrier and the choroid plexus—cerebrospinal fluid barriers. T4 is the main source of brain T3—after attack by 5’deiodinase—but circulating T3 also crosses the blood-brain barrier through active transport.

Thyroid hormones accumulate in the locus ceruleus and other central noradrenergic structures and are distributed widely in the brain along noradrenergic pathways.^5-7 The mechanism of their therapeutic effect for MDD is not well understood, and various hypotheses have been proposed.

Subclinical hypothyroidism. Early studies such as by Howland⁸ of treatment-refractory MDD suggested that thyroid hormone augmentation might correct a hypothyroid state. However, blood thyroid hormone levels are not associated with resistance to antidepressant treatment, according to studies of MDD populations.^9-10 Also, thyroid hormones’ therapeutic action in MDD appears unlikely to be related to treating subclinical hypothyroidism because patients’ euthyroid status was verified in all adjuvant studies since 1980.

Joffe et al¹¹ proposed that MDD is characterized by a relative excess of T4 versus T3—probably related to a deficit in converting T4 to T3 in the periphery—and administering T3 would therefore correct this imbalance. They offered no strong evidence for an increased T4 level, however, and later studies failed to detect the postulated blood T3 abnormalities in MDD.^9-10 Also—as suggested by studies with high-dose T4 augmentation^12,13—the adjuvant antidepressant effect of thyroid hormones is not restricted to T3, although T3 may be more efficacious than T4.¹⁴

Neurotransmitter effects. Thyroid hormones’ role in increasing serotonin (5-HT) release could partially explain the benefit of adjuvant thyroid hormone therapy in MDD. Researchers found:

• T3 increased cortical 5-HT levels, probably by reducing the autoinhibitory effect of the presynaptic 5-HT_1A receptor¹⁵
• adding T3 to clomipramine therapy increased 5-HT levels to a greater extent than T3 or clomipramine used alone¹⁶
• Low 5-HT activity, shown in hypothyroid patients, increased after T4 replacement.¹⁷

This 5-HT release theory cannot explain why thyroid hormones have a rapid clinical effect in MDD. Most studies report the hormones have clinical efficacy in MDD within 4 weeks.¹⁸ Similarly, selective serotonin reuptake inhibitors (SSRIs) increase 5-HT levels within hours of treatment onset, but the clinical effect occurs 4 to 6 weeks later.¹⁹ Therefore, increased 5-HT levels cannot fully explain thyroid hormones’ early effect.

Close interaction between thyroid hormones and the noradrenergic system also has been examined. Brain T3 is primarily localized in the central noradrenergic systems, with axonal anterograde transport of T3 from the locus ceruleus. T3 is processed and accumulated in the noradrenergic system, carried via axonal transport, then delivered from nerve cell bodies to its neuronal targets.^5,7 T3 thus functions as a coneurotransmitter with norepinephrine.

Cellular energy metabolism. We recently reported that thyroid hormones’ antidepressant effect may be related to brain cellular energy metabolism. Thyroid hormones increase cellular levels of adenosine triphosphate (ATP) and phosphocreatine (PCr) in the hypothyroid brain.²⁰ Brain imaging—phosphorus-31 nuclear magnetic resonance spectroscopy (31P-MRS)—of subjects with MDD shows decreased brain levels of ATP and increased PCr.²¹

Our group showed that the antidepressant effect of T3 augmentation of SSRIs is correlated with significant increases in ATP levels and decreases in PCr. This effect—which appears to represent re-normalization of brain bioenergetics in treatment responders—did not occur in nonresponders (Iosifescu et al, presented at APA, 2004).

The effect of thyroid hormones on bioenergetic metabolism is compatible with the hypothesized effects on noradrenergic and serotonergic systems.^5,7 These mechanisms may represent different links in the same chain of events.

Antidepressant boosters

Thyroid hormones have been used extensively to treat MDD since the 1950s, when researchers reported that T3 monotherapy was efficacious for treating depression. These early studies had important methodologic limitations, including open designs and poorly defined diagnostic criteria and response.

For MDD, the most extensively researched uses of thyroid hormones are to augment therapy for antidepressant nonresponders and to accelerate partial response to antidepressants.

Tricyclics. Open studies primarily among outpatients in the 1970s and ‘80s suggested that thyroid hormones are a valid augmentation strategy for nonresponders to tricyclic antidepressants. Most—but not all—reported response rates >50% with T3 dosages of 20 to 50 mcg/d.^22,23

Compared with outpatient studies, however, an open trial of T3 augmentation by Birkenhager et al²⁴ found no evidence of efficacy in 14 severely depressed inpatients who had not responded to 6 weeks of tricyclics. These patients—mainly with melancholic and/or psychotic depression—showed greater response to a monoamine oxidase inhibitor (MAOI) or electroconvulsive therapy than to thyroid hormone.

Three of five double-blind controlled studies of thyroid hormone augmentation of tricyclics reported response rates of 50 to 65% (Table).^14,18,25 Earlier controlled studies, including two negative studies^26,27 had important methodologic limitations: all included few subjects (≤16), and two studies included both unipolar and bipolar patients. Joffe et al partially addressed these problems with two randomized, double-blind studies that were controlled with placebo or T4:

• In a 3-week trial, T3 was more effective than T4 when added to imipramine or desipramine.¹⁴
• In a 2-week trial, T3 was significantly more effective than placebo when added to imipramine or desipramine.²⁵

In the latter study, T3 and lithium augmentation appeared equally effective. Conversely, T4 was more effective than lithium as the first augmentation strategy in a double-blind, crossover study by Spoov and Lahdelma.²⁸

In conclusion, depressed patients given T3 with tricyclic antidepressants may be twice as likely as controls to respond to treatment, according to a meta-analysis of eight studies totaling 292 patients. This analysis by Aronson et al²⁹ supports T3 augmentation while addressing the surveyed studies’ limitations.

Table

Treatment-resistant MDD: Controlled studies of thyroid hormone augmentation

MAO inhibitors. One small report has addressed the efficacy of thyroid hormones as adjuvants to MAOIs.³⁰ In two patients, adding T3 to phenelzine enhanced the antidepressant response.

High-dose T4. Two open studies of patients with treatment-resistant bipolar or unipolar depression^12,13 have examined the efficacy of high-dose T4 augmentation. These patients were taking a variety of antidepressants, including TCAs and SSRIs.

• In the study by Baurer et al,¹² clinical remission (Hamilton Depression Scale [HAM-D] score ≤10) occurred in 4 of 5 patients with severe treatment-resistant unipolar depression who received adjunctive T4, mean 482±72 mcg/d, with antidepressants.
• In the study by Rudas et al,¹³ clinical remission (HAM-D ≤9) occurred in 7 of 9 patients with treatment-resistant MDD after T4, 150 to 300 mcg/d, was added to their antidepressant therapy. Side effects may limit this high-dose strategy, however, because 2 of the patients dropped out with thyrotoxicosis symptoms.

SSRIs. Three open trials to date have investigated using thyroid hormones to augment SSRIs in treatment-resistant MDD. In a prospective study by Agid and Lerer,³¹ 10 of 25 (40%) patients who did not respond to SSRI treatment did so after T3 was added. No men improved, however, which led the authors to suggest that men and women might respond differently to T3 augmentation of SSRIs.

In our study, 7 of 20 patients (35%) with MDD who did not respond to 8 weeks of SSRI therapy did so when we added T3, 50 mcg/d, for 4 weeks (Figure). Response rates were high (5/5, 100%) in patients with atypical features by DSMIV criteria and low (1/8, 12.5%) in those with melancholic features.³²

Abraham et al³³ added T3, 50 mcg/d, to the regimens of 12 patients with MDD who did not respond to SSRIs alone. One patient dropped out with side effects. After 4 weeks of T3 augmentation, 5 patients (42%) showed 50% or greater improvement in HAM-D scores from baseline.

Figure T3 augmentation of SSRIs in 20 patients with resistant major depressive disorder

Open T3 augmentation, 50 mcg/d, given to 20 nonresponders to 8 weeks of selective serotonin reuptake inhibitors (SSRIs) improved baseline CGI-S scores significantly (P=0.006) at 4 weeks in those with atypical depression and modestly (P>0.05) in those with melancholic depression.

Source: Reference 32Antidepressant accelerators. Five of seven early double-blind, controlled studies indicated that adding small doses of thyroid hormones at the beginning of antidepressant treatment accelerated treatment response. All were limited by small sample sizes and other methodologic problems. A more-recent meta-analysis of six studies totalling 125 patients by Altshuler et al³⁴ found:

• T3 was significantly more effective than placebo in accelerating clinical response to tricyclics
• the acceleration effect was more pronounced for women than for men.

Clinical recommendations

Thyroid hormones can be useful to augment and accelerate treatment of MDD. Evidence strongly supports their use with tricyclic antidepressants and suggests they also can be effective adjuvants for patients who do not respond to SSRIs.

Either T3 (up to 50 mcg/d) or T4 (up to 150 mcg/d) can be used as augmentation. T3’s antidepressant properties are considered more effective than those of T4, but the only head-to-head study supporting this conclusion was small (38 patients).¹⁴ Some T4 augmentation studies used very high dosages (300 to 600 mcg/d),¹² which increase the risk of acute overdose.

Start T3 augmentation at 25 mcg/d and increase, if tolerated, to 50 mcg/d after 1 week. Measure baseline serum thyroid-stimulating hormone (TSH), and do not treat patients with TSH <0.5 mIU/L). Baseline TSH, T4, or T3 levels do not predict response to T3 augmentation in euthyroid MDD patients.³²

Common side effects. Adjuvant T3, 25 to 50 mcg/d, was well-tolerated in our study of 20 patients also taking SSRIs:

• 2 (10%) experienced fatigue and diaphoresis
• 1 each (5%) had tremor, dry mouth, headaches, muscle aches, and vivid dreams.³²

We saw no significant changes in blood pressure, but heart rates increased significantly in our 4-week study—from 76±12 bpm (range 60 to 96) to 82±9 bpm (range 66 to 96). Thus, T3 augmentation may not be indicated for patients with coronary artery disease or chronic heart failure. Patients’ weight decreased an average 2.5±6.6 lbs (range –20 to +7).

Thyroid hormones may cause hypoglycemia and change insulin requirements in patients with diabetes. High doses of T3 or T4 may be associated with hyperthyroidism, weight loss, nervousness, sweating, tachycardia, insomnia, heat intolerance, menstrual irregularities, palpitations, psychosis, or fever. Discontinue treatment if these symptoms develop.

Onset of antidepressant effect. Assess patient response in 4 to 6 weeks, whether using augmentation to address antidepressant nonresponse^14,25 or to accelerate response.³³ If you detect only partial improvement, studies support continuing treatment up to 8 weeks.

Treatment duration. No guidelines exist on how long to continue thyroid hormones after the initial antidepressant response. TSH levels become suppressed (TSH <0.1 mIU/L) after 4 weeks of T3, 50 mcg/d, in patients with normal baseline thyroid function.³² This suggests thyroid hormone’s booster effect is self limited, and augmentation may not need to continue after 2 to 3 months—even in responders.

T3 augmentation at 25 mcg/d can be discontinued immediately. For 50 to 75 mcg/d, taper across 1 to 2 weeks. The hypothalamic-pituitary-thyroid axis returns to normal function 6 to 8 weeks after T3 augmentation is stopped.

In this model, thyroid hormone augmentation can be used to boost antidepressant efficacy several months at a time. If effective, the same strategy could be tried again for subsequent MDD episodes.

Related resources

• DeBattista C. Augmentation and combination strategies for depression. J Psychopharmacol 2006;20(3):11-18.
• Massachusetts General Hospital Psychiatric Academy (including web-casts on treatment-resistant depression. www.mghcme.com

Drug brand names

• Desipramine • Norpramin
• Imipramine • Tofranil
• Levothyroxine (T4) • Levoxyl, Levothroid, Synthroid, others
• Liothyronine (synthetic T3) • Cytomel

Disclosures

The author receives research support from Aspect Medical Systems, Forest Laboratories, and Janssen Pharmaceutica; is a consultant to Pfizer, Inc., and Forest Laboratories; and a speaker for Eli Lilly and Co., Pfizer, Inc., and Cephalon.

Prescribing thyroid hormones with antidepressants—whether to augment the antidepressant effect or accelerate patient response—is a well-researched strategy for treatment-resistant major depressive disorder (MDD). Thyroid hormones are known to boost response to tricyclics, and preliminary evidence shows they may be useful adjuvants to selective serotonin reuptake inhibitors (SSRIs) as well.

Thyroid hormones enter the brain slowly across the blood-brain barrier and choroid plexus. They accumulate in the locus ceruleus and other structures and are distributed widely along noradrenergic pathways.

Effective treatments are available for MDD, although 30% to 40% of patients do not respond to one or more antidepressant trials (Box).^1-4 This article offers:

• new information about why triiodothyronine (T3) and thyroxine (T4) can “super-charge” antidepressant response
• tips on how to use thyroid hormones in patients with MDD, including effective dosages, patient monitoring, and treatment durations.

Box

Why thyroid hormones?

Thyroid hormones enter the brain slowly across the blood-brain barrier and the choroid plexus—cerebrospinal fluid barriers. T4 is the main source of brain T3—after attack by 5’deiodinase—but circulating T3 also crosses the blood-brain barrier through active transport.

Thyroid hormones accumulate in the locus ceruleus and other central noradrenergic structures and are distributed widely in the brain along noradrenergic pathways.^5-7 The mechanism of their therapeutic effect for MDD is not well understood, and various hypotheses have been proposed.

Subclinical hypothyroidism. Early studies such as by Howland⁸ of treatment-refractory MDD suggested that thyroid hormone augmentation might correct a hypothyroid state. However, blood thyroid hormone levels are not associated with resistance to antidepressant treatment, according to studies of MDD populations.^9-10 Also, thyroid hormones’ therapeutic action in MDD appears unlikely to be related to treating subclinical hypothyroidism because patients’ euthyroid status was verified in all adjuvant studies since 1980.

Joffe et al¹¹ proposed that MDD is characterized by a relative excess of T4 versus T3—probably related to a deficit in converting T4 to T3 in the periphery—and administering T3 would therefore correct this imbalance. They offered no strong evidence for an increased T4 level, however, and later studies failed to detect the postulated blood T3 abnormalities in MDD.^9-10 Also—as suggested by studies with high-dose T4 augmentation^12,13—the adjuvant antidepressant effect of thyroid hormones is not restricted to T3, although T3 may be more efficacious than T4.¹⁴

Neurotransmitter effects. Thyroid hormones’ role in increasing serotonin (5-HT) release could partially explain the benefit of adjuvant thyroid hormone therapy in MDD. Researchers found:

• T3 increased cortical 5-HT levels, probably by reducing the autoinhibitory effect of the presynaptic 5-HT_1A receptor¹⁵
• adding T3 to clomipramine therapy increased 5-HT levels to a greater extent than T3 or clomipramine used alone¹⁶
• Low 5-HT activity, shown in hypothyroid patients, increased after T4 replacement.¹⁷

This 5-HT release theory cannot explain why thyroid hormones have a rapid clinical effect in MDD. Most studies report the hormones have clinical efficacy in MDD within 4 weeks.¹⁸ Similarly, selective serotonin reuptake inhibitors (SSRIs) increase 5-HT levels within hours of treatment onset, but the clinical effect occurs 4 to 6 weeks later.¹⁹ Therefore, increased 5-HT levels cannot fully explain thyroid hormones’ early effect.

Close interaction between thyroid hormones and the noradrenergic system also has been examined. Brain T3 is primarily localized in the central noradrenergic systems, with axonal anterograde transport of T3 from the locus ceruleus. T3 is processed and accumulated in the noradrenergic system, carried via axonal transport, then delivered from nerve cell bodies to its neuronal targets.^5,7 T3 thus functions as a coneurotransmitter with norepinephrine.

Cellular energy metabolism. We recently reported that thyroid hormones’ antidepressant effect may be related to brain cellular energy metabolism. Thyroid hormones increase cellular levels of adenosine triphosphate (ATP) and phosphocreatine (PCr) in the hypothyroid brain.²⁰ Brain imaging—phosphorus-31 nuclear magnetic resonance spectroscopy (31P-MRS)—of subjects with MDD shows decreased brain levels of ATP and increased PCr.²¹

Our group showed that the antidepressant effect of T3 augmentation of SSRIs is correlated with significant increases in ATP levels and decreases in PCr. This effect—which appears to represent re-normalization of brain bioenergetics in treatment responders—did not occur in nonresponders (Iosifescu et al, presented at APA, 2004).

The effect of thyroid hormones on bioenergetic metabolism is compatible with the hypothesized effects on noradrenergic and serotonergic systems.^5,7 These mechanisms may represent different links in the same chain of events.

Antidepressant boosters

Thyroid hormones have been used extensively to treat MDD since the 1950s, when researchers reported that T3 monotherapy was efficacious for treating depression. These early studies had important methodologic limitations, including open designs and poorly defined diagnostic criteria and response.

