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 tryptophan hydroxylase (TPH) gene variant on the antidepressant activity of fluvoxamine in a sample of major and bipolar depressives, with or without psychotic features. Two hundred and seventeen inpatients were treated with fluvoxamine 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 subjects not taking pindolol (P = 0.001). This effect was independent from the previously reported influence of 5-HTTLPR polymorphism. If confirmed, these results may shed further light on the genetically determined component of the response to pharmacological treatments, thus helping the clinician to individualize each patient's therapy according to their genetic pattern.
Serretti
A
A
Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Milan, Italy. serretti.alessandro@hsr.it
Zanardi
R
R
Rossini
D
D
Cusin
C
C
Lilli
R
R
Smeraldi
E
E
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D003702:Delusions; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004357:Drug Synergism; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010869:Pindolol / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D016666:Fluvoxamine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010869:Pindolol; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase; C493230:SLC6A4 protein, human