Novel antipsychotics: comparison of weight gain liabilities.
BACKGROUND
We performed a retrospective analysis of 122 clinical records of 92 male patients with DSM-III-R schizophrenia to examine the relative weight gain liabilities of clozapine, risperidone, olanzapine, and sertindole compared with haloperidol. We hypothesized that the unique pharmacodynamic profiles of these agents would contribute to different amounts and patterns of weight gain.


METHODS
Data were analyzed to determine differences in weight gain during treatment among patients receiving 5 different drug treatments (clozapine [N = 20], olanzapine [N = 13], risperidone [N = 38], haloperidol [N = 43], and sertindole [N = 8]). Measures of maximal weight gain, final weight, and duration to maximal weight gain were calculated.


RESULTS
Repeated measures analyses of variance controlling for age, treatment duration, and initial weight revealed statistically significant differences between groups on all 3 measures. Clozapine and olanzapine had the greatest maximal weight gain liability (F = 4.13, df = 4,23; p = .01). Weight gain with clozapine, but not olanzapine or risperidone, appears to persist (as reflected by final weight) despite behavioral interventions (e.g., nutritional consultation, suggested exercise regimen; F = 5.69, df = 4,23; p = .003). Clozapine- and olanzapine-treated subjects appeared to gain weight over a prolonged period of time, whereas risperidone-and sertindole-treated subjects had a more limited period of weight gain (F = 2.95, df = 4,25; p = .04).


CONCLUSIONS
Clozapine and olanzapine caused the most weight gain, risperidone was intermediate, and sertindole had less associated weight gain than haloperidol. The relative receptor affinities of the novel antipsychotics for histamine H1 appear to be the most robust correlate of these clinical findings.
Department of Psychiatry, V.A. Greater Los Angeles Healthcare System, CA 90073, USA. ames@ucla.edu
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Wirshing
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Wirshing
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Berisford
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Goldstein
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Mintz
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Marder
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009765:Obesity / Q000139:chemically induced; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010919:Placebos; D012189:Retrospective Studies; D018967:Risperidone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D010919:Placebos; D001569:Benzodiazepines; D010890:Pirenzepine; C066304:sertindole; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine