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

Introduction To assess the risk of occurrence and potential determinants of metabolic disorders in adult patients treated with second-generation antipsychotics (SGAs) under real-world practice conditions. Methods MEDLINE, EMBASE, and PsycInfo were searched in July 2019 from database inception. We included population-based, longitudinal, comparative studies that report the results of the outcomes of interest for adult participants, including diabetes, ketoacidosis, hyperosmolar hyperglycemic state, weight gain/obesity, dyslipidemia, hypertension, and metabolic syndrome. Two reviewers independently extracted data on the study design, study quality, and study outcomes. Results We included 40 studies. Most studies showed that clozapine and olanzapine were associated with an increased likelihood of developing diabetes, while the results for risperidone and quetiapine were mixed. Although less well studied, ziprasidone and aripiprazole appeared to not be associated with the occurrence of diabetes. Information on antipsychotic-induced weight gain/obesity is extremely scarce. Regarding dyslipidemia, aripiprazole was not associated with an increased likelihood of developing dyslipidemia, clozapine was associated with an increased likelihood of developing dyslipidemia, and risperidone, olanzapine, quetiapine, and ziprasidone showed mixed results. Two studies suggested an association between ziprasidone and the occurrence of hypertension. Several studies found that the occurrence of a metabolic disorder acted as a risk factor for the development of other metabolic disorders. We did not find information on brexpiprazole, cariprazine, or lurasidone, and data on any long-acting SGA were lacking. Conclusion Although there are relevant differences among SGAs concerning the risk of metabolic disorders, it appears that none of the SGAs included in our review are fully devoid of these disturbances. Plain Language Summary 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.