Background: We performed a retrospective analysis of 122 clinical records o
f 92 male patients with DSM-III-R schizophrenia to examine the relative wei
ght 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.
Method: Data were analyzed to determine differences in weight gain during t
reatment among patients receiving 5 different drug treatments (clozapine [N
= 20], olanzapine [N = 13], risperidone [N = 38], haloperidol [N = 43], an
d sertindole [N = 8]). Measures of maximal weight gain, final weight, and d
uration to maximal weight gain were calculated.
Results: Repeated measures analyses of variance controlling for age, treatm
ent duration, and initial weight revealed statistically significant differe
nces between groups on all 3 measures. Clozapine and olanzapine had the gre
atest 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., nutr
itional consultation, suggested exercise regimen; F = 5.69, df = 4,23; p =
.003). Clozapine- and olanzapine-treated subjects appeared to gain weight o
ver 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).
Conclusion: Clozapine and olanzapine caused the most weight gain, risperido
ne was intermediate, and sertindole had less associated weight gain than ha
loperidol. The relative receptor affinities of the novel antipsychotics for
histamine H-1 appear to be the most robust correlate of these clinical fin
dings.