Although the mechanisms explaining metabolic impairments observed during antipsychotic treatment are not well known, there are important differences between drugs regarding the possibility of inducing lipidic and glucose impairments.

To assess the effects of atypical and typical antipsychotics -olanzapine, aripiprazole, risperidone and haloperidol over the weight, glucose and HDL-cholesterol levels, during 24 weeks of treatment.

A 43 patients group, 30 male and 13 female, mean age 42.1, admitted during an acute phase of chronic schizophrenia (DSM-IV-TR), were distributed on flexible dose of olanzapine (N=12) 10-20 mg/day, aripiprazole (N=11) 15-30 mg/day, risperidone (N=10) 4-8 mg/day or haloperidol (N=10) 10-20 mg/day. Weight, fasting glucose and HDL-cholesterol were weekly monitored during the first month and monthly after that. Inclusion criteria: baseline glucose and HDL-cholesterol levels within normal range. Exclusion criteria: familial history of diabetus mellitus or obesity.

Regarding the weight gain, the safest antipsychotic is aripiprazole (+0.4+/-0.2 kg at endpoint), followed by haloperidol (+1.9+/-0.2 kg), while olanzapine (+5.6+/-1.1 kg) and risperidone (+3.4+/-0.5 kg) are less tolerated. The glucose level >125 mg/dl was observed at endpoint in 3 patients with risperidone, 6 with olanzapine, 2 with haloperidol. The HDL-cholesterol over 40 mg/dl (men) and over 50 mg/dl (female) appeared in 4 cases of olanzapine and 3 cases of risperidone treated patients.

There are quantitative differences in the level of weight gain, HDL-cholesterol and glucose level induced by antipsychotics. The safest antipsychotic agent is aripiprazole because it doesn't induce significant weight gain or other metabolic complications.