UGT2B7 372A>G Polymorphism is related to a Therapeutic Response to Lamotrigine Augmentation Therapy in Depressed Patients Who Did Not Respond to Adequate Treatment: A Preliminary Study
Purpose: Lamotrigine is mainly metabolized by UGT1A4 and UGT2B7, both of which are expressed in the blood-brain barrier. Polymorphisms of said UDPglucuronosyltransferases, (UGTs) that affect enzyme activities have been reported. This study investigated the relationship between these polymorphisms and its therapeutic effect in 55 depressed patients who did not respond to adequate treatment during an 8-week treatment of lamotrigine augmentation using an open-study design.
Patients and Methods: The subjects were 55 depressed patients who had already shown insufficientc response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n=22), bipolar I disorder (n=9), and bipolar II disorder (n=24). The final doses of lamotrigine were 100 mg/d for 33 subjects who were not taking valproate and 75 mg/d for 22 subjects taking valproate, respectively. Depressive symptoms were evaluated by the Montgomery Åsberg Depression Rating Scale before and after the 8-week treatment. Blood sampling was performed at week 8. The genotypes of these polymorphisms were identified by Polymerase Chain Reaction (PCR).
Results: Percentage improvements at week 8 were significantly (P<0.05) higher in the patients with A/A genotype of UGT2B7 372A>G (48.8 ± 29.8%) than in those with A/G or G/G genotype (31.5 ± 27.6%). There was no significant relationship between the percent improvements and the UGT1A4 142T>G or UGT2B7- 161C>T polymorphism.
Conclusion: The present study suggests that the UGT2B7 372A>G polymorphism may be partially related to a therapeutic response to lamotrigine augmentation therapy in depressed patients who did not respond to adequate treatment.