CNS Drugs

, Volume 22, Issue 6, pp 477–495 | Cite as

Pharmacological Management of Atypical Antipsychotic-Induced Weight Gain

  • Trino Baptista
  • Yamily ElFakih
  • Euderruh Uzcátegui
  • Ignacio Sandia
  • Eduardo Tálamo
  • Enma Araujo de Baptista
  • Serge Beaulieu
Review Article


Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p < 0.001).

Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics.

In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate.

More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient’s personal and family history of bodyweight gain and metabolic dysfunction.


Metformin Clozapine Risperidone Olanzapine Quetiapine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This article was supported by Fondo Nacional de Ciencia, Tecnología e Investigación (FONACIT), Caracas, Venezuela, grant no. 2005-000-384. The authors have no other conflicts of interest that are directly relevant to the content of this review. The authors particularly thank Françoise Meyer for her editorial assistance.


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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Trino Baptista
    • 1
  • Yamily ElFakih
    • 2
  • Euderruh Uzcátegui
    • 2
  • Ignacio Sandia
    • 2
  • Eduardo Tálamo
    • 3
  • Enma Araujo de Baptista
    • 4
  • Serge Beaulieu
    • 5
  1. 1.Department of PhysiologyLos Andes University Medical SchoolMéridaVenezuela
  2. 2.Department of PsychiatryLos Andes University Medical SchoolMéridaVenezuela
  3. 3.Private PsychiatristBarquisimetoVenezuela
  4. 4.Department of MicrobiologyLos Andes University Pharmacy SchoolMéridaVenezuela
  5. 5.Douglas Hospital Research CenterMcGill UniversityVerdunCanada

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