Cognitive deficits are a fundamental feature of the psychopathology of schizophrenia. Yet the effect of treatment on this dimension of the illness has been unclear. Atypical antipsychotic medications have been reported to reduce the neurocognitive impairment associated with schizophrenia. However, studies of the pattern and degree of cognitive improvement with these compounds have been methodologically limited and have produced variable results, and few findings have been replicated. To clarify our understanding of the effects of atypical antipsychotic drugs on neurocognitive deficits in patients with schizophrenia, we have (1) reported on newly established standards for research design in studies of treatment effects on cognitive function in schizophrenia, (2) reviewed the literature on this topic and determined the extent to which 15 studies on the effect of atypical antipsychotics met these standards, (3) performed a meta-analysis of the 15 studies, which suggested general cognitive enhancement with atypical antipsychotics, and (4) described the pharmacological profile of these agents and considered the pharmacological basis for their effects on neurocognition. Finally, we suggest directions for the development of new therapeutic strategies.

Objective The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared to placebo. Background Depression is common among HF patients. It is associated with increased hospitalization and mortality. Methods SADHART-CHF was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse facilitated support. Eligible patients were age ≥45 years with HF (LVEF ≤45%, NYHA class II-IV) and clinical depression (DSM-IV criteria for current major depressive disorder). Significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were exclusions. Primary endpoints were change in depression severity (Hamilton Depression Rating Scale [HDRS] total score) and composite cardiovascular status at12-weeks. Results 469 patients were randomized (N=234 sertraline, N=235 placebo). The mean ± SE change from baseline to 12-weeks in the HDRS total score was -7.1 ± 0.5 (sertraline) and -6.8 ± 0.5 (placebo) (P<.001 from baseline, P=.89 between groups, mean change between groups -0.4, 95% CI -1.7, 0.92). The proportion whose composite cardiovascular score worsened, improved, or was unchanged was 29.9%, 40.6%, and 29.5% in the sertraline group and 31.1%, 43.8%, and 25.1% in the placebo group (P=0.78). Discussion Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression.

Further research is needed to determine if treatments based on these findings might alter the clinical course of HIV-1 infection.