CYP2D6 Genetic Variation and Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis

Area of Science:

• Pharmacogenomics
• Metabolic disorders
• Psychiatric pharmacotherapy

Background:

• Antipsychotic-induced weight gain is a significant issue impacting the health and life expectancy of individuals with psychotic disorders.
• The liver enzyme CYP2D6 plays a crucial role in metabolizing many common antipsychotic medications.
• Understanding the influence of genetic variations in CYP2D6 on weight changes during antipsychotic treatment is important for personalized medicine.

Purpose of the Study:

• To investigate the association between CYP2D6 genetic variations and antipsychotic-induced weight gain or BMI changes.
• To synthesize existing evidence through a systematic review and meta-analysis.

Main Methods:

• A systematic review and random-effects meta-analysis of studies reporting BMI and/or weight measurements in patients on long-term antipsychotics.
• Patients were categorized into CYP2D6 metabolic groups: poor, intermediate, normal/extensive, and ultra-rapid metabolizers.
• Databases searched included Pubmed, Embase, PsychInfo, and CENTRAAL.

Main Results:

• Twelve studies were included in the systematic review; cohort studies suggested an association between reduced CYP2D6 function and greater weight gain, while cross-sectional studies did not.
• The meta-analysis included 17 studies with 2,041 patients. No significant associations were found between CYP2D6 metabolic groups (PM, IM, NM, UM) and weight or BMI.
• Pooled standardized differences for PM vs. NM and IM vs. NM comparisons showed no statistically significant impact on weight or BMI.

Conclusions:

• While cohort studies suggest a potential link between CYP2D6 poor metabolizer status and higher BMI, the meta-analysis and cross-sectional data did not support this.
• The current literature is limited by small sample sizes, particularly for extreme CYP2D6 metabolizer groups (poor and ultra-rapid).
• Larger studies focusing on extreme metabolizers are needed to determine the clinical utility of CYP2D6 genotyping for guiding antipsychotic treatment and managing weight-related side effects.