In Treatment in Psychiatry, Balon (p. 1504) reviews the prevalence, comorbidity, evaluation, and management of the sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Estimates of their prevalence vary from small percentages to more than 80%, and they can discourage adherence to treatment. Few of the numerous approaches proposed have been reliably tested. Several of these strategies are discussed, along with the caution to also consider psychological factors, other medical conditions, and substance use.

The later stages of STAR*D (Sequenced Treatment Alternatives to Relieve Depression) offered different drugs or drug combinations to patients who had experienced inadequate benefits or drug intolerance in at least two previous drug trials. Nierenberg et al. (p. 1519) report on the augmentation of antidepressant treatment with either lithium or triiodothyronine (T₃), a thyroid hormone (see Images in Neuroscience, p. 1492). The differences fell short of statistical significance, but T₃ produced a higher rate of remission than lithium (25% versus 16%). McGrath et al. (p. 1531 CME) describe a comparison of the antidepressant tranylcypromine, a monoamine oxidase inhibitor, with the combination of two newer antidepressants, extended-release venlafaxine and mirtazapine, which enhance both norepinephrine and serotonin transmission. The remission rates for both tranylcypromine (7%) and the venlafaxine-mirtazapine combination (14%) were low, but the percentage reduction in depressive symptoms was significantly greater with the venlafaxine-mirtazapine combination (25% versus 6%). Both trials had modest remission rates but suggest preferred strategies for treatment-resistant patients. The results are more generalizable than previous findings because STAR*D included the broad range of depressed outpatients seen in typical psychiatric and family practices, many of whom have coexisting psychiatric and other medical disorders. Perspectives are given in editorials by Dr. Marcia Valenstein (p. 1484) on treatment resistance and by Dr. Frank deGruy on treatment of depression by family practitioners and psychiatrists (p. 1487).

Research on the workplace costs of mood disorders has focused on major depression. In the National Comorbidity Survey Replication, the depressive episodes of bipolar disorder caused much greater work loss. Kessler et al. (p. 1561) found that the persistence and severity of bipolar depression were greater than in major, or unipolar, depression. The difference affects workplace costs and underscores the need for correct differential diagnosis of depressive episodes, which can overshadow hypomanic symptoms in patients with bipolar disorder. Adler et al. (p. 1569) report that asking depressed patients specific questions about their functioning at work revealed deficits in mental and interpersonal tasks, time management, output, and physical tasks. Improvement on these measures followed improvement in depression over 18 months, but job performance did not reach the levels of healthy subjects (see figure above). At baseline, 44% of the patients were taking antidepressants but were still clinically depressed. Workplace supports may help depressed patients overcome specific impairments, but more monitoring and adjustment of treatment are needed. An editorial by Dr. Howard Goldman on better treatment of depression and its effect on workplace function appears on p. 1490.

An intrinsic difference in neurotransmission underlying major depression has been clarified by Bhagwagar et al. (p. 1580). Using positron emission tomography and a recently developed chemical tracer, they measured the binding potential of serotonin 2A (5-HT_2A) receptors in medication-free patients who had recovered from depression. Binding potential in the occipital, parietal, and frontal cortices was higher among the patients than among never-depressed comparison subjects. It also correlated with dysfunctional attitudes among patients, but not comparison subjects. Higher binding potential suggests greater density of 5-HT_2A receptors.