Real-World Data on the Adverse Metabolic Effects of Second-Generation Antipsychotics and Their Potential Determinants in Adult Patients: A Systematic Review of Population-Based Studies

Patients with severe mental disorders often present metabolic disorders such as obesity, increased blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels. Treatment with antipsychotics may contribute to the occurrence of these disorders. Using a systematic review, we have evaluated the risk of occurrence of these metabolic disorders associated with the most frequently used antipsychotics—the so-called second-generation antipsychotics (SGAs)—and which factors increase the patient chances of presenting a metabolic disorder when they are treated with these drugs under routine clinical practice. After reviewing 40 studies, we found that, although there are relevant differences among SGAs concerning the risk of metabolic disorders, it appears that none of the drugs included in our review are fully free of these disturbances. Among the factors that increase the chances of these disturbances, we highlight that the presence of a particular metabolic disorder (e.g., increased blood pressure) acts as a risk factor for the occurrence of other metabolic disorders (e.g., high blood sugar), and that the duration of treatment could be a relevant factor for the occurrence of these disorders. Finally, we also found important gaps in our knowledge about this matter, mainly the limited information on the SGAs apparently associated with lower risk of metabolic disorders in experimental studies (that is, few studies evaluating ziprasidone and aripiprazole, and none evaluating brexpiprazole, cariprazine, or lurasidone) and the lack of information on long-acting injectable (that is, antipsychotics that are usually given every 2–4 weeks) SGAs.