No abstract

Background: Weight gain and associated medical morbidity offset the reduction of extrapyramidal side effects associated with atypical antipsychotics. Efforts to control weight in antipsychotic-treated patients have yielded limited success. Methods: We studied the impact of an intensive 24-week program of diet, exercise, and counseling in 17 chronically psychotic patients (10 women, seven men) who entered at high average body weight (105.0718.4 kg) and body mass index (BMI) (36.674.6 kg/m 2 ). A total of 12 subjects who completed the initial 24 weeks elected to participate in an additional 24-week, less intensive extension phase. Results: By 24 weeks, weight-loss/patient averaged 6.0 kg (5.7%) and BMI decreased to 34.5 (by 5.7%). Blood pressure decreased from 130/83 to 116/74 (11% improvement), pulse fell slightly, and serum cholesterol and triglyceride concentrations changed nonsignificantly. With less intensive management for another 24 weeks, subjects regained minimal weight (0.43 kg). Conclusions: These findings add to the emerging view that weight gain is a major health problem associated with modern antipsychotic drugs and that labor-intensive weight-control efforts in patients requiring antipsychotic treatment yield clinically promising benefits. Improved treatments without weight-gain risk are needed.

Postnatal development of dopamine D₁-like (D₁/D₅) receptors in rat caudate-putamen (CPu), nucleus accumbens (NAc), hippocampus, frontal and entorhinal cerebral cortex was assessed between postnatal days (PD) 7–60 by in vitro receptor autoradiography. Density of [³H]SCH-23390 binding to D₁-like receptors increased from PD-7 to a peak at PD-28 in CPu (11-fold) and NAc (23-fold), then declined by 20–40% in both regions over PD-35–60, to adult levels. In hippocampus, frontal and entorhinal cortex, D₁-like receptors increased by lesser amounts (3- to 4-fold) from PD-7 to stable, maximal adult levels at PD-60. Evidently, excess D₁-like receptors were eliminated during maturation of CPu and NAc, but not in the other forebrain regions. Postnatal D₁-like receptor development in rat forebrain paralleled that of D₂- and D₄-like receptors in the same regions.