• atypical antipsychotics;
  • chronic treatments;
  • metabolic safety;
  • overweight


The increased rates of both overweight and obesity reported in severely mentally-ill patients are prevalently due to the use of second-generation antipsychotics (SGAs). Hence, the main purpose of this article is to analyze systematically potential patient- and drug-related factors which may increase the risk of weight gain during long-term treatment with such medications. Literature information published in English since 1966 and last updated on 17 January 2009 was identified through different databases and using various combinations of search terms. Searches provided 242 articles, whereas 6 additional references were identified manually. Peer-reviewed articles focusing on the risk of weight gain during SGA-chronic treatment (at least 52 weeks, N = 81) were acquired. Data were extracted from the 39 peer-reviewed articles which investigated factors potentially associated with an increased risk of this event. Evidence-based information suggests that a number of factors, either patient- (age, baseline BMI/bodyweight, recent onset of psychotic episodes, need of concomitant psychotropic medications) or drug-specific (relative receptorial affinity, timing of weight changes plateau, daily dose, iatrogenic concomitant changes in biochemical metabolic parameters) may contribute to increase either rates and/or magnitude of this effect during long-term treatments with specific SGAs. All contributors and their relationship with specific drugs should be taken into consideration when designing a long-term therapy with SGAs. Among the best studied agents (clozapine, olanzapine, and risperidone) of this class, the latter seems to be the most susceptible drug to the amplifying effects of both patient- and drug-related factors on the risk of inducing weight changes during chronic treatments.