Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity

The aim of the present study was to test a possible effect of the A218C try ptophan hydroxylase (TPH) gene variant on the antidepressant activity of fl uvoxamine in a sample of major and bipolar depressives, with or without psy chotic features. Two hundred and seventeen inpatients were treated with flu voxamine 300 mg and either placebo or pindolol in a double blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. TPH allelic variants were determined in each subject by using a PCR-based technique. No significant finding was observed in the overall sample as well as in the pindolol group, while TPH* A/A was associated with a slower response to fluvoxamine treatment in subje cts not taking pindolol (P = 0.001). This effect was independent from the p reviously reported influence of 5-HTTLPR polymorphism. If confirmed, these results may shed further light on the genetically determined component of t he response to pharmacological treatments, thus helping the clinician to in dividualize each patient's therapy according to their genetic pattern.