For MDD, the most extensively researched uses of thyroid hormones are to augment therapy for antidepressant nonresponders and to accelerate partial response to antidepressants.

Tricyclics. Open studies primarily among outpatients in the 1970s and ‘80s suggested that thyroid hormones are a valid augmentation strategy for nonresponders to tricyclic antidepressants. Most—but not all—reported response rates >50% with T3 dosages of 20 to 50 mcg/d.^22,23

Compared with outpatient studies, however, an open trial of T3 augmentation by Birkenhager et al²⁴ found no evidence of efficacy in 14 severely depressed inpatients who had not responded to 6 weeks of tricyclics. These patients—mainly with melancholic and/or psychotic depression—showed greater response to a monoamine oxidase inhibitor (MAOI) or electroconvulsive therapy than to thyroid hormone.

Three of five double-blind controlled studies of thyroid hormone augmentation of tricyclics reported response rates of 50 to 65% (Table).^14,18,25 Earlier controlled studies, including two negative studies^26,27 had important methodologic limitations: all included few subjects (≤16), and two studies included both unipolar and bipolar patients. Joffe et al partially addressed these problems with two randomized, double-blind studies that were controlled with placebo or T4:

• In a 3-week trial, T3 was more effective than T4 when added to imipramine or desipramine.¹⁴
• In a 2-week trial, T3 was significantly more effective than placebo when added to imipramine or desipramine.²⁵

In the latter study, T3 and lithium augmentation appeared equally effective. Conversely, T4 was more effective than lithium as the first augmentation strategy in a double-blind, crossover study by Spoov and Lahdelma.²⁸

In conclusion, depressed patients given T3 with tricyclic antidepressants may be twice as likely as controls to respond to treatment, according to a meta-analysis of eight studies totaling 292 patients. This analysis by Aronson et al²⁹ supports T3 augmentation while addressing the surveyed studies’ limitations.

Table

Treatment-resistant MDD: Controlled studies of thyroid hormone augmentation

MAO inhibitors. One small report has addressed the efficacy of thyroid hormones as adjuvants to MAOIs.³⁰ In two patients, adding T3 to phenelzine enhanced the antidepressant response.

High-dose T4. Two open studies of patients with treatment-resistant bipolar or unipolar depression^12,13 have examined the efficacy of high-dose T4 augmentation. These patients were taking a variety of antidepressants, including TCAs and SSRIs.

• In the study by Baurer et al,¹² clinical remission (Hamilton Depression Scale [HAM-D] score ≤10) occurred in 4 of 5 patients with severe treatment-resistant unipolar depression who received adjunctive T4, mean 482±72 mcg/d, with antidepressants.
• In the study by Rudas et al,¹³ clinical remission (HAM-D ≤9) occurred in 7 of 9 patients with treatment-resistant MDD after T4, 150 to 300 mcg/d, was added to their antidepressant therapy. Side effects may limit this high-dose strategy, however, because 2 of the patients dropped out with thyrotoxicosis symptoms.

SSRIs. Three open trials to date have investigated using thyroid hormones to augment SSRIs in treatment-resistant MDD. In a prospective study by Agid and Lerer,³¹ 10 of 25 (40%) patients who did not respond to SSRI treatment did so after T3 was added. No men improved, however, which led the authors to suggest that men and women might respond differently to T3 augmentation of SSRIs.

In our study, 7 of 20 patients (35%) with MDD who did not respond to 8 weeks of SSRI therapy did so when we added T3, 50 mcg/d, for 4 weeks (Figure). Response rates were high (5/5, 100%) in patients with atypical features by DSMIV criteria and low (1/8, 12.5%) in those with melancholic features.³²

Abraham et al³³ added T3, 50 mcg/d, to the regimens of 12 patients with MDD who did not respond to SSRIs alone. One patient dropped out with side effects. After 4 weeks of T3 augmentation, 5 patients (42%) showed 50% or greater improvement in HAM-D scores from baseline.

Figure T3 augmentation of SSRIs in 20 patients with resistant major depressive disorder

Open T3 augmentation, 50 mcg/d, given to 20 nonresponders to 8 weeks of selective serotonin reuptake inhibitors (SSRIs) improved baseline CGI-S scores significantly (P=0.006) at 4 weeks in those with atypical depression and modestly (P>0.05) in those with melancholic depression.

Source: Reference 32Antidepressant accelerators. Five of seven early double-blind, controlled studies indicated that adding small doses of thyroid hormones at the beginning of antidepressant treatment accelerated treatment response. All were limited by small sample sizes and other methodologic problems. A more-recent meta-analysis of six studies totalling 125 patients by Altshuler et al³⁴ found:

• T3 was significantly more effective than placebo in accelerating clinical response to tricyclics
• the acceleration effect was more pronounced for women than for men.

Clinical recommendations

Thyroid hormones can be useful to augment and accelerate treatment of MDD. Evidence strongly supports their use with tricyclic antidepressants and suggests they also can be effective adjuvants for patients who do not respond to SSRIs.

Either T3 (up to 50 mcg/d) or T4 (up to 150 mcg/d) can be used as augmentation. T3’s antidepressant properties are considered more effective than those of T4, but the only head-to-head study supporting this conclusion was small (38 patients).¹⁴ Some T4 augmentation studies used very high dosages (300 to 600 mcg/d),¹² which increase the risk of acute overdose.

Start T3 augmentation at 25 mcg/d and increase, if tolerated, to 50 mcg/d after 1 week. Measure baseline serum thyroid-stimulating hormone (TSH), and do not treat patients with TSH <0.5 mIU/L). Baseline TSH, T4, or T3 levels do not predict response to T3 augmentation in euthyroid MDD patients.³²

Common side effects. Adjuvant T3, 25 to 50 mcg/d, was well-tolerated in our study of 20 patients also taking SSRIs:

• 2 (10%) experienced fatigue and diaphoresis
• 1 each (5%) had tremor, dry mouth, headaches, muscle aches, and vivid dreams.³²

We saw no significant changes in blood pressure, but heart rates increased significantly in our 4-week study—from 76±12 bpm (range 60 to 96) to 82±9 bpm (range 66 to 96). Thus, T3 augmentation may not be indicated for patients with coronary artery disease or chronic heart failure. Patients’ weight decreased an average 2.5±6.6 lbs (range –20 to +7).

Thyroid hormones may cause hypoglycemia and change insulin requirements in patients with diabetes. High doses of T3 or T4 may be associated with hyperthyroidism, weight loss, nervousness, sweating, tachycardia, insomnia, heat intolerance, menstrual irregularities, palpitations, psychosis, or fever. Discontinue treatment if these symptoms develop.

Onset of antidepressant effect. Assess patient response in 4 to 6 weeks, whether using augmentation to address antidepressant nonresponse^14,25 or to accelerate response.³³ If you detect only partial improvement, studies support continuing treatment up to 8 weeks.

Treatment duration. No guidelines exist on how long to continue thyroid hormones after the initial antidepressant response. TSH levels become suppressed (TSH <0.1 mIU/L) after 4 weeks of T3, 50 mcg/d, in patients with normal baseline thyroid function.³² This suggests thyroid hormone’s booster effect is self limited, and augmentation may not need to continue after 2 to 3 months—even in responders.

T3 augmentation at 25 mcg/d can be discontinued immediately. For 50 to 75 mcg/d, taper across 1 to 2 weeks. The hypothalamic-pituitary-thyroid axis returns to normal function 6 to 8 weeks after T3 augmentation is stopped.

In this model, thyroid hormone augmentation can be used to boost antidepressant efficacy several months at a time. If effective, the same strategy could be tried again for subsequent MDD episodes.

Related resources

• DeBattista C. Augmentation and combination strategies for depression. J Psychopharmacol 2006;20(3):11-18.
• Massachusetts General Hospital Psychiatric Academy (including web-casts on treatment-resistant depression. www.mghcme.com

Drug brand names

• Desipramine • Norpramin
• Imipramine • Tofranil
• Levothyroxine (T4) • Levoxyl, Levothroid, Synthroid, others
• Liothyronine (synthetic T3) • Cytomel

Disclosures

The author receives research support from Aspect Medical Systems, Forest Laboratories, and Janssen Pharmaceutica; is a consultant to Pfizer, Inc., and Forest Laboratories; and a speaker for Eli Lilly and Co., Pfizer, Inc., and Cephalon.

Ms. A has been compulsively shopping and spending since age 19 when she first obtained credit cards. After years of intense urges to shop and remorse over the financial consequences, she seeks psychiatric help. Now age 37 and divorced, she has controlled her spending only for two 1- to 2-year periods that coincided with bankruptcy proceedings.

With easy access to credit, many persons such as Ms. A develop what is variously called compulsive buying, compulsive shopping, addictive shopping, or shopaholism. Although “medicalizing” excessive shopping may seem to obscure its broader cultural and social causes,¹ increasing evidence points to a discrete shopping disorder.

Our group has contributed to compulsive buying research and continues to evaluate potential treatments. We offer evidence and practical advice to help you:

• identify compulsive shopping disorder using the patient’s history and three screening questions
  
• differentiate compulsive shopping from manic or hypomanic shopping sprees
  
• educate patients about four steps to control compulsive shopping.
  

Table 1

Compulsive shopping disorder’s clinical signs

An Evolving Picture

Ms. A says shopping is her primary social activity and entertainment. Though she works full time, she shops three or more times a week, cruising expensive department stores and discount outlets on evenings and weekends. She buys clothing, shoes, makeup, jewelry, antiques, household electronics, and other items.

She says her shopping is spontaneous and impulsive. Shopping gives her an emotional “rush” that is frequently followed by periods of guilt, and she often returns or gives away purchased items. She is disappointed at her inability to control her shopping behavior and ashamed of the financial crises she has caused.

Compulsive buying is characterized by persistent or poorly controlled preoccupations, urges, or behaviors regarding shopping or spending, leading to adverse consequences.² Onset in late adolescence to early adulthood is the usual pattern, and the disorder is thought to be chronic or recurrent. It is not listed in DSM-IV-TR but is considered an example of an impulse control disorder not otherwise specified. For this paper, we use the terms compulsive shopping and compulsive buying interchangeably.

The disorder’s tentative classification reflects debate about its conceptualization. Some clinicians and researchers consider compulsive buying an addiction similar to drug or alcohol misuse; others have linked it to depression or anxiety. Hollander³ and others have commented on its similarities with obsessive-compulsive disorder (OCD), and a recent study noted that compulsive buying is more common in patients with OCD than in matched controls.⁴ Still others—drawing on Kraepelin’s and Bleuler’s early work—consider compulsive buying an impulse control disorder, having features in common with pathological gambling and kleptomania.⁵

Prevalence. One survey estimates 2% to 8% of U.S. adults meet criteria for a compulsive shopping disorder, and community-based and clinical surveys suggest that 86% to 95% of them are women.⁵ The reported gender difference may be artifactual; women readily acknowledge that they enjoy shopping, whereas men are more likely to report that they “collect.”

Behavior patterns. No careful, longitudinal studies have examined compulsive buying disorder, but case reports suggest the condition is chronic, with a waxing and waning course and wide variance in symptom severity. In 20 consecutive patients with compulsive buying symptoms, one-half reported that irresistible urges prompted spending and three-quarters preferred to shop alone.⁶

Compulsive shoppers tend to shop frequently and spend inappropriately:

• at department and discount stores, specialty shops, and boutiques
  
• from mail order, television, and online merchants.
  

While shopping, compulsive shoppers may report feeling intensely excited, happy, and powerful. These emotions are frequently followed by distress or guilt. They may return purchases or hide them in closets or attics, never to be used.

Low-income persons who shop compulsively may do so at consignment shops or garage sales. In one of our studies, the most severe compulsive buyers had the lowest incomes,⁶ suggesting that:

• lack of money does not prevent compulsive shopping disorder from developing
  
• severe compulsive shoppers lack the ability to delay their shopping.
  

Psychiatric comorbidity

Compulsive buyers differ from matched controls when dimensional scales are used to measure psychopathology. One study found that compulsive buyers had elevated scores on the Beck Depression Inventory, the Spielberger Trait Anxiety Scale, and the Maudsley Obsessive Compulsive Inventory.²

Compulsive buyers and their first-degree relatives often have comorbid psychiatric disorders, particularly mood, anxiety, substance use, and eating disorders.⁵ Axis II disorders are also common; no particular type predominates, but the obsessive-compulsive, borderline, and avoidant personality types are seen most frequently.

McElroy et al⁷ defined compulsive buying disorder as:

• uncontrollable
  
• markedly distressing, time-consuming, and/or resulting in family, social, vocational, and/or financial difficulties
  
• not occurring only in the context of hypomanic or manic symptoms.
  

In a larger controlled study, our group⁸ compared 33 individuals who met the McElroy et al criteria for compulsive buying disorder and 22 control patients. The 137 first-degree relatives of the compulsive shoppers were significantly more likely than the controls’ relatives to have histories of depression, alcoholism, substance use, or multiple psychiatric diagnoses (as measured by the Family History Research Diagnostic Criteria).

Identifying a patient’s psychiatric comorbidities can help you develop:

• a biopsychosocial counseling plan—such as for a patient with borderline personality disorder who shops to relieve tension from relationship stress
  
• pharmacologic treatment strategies—such as prescribing a selective serotonin reuptake inhibitor (SSRI) for patients with comorbid major depression.
  

Manic versus compulsive behavior

Manic and hypomanic symptoms may be associated with impulsive and reckless spending. Thus, when evaluating excessive spending, always carefully evaluate patients for bipolar disorder.

Bipolar mania and excessive spending related to a compulsive buying disorder are relatively easy to differentiate:

• The manic patient’s unrestrained spending sprees correspond to manic episodes and are accompanied by euphoric mood, grandiosity, unrealistic plans, and often a giddy, overly bright affect.
  
• The compulsive shopper’s spending occurs year-round in a pattern suggesting ongoing preoccupation.
  

Not so for the manic, who may boast of his or her spending, display the evidence, and try to convince family and friends that the purchase is necessary or fits into some grandiose scheme. “Who doesn’t need two BMWs?” a manic patient said to one of the authors [DWB].

Screening and diagnosis

As with any psychiatric disorder, gathering an accurate history through a careful interview is important. This can be challenging with compulsive shopping disorder, however, because the patient may minimize symptoms out of embarrassment or denial. Your goal is to identify the shopping problem through nonjudgmental inquiries.

Diagnostic instruments. Researchers use assessment tools such as Faber and O’Guinn’s 7-item Compulsive Buying Scale⁹ to help diagnose this disorder. Our group developed a shopping version of the Yale-Brown Obsessive Compulsive Scale (YBOCS-SV) to help rate severity and change during clinical trials.¹⁰

Formal instruments may help in the clinical setting, but you can often elicit compulsive buying symptoms with a few screening questions (Table 2). If screening indicates a positive response, move to more detailed questions about:

• frequency of excessive shopping
  
• time spent shopping
  
• factors that trigger or worsen the shopping behavior
  
• amount of money spent.
  

Table 2

Is your patient a compulsive shopper? Ask these screening questions

Stopping uncontrolled shopping

Compulsive shopping has no standard treatment, but evidence shows benefit from some SSRIs and psychotherapies.

Fluvoxamine. An early case series suggested antidepressants could curb compulsive buying,⁵ but later research has yielded mixed results.

Ms. A entered an experimental drug trial. She was randomly assigned to receive fluvoxamine and—despite difficulties with oversedation—tolerated a sustained dosage of 100 mg/d. After the 9-week trial, Ms. A said she thought less frequently about shopping, felt less compulsion to shop, and was spending less money and time shopping.

This open-label trial we conducted indicated that fluvoxamine, up to 300 mg/d, could be an effective treatment for compulsive buying.¹¹ Two subsequent randomized controlled trials, however, found fluvoxamine did no better than placebo when treating compulsive shoppers.^12,13

Citalopram. In an open-label trial,¹⁴ 23 women and 1 man who met diagnostic criteria for compulsive shopping disorder (YBOCS-SV scores ≥17) received citalopram for 7 weeks. Dosages started at 20 mg/d and were increased as tolerated to 60 mg/d. Fifteen patients (63%) met response criteria—“much improved” or “very much improved” as measured by the Clinical Global Impressions-Improvement scale and a ≥50% decrease in YBOCS-SV score. Three patients (13%) discontinued treatment because of adverse effects (headache, rash, insomnia).

The 15 responders were then enrolled in a 9-week double-blind, placebo-controlled trial. Compulsive shopping symptoms recurred in 5 of 8 patients (63%) assigned to placebo, compared with none of the 7 who continued taking citalopram.

