The International Journal of Neuropsychopharmacology

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

Cristina  Cusin  a1, Alessandro  Serretti  a1 c1, Raffaella  Zanardi  a1, Enrico  Lattuada  a1, David  Rossini  a1, Roberta  Lilli  a1, Cristina  Lorenzi  a1 and Enrico  Smeraldi  a1
a1 Department of Psychiatry, Vita-Salute University, Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy


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.

(Received July 30 2001)
(Reviewed October 7 2001)
(Revised October 28 2001)
(Accepted November 4 2001)

Key Words: Antidepressant treatment; fluvoxamine; mood disorders; paroxetine; pharmacogenetics; pindolol.

c1 Address for correspondence: Dr A. Serretti, Department of Psychiatry, Istituto Scientifico H. San Raffaele, Vita-Salute University, Via Stamira D'Ancona 20 – 20127, Milano, Italy. Tel.: 39 02 2643 3250 Fax: 39 02 2643 3265 E-mail: