Weight gain as a side effect of antipsychotic treatment has been well documented for over 40 years (29,30) but its importance in the clinical management of chronic schizophrenia has been downplayed (31). Like antidepressants, it is also a common reason for medication non-compliance (31-33). Although numerous mechanisms have been proposed to explain such medication-induced weight gain, the mechanism(s) involved are even less clear than those for antidepressants; some data sup port a role for changes in appetite and food intake, as well as energy expenditure. Mefferd et al. (29) have suggested that increased appetite can account for weight gain, although this is poorly understood. It is possible that increases in thirst (resulting from the anticholinergic action of many drugs) result in increased caloric intake through increased fluid consumption (34), or from inactivity resulting from medication-related sedation (34), although these are presently only hypotheses.
Phenothiazines have been shown to be weight promoting during the chronic treatment of schizeph-renia. Chlorpromazine (35), chlordiazepoxide (36) and thioridazine (36) increased weight significantly, compared to placebo. Ganguli (37) reported weight gain with haloperidol, thiothixane and flu-phenazine. It has been suggested that weight gain is not proportional to dose, since depot injections of varying dosages did not correlate positively with weight gain (37—39). The weight gain can vary between 1—5 kg over several years to exorbitant weight increases in a few months of more than 28 kg, as illustrated in the cases shown in Figure 191.
Clozapine is clearly associated with weight gain during treatment, and is among the greatest weight promoters of the antipsychotics (40,41), while molindone appears to be the only novel compound without weight promoting effects (41). Both clozapine and olanzapine appear to increase body weight through a leptin-mediated mechanism, since serum leptin levels increased during treatment with these compounds (42,43). A recent review ranked weight gain among the novel antipsychotics as follows: clozapine and olanzapine, risperidone and sertindole (44). The authors suggest a strong correlation with the histamine binding properties of these compounds (44) as a possible mechanism of action. Finally, weight gain and obesity may also arise in children after prenatal exposure to anti-psychotic drugs such as haloperidol, which in the case reported by Breum (45) was prescribed as an
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