By comparison, escitalopram, 10 to 20 mg/d, showed little effect for compulsive shopping symptoms in an identically designed discontinuation trial by the same investigators. During the 7-week, open-label trial, 19 of 26 patients met response criteria. In the 9-week double-blind, controlled phase, however, 63% of initial responders relapsed while taking escitalopram, compared with 67% of those randomized to placebo.¹⁵

A naturalistic follow-up study of 24 patients treated with citalopram, 20 to 60 mg/d, noted that patients who responded at 3 months were more likely to be symptom-free after 1 year than those who did not respond to acute treatment.¹⁶ Responders’ mean 2-week compulsive spending declined from $773 before treatment to $351 at 12 months, and their mean total debt declined from $17,833 to $16,752.

Because remission was not significantly associated with taking citalopram, however, the authors concluded that the mechanisms responsible for maintaining remission were unclear.

Psychotherapy. Cognitive-behavioral therapy (CBT) may help, but few therapists are familiar with this disorder. CBT challenges the patient’s cognitive distortions and faulty schemas about shopping, such as:

• “Having the latest fashions will make me more popular.”
  
• “Having 5 pair of new shoes will make me a happier and better person.”
  

Our recommendations. Medication—such as an antidepressant for major depression or a mood stabilizer for bipolar disorder—may improve compulsive shopping in patients with a comorbid psychiatric disorder. For other compulsive shoppers, however, medication trials provide little guidance for treatment.

We inform patients such as Ms. A that they cannot rely on medication to control their behavior. Instead, we recommend a four-step approach to break the compulsive shopping habit (Table 3).

Financial counseling, provided free of charge by many banks, benefits some patients. Self-help books describe strategies to overcome compulsive spending (Related resources). Debtors Anonymous, a 12-step program patterned after Alcoholics Anonymous, also can help by offering acceptance, belonging, forgiveness, and understanding.

In the most severe cases we recommend appointing a financial conservator to control the patient’s finances. We rarely advise this strategy but have encountered cases in which there seemed to be no other option. Having a conservator controls the patient’s spending but does not reverse the preoccupation with shopping.

Table 3

Patient education: 4 steps to control compulsive spending

For clinicians

• Black DW. Assessment of compulsive buying. In: Benson AL (ed). I shop, therefore I am: Compulsive buying and the search for self. Northvale, NJ: Jason Aronson; 2000:191-216.
  

• Arenson G. Born to spend: how to overcome compulsive spending. Blue Ridge Summit, PA: Tab Books, 1991.
  
• Benson AL. Stopping Overshopping. A site for shopaholics and the people who love them. www.stoppingovershopping.com.
  
• Mellan O. Money harmony: resolving money conflicts in your life and relationships. New York: Walker, 2005.
  

• Citalopram • Celexa
  
• Escitalopram • Lexapro
  
• Fluvoxamine • Luvox
  

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

Dr. Black receives grant/research support or is a consultant or speaker for Forest Laboratories and Shire Pharmaceuticals

Ms. A has been compulsively shopping and spending since age 19 when she first obtained credit cards. After years of intense urges to shop and remorse over the financial consequences, she seeks psychiatric help. Now age 37 and divorced, she has controlled her spending only for two 1- to 2-year periods that coincided with bankruptcy proceedings.

With easy access to credit, many persons such as Ms. A develop what is variously called compulsive buying, compulsive shopping, addictive shopping, or shopaholism. Although “medicalizing” excessive shopping may seem to obscure its broader cultural and social causes,¹ increasing evidence points to a discrete shopping disorder.

Our group has contributed to compulsive buying research and continues to evaluate potential treatments. We offer evidence and practical advice to help you:

• identify compulsive shopping disorder using the patient’s history and three screening questions
  
• differentiate compulsive shopping from manic or hypomanic shopping sprees
  
• educate patients about four steps to control compulsive shopping.
  

Table 1

Compulsive shopping disorder’s clinical signs

An Evolving Picture

Ms. A says shopping is her primary social activity and entertainment. Though she works full time, she shops three or more times a week, cruising expensive department stores and discount outlets on evenings and weekends. She buys clothing, shoes, makeup, jewelry, antiques, household electronics, and other items.

She says her shopping is spontaneous and impulsive. Shopping gives her an emotional “rush” that is frequently followed by periods of guilt, and she often returns or gives away purchased items. She is disappointed at her inability to control her shopping behavior and ashamed of the financial crises she has caused.

Compulsive buying is characterized by persistent or poorly controlled preoccupations, urges, or behaviors regarding shopping or spending, leading to adverse consequences.² Onset in late adolescence to early adulthood is the usual pattern, and the disorder is thought to be chronic or recurrent. It is not listed in DSM-IV-TR but is considered an example of an impulse control disorder not otherwise specified. For this paper, we use the terms compulsive shopping and compulsive buying interchangeably.

The disorder’s tentative classification reflects debate about its conceptualization. Some clinicians and researchers consider compulsive buying an addiction similar to drug or alcohol misuse; others have linked it to depression or anxiety. Hollander³ and others have commented on its similarities with obsessive-compulsive disorder (OCD), and a recent study noted that compulsive buying is more common in patients with OCD than in matched controls.⁴ Still others—drawing on Kraepelin’s and Bleuler’s early work—consider compulsive buying an impulse control disorder, having features in common with pathological gambling and kleptomania.⁵

Prevalence. One survey estimates 2% to 8% of U.S. adults meet criteria for a compulsive shopping disorder, and community-based and clinical surveys suggest that 86% to 95% of them are women.⁵ The reported gender difference may be artifactual; women readily acknowledge that they enjoy shopping, whereas men are more likely to report that they “collect.”

Behavior patterns. No careful, longitudinal studies have examined compulsive buying disorder, but case reports suggest the condition is chronic, with a waxing and waning course and wide variance in symptom severity. In 20 consecutive patients with compulsive buying symptoms, one-half reported that irresistible urges prompted spending and three-quarters preferred to shop alone.⁶

Compulsive shoppers tend to shop frequently and spend inappropriately:

• at department and discount stores, specialty shops, and boutiques
  
• from mail order, television, and online merchants.
  

While shopping, compulsive shoppers may report feeling intensely excited, happy, and powerful. These emotions are frequently followed by distress or guilt. They may return purchases or hide them in closets or attics, never to be used.

Low-income persons who shop compulsively may do so at consignment shops or garage sales. In one of our studies, the most severe compulsive buyers had the lowest incomes,⁶ suggesting that:

• lack of money does not prevent compulsive shopping disorder from developing
  
• severe compulsive shoppers lack the ability to delay their shopping.
  

Psychiatric comorbidity

Compulsive buyers differ from matched controls when dimensional scales are used to measure psychopathology. One study found that compulsive buyers had elevated scores on the Beck Depression Inventory, the Spielberger Trait Anxiety Scale, and the Maudsley Obsessive Compulsive Inventory.²

Compulsive buyers and their first-degree relatives often have comorbid psychiatric disorders, particularly mood, anxiety, substance use, and eating disorders.⁵ Axis II disorders are also common; no particular type predominates, but the obsessive-compulsive, borderline, and avoidant personality types are seen most frequently.

McElroy et al⁷ defined compulsive buying disorder as:

• uncontrollable
  
• markedly distressing, time-consuming, and/or resulting in family, social, vocational, and/or financial difficulties
  
• not occurring only in the context of hypomanic or manic symptoms.
  

In a larger controlled study, our group⁸ compared 33 individuals who met the McElroy et al criteria for compulsive buying disorder and 22 control patients. The 137 first-degree relatives of the compulsive shoppers were significantly more likely than the controls’ relatives to have histories of depression, alcoholism, substance use, or multiple psychiatric diagnoses (as measured by the Family History Research Diagnostic Criteria).

Identifying a patient’s psychiatric comorbidities can help you develop:

• a biopsychosocial counseling plan—such as for a patient with borderline personality disorder who shops to relieve tension from relationship stress
  
• pharmacologic treatment strategies—such as prescribing a selective serotonin reuptake inhibitor (SSRI) for patients with comorbid major depression.
  

Manic versus compulsive behavior

Manic and hypomanic symptoms may be associated with impulsive and reckless spending. Thus, when evaluating excessive spending, always carefully evaluate patients for bipolar disorder.

Bipolar mania and excessive spending related to a compulsive buying disorder are relatively easy to differentiate:

• The manic patient’s unrestrained spending sprees correspond to manic episodes and are accompanied by euphoric mood, grandiosity, unrealistic plans, and often a giddy, overly bright affect.
  
• The compulsive shopper’s spending occurs year-round in a pattern suggesting ongoing preoccupation.
  

Not so for the manic, who may boast of his or her spending, display the evidence, and try to convince family and friends that the purchase is necessary or fits into some grandiose scheme. “Who doesn’t need two BMWs?” a manic patient said to one of the authors [DWB].

Screening and diagnosis

As with any psychiatric disorder, gathering an accurate history through a careful interview is important. This can be challenging with compulsive shopping disorder, however, because the patient may minimize symptoms out of embarrassment or denial. Your goal is to identify the shopping problem through nonjudgmental inquiries.

Diagnostic instruments. Researchers use assessment tools such as Faber and O’Guinn’s 7-item Compulsive Buying Scale⁹ to help diagnose this disorder. Our group developed a shopping version of the Yale-Brown Obsessive Compulsive Scale (YBOCS-SV) to help rate severity and change during clinical trials.¹⁰

Formal instruments may help in the clinical setting, but you can often elicit compulsive buying symptoms with a few screening questions (Table 2). If screening indicates a positive response, move to more detailed questions about:

• frequency of excessive shopping
  
• time spent shopping
  
• factors that trigger or worsen the shopping behavior
  
• amount of money spent.
  

Table 2

Is your patient a compulsive shopper? Ask these screening questions

Stopping uncontrolled shopping

Compulsive shopping has no standard treatment, but evidence shows benefit from some SSRIs and psychotherapies.

Fluvoxamine. An early case series suggested antidepressants could curb compulsive buying,⁵ but later research has yielded mixed results.

Ms. A entered an experimental drug trial. She was randomly assigned to receive fluvoxamine and—despite difficulties with oversedation—tolerated a sustained dosage of 100 mg/d. After the 9-week trial, Ms. A said she thought less frequently about shopping, felt less compulsion to shop, and was spending less money and time shopping.

This open-label trial we conducted indicated that fluvoxamine, up to 300 mg/d, could be an effective treatment for compulsive buying.¹¹ Two subsequent randomized controlled trials, however, found fluvoxamine did no better than placebo when treating compulsive shoppers.^12,13

Citalopram. In an open-label trial,¹⁴ 23 women and 1 man who met diagnostic criteria for compulsive shopping disorder (YBOCS-SV scores ≥17) received citalopram for 7 weeks. Dosages started at 20 mg/d and were increased as tolerated to 60 mg/d. Fifteen patients (63%) met response criteria—“much improved” or “very much improved” as measured by the Clinical Global Impressions-Improvement scale and a ≥50% decrease in YBOCS-SV score. Three patients (13%) discontinued treatment because of adverse effects (headache, rash, insomnia).

The 15 responders were then enrolled in a 9-week double-blind, placebo-controlled trial. Compulsive shopping symptoms recurred in 5 of 8 patients (63%) assigned to placebo, compared with none of the 7 who continued taking citalopram.

By comparison, escitalopram, 10 to 20 mg/d, showed little effect for compulsive shopping symptoms in an identically designed discontinuation trial by the same investigators. During the 7-week, open-label trial, 19 of 26 patients met response criteria. In the 9-week double-blind, controlled phase, however, 63% of initial responders relapsed while taking escitalopram, compared with 67% of those randomized to placebo.¹⁵

A naturalistic follow-up study of 24 patients treated with citalopram, 20 to 60 mg/d, noted that patients who responded at 3 months were more likely to be symptom-free after 1 year than those who did not respond to acute treatment.¹⁶ Responders’ mean 2-week compulsive spending declined from $773 before treatment to $351 at 12 months, and their mean total debt declined from $17,833 to $16,752.

Because remission was not significantly associated with taking citalopram, however, the authors concluded that the mechanisms responsible for maintaining remission were unclear.

Psychotherapy. Cognitive-behavioral therapy (CBT) may help, but few therapists are familiar with this disorder. CBT challenges the patient’s cognitive distortions and faulty schemas about shopping, such as:

• “Having the latest fashions will make me more popular.”
  
• “Having 5 pair of new shoes will make me a happier and better person.”
  

Our recommendations. Medication—such as an antidepressant for major depression or a mood stabilizer for bipolar disorder—may improve compulsive shopping in patients with a comorbid psychiatric disorder. For other compulsive shoppers, however, medication trials provide little guidance for treatment.

We inform patients such as Ms. A that they cannot rely on medication to control their behavior. Instead, we recommend a four-step approach to break the compulsive shopping habit (Table 3).

Financial counseling, provided free of charge by many banks, benefits some patients. Self-help books describe strategies to overcome compulsive spending (Related resources). Debtors Anonymous, a 12-step program patterned after Alcoholics Anonymous, also can help by offering acceptance, belonging, forgiveness, and understanding.

In the most severe cases we recommend appointing a financial conservator to control the patient’s finances. We rarely advise this strategy but have encountered cases in which there seemed to be no other option. Having a conservator controls the patient’s spending but does not reverse the preoccupation with shopping.

Table 3

Patient education: 4 steps to control compulsive spending

For clinicians

• Black DW. Assessment of compulsive buying. In: Benson AL (ed). I shop, therefore I am: Compulsive buying and the search for self. Northvale, NJ: Jason Aronson; 2000:191-216.
  

• Arenson G. Born to spend: how to overcome compulsive spending. Blue Ridge Summit, PA: Tab Books, 1991.
  
• Benson AL. Stopping Overshopping. A site for shopaholics and the people who love them. www.stoppingovershopping.com.
  
• Mellan O. Money harmony: resolving money conflicts in your life and relationships. New York: Walker, 2005.
  

• Citalopram • Celexa
  
• Escitalopram • Lexapro
  
• Fluvoxamine • Luvox
  

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

Dr. Black receives grant/research support or is a consultant or speaker for Forest Laboratories and Shire Pharmaceuticals

Ms. A has been compulsively shopping and spending since age 19 when she first obtained credit cards. After years of intense urges to shop and remorse over the financial consequences, she seeks psychiatric help. Now age 37 and divorced, she has controlled her spending only for two 1- to 2-year periods that coincided with bankruptcy proceedings.

With easy access to credit, many persons such as Ms. A develop what is variously called compulsive buying, compulsive shopping, addictive shopping, or shopaholism. Although “medicalizing” excessive shopping may seem to obscure its broader cultural and social causes,¹ increasing evidence points to a discrete shopping disorder.

Our group has contributed to compulsive buying research and continues to evaluate potential treatments. We offer evidence and practical advice to help you:

• identify compulsive shopping disorder using the patient’s history and three screening questions
  
• differentiate compulsive shopping from manic or hypomanic shopping sprees
  
• educate patients about four steps to control compulsive shopping.
  

Table 1

Compulsive shopping disorder’s clinical signs

An Evolving Picture

Ms. A says shopping is her primary social activity and entertainment. Though she works full time, she shops three or more times a week, cruising expensive department stores and discount outlets on evenings and weekends. She buys clothing, shoes, makeup, jewelry, antiques, household electronics, and other items.

She says her shopping is spontaneous and impulsive. Shopping gives her an emotional “rush” that is frequently followed by periods of guilt, and she often returns or gives away purchased items. She is disappointed at her inability to control her shopping behavior and ashamed of the financial crises she has caused.

Compulsive buying is characterized by persistent or poorly controlled preoccupations, urges, or behaviors regarding shopping or spending, leading to adverse consequences.² Onset in late adolescence to early adulthood is the usual pattern, and the disorder is thought to be chronic or recurrent. It is not listed in DSM-IV-TR but is considered an example of an impulse control disorder not otherwise specified. For this paper, we use the terms compulsive shopping and compulsive buying interchangeably.

The disorder’s tentative classification reflects debate about its conceptualization. Some clinicians and researchers consider compulsive buying an addiction similar to drug or alcohol misuse; others have linked it to depression or anxiety. Hollander³ and others have commented on its similarities with obsessive-compulsive disorder (OCD), and a recent study noted that compulsive buying is more common in patients with OCD than in matched controls.⁴ Still others—drawing on Kraepelin’s and Bleuler’s early work—consider compulsive buying an impulse control disorder, having features in common with pathological gambling and kleptomania.⁵

Prevalence. One survey estimates 2% to 8% of U.S. adults meet criteria for a compulsive shopping disorder, and community-based and clinical surveys suggest that 86% to 95% of them are women.⁵ The reported gender difference may be artifactual; women readily acknowledge that they enjoy shopping, whereas men are more likely to report that they “collect.”

Behavior patterns. No careful, longitudinal studies have examined compulsive buying disorder, but case reports suggest the condition is chronic, with a waxing and waning course and wide variance in symptom severity. In 20 consecutive patients with compulsive buying symptoms, one-half reported that irresistible urges prompted spending and three-quarters preferred to shop alone.⁶

Compulsive shoppers tend to shop frequently and spend inappropriately:

• at department and discount stores, specialty shops, and boutiques
  
• from mail order, television, and online merchants.
  

