Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial.

A double-blind, placebo-controlled, multicenter study, was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia cluster scores (all P < 0.05). Similarly, the percentages of patients classified as responders on the BPRS (> or = 30% reduction) and the CGI improvement (score < or = 2) were significantly greater with ziprasidone 120 mg/day compared with placebo (P < 0.05). The number of patients who experienced an adverse event was similar in all three treatment groups, and discontinuation due to adverse events was rare (five of 91 ziprasidone-treated patients). The most frequently reported adverse events, that were more common in either ziprasidone group than in the placebo group, were dyspepsia, constipation, nausea and abdominal pain. There was a notably low incidence extrapyramidal side-effects (including akathisia) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain. Ziprasidone-treated patients were not clinically different from placebo-treated patients on the Simpson-Angus Rating scale, Barnes Akathisia scale and AIMS assessments. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive, negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden.

Drug effects on REM sleep and on endogenous depression.

In earlier work REM sleep deprivation (RSD) by arousals improved endogenous depression. This suggested that drugs producing a similar RSD would have antidepressant activity. The arousal RSD was large, persisted for weeks, and was followed by a REM rebound. We call RSD with these properties arousal-type RSD. The present study reviewed literature from 1962 to 1989 on drug REM sleep effects to examine the hypothesis that drugs producing arousal-type RSD improve endogenous depression. The literature reviewed concerned the REM sleep effects of amine precursors, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, other hypnotics, drugs affecting cholinergic and noradrenergic neurotransmission, ethanol, lithium and narcotics. Four hundred and sixty-eight relevant papers were read and 215 contributed information that could be used in the review. The findings indicated that all drugs producing arousal-type RSD improved endogenous depression. Four drugs that improved endogenous depression did not produce arousal-type RSD.