Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: findings of a randomized clinical trial in a drug-naïve population

Schizophr Res. 2008 Feb;99(1-3):13-22. doi: 10.1016/j.schres.2007.10.022. Epub 2007 Dec 3.


Background: There is little information about weight gain induced by antipsychotics at long-term.

Objective: To quantify the weight gain induced by first (haloperidol) and second generation antipsychotics (olanzapine and risperidone) in a cohort of drug-naïve subjects after 1 year of treatment.

Methods: This is a prospective, randomized clinical trial, including a representative sample of first episode psychotic incident cases from a population area of 555.000 people. The main outcome measures were changes in body weight and body mass index at 3 months and at 12 months. Both a per protocol analysis and an intention to treat analysis were conducted.

Results: A total of 164 drug-naïve patients were included. At 12 months 144 patients were evaluated. Of them, 66% completed the protocol and 34% needed treatment switch. We found statistically significant differences in weight gain at 3 months: 3.8 kg (+/-4.1) for haloperidol, 5.9 kg (+/-5.1) for risperidone and 8.4 kg (+/-5.0) for olanzapine (F=7.045; p=0.002). After 1 year the difference in weight gain had disappeared: 9.7 kg (+/-5.7) for haloperidol, 8.9 kg (+/-8.8) for risperidone and 10.9 kg (+/-7.2) for olanzapine (F=0.817; p=0.445).

Conclusions: Drug-naïve patients experience an extraordinary weight gain after 1 year of treatment with haloperidol, olanzapine or risperidone. The main difference among these treatments is the pattern of weight gain but not the final amount of weight gain.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use
  • Body Mass Index
  • Chronic Disease
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Haloperidol / adverse effects*
  • Haloperidol / therapeutic use
  • Humans
  • Long-Term Care
  • Male
  • Middle Aged
  • Olanzapine
  • Risperidone / adverse effects*
  • Risperidone / therapeutic use
  • Spain
  • Treatment Outcome
  • Weight Gain / drug effects*


  • Antipsychotic Agents
  • Benzodiazepines
  • Haloperidol
  • Risperidone
  • Olanzapine