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October 2008

Two Drugs for Fibromyalgia
Pregabalin (Lyrica) and duloxetine (Cymbalta) are approved in the United States for the treatment of fibromyalgia.

Preventing Poststroke Depression
In a 2008 study by Robinson and colleagues, escitalopram (Lexapro) and problem-solving therapy decreased the likelihood of poststroke depression.

Duloxetine for Elderly Patients with GAD
Due to possible adverse events, duloxetine (Cymbalta) should be a second-line option for elderly patients with generalized anxiety disorder.

In Brief
Switch to Aripiprazole Reduces Cardiovascular Risk in Schizophrenia; SSRIs Are Effective for Treating PMS/PMDD; Statins May Protect Against Dementia

Antidepressants for Social Anxiety Disorder
Sertraline (Zoloft and others), paroxetine (Paxil and others), venlafaxine (Effexor and others), and fluvoxamine (Luvox and others) appear to be the most efficacious antidepressants for the treatment of social anxiety disorder, with escitalopram (Lexapro) a reasonable alternative.

Antidepressants for Social Anxiety Disorder

October 2008

Social anxiety disorder (SAD), also known as social phobia, became an official psychiatric diagnosis with publication of the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (DSM-III) in 1980.1 DSM-IV-TR defines SAD as marked and persistent fear of social or performance circumstances, intense anxiety and distress when exposed to feared situations, and avoidance of these situation when possible.2 Subdivided into generalized and nongeneralized (specific) subtypes, SAD is the third most common psychiatric disorder, following depression and alcohol dependence.3 It typically begins in the teens, is more common in women than in men, and has a lifetime prevalence of 12.1%.4 SAD impairs psychosocial functioning, work, and quality of life.

Performance anxiety may be alleviated by as-needed doses of beta-blockers or behavioral treatment. Beta-blockers can also control the autonomic symptoms of generalized SAD, such as tachycardia, palpitations, excessive sweating, dry mouth, blushing, tremor, muscle tension, nausea, and diarrhea. Benzodiazepines may alleviate symptoms, although at the risk of producing dependence and withdrawal reactions. Monoamine oxidase inhibitors are probably effective but require dietary restrictions and cause medication interactions.

Sertraline (Zoloft and others), paroxetine (Paxil and others), venlafaxine (Effexor and others), and fluvoxamine (Luvox and others) carry labeling from the US Food and Drug Administration (FDA) for the treatment of SAD. Hansen and collaborators conducted a systematic review and meta-analysis to evaluate the comparative efficacy and tolerability of modern antidepressants for SAD. They analyzed data on bupropion (Wellbutrin), citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac and others), fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, and venlafaxine.5

The four drugs labeled by the FDA for the treatment of SAD have clearly established efficacy in the treatment of this condition. (The FDA's approval of fluvoxamine for SAD followed publication of the Hansen et al review.) Limited evidence suggests efficacy for escitalopram as well. The authors identified only one study on the efficacy of fluoxetine and no studies involving bupropion, citalopram, duloxetine, or mirtazapine.

Neither the few head-to-head trials nor a network meta-analysis revealed meaningful differences in efficacy among the drugs studied. Overall, patients randomly assigned in clinical trials to receive escitalopram, fluvoxamine, paroxetine, sertraline, or venlafaxine had a 40% to 85% chance of clinically meaningful improvement. Symptom reduction with these antidepressants was on average 20% greater than with placebo in similar patients. As symptoms improved, function in social and work domains did as well. While there was no evident difference in efficacy among the antidepressants studied, differences in side effects—such as insomnia, somnolence, and "asthenia" (lack of energy or strength)—did emerge.

Generalized SAD burdens patients and their families. Treatment can improve quality of life and function. Doctors should advise patients of the full range of treatment options, including behavioral and pharmacologic. If pharmacotherapy is elected, the best evidence supports the four FDA-labeled antidepressants: sertraline, paroxetine, venlafaxine, and fluvoxamine. Escitalopram seems to be a reasonable alternative. Adjunctive use of benzodiazepines may offer symptomatic improvement, albeit with well-known risks.

1American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. Arlington, VA, American Psychiatric Association, 1980.

2American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision. Arlington, VA, American Psychiatric Association, 2000.

3Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS: Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:8-19.

4Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE: Prevalence, severity, and comorbidity of 12-month