Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-httlpr in delusional and nondelusional depression

• Published in: Biological psychiatry (1969) Vol. 50; no. 5; pp. 323 - 330
• Main Authors: Zanardi, Raffaella, Serretti, Alessandro, Rossini, David, Franchini, Linda, Cusin, Cristina, Lattuada, Enrico, Dotoli, Danilo, Smeraldi, Enrico
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-09-2001; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; Antidepressive Agents - administration & dosage; Antidepressive Agents - adverse effects; Biological and medical sciences; Bipolar Disorder - diagnosis; Bipolar Disorder - drug therapy; Bipolar Disorder - genetics; Carrier Proteins - genetics; Delusions - diagnosis; Delusions - drug therapy; Delusions - genetics; depression; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Double-Blind Method; Drug Therapy, Combination; Female; fluvoxamine; Fluvoxamine - administration & dosage; Fluvoxamine - adverse effects; Genetic Variation; Genotype; Humans; Male; Medical sciences; Membrane Glycoproteins - genetics; Membrane Transport Proteins; Middle Aged; Miscellaneous; Mood disorders; Nerve Tissue Proteins; Neuropharmacology; pharmacogenetics; Pharmacology. Drug treatments; pindolol; Pindolol - administration & dosage; Pindolol - adverse effects; Polymorphism, Genetic - genetics; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Serotonin Plasma Membrane Transport Proteins; Serotonin transporter; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - adverse effects; Treatment Outcome; treatment response; Serotonin transporter; fluvoxamine; depression; pindolol; treatment response; pharmacogenetics; Human; Mood disorder; Pharmacogenetics; Serotonin; Psychotropic; Biological transport; Depression; Bipolar disorder; Reuptake inhibitor; Biological activity; Chemotherapy; Treatment; Interindividual comparison; Neurotransmitter; Antidepressant agent; Genetics; Antagonist; Fluvoxamine; Beta blocking agent; Polymorphism
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(01)01118-0

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.