Influence of monoamine oxidase A and serotonin receptor 2A polymorphisms in SSRI antidepressant activity

• Published in: The international journal of neuropsychopharmacology Vol. 5; no. 1; pp. 27 - 35
• Main Authors: Cusin, Cristina, Serretti, Alessandro, Zanardi, Raffaella, Lattuada, Enrico, Rossini, David, Lilli, Roberta, Lorenzi, Cristina, Smeraldi, Enrico
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.03.2002; Oxford University Press
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Antidepressive Agents, Second-Generation - therapeutic use; Antimanic Agents - therapeutic use; Depressive Disorder - drug therapy; Depressive Disorder - genetics; Depressive Disorder - psychology; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - psychology; Double-Blind Method; Drug Synergism; Female; Fluvoxamine - therapeutic use; Genotype; Humans; Lithium - therapeutic use; Male; Middle Aged; Monoamine Oxidase - genetics; Paroxetine - therapeutic use; Pindolol - therapeutic use; Polymorphism, Genetic - genetics; Polymorphism, Genetic - physiology; Psychiatric Status Rating Scales; Receptor, Serotonin, 5-HT2A - genetics; Receptor, Serotonin, 5-HT2A - physiology; Serotonin Uptake Inhibitors - therapeutic use; Sex Characteristics; paroxetine; Antidepressant treatment; fluvoxamine; pindolol; mood disorders; pharmacogenetics
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145701002711

The aim of the present study was to test a possible effect of the monoamine oxidase A (MAOA) and serotonin receptor 2A (5-HT-2A) gene variants on the antidepressant activity of fluvoxamine and paroxetine in a sample of major (n = 248) and bipolar (n = 195) depressives, with or without psychotic features. A total of 443 in-patients were treated with 300 mg fluvoxamine (n = 307) or 20–40 mg paroxetine (n = 136) for 6 wk. The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression (HAMD). Allele variants were determined in each subject using a PCR-based technique. We observed a marginal association between 5-HT-2A variants and antidepressant response while MAOA genotypes were not associated. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, HAMD scores at baseline, pindolol augmentation and SSRIs plasma levels did not significantly influence the observed results. The investigated MAOA and 5-HT-2A gene variants, therefore, do not seem to play a major role in SSRI antidepressant activity.