Weight gain in the treatment with "atypical neuroleptics" - an underestimated side-effect?

After the introduction of the so-called "atypical neuroleptics" in the clin ical experience a marked weight gain was frequently observed in patients tr eated with some of these agents. In this review the frequency, amount and c onditions of weight gain during the medication with 'atypical' neuroleptics were evaluated. A comparison is limited by the different designs and recru itment procedures of the reviewed studies. The available data show that the frequency as well as the amount of weight gain is particularly high in pat ients treated with clozapine, olanzapine, and likely also quetiapine and zo tepine. Moderate changes of weight have been observed in the treatment with risperidone and probably also with amisulpride, while ziprasidone seems to induce only clinically irrelevant weight changes. Weight gain most frequen tly occurs in the first weeks of treatment. Underweighted patients are at h ighest risk to gain weight. The underlying pathomechanism still remains wid ely unclear. The relative receptor affinities of the atypical antipsychotic s for histamine H-1 as well as their quotient of 5-HT2/D-2 receptor affinit y appear to be a correlate of weight gain. Furthermore, the induction of le ptin secrection may have an important impact on weight gain in subjects tre ated with atypical neuroleptics. Although many questions concerning the con ditions of weight gain remain unsolved, this side-effect has to be consider ed in the medication with many atypical neuroleptics, particularly in view of compliance in long-term treatment and possible medical complications.