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 serotonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTTLPR) 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 features.


METHODS
One hundred fifty-five 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. Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique.


RESULTS
5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the severity of depressive symptomatology did not influence this association. Conversely, pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects, thus reducing the difference in the response rate among the genotype variants.


CONCLUSIONS
If confirmed, these results may improve patient care by helping the clinician to individualize treatment according to the patient's genetic 5-HTTLPR pattern.
Zanardi
R
R
Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Via Prinetti, Milan 29-20127, Italy.
Serretti
A
A
Rossini
D
D
Franchini
L
L
Cusin
C
C
Lattuada
E
E
Dotoli
D
D
Smeraldi
E
E
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D003702:Delusions / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000008:administration & dosage* / Q000009:adverse effects; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010869:Pindolol / Q000008:administration & dosage* / Q000009:adverse effects; D011110:Polymorphism, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000928:Antidepressive Agents; 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; C493230:SLC6A4 protein, human