Two large-scale studies add to the evidence that antidepressant drugs decrease, rather than increase, the risk of suicidal behavior. Simon et al. (CME, p. 1029) report patterns of suicide attempts among 109,256 individuals in a prepaid health plan who were treated for depression. Suicide attempts were most common in the month before treatment began, next highest in the first month of treatment, and still lower as treatment continued. This progression occurred for both medication and psychotherapy and also was seen in adolescents and young adults specifically. A decline in suicide attempts after the start of antidepressant treatment was also demonstrated by Gibbons et al. (p. 1044). Data on 226,866 depressed veterans showed both a decrease within the same patients after treatment and a lower rate of suicide attempts in patients taking selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants than in patients who did not receive antidepressants. These differences were seen for all age groups, including 18–25-year-olds. Posner et al. (CME, p. 1035) describe the system used to classify suicidal events in the Food and Drug Administration’s analysis of the suicidality risk for children and adolescents in antidepressant clinical trials, as well as in adult clinical trials of antidepressants and numerous other centrally acting agents, including anticonvulsants and cannabinoid 1 receptor inverse agonists. Compared to the pharmaceutical companies that conducted the pediatric trials, the raters using the Columbia Classification Algorithm for Suicide Assessment identified more adverse events as possibly suicidal, but they classified only half as many as actual suicide attempts. An editorial by Dr. David Brent on p. 989 reviews these findings.

Three widely prescribed second-generation antipsychotic drugs have similar efficacy and neurocognitive effects for patients with early psychotic illness. McEvoy et al. (p. 1050) describe the efficacy and tolerability of olanzapine, risperidone, or quetiapine for 400 patients who had been ill with schizophrenia or other psychotic illness for less than 5 years and had limited exposure to antipsychotics. More than half the patients met the criteria for response at some point over the 1-year trial, and total symptom scores at 12 weeks did not differ between treatments. Approximately 70% of each group discontinued treatment early. The reasons were generally similar, and of those who discontinued treatment, only 10% in each treatment group left because of drug side effects. Keefe et al. (p. 1061) report that the same three treatment groups had similar overall improvements in cognition. At 12 weeks, the patients taking quetiapine showed greater increases in verbal fluency and processing speed than the other groups; quetiapine was also superior to olanzapine for vigilance. Better vocational and social functioning at weeks 12 and 52 was related to cognitive improvement but may have also been due to general treatment response. Dr. Michael Green comments on these studies in an editorial on p. 992.

Since white matter is the infrastructure for connections between neurons, these abnormalities may underlie the faulty neural connectivity in schizophrenia. Buchsbaum et al. (p. 1072) found that relative metabolic rates in white matter tracts throughout the brain were higher in medication-free patients with schizophrenia than in comparison subjects. Higher metabolism suggests inefficiency in brain circuitry, tissue pathology, or axon density effects. Whitford et al. (p. 1082) detected higher white matter volume at the junction of the frontal and parietal lobes in patients experiencing their first episode of schizophrenia than in healthy subjects. The patients had low volumes, however, in the white matter of the frontal and temporal lobes, and repeat scans 2–3 years later demonstrated further loss in the middle and inferior temporal cortex. Dr. Kelvin Lim discusses these results in an editorial on p. 995. White matter tracts are shown in Images in Neuroscience, p. 1005.