While shopping, compulsive shoppers may report feeling intensely excited, happy, and powerful. These emotions are frequently followed by distress or guilt. They may return purchases or hide them in closets or attics, never to be used.

Low-income persons who shop compulsively may do so at consignment shops or garage sales. In one of our studies, the most severe compulsive buyers had the lowest incomes,⁶ suggesting that:

• lack of money does not prevent compulsive shopping disorder from developing
  
• severe compulsive shoppers lack the ability to delay their shopping.
  

Psychiatric comorbidity

Compulsive buyers differ from matched controls when dimensional scales are used to measure psychopathology. One study found that compulsive buyers had elevated scores on the Beck Depression Inventory, the Spielberger Trait Anxiety Scale, and the Maudsley Obsessive Compulsive Inventory.²

Compulsive buyers and their first-degree relatives often have comorbid psychiatric disorders, particularly mood, anxiety, substance use, and eating disorders.⁵ Axis II disorders are also common; no particular type predominates, but the obsessive-compulsive, borderline, and avoidant personality types are seen most frequently.

McElroy et al⁷ defined compulsive buying disorder as:

• uncontrollable
  
• markedly distressing, time-consuming, and/or resulting in family, social, vocational, and/or financial difficulties
  
• not occurring only in the context of hypomanic or manic symptoms.
  

In a larger controlled study, our group⁸ compared 33 individuals who met the McElroy et al criteria for compulsive buying disorder and 22 control patients. The 137 first-degree relatives of the compulsive shoppers were significantly more likely than the controls’ relatives to have histories of depression, alcoholism, substance use, or multiple psychiatric diagnoses (as measured by the Family History Research Diagnostic Criteria).

Identifying a patient’s psychiatric comorbidities can help you develop:

• a biopsychosocial counseling plan—such as for a patient with borderline personality disorder who shops to relieve tension from relationship stress
  
• pharmacologic treatment strategies—such as prescribing a selective serotonin reuptake inhibitor (SSRI) for patients with comorbid major depression.
  

Manic versus compulsive behavior

Manic and hypomanic symptoms may be associated with impulsive and reckless spending. Thus, when evaluating excessive spending, always carefully evaluate patients for bipolar disorder.

Bipolar mania and excessive spending related to a compulsive buying disorder are relatively easy to differentiate:

• The manic patient’s unrestrained spending sprees correspond to manic episodes and are accompanied by euphoric mood, grandiosity, unrealistic plans, and often a giddy, overly bright affect.
  
• The compulsive shopper’s spending occurs year-round in a pattern suggesting ongoing preoccupation.
  

Not so for the manic, who may boast of his or her spending, display the evidence, and try to convince family and friends that the purchase is necessary or fits into some grandiose scheme. “Who doesn’t need two BMWs?” a manic patient said to one of the authors [DWB].

Screening and diagnosis

As with any psychiatric disorder, gathering an accurate history through a careful interview is important. This can be challenging with compulsive shopping disorder, however, because the patient may minimize symptoms out of embarrassment or denial. Your goal is to identify the shopping problem through nonjudgmental inquiries.

Diagnostic instruments. Researchers use assessment tools such as Faber and O’Guinn’s 7-item Compulsive Buying Scale⁹ to help diagnose this disorder. Our group developed a shopping version of the Yale-Brown Obsessive Compulsive Scale (YBOCS-SV) to help rate severity and change during clinical trials.¹⁰

Formal instruments may help in the clinical setting, but you can often elicit compulsive buying symptoms with a few screening questions (Table 2). If screening indicates a positive response, move to more detailed questions about:

• frequency of excessive shopping
  
• time spent shopping
  
• factors that trigger or worsen the shopping behavior
  
• amount of money spent.
  

Table 2

Is your patient a compulsive shopper? Ask these screening questions

Stopping uncontrolled shopping

Compulsive shopping has no standard treatment, but evidence shows benefit from some SSRIs and psychotherapies.

Fluvoxamine. An early case series suggested antidepressants could curb compulsive buying,⁵ but later research has yielded mixed results.

Ms. A entered an experimental drug trial. She was randomly assigned to receive fluvoxamine and—despite difficulties with oversedation—tolerated a sustained dosage of 100 mg/d. After the 9-week trial, Ms. A said she thought less frequently about shopping, felt less compulsion to shop, and was spending less money and time shopping.

This open-label trial we conducted indicated that fluvoxamine, up to 300 mg/d, could be an effective treatment for compulsive buying.¹¹ Two subsequent randomized controlled trials, however, found fluvoxamine did no better than placebo when treating compulsive shoppers.^12,13

Citalopram. In an open-label trial,¹⁴ 23 women and 1 man who met diagnostic criteria for compulsive shopping disorder (YBOCS-SV scores ≥17) received citalopram for 7 weeks. Dosages started at 20 mg/d and were increased as tolerated to 60 mg/d. Fifteen patients (63%) met response criteria—“much improved” or “very much improved” as measured by the Clinical Global Impressions-Improvement scale and a ≥50% decrease in YBOCS-SV score. Three patients (13%) discontinued treatment because of adverse effects (headache, rash, insomnia).

The 15 responders were then enrolled in a 9-week double-blind, placebo-controlled trial. Compulsive shopping symptoms recurred in 5 of 8 patients (63%) assigned to placebo, compared with none of the 7 who continued taking citalopram.

By comparison, escitalopram, 10 to 20 mg/d, showed little effect for compulsive shopping symptoms in an identically designed discontinuation trial by the same investigators. During the 7-week, open-label trial, 19 of 26 patients met response criteria. In the 9-week double-blind, controlled phase, however, 63% of initial responders relapsed while taking escitalopram, compared with 67% of those randomized to placebo.¹⁵

A naturalistic follow-up study of 24 patients treated with citalopram, 20 to 60 mg/d, noted that patients who responded at 3 months were more likely to be symptom-free after 1 year than those who did not respond to acute treatment.¹⁶ Responders’ mean 2-week compulsive spending declined from $773 before treatment to $351 at 12 months, and their mean total debt declined from $17,833 to $16,752.

Because remission was not significantly associated with taking citalopram, however, the authors concluded that the mechanisms responsible for maintaining remission were unclear.

Psychotherapy. Cognitive-behavioral therapy (CBT) may help, but few therapists are familiar with this disorder. CBT challenges the patient’s cognitive distortions and faulty schemas about shopping, such as:

• “Having the latest fashions will make me more popular.”
  
• “Having 5 pair of new shoes will make me a happier and better person.”
  

Our recommendations. Medication—such as an antidepressant for major depression or a mood stabilizer for bipolar disorder—may improve compulsive shopping in patients with a comorbid psychiatric disorder. For other compulsive shoppers, however, medication trials provide little guidance for treatment.

We inform patients such as Ms. A that they cannot rely on medication to control their behavior. Instead, we recommend a four-step approach to break the compulsive shopping habit (Table 3).

Financial counseling, provided free of charge by many banks, benefits some patients. Self-help books describe strategies to overcome compulsive spending (Related resources). Debtors Anonymous, a 12-step program patterned after Alcoholics Anonymous, also can help by offering acceptance, belonging, forgiveness, and understanding.

In the most severe cases we recommend appointing a financial conservator to control the patient’s finances. We rarely advise this strategy but have encountered cases in which there seemed to be no other option. Having a conservator controls the patient’s spending but does not reverse the preoccupation with shopping.

Table 3

Patient education: 4 steps to control compulsive spending

For clinicians

• Black DW. Assessment of compulsive buying. In: Benson AL (ed). I shop, therefore I am: Compulsive buying and the search for self. Northvale, NJ: Jason Aronson; 2000:191-216.
  

• Arenson G. Born to spend: how to overcome compulsive spending. Blue Ridge Summit, PA: Tab Books, 1991.
  
• Benson AL. Stopping Overshopping. A site for shopaholics and the people who love them. www.stoppingovershopping.com.
  
• Mellan O. Money harmony: resolving money conflicts in your life and relationships. New York: Walker, 2005.
  

• Citalopram • Celexa
  
• Escitalopram • Lexapro
  
• Fluvoxamine • Luvox
  

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

Dr. Black receives grant/research support or is a consultant or speaker for Forest Laboratories and Shire Pharmaceuticals

Matt, age 17, grew up in a household of gamblers. He learned to play poker from his father at age 8 and bet on sports with his friends in the 5th grade. For 2 years he has been playing poker three to four nights per week and watching a lot of televised poker. His parents worry he might be “addicted” to gambling and bring him for evaluation.

Easy access to gambling through casinos, lotteries, and Internet games has affected many social groups, particularly adolescents.¹ Teens such as Matt are more likely than adults to become pathological gamblers,² and they often have psychiatric disorders and antisocial behavior patterns that interfere with normal development. This article:

• suggests screening tools to identify problem teen gambling
  
• discusses how to use psychotherapy, medications, and other options to help gambling-obsessed adolescents change their high-risk behavior.
  

Why adolescents gamble

Gambling activates the same neural reward pathways affected by cocaine and amphetamines.³ Even so, many adolescents view gambling as less harmful than drugs⁴ and consider it a rite of passage:

• 90% report having gambled for money
  
• 75% have gambled at home for money
  
• 85% of parents do not object to gambling behaviors, teens say.^4,5
  

Adolescent gambling behavior. For approximately 85% of adolescents, gambling becomes no more than a social activity. For others, it can become problematic or even pathological (Table 1).^5,7 Approximately 4 to 8% of adolescents meet criteria for pathological gambling, compared with 1% of adults.

Adolescents’ higher rate might reflect pathological gambling’s natural course—peaking during adolescence, then tapering during adulthood. Some adolescents may adapt their gambling behavior over time. Problem gambling tends to be more transient and episodic than pathological gambling, remitting when adolescents take on new responsibilities (such as with college, marriage, employment, or death of parents).⁸

Table 1

Adolescent gambling: From entertainment to mental illness

Case continued: ‘Up big-time’

Matt says he loves to gamble and believes he is more gifted at poker than his peers. He also recognizes his behavior could be addictive and admits lying to his parents about his gambling. He plays Internet poker 3 to 4 hours per day and claims he wins more often than he loses. “I’m up big time,” he boasts.

Matt denies going to casinos or using bookies. He says he is managing school and home responsibilities without difficulty. He denies mood or anxiety symptoms but admits using methylphenidate while gambling. He obtains the stimulant from friends at school and usually snorts it to get “a bigger rush.”

Matt is clearly at risk for problem gambling. He was exposed to gambling early, is becoming preoccupied with it, lies about how much he gambles, and combines gambling with substance abuse. progress more rapidly and can become problem gamblers within 12 to 14 months.²

Neurobiologic differences between adolescent and adult pathological gamblers are not well-defined. Adults show evidence of dysregulated dopamine, norepinephrine, and serotonin neuro-transmission.⁹ Neuroimaging in adult pathological gamblers shows perturbations in reward processing centers and frontal lobe structures that control inhibition. These factors have been examined little in adolescents.

Identifying problem gambling in teens

Diagnostic “red flags” for problem gambling in adolescents include declining school performance, sleep disturbance, generalized anxiety or irritability, or possibly lack of response to general psychiatric treatment. Three tools can be useful for screening adolescents:

The Lie-Bet Questionnaire¹⁰ is a 2-question screen for problem gambling:

• Have you ever lied to anyone important about how often you gamble?
  
• Have you ever had to increase your bet to get the same excitement from gambling?
  

The South-Oaks Gambling Screen¹¹ is the standard pathological gambling screen for adults. Like the (SOGS-RA) is based and validated using DSM-III criteria (see Related resources). A score of 2 to 5 indicates at-risk gambling behaviors, and ≥6 indicate need for treatment.

The Gamblers Anonymous questionnaire¹² comprises 20 questions that identify negative social, physical, and emotional consequences of gambling behaviors (Box). Seven or more positive responses indicate probable pathological gambling. This screen has shown reliability in adolescents.

Use one or more of these quick screens with every adolescent presenting for treatment—especially in substance abuse treatment settings. When results are positive, probe for gambling behaviors and consequences. Rely on DSM-IV-TR criteria and clinical presentation to differentiate social gambling from pathological gambling.

Box

Behaviors and comorbidities

Negative consequences. Pathological gambling often consumes 10 to 20 hours per week of the adolescent’s time,¹³ hurting school performance and delaying developmental milestones. Teen gamblers may abandon extracurricular school activities, and their few friends often gamble, too. They are at risk for delinquency, criminal activity, and antisocial behaviors (such as selling drugs, engaging in prostitution)¹⁴ unprotected sexual activity, drug use, reckless driving, and carrying weapons.^15,16

Psychiatric comorbidity is the rule and often what brings adolescent gamblers to treatment. Substance abuse, major depression, attention-deficit/hyperactivity disorder, and personality disorders are most common (Table 2) Adolescent substance abuse at least triples the risk of pathological gambling.¹⁸

Adolescent pathological gamblers have increased rates of suicidal ideation and suicide attempts.¹⁷ They are at risk for other impulsive behaviors as well,¹⁹ although they are unlikely to volunteer this information. The Minnesota Impulsive Disorders Interview help identify comorbid pathological gambling, trichotillomania, kleptomania, pyromania, intermittent explosive disorder, compulsive buying, and compulsive sexual behaviors.¹⁹ Screen for these comorbidities during the first sessions or if a patient does not respond to treatment of gambling behavior.

Table 2

Risk factors for pathological adolescent gambling

Treating adolescent gamblers

Matt’s answers to the gambling screening questionnaires (one “yes” to the Lie-Bet Questionnaire, a SOGS-RA score of 4, and a GA-20 Questions score of 5) indicate problem gambling but not pathological gambling. You recommend that he attend Gamblers Anonymous, but he refuses. He also rejects individual therapy or taking medications.

Matt acknowledges misusing methylphenidate, however, and agrees to consider an outpatient substance abuse program. He also agrees to six sessions with a gambling treatment specialist to learn about problem gambling’s signs and symptoms, how to cope with betting loses, and how to reduce his preoccupation with gambling.

No guidelines exist for treating adolescent pathological gamblers, and specialized teen treatment programs are rare. Most services are provided in mental health or substance abuse settings, using adult treatments modified for adolescents.

Cognitive behavioral therapy (CBT) can be successful for highly motivated gamblers, although adolescents might not want to change their pathological behaviors. In case reports, four adolescents achieved remission after 6 months of CBT.^20,21 CBT appears to have long-term benefits for adults, but this has not been evaluated in teens. Even so, individual CBT may be ideal for adolescent gamblers because side effects are minimal.

Gamblers Anonymous (GA) in adults has shown a low retention rate and a 1-year abstinence rate of 22 Its effectiveness for adolescents lacks empiric support, but the 12-step program’s availability, structure, and fellowship may be useful.

Medications. Consider medication as first-line treatment for adolescents with psychiatric comorbidity. Try psychosocial treatment first for those without psychiatric comorbidity; consider medication as second-line therapy if response to psychosocial treatment is inadequate.

No medications are FDA-approved for pathological gambling, and no studies have examined medication use for adolescent gamblers. Controlled trials with adults suggest some medications may reduce urges and cravings or decrease gambling behaviors. These include:

• selective serotonin reuptake inhibitors
  
• opioid antagonists such as naltrexone or its analogue nalmefene
  
• or mood stabilizers such as lithium, divalproex sodium, or possibly topiramate.²³
  

Working with families. Many parents are aware of the destructive potential of substance abuse but not of gambling. They may feel shame that they did not recognize their teen’s gambling problem or “control” their child’s behavior. The adolescent may feel remorse for having bet with the parents’ money.

Even when the family recognizes the teen’s problem, denial or enabling can perpetuate the behavior. For teens such as Matt who learned to gamble at a home, advise the parents to abstain from gambling as well. Consider screening the parents for pathological gambling, given its high rate of heritability.

Address guilt and shame by acknowledging that pathological gambling is a psychiatric disease caused by biological, psychological, and social factors—not dysfunctional family relations. Emphasize that treatment works. Because gambling is easily hidden, educate families about relapse signs, such as preoccupation with money, personality changes, or failing to fulfill family responsibilities.²⁵

Related resources

• Wiebe JM, Cox BJ, Mehmel BG. The South Oaks Gambling Screen Revised for Adolescents (SOGS-RA): further psychometric findings from a community sample. J Gambl Stud 2000;16(2-3):275-88.
  
• Gamblers Anonymous. www.gamblersanonymous.org.
  
• National Council on Problem Gambling. www.ncpgambling.org.
  
• International Centre for Youth Gambling Problems and High-Risk Behaviors. www.youthgambling.com.
  

• Nalmefene • Revex
  
• Naltrexone • ReVia
  
• Lithium • Lithobid, others
  
• Divalproex sodium • Depakote, others
  
• Topiramate • Topamax
  

Dr. Fong receives grant/research support from Ortho McNeil Pharmaceutical and Somaxon Pharmaceuticals and is a speaker for Forest Pharmaceuticals.

