Meta-analysis of the Metabolic Effects of Second-generation Antipsychotics

Introduction

In the therapy of schizophrenia, second-generation antipsychotics are currently the first-line treatment. Their advantages mainly include reduced risk of disease relapse, relatively low incidence of bothersome side effects (unlike first-generation antipsychotics), and the availability of some medications in depot injection form. However, common side effects include weight gain and negative impact on energy metabolism, which can lead to the development of type 2 diabetes and increased levels of cholesterol and triglycerides in the blood, with all associated consequences.

Analyzed Data

The effects of second-generation antipsychotics on body weight and metabolic parameters were examined in a meta-analysis of randomized controlled and observational studies, published from June 2009 to November 2020. Parameters (weight, BMI, levels of total, HDL and LDL cholesterol, triglycerides, glycemia, and blood pressure values) measured before treatment initiation and at the end of observation were compared. The evaluated drugs were lurasidone, aripiprazole, olanzapine, paliperidone in extended-release form (XR), quetiapine XR, and risperidone.

Out of 3076 available studies, 79 were selected for the meta-analysis. These comprised prospective (34%), retrospective (5%), and randomized controlled trials (61%). The total number of participants was 37,467, with an average age of 36 years, and 62% were men. A total of 49 studies evaluated olanzapine, 27 risperidone, 20 aripiprazole, 19 lurasidone, 13 quetiapine, and 6 paliperidone.

Findings

The lowest body weight gain was observed with lurasidone therapy (+0.43 kg), accompanied by a decrease in BMI (−0.10 kg/m²). This antipsychotic also reduced levels of total cholesterol (−0.21 mmol/l) and triglycerides (−0.06 mmol/l), while increasing HDL cholesterol (+0.05 mmol/l). Conversely, the highest weight gain was noted with olanzapine (+4.52 kg) and risperidone (+4.19 kg). Olanzapine therapy was also associated with the greatest increase in BMI (+1.59 kg/m²), triglycerides (+0.37 mmol/l), and fasting glycemia (+0.3 mmol/l). The most significant increase in total cholesterol was found with paliperidone (+0.38 mmol/l). The greatest impact on blood pressure was seen with quetiapine XR (increase of 2.60/2.77 mmHg).

Discussion and Conclusion

Schizophrenia is a serious psychiatric disorder that can significantly impact the health and socioeconomic status of the patient and their family. Compared to the general population, patients with schizophrenia have nearly twice the risk of developing diabetes and metabolic syndrome, and their cardiovascular mortality is also significantly higher. This may partly be due to the lifestyle influenced by psychiatric illness. However, side effects of antipsychotics also undoubtedly play a role. Without their use, the consequences of the illness would be devastating for the patient.

The best metabolic and cardiovascular profile in the cited meta-analysis was observed with lurasidone, which decreased BMI, total cholesterol, triglycerides, and fasting glycemia. The least favorable metabolic profile was associated with olanzapine and risperidone, where weight gain and disruption of the lipid spectrum were noted.

Despite some limitations (such as different dosing schedules among patients and not including some other side effects), this meta-analysis provided a fairly accurate assessment of the metabolic and cardiovascular risks of individual second-generation antipsychotics. The results can serve as a basis for decision-making in clinical practice and for further research.

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Source: Rognoni C., Bertolani A., Jommi C. Second-generation antipsychotic drugs for patients with schizophrenia: systematic literature review and meta-analysis of metabolic and cardiovascular side effects. Clin Drug Investig 2021 Apr; 41 (4): 303−319, doi: 10.1007/s40261-021-01000-1.