Factors affecting fluvoxamine antidepressant activity: Influence of pindolol and 5-HTTLPR in delusional and nondelusional depression

Background: It has been recently reported that the short variant of the ser otonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTT LPR) influences the antidepressant response to certain selective serotonin reuptake inhibitors. The aim of the present study was to test this finding in a sample of major and bipolar depressives, with or without psychotic fea tures. Methods: One hundred fifty-five inpatients were treated with fluvoxamine 30 0 mg and either placebo or pindolol in a double-blind design for 6 weeks. T he severity of depressive symptoms was weekly assessed with the Hamilton Ra ting Scale for Depression. Allelic variation of 5-HTTLPR in each subject wa s determined using a polymerase chain reaction-based technique. Results: 5-HTTLPR short variant was associated with a poor response to fluv oxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the s everity of depressive symptomatology did not influence this association. Co nversely, pindolol augmentation may ameliorate the rate of response in 5-HT TLPR short van. ant subjects, thus reducing the difference in the response rate among the genotype variants. Conclusions: If confirmed, these results may improve patient care by helpin g the clinician to individualize treatment according to the patient's genet ic 5-HTTLPR pattern. Biol Psychiatry 2001;50:323-330 (C) 2001 Society of Bi ological Psychiatry.