Matt, age 17, grew up in a household of gamblers. He learned to play poker from his father at age 8 and bet on sports with his friends in the 5th grade. For 2 years he has been playing poker three to four nights per week and watching a lot of televised poker. His parents worry he might be “addicted” to gambling and bring him for evaluation.

Easy access to gambling through casinos, lotteries, and Internet games has affected many social groups, particularly adolescents.¹ Teens such as Matt are more likely than adults to become pathological gamblers,² and they often have psychiatric disorders and antisocial behavior patterns that interfere with normal development. This article:

• suggests screening tools to identify problem teen gambling
  
• discusses how to use psychotherapy, medications, and other options to help gambling-obsessed adolescents change their high-risk behavior.
  

Why adolescents gamble

Gambling activates the same neural reward pathways affected by cocaine and amphetamines.³ Even so, many adolescents view gambling as less harmful than drugs⁴ and consider it a rite of passage:

• 90% report having gambled for money
  
• 75% have gambled at home for money
  
• 85% of parents do not object to gambling behaviors, teens say.^4,5
  

Adolescent gambling behavior. For approximately 85% of adolescents, gambling becomes no more than a social activity. For others, it can become problematic or even pathological (Table 1).^5,7 Approximately 4 to 8% of adolescents meet criteria for pathological gambling, compared with 1% of adults.

Adolescents’ higher rate might reflect pathological gambling’s natural course—peaking during adolescence, then tapering during adulthood. Some adolescents may adapt their gambling behavior over time. Problem gambling tends to be more transient and episodic than pathological gambling, remitting when adolescents take on new responsibilities (such as with college, marriage, employment, or death of parents).⁸

Table 1

Adolescent gambling: From entertainment to mental illness

Case continued: ‘Up big-time’

Matt says he loves to gamble and believes he is more gifted at poker than his peers. He also recognizes his behavior could be addictive and admits lying to his parents about his gambling. He plays Internet poker 3 to 4 hours per day and claims he wins more often than he loses. “I’m up big time,” he boasts.

Matt denies going to casinos or using bookies. He says he is managing school and home responsibilities without difficulty. He denies mood or anxiety symptoms but admits using methylphenidate while gambling. He obtains the stimulant from friends at school and usually snorts it to get “a bigger rush.”

Matt is clearly at risk for problem gambling. He was exposed to gambling early, is becoming preoccupied with it, lies about how much he gambles, and combines gambling with substance abuse. progress more rapidly and can become problem gamblers within 12 to 14 months.²

Neurobiologic differences between adolescent and adult pathological gamblers are not well-defined. Adults show evidence of dysregulated dopamine, norepinephrine, and serotonin neuro-transmission.⁹ Neuroimaging in adult pathological gamblers shows perturbations in reward processing centers and frontal lobe structures that control inhibition. These factors have been examined little in adolescents.

Identifying problem gambling in teens

Diagnostic “red flags” for problem gambling in adolescents include declining school performance, sleep disturbance, generalized anxiety or irritability, or possibly lack of response to general psychiatric treatment. Three tools can be useful for screening adolescents:

The Lie-Bet Questionnaire¹⁰ is a 2-question screen for problem gambling:

• Have you ever lied to anyone important about how often you gamble?
  
• Have you ever had to increase your bet to get the same excitement from gambling?
  

The South-Oaks Gambling Screen¹¹ is the standard pathological gambling screen for adults. Like the (SOGS-RA) is based and validated using DSM-III criteria (see Related resources). A score of 2 to 5 indicates at-risk gambling behaviors, and ≥6 indicate need for treatment.

The Gamblers Anonymous questionnaire¹² comprises 20 questions that identify negative social, physical, and emotional consequences of gambling behaviors (Box). Seven or more positive responses indicate probable pathological gambling. This screen has shown reliability in adolescents.

Use one or more of these quick screens with every adolescent presenting for treatment—especially in substance abuse treatment settings. When results are positive, probe for gambling behaviors and consequences. Rely on DSM-IV-TR criteria and clinical presentation to differentiate social gambling from pathological gambling.

Box

Behaviors and comorbidities

Negative consequences. Pathological gambling often consumes 10 to 20 hours per week of the adolescent’s time,¹³ hurting school performance and delaying developmental milestones. Teen gamblers may abandon extracurricular school activities, and their few friends often gamble, too. They are at risk for delinquency, criminal activity, and antisocial behaviors (such as selling drugs, engaging in prostitution)¹⁴ unprotected sexual activity, drug use, reckless driving, and carrying weapons.^15,16

Psychiatric comorbidity is the rule and often what brings adolescent gamblers to treatment. Substance abuse, major depression, attention-deficit/hyperactivity disorder, and personality disorders are most common (Table 2) Adolescent substance abuse at least triples the risk of pathological gambling.¹⁸

Adolescent pathological gamblers have increased rates of suicidal ideation and suicide attempts.¹⁷ They are at risk for other impulsive behaviors as well,¹⁹ although they are unlikely to volunteer this information. The Minnesota Impulsive Disorders Interview help identify comorbid pathological gambling, trichotillomania, kleptomania, pyromania, intermittent explosive disorder, compulsive buying, and compulsive sexual behaviors.¹⁹ Screen for these comorbidities during the first sessions or if a patient does not respond to treatment of gambling behavior.

Table 2

Risk factors for pathological adolescent gambling

Treating adolescent gamblers

Matt’s answers to the gambling screening questionnaires (one “yes” to the Lie-Bet Questionnaire, a SOGS-RA score of 4, and a GA-20 Questions score of 5) indicate problem gambling but not pathological gambling. You recommend that he attend Gamblers Anonymous, but he refuses. He also rejects individual therapy or taking medications.

Matt acknowledges misusing methylphenidate, however, and agrees to consider an outpatient substance abuse program. He also agrees to six sessions with a gambling treatment specialist to learn about problem gambling’s signs and symptoms, how to cope with betting loses, and how to reduce his preoccupation with gambling.

No guidelines exist for treating adolescent pathological gamblers, and specialized teen treatment programs are rare. Most services are provided in mental health or substance abuse settings, using adult treatments modified for adolescents.

Cognitive behavioral therapy (CBT) can be successful for highly motivated gamblers, although adolescents might not want to change their pathological behaviors. In case reports, four adolescents achieved remission after 6 months of CBT.^20,21 CBT appears to have long-term benefits for adults, but this has not been evaluated in teens. Even so, individual CBT may be ideal for adolescent gamblers because side effects are minimal.

Gamblers Anonymous (GA) in adults has shown a low retention rate and a 1-year abstinence rate of 22 Its effectiveness for adolescents lacks empiric support, but the 12-step program’s availability, structure, and fellowship may be useful.

Medications. Consider medication as first-line treatment for adolescents with psychiatric comorbidity. Try psychosocial treatment first for those without psychiatric comorbidity; consider medication as second-line therapy if response to psychosocial treatment is inadequate.

No medications are FDA-approved for pathological gambling, and no studies have examined medication use for adolescent gamblers. Controlled trials with adults suggest some medications may reduce urges and cravings or decrease gambling behaviors. These include:

• selective serotonin reuptake inhibitors
  
• opioid antagonists such as naltrexone or its analogue nalmefene
  
• or mood stabilizers such as lithium, divalproex sodium, or possibly topiramate.²³
  

Working with families. Many parents are aware of the destructive potential of substance abuse but not of gambling. They may feel shame that they did not recognize their teen’s gambling problem or “control” their child’s behavior. The adolescent may feel remorse for having bet with the parents’ money.

Even when the family recognizes the teen’s problem, denial or enabling can perpetuate the behavior. For teens such as Matt who learned to gamble at a home, advise the parents to abstain from gambling as well. Consider screening the parents for pathological gambling, given its high rate of heritability.

Address guilt and shame by acknowledging that pathological gambling is a psychiatric disease caused by biological, psychological, and social factors—not dysfunctional family relations. Emphasize that treatment works. Because gambling is easily hidden, educate families about relapse signs, such as preoccupation with money, personality changes, or failing to fulfill family responsibilities.²⁵

Related resources

• Wiebe JM, Cox BJ, Mehmel BG. The South Oaks Gambling Screen Revised for Adolescents (SOGS-RA): further psychometric findings from a community sample. J Gambl Stud 2000;16(2-3):275-88.
  
• Gamblers Anonymous. www.gamblersanonymous.org.
  
• National Council on Problem Gambling. www.ncpgambling.org.
  
• International Centre for Youth Gambling Problems and High-Risk Behaviors. www.youthgambling.com.
  

• Nalmefene • Revex
  
• Naltrexone • ReVia
  
• Lithium • Lithobid, others
  
• Divalproex sodium • Depakote, others
  
• Topiramate • Topamax
  

Dr. Fong receives grant/research support from Ortho McNeil Pharmaceutical and Somaxon Pharmaceuticals and is a speaker for Forest Pharmaceuticals.

Matt, age 17, grew up in a household of gamblers. He learned to play poker from his father at age 8 and bet on sports with his friends in the 5th grade. For 2 years he has been playing poker three to four nights per week and watching a lot of televised poker. His parents worry he might be “addicted” to gambling and bring him for evaluation.

Easy access to gambling through casinos, lotteries, and Internet games has affected many social groups, particularly adolescents.¹ Teens such as Matt are more likely than adults to become pathological gamblers,² and they often have psychiatric disorders and antisocial behavior patterns that interfere with normal development. This article:

• suggests screening tools to identify problem teen gambling
  
• discusses how to use psychotherapy, medications, and other options to help gambling-obsessed adolescents change their high-risk behavior.
  

Why adolescents gamble

Gambling activates the same neural reward pathways affected by cocaine and amphetamines.³ Even so, many adolescents view gambling as less harmful than drugs⁴ and consider it a rite of passage:

• 90% report having gambled for money
  
• 75% have gambled at home for money
  
• 85% of parents do not object to gambling behaviors, teens say.^4,5
  

Adolescent gambling behavior. For approximately 85% of adolescents, gambling becomes no more than a social activity. For others, it can become problematic or even pathological (Table 1).^5,7 Approximately 4 to 8% of adolescents meet criteria for pathological gambling, compared with 1% of adults.

Adolescents’ higher rate might reflect pathological gambling’s natural course—peaking during adolescence, then tapering during adulthood. Some adolescents may adapt their gambling behavior over time. Problem gambling tends to be more transient and episodic than pathological gambling, remitting when adolescents take on new responsibilities (such as with college, marriage, employment, or death of parents).⁸

Table 1

Adolescent gambling: From entertainment to mental illness

Case continued: ‘Up big-time’

Matt says he loves to gamble and believes he is more gifted at poker than his peers. He also recognizes his behavior could be addictive and admits lying to his parents about his gambling. He plays Internet poker 3 to 4 hours per day and claims he wins more often than he loses. “I’m up big time,” he boasts.

Matt denies going to casinos or using bookies. He says he is managing school and home responsibilities without difficulty. He denies mood or anxiety symptoms but admits using methylphenidate while gambling. He obtains the stimulant from friends at school and usually snorts it to get “a bigger rush.”

Matt is clearly at risk for problem gambling. He was exposed to gambling early, is becoming preoccupied with it, lies about how much he gambles, and combines gambling with substance abuse. progress more rapidly and can become problem gamblers within 12 to 14 months.²

Neurobiologic differences between adolescent and adult pathological gamblers are not well-defined. Adults show evidence of dysregulated dopamine, norepinephrine, and serotonin neuro-transmission.⁹ Neuroimaging in adult pathological gamblers shows perturbations in reward processing centers and frontal lobe structures that control inhibition. These factors have been examined little in adolescents.

Identifying problem gambling in teens

Diagnostic “red flags” for problem gambling in adolescents include declining school performance, sleep disturbance, generalized anxiety or irritability, or possibly lack of response to general psychiatric treatment. Three tools can be useful for screening adolescents:

The Lie-Bet Questionnaire¹⁰ is a 2-question screen for problem gambling:

• Have you ever lied to anyone important about how often you gamble?
  
• Have you ever had to increase your bet to get the same excitement from gambling?
  

The South-Oaks Gambling Screen¹¹ is the standard pathological gambling screen for adults. Like the (SOGS-RA) is based and validated using DSM-III criteria (see Related resources). A score of 2 to 5 indicates at-risk gambling behaviors, and ≥6 indicate need for treatment.

The Gamblers Anonymous questionnaire¹² comprises 20 questions that identify negative social, physical, and emotional consequences of gambling behaviors (Box). Seven or more positive responses indicate probable pathological gambling. This screen has shown reliability in adolescents.

Use one or more of these quick screens with every adolescent presenting for treatment—especially in substance abuse treatment settings. When results are positive, probe for gambling behaviors and consequences. Rely on DSM-IV-TR criteria and clinical presentation to differentiate social gambling from pathological gambling.

Box

Behaviors and comorbidities

Negative consequences. Pathological gambling often consumes 10 to 20 hours per week of the adolescent’s time,¹³ hurting school performance and delaying developmental milestones. Teen gamblers may abandon extracurricular school activities, and their few friends often gamble, too. They are at risk for delinquency, criminal activity, and antisocial behaviors (such as selling drugs, engaging in prostitution)¹⁴ unprotected sexual activity, drug use, reckless driving, and carrying weapons.^15,16

Psychiatric comorbidity is the rule and often what brings adolescent gamblers to treatment. Substance abuse, major depression, attention-deficit/hyperactivity disorder, and personality disorders are most common (Table 2) Adolescent substance abuse at least triples the risk of pathological gambling.¹⁸

Adolescent pathological gamblers have increased rates of suicidal ideation and suicide attempts.¹⁷ They are at risk for other impulsive behaviors as well,¹⁹ although they are unlikely to volunteer this information. The Minnesota Impulsive Disorders Interview help identify comorbid pathological gambling, trichotillomania, kleptomania, pyromania, intermittent explosive disorder, compulsive buying, and compulsive sexual behaviors.¹⁹ Screen for these comorbidities during the first sessions or if a patient does not respond to treatment of gambling behavior.

Table 2

Risk factors for pathological adolescent gambling

Treating adolescent gamblers

Matt’s answers to the gambling screening questionnaires (one “yes” to the Lie-Bet Questionnaire, a SOGS-RA score of 4, and a GA-20 Questions score of 5) indicate problem gambling but not pathological gambling. You recommend that he attend Gamblers Anonymous, but he refuses. He also rejects individual therapy or taking medications.

Matt acknowledges misusing methylphenidate, however, and agrees to consider an outpatient substance abuse program. He also agrees to six sessions with a gambling treatment specialist to learn about problem gambling’s signs and symptoms, how to cope with betting loses, and how to reduce his preoccupation with gambling.

No guidelines exist for treating adolescent pathological gamblers, and specialized teen treatment programs are rare. Most services are provided in mental health or substance abuse settings, using adult treatments modified for adolescents.

Cognitive behavioral therapy (CBT) can be successful for highly motivated gamblers, although adolescents might not want to change their pathological behaviors. In case reports, four adolescents achieved remission after 6 months of CBT.^20,21 CBT appears to have long-term benefits for adults, but this has not been evaluated in teens. Even so, individual CBT may be ideal for adolescent gamblers because side effects are minimal.

Gamblers Anonymous (GA) in adults has shown a low retention rate and a 1-year abstinence rate of 22 Its effectiveness for adolescents lacks empiric support, but the 12-step program’s availability, structure, and fellowship may be useful.

Medications. Consider medication as first-line treatment for adolescents with psychiatric comorbidity. Try psychosocial treatment first for those without psychiatric comorbidity; consider medication as second-line therapy if response to psychosocial treatment is inadequate.

No medications are FDA-approved for pathological gambling, and no studies have examined medication use for adolescent gamblers. Controlled trials with adults suggest some medications may reduce urges and cravings or decrease gambling behaviors. These include:

• selective serotonin reuptake inhibitors
  
• opioid antagonists such as naltrexone or its analogue nalmefene
  
• or mood stabilizers such as lithium, divalproex sodium, or possibly topiramate.²³
  

Working with families. Many parents are aware of the destructive potential of substance abuse but not of gambling. They may feel shame that they did not recognize their teen’s gambling problem or “control” their child’s behavior. The adolescent may feel remorse for having bet with the parents’ money.

Even when the family recognizes the teen’s problem, denial or enabling can perpetuate the behavior. For teens such as Matt who learned to gamble at a home, advise the parents to abstain from gambling as well. Consider screening the parents for pathological gambling, given its high rate of heritability.

Address guilt and shame by acknowledging that pathological gambling is a psychiatric disease caused by biological, psychological, and social factors—not dysfunctional family relations. Emphasize that treatment works. Because gambling is easily hidden, educate families about relapse signs, such as preoccupation with money, personality changes, or failing to fulfill family responsibilities.²⁵

Related resources

• Wiebe JM, Cox BJ, Mehmel BG. The South Oaks Gambling Screen Revised for Adolescents (SOGS-RA): further psychometric findings from a community sample. J Gambl Stud 2000;16(2-3):275-88.
  
