Tryptophan hydroxylase gene associated with paroxetine antidepressant activity

The possible association of the A218C tryptophan hydroxylase (TPH) gene var iant with the antidepressant activity of paroxetine was investigated in a s ample of 121 inpatients affected by a major depressive episode and treated with paroxetine 20-40 mg with either placebo or pindolol in a double blind design for 4 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. TPH allelic variants were d etermined in each subject using a PCR-based technique. TPH*A/A and TPH*A/C variants were associated with a poorer response to paroxetine treatment whe n compared to TPH*C/C (P = 0.005); this difference was not present in the p indolol augmented group. Other variables, such as sex, diagnosis, presence of psychotic features, severity of depressive symptomatology at baseline an d paroxetine plasma level, were not associated with the outcome. TPH gene v ariants are therefore a possible modulator of paroxetine antidepressant act ivity. (C) 2001 Elsevier Science B.V. All rights reserved.