Is the CYP2D6 Genotype Associated with Antipsychotic-Induced Weight Gain?

Area of Science:

• Pharmacogenomics
• Clinical Pharmacology
• Psychiatry

Background:

• Antipsychotic-induced weight gain (AIWG) is a significant adverse effect of antipsychotic medications.
• Previous studies suggest a link between genetically predicted CYP2D6 metabolic capacity and AIWG, but the evidence is inconsistent.

Purpose of the Study:

• To investigate the association between genetically predicted CYP2D6 metabolic capacity and AIWG.
• To analyze data from a randomized controlled trial (RCT) on the clinical utility of routine CYP2D6 and CYP2C19 genotyping in schizophrenia patients.

Main Methods:

• Multiple regression analyses were performed on data from 211 schizophrenia patients.
• Genetically predicted CYP2D6 metabolic capacity (poor metabolizers and ultrarapid metabolizers) was examined in relation to AIWG.
• Covariates including baseline body mass index and chlorpromazine equivalents were adjusted for.

Main Results:

• Significant weight gain was observed in both CYP2D6 poor metabolizers (PMs) (4.00 kg) and ultrarapid metabolizers (UMs) (6.50 kg).
• These findings remained significant after adjusting for covariates (PMs: 4.26 kg, UMs: 7.26 kg).
• Baseline BMI and antipsychotic dosage (chlorpromazine equivalents) were also significantly associated with weight change.

Conclusions:

• Genetically predicted CYP2D6 metabolic capacity plays a role in AIWG.
• Routine genotyping of CYP2D6 may help predict and manage AIWG in patients with schizophrenia.
• Further research is warranted to elucidate the mechanisms and clinical implications.