• Gamblers Anonymous. www.gamblersanonymous.org.
  
• National Council on Problem Gambling. www.ncpgambling.org.
  
• International Centre for Youth Gambling Problems and High-Risk Behaviors. www.youthgambling.com.
  

• Nalmefene • Revex
  
• Naltrexone • ReVia
  
• Lithium • Lithobid, others
  
• Divalproex sodium • Depakote, others
  
• Topiramate • Topamax
  

Dr. Fong receives grant/research support from Ortho McNeil Pharmaceutical and Somaxon Pharmaceuticals and is a speaker for Forest Pharmaceuticals.

Can corticosteroids “unlock” hidden potential for mania, or are steroid-induced mood symptoms a temporary reaction? And when these mood symptoms occur, what is the best way to treat them?

Psychiatric symptoms develop in 5% to 18% of patients treated with corticosteroids. These effects—most often mania or depression—emerge within days to weeks of starting steroids. To help you head off manic and mixed mood symptoms, this paper examines how to:

• treat steroid-induced mania or mixed bipolar symptoms
• reduce the risk of a mood episode in patients who require sustained corticosteroid therapy.

‘Steroid psychosis’

Jane Pauley, NBC’s Today Show broadcaster, described in her autobiography how hypomania developed within weeks after she started corticosteroids for idiopathic urticaria edema: “I was so energized that I didn’t just walk down the hall, I felt like I was motoring down the hall. I was suddenly the equal of my high-energy friends who move fast and talk fast and loud. I told everyone that I could understand why men felt like they could run the world, because I felt like that. This was a new me, and I liked her!”¹

Pauley’s hypomania led to a manic episode and eventually to depression. She was started on antidepressants, which triggered another manic episode. Pauley—who had no history of bipolar disorder—spent 3 weeks in a New York psychiatric hospital.¹

Diagnostic symptoms. Corticosteroids’ psychiatric effects—cognitive, mood, anxiety, and psychotic symptoms—were first described as “steroid psychosis.” Psychosis can occur, but mood symptoms are more common:

• Among 122 patients, 40% experienced depression, followed by mania (28%), psychosis (14%), delirium (10%), and mixed mood episodes (8%).²
• Among 130 patients, mania was most prevalent (35%), followed by depression (28%), mixed mood episodes (12%), delirium (13%), and psychosis (11%).³
• Corticosteroids caused 54% of organic mania cases on a hospital psychiatric consult service.⁴
• In a prospective study of 50 patients treated with corticosteroids, 13 developed hypomania and 5 developed depression.⁵

Steroid-induced symptoms emerge from 3 to 4 days to a median of 11 days after a patient starts corticosteroid therapy. After steroids are discontinued, depressive symptoms persist approximately 4 weeks, mania 3 weeks, and delirium a few days. Approximately one-half of patients with steroid psychosis improve in 4 days and one-half within 2 weeks.^2,6

Continue to: Who is at risk?

Who is at risk?

Corticosteroids include the steroids produced in the adrenal gland (such as corticosterone) and their synthetic—and often more potent—analogues (such as prednisone).⁷ Because of their glucocorticoid, immunosuppressant, mineralocorticoid, and anti-inflammatory properties, steroids are used as replacement therapy and to treat a wide variety of illnesses (Table 1).

Table 1

Medical conditions for which corticosteroids are commonly used

Age and gender. Patient age appears unrelated to development of psychiatric symptoms after corticosteroid use.² One study suggested women are twice as likely as men to develop psychiatric symptoms (77 versus 38 cases in 115 patients),³ but many illnesses that require corticosteroid treatment occur more frequently in women. Other researchers found a slight female predominance (58% versus 42% of cases) when they excluded patients with systemic lupus erythematosus and rheumatoid arthritis, which are more common in women than in men.²

Dosage. Higher corticosteroid dosages increase the risk of psychiatric symptoms. In patients taking prednisone, the Boston Collaborative Drug Surveillance Project⁸ found the incidence of psychiatric side effects to be:

• 1.3% in patients taking
• 4.6% in those taking 41 to 80 mg
• 18.4% in those taking >80 mg.

Psychiatric history. Past psychiatric illness does not seem to be a risk factor for psychiatric side effects of corticosteroids,⁹ although patients with a history of posttraumatic stress disorder are more likely to suffer depression while taking corticosteroids.¹⁰

Corticosteroid exposure. Patients who did not experience psychiatric side effects with corticosteroids in the past appear not to be protected if corticosteroids are used again. One report examined 17 cases of steroid-induced psychiatric illness in patients with previous exposure to corticosteroid therapy. Six patients had previous psychiatric side effects while taking corticosteroids, and 11 did not.²

Bipolar trigger?

Do corticosteroids’ acute psychiatric side effects have long-term sequelae? Longitudinal evidence is scarce, but a few reports suggest corticosteroids could play a role in the onset of primary bipolar I disorder:

• A 28-year-old woman with no known mood symptoms before a short course of prednisone experienced six episodes of mania and depression when not taking corticosteroids during the subsequent 18 months.¹¹
• Among 16 patients with first-onset mood symptoms after corticosteroid use, a retrospective chart review found 7 had recurrent manic and depressive symptoms unrelated to additional corticosteroid use.¹²

Continue to: ... case reports are inconclusive...

Although intriguing, these case reports are inconclusive. Because bipolar type I incidence in the general population is 1.5%,¹³ many persons with bipolar disorder undergo corticosteroid treatment. Nevertheless, these results—especially from the retrospective review¹²—suggest that corticosteroid use may contribute to the onset of bipolar I illness.

Symptomatic treatment

Corticosteroid-induced side effects are usually managed by tapering off the steroids and treating the psychiatric symptoms.^2,3 Simply tapering off the steroids—without additional treatments—led to recovery in 33 of 36 patients.² Stopping corticosteroids is not always possible or desirable, however, especially in many medically complicated cases seen by psychiatric consult services.

In a recent case, I was asked to see a man, age 69, on the oncology service who was receiving corticosteroids every 2 weeks as part of his chemotherapy. The patient was admitted to the hospital for acute mental status changes 2 days after his last corticosteroid dose. He had pressured speech, grandiosity, and had not slept in 2 days. We started risperidone, 1 mg bid, and most of his manic symptoms resolved within 2 days. His chemotherapy was continued without corticosteroids. If this had not been not possible, I would have recommended continuing risperidone prophylactically.

No double-blind, placebo-controlled studies have examined prevention or treatment of steroid-induced mania or other psychiatric symptoms. Uncontrolled trials and case reports suggest benefit from some symptomatic and preventive treatments (Table 2).

Table 2

Mood stabilizers with evidence of benefit in treating corticosteroid-induced mania

Treating manic and mixed mood symptoms. Twelve outpatients with manic or mixed symptoms from corticosteroid use received olanzapine in a 5-week, open-label trial. Flexible dosing started at 2.5 mg/d and was increased as needed (maximum 20 mg/d). One patient dropped out for lack of efficacy. For the others, manic and mixed symptoms improved significantly, as indicated by scores on the Young Mania Rating Scale, Hamilton Rating Scale for Depression, and Brief Psychotic Rating Scale.¹⁴ Patient weight, blood glucose, and involuntary movements did not change significantly.

Evidence from case reports indicates that lithium,¹⁵ carbamazepine,^12,16 haloperidol,^12,16 or quetiapine¹⁷ also can successfully treat steroid-induced manic symptoms.

Continue to: Treating other psychiatric symptoms

Treating other psychiatric symptoms. Case reports support electroconvulsive therapy,^2,15 fluoxetine,¹⁸ amitriptyline,¹² lamotrigine,¹⁹ or lithium^20,21 for steroid-induced depression, and haloperidol²² or risperidone²³ for steroid-induced psychosis.

In four cases,⁶ tricyclic antidepressants appeared to worsen corticosteroids’ psychiatric side effects. These case patients might have had steroid-induced delirium instead of mood disorders or psychosis, however, and the tricyclics’ anticholinergic effects could have worsened the delirium.⁹

Preventing steroid-induced symptoms

Although clear guidelines on when to start preventive treatments do not exist, potential candidates for pretreatment with lithium or other agents include patients who:

• have developed psychiatric symptoms multiple times after repeated corticosteroid use
• are at high risk if psychiatric side effects occur.

Lithium. Prophylactic lithium was given to 27 patients with multiple sclerosis and taking corticosteroids for acute exacerbations. None developed psychiatric symptoms.²⁴ At the same clinic, 6 of 44 patients with multiple sclerosis or retrobulbar neuritis developed psychiatric side effects after using corticosteroids without lithium.

Be cautious when using prophylactic lithium because some conditions treated with corticosteroids—such as systemic lupus erythematosus—can impair renal function.²⁰ Corticosteroids also can affect sodium balance and increase the risk of lithium intoxication.²⁵

Check renal function before and during lithium titration, and initiate corticosteroid therapy when lithium is at effective blood levels (0.8 to 1.2 mEq/L). Monitor lithium levels and renal function frequently during steroid treatment.

Other mood stabilizers. Two case reports describe patients who repeatedly developed manic symptoms after multiple corticosteroid doses. Carbamazepine, 600 mg qd,¹⁶ and gabapentin, 300 mg tid,²⁶ prevented manic symptoms after additional corticosteroid pulses.

Related resources

• Brown ES, Chandler PA. Mood and cognitive changes during systemic corticosteroid therapy. Prim Care Companion J Clin Psychiatry 2001;3(1):17-21. www.psychiatrist.com/pcc/abstracts/pcc030103.htm.
• Merrill W. Case 35-1998: use of lithium to prevent corticosteroid-induced mania. N Engl J Med 1999;340:1123.

Drug brand names

• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Haloperidol • Haldol
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal

Can corticosteroids “unlock” hidden potential for mania, or are steroid-induced mood symptoms a temporary reaction? And when these mood symptoms occur, what is the best way to treat them?

Psychiatric symptoms develop in 5% to 18% of patients treated with corticosteroids. These effects—most often mania or depression—emerge within days to weeks of starting steroids. To help you head off manic and mixed mood symptoms, this paper examines how to:

• treat steroid-induced mania or mixed bipolar symptoms
• reduce the risk of a mood episode in patients who require sustained corticosteroid therapy.

‘Steroid psychosis’

Jane Pauley, NBC’s Today Show broadcaster, described in her autobiography how hypomania developed within weeks after she started corticosteroids for idiopathic urticaria edema: “I was so energized that I didn’t just walk down the hall, I felt like I was motoring down the hall. I was suddenly the equal of my high-energy friends who move fast and talk fast and loud. I told everyone that I could understand why men felt like they could run the world, because I felt like that. This was a new me, and I liked her!”¹

Pauley’s hypomania led to a manic episode and eventually to depression. She was started on antidepressants, which triggered another manic episode. Pauley—who had no history of bipolar disorder—spent 3 weeks in a New York psychiatric hospital.¹

Diagnostic symptoms. Corticosteroids’ psychiatric effects—cognitive, mood, anxiety, and psychotic symptoms—were first described as “steroid psychosis.” Psychosis can occur, but mood symptoms are more common:

• Among 122 patients, 40% experienced depression, followed by mania (28%), psychosis (14%), delirium (10%), and mixed mood episodes (8%).²
• Among 130 patients, mania was most prevalent (35%), followed by depression (28%), mixed mood episodes (12%), delirium (13%), and psychosis (11%).³
• Corticosteroids caused 54% of organic mania cases on a hospital psychiatric consult service.⁴
• In a prospective study of 50 patients treated with corticosteroids, 13 developed hypomania and 5 developed depression.⁵

Steroid-induced symptoms emerge from 3 to 4 days to a median of 11 days after a patient starts corticosteroid therapy. After steroids are discontinued, depressive symptoms persist approximately 4 weeks, mania 3 weeks, and delirium a few days. Approximately one-half of patients with steroid psychosis improve in 4 days and one-half within 2 weeks.^2,6

Continue to: Who is at risk?

Who is at risk?

Corticosteroids include the steroids produced in the adrenal gland (such as corticosterone) and their synthetic—and often more potent—analogues (such as prednisone).⁷ Because of their glucocorticoid, immunosuppressant, mineralocorticoid, and anti-inflammatory properties, steroids are used as replacement therapy and to treat a wide variety of illnesses (Table 1).

Table 1

Medical conditions for which corticosteroids are commonly used

Age and gender. Patient age appears unrelated to development of psychiatric symptoms after corticosteroid use.² One study suggested women are twice as likely as men to develop psychiatric symptoms (77 versus 38 cases in 115 patients),³ but many illnesses that require corticosteroid treatment occur more frequently in women. Other researchers found a slight female predominance (58% versus 42% of cases) when they excluded patients with systemic lupus erythematosus and rheumatoid arthritis, which are more common in women than in men.²

Dosage. Higher corticosteroid dosages increase the risk of psychiatric symptoms. In patients taking prednisone, the Boston Collaborative Drug Surveillance Project⁸ found the incidence of psychiatric side effects to be:

• 1.3% in patients taking
• 4.6% in those taking 41 to 80 mg
• 18.4% in those taking >80 mg.

Psychiatric history. Past psychiatric illness does not seem to be a risk factor for psychiatric side effects of corticosteroids,⁹ although patients with a history of posttraumatic stress disorder are more likely to suffer depression while taking corticosteroids.¹⁰

Corticosteroid exposure. Patients who did not experience psychiatric side effects with corticosteroids in the past appear not to be protected if corticosteroids are used again. One report examined 17 cases of steroid-induced psychiatric illness in patients with previous exposure to corticosteroid therapy. Six patients had previous psychiatric side effects while taking corticosteroids, and 11 did not.²

Bipolar trigger?

Do corticosteroids’ acute psychiatric side effects have long-term sequelae? Longitudinal evidence is scarce, but a few reports suggest corticosteroids could play a role in the onset of primary bipolar I disorder:

• A 28-year-old woman with no known mood symptoms before a short course of prednisone experienced six episodes of mania and depression when not taking corticosteroids during the subsequent 18 months.¹¹
• Among 16 patients with first-onset mood symptoms after corticosteroid use, a retrospective chart review found 7 had recurrent manic and depressive symptoms unrelated to additional corticosteroid use.¹²

Continue to: ... case reports are inconclusive...

Although intriguing, these case reports are inconclusive. Because bipolar type I incidence in the general population is 1.5%,¹³ many persons with bipolar disorder undergo corticosteroid treatment. Nevertheless, these results—especially from the retrospective review¹²—suggest that corticosteroid use may contribute to the onset of bipolar I illness.

Symptomatic treatment

Corticosteroid-induced side effects are usually managed by tapering off the steroids and treating the psychiatric symptoms.^2,3 Simply tapering off the steroids—without additional treatments—led to recovery in 33 of 36 patients.² Stopping corticosteroids is not always possible or desirable, however, especially in many medically complicated cases seen by psychiatric consult services.

In a recent case, I was asked to see a man, age 69, on the oncology service who was receiving corticosteroids every 2 weeks as part of his chemotherapy. The patient was admitted to the hospital for acute mental status changes 2 days after his last corticosteroid dose. He had pressured speech, grandiosity, and had not slept in 2 days. We started risperidone, 1 mg bid, and most of his manic symptoms resolved within 2 days. His chemotherapy was continued without corticosteroids. If this had not been not possible, I would have recommended continuing risperidone prophylactically.

No double-blind, placebo-controlled studies have examined prevention or treatment of steroid-induced mania or other psychiatric symptoms. Uncontrolled trials and case reports suggest benefit from some symptomatic and preventive treatments (Table 2).

Table 2

Mood stabilizers with evidence of benefit in treating corticosteroid-induced mania

Treating manic and mixed mood symptoms. Twelve outpatients with manic or mixed symptoms from corticosteroid use received olanzapine in a 5-week, open-label trial. Flexible dosing started at 2.5 mg/d and was increased as needed (maximum 20 mg/d). One patient dropped out for lack of efficacy. For the others, manic and mixed symptoms improved significantly, as indicated by scores on the Young Mania Rating Scale, Hamilton Rating Scale for Depression, and Brief Psychotic Rating Scale.¹⁴ Patient weight, blood glucose, and involuntary movements did not change significantly.

Evidence from case reports indicates that lithium,¹⁵ carbamazepine,^12,16 haloperidol,^12,16 or quetiapine¹⁷ also can successfully treat steroid-induced manic symptoms.

Continue to: Treating other psychiatric symptoms

Treating other psychiatric symptoms. Case reports support electroconvulsive therapy,^2,15 fluoxetine,¹⁸ amitriptyline,¹² lamotrigine,¹⁹ or lithium^20,21 for steroid-induced depression, and haloperidol²² or risperidone²³ for steroid-induced psychosis.

In four cases,⁶ tricyclic antidepressants appeared to worsen corticosteroids’ psychiatric side effects. These case patients might have had steroid-induced delirium instead of mood disorders or psychosis, however, and the tricyclics’ anticholinergic effects could have worsened the delirium.⁹

Preventing steroid-induced symptoms

Although clear guidelines on when to start preventive treatments do not exist, potential candidates for pretreatment with lithium or other agents include patients who:

• have developed psychiatric symptoms multiple times after repeated corticosteroid use
• are at high risk if psychiatric side effects occur.

Lithium. Prophylactic lithium was given to 27 patients with multiple sclerosis and taking corticosteroids for acute exacerbations. None developed psychiatric symptoms.²⁴ At the same clinic, 6 of 44 patients with multiple sclerosis or retrobulbar neuritis developed psychiatric side effects after using corticosteroids without lithium.

Be cautious when using prophylactic lithium because some conditions treated with corticosteroids—such as systemic lupus erythematosus—can impair renal function.²⁰ Corticosteroids also can affect sodium balance and increase the risk of lithium intoxication.²⁵

Check renal function before and during lithium titration, and initiate corticosteroid therapy when lithium is at effective blood levels (0.8 to 1.2 mEq/L). Monitor lithium levels and renal function frequently during steroid treatment.

Other mood stabilizers. Two case reports describe patients who repeatedly developed manic symptoms after multiple corticosteroid doses. Carbamazepine, 600 mg qd,¹⁶ and gabapentin, 300 mg tid,²⁶ prevented manic symptoms after additional corticosteroid pulses.

Related resources

• Brown ES, Chandler PA. Mood and cognitive changes during systemic corticosteroid therapy. Prim Care Companion J Clin Psychiatry 2001;3(1):17-21. www.psychiatrist.com/pcc/abstracts/pcc030103.htm.
• Merrill W. Case 35-1998: use of lithium to prevent corticosteroid-induced mania. N Engl J Med 1999;340:1123.

Drug brand names

• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Haloperidol • Haldol
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal

Can corticosteroids “unlock” hidden potential for mania, or are steroid-induced mood symptoms a temporary reaction? And when these mood symptoms occur, what is the best way to treat them?

Psychiatric symptoms develop in 5% to 18% of patients treated with corticosteroids. These effects—most often mania or depression—emerge within days to weeks of starting steroids. To help you head off manic and mixed mood symptoms, this paper examines how to:

• treat steroid-induced mania or mixed bipolar symptoms
• reduce the risk of a mood episode in patients who require sustained corticosteroid therapy.

‘Steroid psychosis’

Jane Pauley, NBC’s Today Show broadcaster, described in her autobiography how hypomania developed within weeks after she started corticosteroids for idiopathic urticaria edema: “I was so energized that I didn’t just walk down the hall, I felt like I was motoring down the hall. I was suddenly the equal of my high-energy friends who move fast and talk fast and loud. I told everyone that I could understand why men felt like they could run the world, because I felt like that. This was a new me, and I liked her!”¹

Pauley’s hypomania led to a manic episode and eventually to depression. She was started on antidepressants, which triggered another manic episode. Pauley—who had no history of bipolar disorder—spent 3 weeks in a New York psychiatric hospital.¹

Diagnostic symptoms. Corticosteroids’ psychiatric effects—cognitive, mood, anxiety, and psychotic symptoms—were first described as “steroid psychosis.” Psychosis can occur, but mood symptoms are more common:

• Among 122 patients, 40% experienced depression, followed by mania (28%), psychosis (14%), delirium (10%), and mixed mood episodes (8%).²
• Among 130 patients, mania was most prevalent (35%), followed by depression (28%), mixed mood episodes (12%), delirium (13%), and psychosis (11%).³
• Corticosteroids caused 54% of organic mania cases on a hospital psychiatric consult service.⁴
• In a prospective study of 50 patients treated with corticosteroids, 13 developed hypomania and 5 developed depression.⁵

Steroid-induced symptoms emerge from 3 to 4 days to a median of 11 days after a patient starts corticosteroid therapy. After steroids are discontinued, depressive symptoms persist approximately 4 weeks, mania 3 weeks, and delirium a few days. Approximately one-half of patients with steroid psychosis improve in 4 days and one-half within 2 weeks.^2,6

Continue to: Who is at risk?

Who is at risk?

Corticosteroids include the steroids produced in the adrenal gland (such as corticosterone) and their synthetic—and often more potent—analogues (such as prednisone).⁷ Because of their glucocorticoid, immunosuppressant, mineralocorticoid, and anti-inflammatory properties, steroids are used as replacement therapy and to treat a wide variety of illnesses (Table 1).

Table 1

Medical conditions for which corticosteroids are commonly used

Age and gender. Patient age appears unrelated to development of psychiatric symptoms after corticosteroid use.² One study suggested women are twice as likely as men to develop psychiatric symptoms (77 versus 38 cases in 115 patients),³ but many illnesses that require corticosteroid treatment occur more frequently in women. Other researchers found a slight female predominance (58% versus 42% of cases) when they excluded patients with systemic lupus erythematosus and rheumatoid arthritis, which are more common in women than in men.²

Dosage. Higher corticosteroid dosages increase the risk of psychiatric symptoms. In patients taking prednisone, the Boston Collaborative Drug Surveillance Project⁸ found the incidence of psychiatric side effects to be:

• 1.3% in patients taking
• 4.6% in those taking 41 to 80 mg
• 18.4% in those taking >80 mg.

Psychiatric history. Past psychiatric illness does not seem to be a risk factor for psychiatric side effects of corticosteroids,⁹ although patients with a history of posttraumatic stress disorder are more likely to suffer depression while taking corticosteroids.¹⁰

Corticosteroid exposure. Patients who did not experience psychiatric side effects with corticosteroids in the past appear not to be protected if corticosteroids are used again. One report examined 17 cases of steroid-induced psychiatric illness in patients with previous exposure to corticosteroid therapy. Six patients had previous psychiatric side effects while taking corticosteroids, and 11 did not.²

Bipolar trigger?

Do corticosteroids’ acute psychiatric side effects have long-term sequelae? Longitudinal evidence is scarce, but a few reports suggest corticosteroids could play a role in the onset of primary bipolar I disorder:

• A 28-year-old woman with no known mood symptoms before a short course of prednisone experienced six episodes of mania and depression when not taking corticosteroids during the subsequent 18 months.¹¹
• Among 16 patients with first-onset mood symptoms after corticosteroid use, a retrospective chart review found 7 had recurrent manic and depressive symptoms unrelated to additional corticosteroid use.¹²

Continue to: ... case reports are inconclusive...

Although intriguing, these case reports are inconclusive. Because bipolar type I incidence in the general population is 1.5%,¹³ many persons with bipolar disorder undergo corticosteroid treatment. Nevertheless, these results—especially from the retrospective review¹²—suggest that corticosteroid use may contribute to the onset of bipolar I illness.

Symptomatic treatment

Corticosteroid-induced side effects are usually managed by tapering off the steroids and treating the psychiatric symptoms.^2,3 Simply tapering off the steroids—without additional treatments—led to recovery in 33 of 36 patients.² Stopping corticosteroids is not always possible or desirable, however, especially in many medically complicated cases seen by psychiatric consult services.

In a recent case, I was asked to see a man, age 69, on the oncology service who was receiving corticosteroids every 2 weeks as part of his chemotherapy. The patient was admitted to the hospital for acute mental status changes 2 days after his last corticosteroid dose. He had pressured speech, grandiosity, and had not slept in 2 days. We started risperidone, 1 mg bid, and most of his manic symptoms resolved within 2 days. His chemotherapy was continued without corticosteroids. If this had not been not possible, I would have recommended continuing risperidone prophylactically.

No double-blind, placebo-controlled studies have examined prevention or treatment of steroid-induced mania or other psychiatric symptoms. Uncontrolled trials and case reports suggest benefit from some symptomatic and preventive treatments (Table 2).

Table 2

Mood stabilizers with evidence of benefit in treating corticosteroid-induced mania

Treating manic and mixed mood symptoms. Twelve outpatients with manic or mixed symptoms from corticosteroid use received olanzapine in a 5-week, open-label trial. Flexible dosing started at 2.5 mg/d and was increased as needed (maximum 20 mg/d). One patient dropped out for lack of efficacy. For the others, manic and mixed symptoms improved significantly, as indicated by scores on the Young Mania Rating Scale, Hamilton Rating Scale for Depression, and Brief Psychotic Rating Scale.¹⁴ Patient weight, blood glucose, and involuntary movements did not change significantly.

Evidence from case reports indicates that lithium,¹⁵ carbamazepine,^12,16 haloperidol,^12,16 or quetiapine¹⁷ also can successfully treat steroid-induced manic symptoms.

Continue to: Treating other psychiatric symptoms

Treating other psychiatric symptoms. Case reports support electroconvulsive therapy,^2,15 fluoxetine,¹⁸ amitriptyline,¹² lamotrigine,¹⁹ or lithium^20,21 for steroid-induced depression, and haloperidol²² or risperidone²³ for steroid-induced psychosis.

In four cases,⁶ tricyclic antidepressants appeared to worsen corticosteroids’ psychiatric side effects. These case patients might have had steroid-induced delirium instead of mood disorders or psychosis, however, and the tricyclics’ anticholinergic effects could have worsened the delirium.⁹

Preventing steroid-induced symptoms

Although clear guidelines on when to start preventive treatments do not exist, potential candidates for pretreatment with lithium or other agents include patients who:

• have developed psychiatric symptoms multiple times after repeated corticosteroid use
• are at high risk if psychiatric side effects occur.

Lithium. Prophylactic lithium was given to 27 patients with multiple sclerosis and taking corticosteroids for acute exacerbations. None developed psychiatric symptoms.²⁴ At the same clinic, 6 of 44 patients with multiple sclerosis or retrobulbar neuritis developed psychiatric side effects after using corticosteroids without lithium.

Be cautious when using prophylactic lithium because some conditions treated with corticosteroids—such as systemic lupus erythematosus—can impair renal function.²⁰ Corticosteroids also can affect sodium balance and increase the risk of lithium intoxication.²⁵

Check renal function before and during lithium titration, and initiate corticosteroid therapy when lithium is at effective blood levels (0.8 to 1.2 mEq/L). Monitor lithium levels and renal function frequently during steroid treatment.

Other mood stabilizers. Two case reports describe patients who repeatedly developed manic symptoms after multiple corticosteroid doses. Carbamazepine, 600 mg qd,¹⁶ and gabapentin, 300 mg tid,²⁶ prevented manic symptoms after additional corticosteroid pulses.

Related resources

• Brown ES, Chandler PA. Mood and cognitive changes during systemic corticosteroid therapy. Prim Care Companion J Clin Psychiatry 2001;3(1):17-21. www.psychiatrist.com/pcc/abstracts/pcc030103.htm.
• Merrill W. Case 35-1998: use of lithium to prevent corticosteroid-induced mania. N Engl J Med 1999;340:1123.

Drug brand names

• Amitriptyline • Elavil
• Carbamazepine • Tegretol
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Haloperidol • Haldol
• Lamotrigine • Lamictal
• Lithium • Eskalith, others
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal

Mr. P, age 39, attacks a convenience store clerk with a knife and is charged with aggravated assault. The judge grants the defense attorney’s request that Mr. P’s competency to stand trial be evaluated. Mr. P’s medical records show paranoid schizophrenia diagnosed at age 22, multiple psychiatric hospitalizations, and chronic medication noncompliance.

You may be called on to determine capacity—such as whether a patient can provide informed consent for a medical procedure. Judges or juries make decisions about competency—often based on a psychiatrist’s opinion about a person’s capacity.

This article describes how to prepare a report stating your opinion about whether a defendant such as Mr. P is competent to stand trial.

What is competency?

The defendant’s attorney usually raises the question of whether a defendant is competent to stand trial, but a judge or prosecuting attorney also may suggest an evaluation. Defense attorneys question their clients’ competence to stand trial in approximately 8% to 15% of felony cases, and up to 50,000 defendants are referred for competency evaluations each year.^1-4 Competency may be questioned when the defendant:

• is obviously mentally ill or has a history of mental illness
  
• appears to be making irrational decisions
  
• has difficulty interacting with the court or defense counsel.⁵
  

“Competency” and “sanity” are often used together in discussions of criminal prosecution of mentally-ill defendants. This article describes evaluating competence to stand trial; we will discuss how to evaluate sanity in a future issue of Current Psychiatry.

Competency is dynamic; the law defines many types, each with a legal definition and requisite capacity. A person may be competent in one area but incompetent in another. He may be incompetent to make a decision about psychiatric hospitalization, for example, yet retain competency to give or withhold informed consent for treatment.

Evaluating competency also is dynamic, depending on the patient’s present state:

• She might be incapable of giving informed consent for surgery while delirious but capable to make a competent decision about treatment after sensorium clears.
  
• A psychotic defendant may be incompetent to stand trial initially but may be restored to competency after treatment.
  

The ‘dusky standard’

Courts have long recognized that the mentally ill may be incapable of defending themselves against criminal charges (Box).⁶ The U.S. Supreme Court in 1960 established in Dusky v. United States that the legal standard for competence to stand trial is “whether [the person] has sufficient present ability to consult with his lawyer with a reasonable degree of rational understanding—and whether he has a rational as well as factual understanding of the proceedings against him.” This standard has been adopted in principle by all states and the federal jurisdiction.⁷

The “Dusky standard” indicates that a defendant is incompetent to stand trial if, because of a mental illness or other condition, he is unable to:

• understand the nature and objectives of the court proceedings
  
• or assist in his defense (Table 1).
  

Judges ultimately determine defendants’ competence to stand trial, but psychiatrists’ opinions are adopted in 90% of cases.^8,9

Box

The ‘Dusky standard’ of competence

How to assess competency

If a judge asks you to evaluate a defendant’s competency, you need to know the standard governing competence to stand trial in the judge’s jurisdiction. All courts in the United States use the Dusky standard, but the wording varies.

Review the defendant’s case records, including court papers (with a list of charges), medical records, and psychiatric records. Then interview the defendant to thoroughly evaluate his mental status and collect a detailed psychiatric history.

If the defendant has a mental disorder, it must impair his ability to understand the proceedings or participate in his defense to result in incompetency. Sources who know the defendant (spouse, family, or friends) may provide useful collateral information.

Assessment tools. Some argue that tools designed to help determine competency can assess understanding of facts related to the trial but not ability to reason. The MacArthur Competency Assessment Tool—Criminal Adjudication is thought to assess both decisional competency and factual understanding.¹⁰ Another new tool, the Evaluation of Competency to Stand Trial-revised (ECST-R), is beginning to be used more frequently to evaluate possible malingering and case-specific information.

These tools can be purchased online through vendors such as www3.parinc.com. Though useful, these tools serve as adjuncts to the clinical interview.

In your report to the court, include relevant information from the mental status evaluation, the diagnosis, and—most important—a clear, concise opinion of the defendant’s current competence to stand trial.

Case: does Mr. P meet the standard?

During your interview, Mr. P endorses chronic auditory hallucinations telling him to harm others. He is alert and oriented to location, date, and current events. He can adequately describe courtroom proceedings and each individual’s role, noting that he had been to court before on a drug possession charge, for which he received probation.

When you ask Mr. P about his attorney, he leans in and whispers, “My attorney and my mother have a secret plan to send me to prison for the rest of my life.” He contends his attorney is telling him to claim he is “crazy” to make him “look bad” in court.

In a separate interview, you question the corrections officer who accompanied Mr. P to the evaluation. He says Mr. P refuses to see his mother and his attorney when they come to visit him in jail and takes his medications only sporadically.

Understanding court proceedings. A defendant such as Mr. P must be able to understand the charges against him, that he is on trial for those charges, and the severity of the charges. He must be able to understand the pleas he can offer (guilty, not guilty, not guilty by reason of insanity, or no contest).

The defendant also must be aware of the roles of trial participants, including defense attorney, prosecutor, witnesses, judge, and jury. He must appreciate the trial’s adversarial nature, that his attorney is acting in his best interests and defending him, and that the prosecutor is trying to convict him.

Ability to assist in defense. A defendant must be able to have logical, coherent discussions with his attorney and be free of paranoid beliefs about the attorney. He must recognize his role as the defendant and maintain no delusions that he is somehow immune to prosecution.

In cooperation with his attorney, he must be able to evaluate the evidence against him and predict the trial’s probable outcome. He must help his attorney formulate a plan for his defense and make reasonable decisions about that plan. If relevant, he must be willing to consider using a mental illness defense at trial; therefore, he must possess a reasonable amount of insight into his mental illness. He also must:

• be able to participate with his attorney in plea bargaining and grasp the meaning and outcome of this process
  
• have sufficient memory and concentration to understand the trial proceedings.
  

Finally, a defendant must be motivated to assist in his defense and free of self-defeating behavior. For example, severely depressed patients seeking to punish themselves by causing an unfavorable trial outcome could be considered incompetent.

Mentally ill and incompetent

Mr. P has a clear history of mental illness, the first criterion for a defendant to be considered incompetent to stand trial. He has psychotic symptoms, but these alone are insufficient to consider him incompetent. Also, having competently stood trial in the past does not necessarily mean he is competent now.

Based on the beginning of the interview, Mr. P appears to understand the nature and objectives of court proceedings. His delusions about his attorney, however, clearly would impair his ability to assist in his defense.

Reporting to the court. A forensic evaluator’s report to the court might say: “It is my opinion, with reasonable medical certainty, that although Mr. P understands the nature and objectives of the court proceedings against him, he has a significant thought disorder that currently impairs his ability to assist in his own defense. In particular, Mr. P maintains delusions (a fixed, false belief held despite evidence to the contrary) that his attorney is plotting against him.”

Treatment to restore competency. Approximately 30% of evaluated defendants are adjudicated incompetent for a variety of reasons (Table 2).¹¹ They often are committed to a forensic mental hospital for treatment to restore competency, which occurs in up to 90% of cases.¹²

Mr. P will likely be committed to restore competency, which may be achieved by treating his schizophrenia.

Defendants with disorders such as dementia or mental retardation may be considered unable to be restored to competency, and their charges are dismissed or held in abeyance. They may then be involuntarily hospitalized if committed through civil proceedings.

Table 2

7 common reasons defendants are found incompetent to stand trial

• Grisso T. Evaluating competencies: forensic assessments and instruments, 2nd ed. New York: Springer; 2002.
  
• Melton GB, Petrila J, Poythress G, Slobogin C. Psychological evaluations for the courts: a handbook for mental health professionals and lawyers, 2nd ed. New York: Guilford Press; 1997.
  
• American Academy of Psychiatry and the Law. www.aapl.org.
  

Mr. P, age 39, attacks a convenience store clerk with a knife and is charged with aggravated assault. The judge grants the defense attorney’s request that Mr. P’s competency to stand trial be evaluated. Mr. P’s medical records show paranoid schizophrenia diagnosed at age 22, multiple psychiatric hospitalizations, and chronic medication noncompliance.

You may be called on to determine capacity—such as whether a patient can provide informed consent for a medical procedure. Judges or juries make decisions about competency—often based on a psychiatrist’s opinion about a person’s capacity.

This article describes how to prepare a report stating your opinion about whether a defendant such as Mr. P is competent to stand trial.

What is competency?

The defendant’s attorney usually raises the question of whether a defendant is competent to stand trial, but a judge or prosecuting attorney also may suggest an evaluation. Defense attorneys question their clients’ competence to stand trial in approximately 8% to 15% of felony cases, and up to 50,000 defendants are referred for competency evaluations each year.^1-4 Competency may be questioned when the defendant:

• is obviously mentally ill or has a history of mental illness
  
• appears to be making irrational decisions
  
• has difficulty interacting with the court or defense counsel.⁵
  

“Competency” and “sanity” are often used together in discussions of criminal prosecution of mentally-ill defendants. This article describes evaluating competence to stand trial; we will discuss how to evaluate sanity in a future issue of Current Psychiatry.

Competency is dynamic; the law defines many types, each with a legal definition and requisite capacity. A person may be competent in one area but incompetent in another. He may be incompetent to make a decision about psychiatric hospitalization, for example, yet retain competency to give or withhold informed consent for treatment.

Evaluating competency also is dynamic, depending on the patient’s present state:

• She might be incapable of giving informed consent for surgery while delirious but capable to make a competent decision about treatment after sensorium clears.
  
• A psychotic defendant may be incompetent to stand trial initially but may be restored to competency after treatment.
  

The ‘dusky standard’

Courts have long recognized that the mentally ill may be incapable of defending themselves against criminal charges (Box).⁶ The U.S. Supreme Court in 1960 established in Dusky v. United States that the legal standard for competence to stand trial is “whether [the person] has sufficient present ability to consult with his lawyer with a reasonable degree of rational understanding—and whether he has a rational as well as factual understanding of the proceedings against him.” This standard has been adopted in principle by all states and the federal jurisdiction.⁷

The “Dusky standard” indicates that a defendant is incompetent to stand trial if, because of a mental illness or other condition, he is unable to:

• understand the nature and objectives of the court proceedings
  
• or assist in his defense (Table 1).
  

Judges ultimately determine defendants’ competence to stand trial, but psychiatrists’ opinions are adopted in 90% of cases.^8,9

Box

The ‘Dusky standard’ of competence

How to assess competency

If a judge asks you to evaluate a defendant’s competency, you need to know the standard governing competence to stand trial in the judge’s jurisdiction. All courts in the United States use the Dusky standard, but the wording varies.

Review the defendant’s case records, including court papers (with a list of charges), medical records, and psychiatric records. Then interview the defendant to thoroughly evaluate his mental status and collect a detailed psychiatric history.

If the defendant has a mental disorder, it must impair his ability to understand the proceedings or participate in his defense to result in incompetency. Sources who know the defendant (spouse, family, or friends) may provide useful collateral information.

Assessment tools. Some argue that tools designed to help determine competency can assess understanding of facts related to the trial but not ability to reason. The MacArthur Competency Assessment Tool—Criminal Adjudication is thought to assess both decisional competency and factual understanding.¹⁰ Another new tool, the Evaluation of Competency to Stand Trial-revised (ECST-R), is beginning to be used more frequently to evaluate possible malingering and case-specific information.

These tools can be purchased online through vendors such as www3.parinc.com. Though useful, these tools serve as adjuncts to the clinical interview.

In your report to the court, include relevant information from the mental status evaluation, the diagnosis, and—most important—a clear, concise opinion of the defendant’s current competence to stand trial.

Case: does Mr. P meet the standard?

During your interview, Mr. P endorses chronic auditory hallucinations telling him to harm others. He is alert and oriented to location, date, and current events. He can adequately describe courtroom proceedings and each individual’s role, noting that he had been to court before on a drug possession charge, for which he received probation.

When you ask Mr. P about his attorney, he leans in and whispers, “My attorney and my mother have a secret plan to send me to prison for the rest of my life.” He contends his attorney is telling him to claim he is “crazy” to make him “look bad” in court.

In a separate interview, you question the corrections officer who accompanied Mr. P to the evaluation. He says Mr. P refuses to see his mother and his attorney when they come to visit him in jail and takes his medications only sporadically.

Understanding court proceedings. A defendant such as Mr. P must be able to understand the charges against him, that he is on trial for those charges, and the severity of the charges. He must be able to understand the pleas he can offer (guilty, not guilty, not guilty by reason of insanity, or no contest).

The defendant also must be aware of the roles of trial participants, including defense attorney, prosecutor, witnesses, judge, and jury. He must appreciate the trial’s adversarial nature, that his attorney is acting in his best interests and defending him, and that the prosecutor is trying to convict him.

Ability to assist in defense. A defendant must be able to have logical, coherent discussions with his attorney and be free of paranoid beliefs about the attorney. He must recognize his role as the defendant and maintain no delusions that he is somehow immune to prosecution.

In cooperation with his attorney, he must be able to evaluate the evidence against him and predict the trial’s probable outcome. He must help his attorney formulate a plan for his defense and make reasonable decisions about that plan. If relevant, he must be willing to consider using a mental illness defense at trial; therefore, he must possess a reasonable amount of insight into his mental illness. He also must:

• be able to participate with his attorney in plea bargaining and grasp the meaning and outcome of this process
  
• have sufficient memory and concentration to understand the trial proceedings.
  

Finally, a defendant must be motivated to assist in his defense and free of self-defeating behavior. For example, severely depressed patients seeking to punish themselves by causing an unfavorable trial outcome could be considered incompetent.

Mentally ill and incompetent

Mr. P has a clear history of mental illness, the first criterion for a defendant to be considered incompetent to stand trial. He has psychotic symptoms, but these alone are insufficient to consider him incompetent. Also, having competently stood trial in the past does not necessarily mean he is competent now.

Based on the beginning of the interview, Mr. P appears to understand the nature and objectives of court proceedings. His delusions about his attorney, however, clearly would impair his ability to assist in his defense.

Reporting to the court. A forensic evaluator’s report to the court might say: “It is my opinion, with reasonable medical certainty, that although Mr. P understands the nature and objectives of the court proceedings against him, he has a significant thought disorder that currently impairs his ability to assist in his own defense. In particular, Mr. P maintains delusions (a fixed, false belief held despite evidence to the contrary) that his attorney is plotting against him.”

Treatment to restore competency. Approximately 30% of evaluated defendants are adjudicated incompetent for a variety of reasons (Table 2).¹¹ They often are committed to a forensic mental hospital for treatment to restore competency, which occurs in up to 90% of cases.¹²

Mr. P will likely be committed to restore competency, which may be achieved by treating his schizophrenia.

Defendants with disorders such as dementia or mental retardation may be considered unable to be restored to competency, and their charges are dismissed or held in abeyance. They may then be involuntarily hospitalized if committed through civil proceedings.

Table 2

7 common reasons defendants are found incompetent to stand trial

• Grisso T. Evaluating competencies: forensic assessments and instruments, 2nd ed. New York: Springer; 2002.
  
• Melton GB, Petrila J, Poythress G, Slobogin C. Psychological evaluations for the courts: a handbook for mental health professionals and lawyers, 2nd ed. New York: Guilford Press; 1997.
  
• American Academy of Psychiatry and the Law. www.aapl.org.
  

Mr. P, age 39, attacks a convenience store clerk with a knife and is charged with aggravated assault. The judge grants the defense attorney’s request that Mr. P’s competency to stand trial be evaluated. Mr. P’s medical records show paranoid schizophrenia diagnosed at age 22, multiple psychiatric hospitalizations, and chronic medication noncompliance.

You may be called on to determine capacity—such as whether a patient can provide informed consent for a medical procedure. Judges or juries make decisions about competency—often based on a psychiatrist’s opinion about a person’s capacity.

This article describes how to prepare a report stating your opinion about whether a defendant such as Mr. P is competent to stand trial.

What is competency?

The defendant’s attorney usually raises the question of whether a defendant is competent to stand trial, but a judge or prosecuting attorney also may suggest an evaluation. Defense attorneys question their clients’ competence to stand trial in approximately 8% to 15% of felony cases, and up to 50,000 defendants are referred for competency evaluations each year.^1-4 Competency may be questioned when the defendant:

• is obviously mentally ill or has a history of mental illness
  
• appears to be making irrational decisions
  
• has difficulty interacting with the court or defense counsel.⁵
  

“Competency” and “sanity” are often used together in discussions of criminal prosecution of mentally-ill defendants. This article describes evaluating competence to stand trial; we will discuss how to evaluate sanity in a future issue of Current Psychiatry.

Competency is dynamic; the law defines many types, each with a legal definition and requisite capacity. A person may be competent in one area but incompetent in another. He may be incompetent to make a decision about psychiatric hospitalization, for example, yet retain competency to give or withhold informed consent for treatment.

Evaluating competency also is dynamic, depending on the patient’s present state:

• She might be incapable of giving informed consent for surgery while delirious but capable to make a competent decision about treatment after sensorium clears.
  
• A psychotic defendant may be incompetent to stand trial initially but may be restored to competency after treatment.
  

The ‘dusky standard’

Courts have long recognized that the mentally ill may be incapable of defending themselves against criminal charges (Box).⁶ The U.S. Supreme Court in 1960 established in Dusky v. United States that the legal standard for competence to stand trial is “whether [the person] has sufficient present ability to consult with his lawyer with a reasonable degree of rational understanding—and whether he has a rational as well as factual understanding of the proceedings against him.” This standard has been adopted in principle by all states and the federal jurisdiction.⁷

The “Dusky standard” indicates that a defendant is incompetent to stand trial if, because of a mental illness or other condition, he is unable to:

• understand the nature and objectives of the court proceedings
  
• or assist in his defense (Table 1).
  

Judges ultimately determine defendants’ competence to stand trial, but psychiatrists’ opinions are adopted in 90% of cases.^8,9

Box

The ‘Dusky standard’ of competence

How to assess competency

If a judge asks you to evaluate a defendant’s competency, you need to know the standard governing competence to stand trial in the judge’s jurisdiction. All courts in the United States use the Dusky standard, but the wording varies.

Review the defendant’s case records, including court papers (with a list of charges), medical records, and psychiatric records. Then interview the defendant to thoroughly evaluate his mental status and collect a detailed psychiatric history.

If the defendant has a mental disorder, it must impair his ability to understand the proceedings or participate in his defense to result in incompetency. Sources who know the defendant (spouse, family, or friends) may provide useful collateral information.

Assessment tools. Some argue that tools designed to help determine competency can assess understanding of facts related to the trial but not ability to reason. The MacArthur Competency Assessment Tool—Criminal Adjudication is thought to assess both decisional competency and factual understanding.¹⁰ Another new tool, the Evaluation of Competency to Stand Trial-revised (ECST-R), is beginning to be used more frequently to evaluate possible malingering and case-specific information.

These tools can be purchased online through vendors such as www3.parinc.com. Though useful, these tools serve as adjuncts to the clinical interview.

In your report to the court, include relevant information from the mental status evaluation, the diagnosis, and—most important—a clear, concise opinion of the defendant’s current competence to stand trial.

Case: does Mr. P meet the standard?

During your interview, Mr. P endorses chronic auditory hallucinations telling him to harm others. He is alert and oriented to location, date, and current events. He can adequately describe courtroom proceedings and each individual’s role, noting that he had been to court before on a drug possession charge, for which he received probation.

When you ask Mr. P about his attorney, he leans in and whispers, “My attorney and my mother have a secret plan to send me to prison for the rest of my life.” He contends his attorney is telling him to claim he is “crazy” to make him “look bad” in court.

In a separate interview, you question the corrections officer who accompanied Mr. P to the evaluation. He says Mr. P refuses to see his mother and his attorney when they come to visit him in jail and takes his medications only sporadically.

Understanding court proceedings. A defendant such as Mr. P must be able to understand the charges against him, that he is on trial for those charges, and the severity of the charges. He must be able to understand the pleas he can offer (guilty, not guilty, not guilty by reason of insanity, or no contest).

The defendant also must be aware of the roles of trial participants, including defense attorney, prosecutor, witnesses, judge, and jury. He must appreciate the trial’s adversarial nature, that his attorney is acting in his best interests and defending him, and that the prosecutor is trying to convict him.

Ability to assist in defense. A defendant must be able to have logical, coherent discussions with his attorney and be free of paranoid beliefs about the attorney. He must recognize his role as the defendant and maintain no delusions that he is somehow immune to prosecution.

In cooperation with his attorney, he must be able to evaluate the evidence against him and predict the trial’s probable outcome. He must help his attorney formulate a plan for his defense and make reasonable decisions about that plan. If relevant, he must be willing to consider using a mental illness defense at trial; therefore, he must possess a reasonable amount of insight into his mental illness. He also must:

• be able to participate with his attorney in plea bargaining and grasp the meaning and outcome of this process
  
• have sufficient memory and concentration to understand the trial proceedings.
  

Finally, a defendant must be motivated to assist in his defense and free of self-defeating behavior. For example, severely depressed patients seeking to punish themselves by causing an unfavorable trial outcome could be considered incompetent.

Mentally ill and incompetent

Mr. P has a clear history of mental illness, the first criterion for a defendant to be considered incompetent to stand trial. He has psychotic symptoms, but these alone are insufficient to consider him incompetent. Also, having competently stood trial in the past does not necessarily mean he is competent now.

Based on the beginning of the interview, Mr. P appears to understand the nature and objectives of court proceedings. His delusions about his attorney, however, clearly would impair his ability to assist in his defense.

Reporting to the court. A forensic evaluator’s report to the court might say: “It is my opinion, with reasonable medical certainty, that although Mr. P understands the nature and objectives of the court proceedings against him, he has a significant thought disorder that currently impairs his ability to assist in his own defense. In particular, Mr. P maintains delusions (a fixed, false belief held despite evidence to the contrary) that his attorney is plotting against him.”

Treatment to restore competency. Approximately 30% of evaluated defendants are adjudicated incompetent for a variety of reasons (Table 2).¹¹ They often are committed to a forensic mental hospital for treatment to restore competency, which occurs in up to 90% of cases.¹²

Mr. P will likely be committed to restore competency, which may be achieved by treating his schizophrenia.

Defendants with disorders such as dementia or mental retardation may be considered unable to be restored to competency, and their charges are dismissed or held in abeyance. They may then be involuntarily hospitalized if committed through civil proceedings.

Table 2

7 common reasons defendants are found incompetent to stand trial

• Grisso T. Evaluating competencies: forensic assessments and instruments, 2nd ed. New York: Springer; 2002.
  
• Melton GB, Petrila J, Poythress G, Slobogin C. Psychological evaluations for the courts: a handbook for mental health professionals and lawyers, 2nd ed. New York: Guilford Press; 1997.
  
• American Academy of Psychiatry and the Law. www.aapl.org.