Clin Psychopharmacol Neurosci.  2012 Apr;10(1):49-53.

No Association between the Response to the Addition of an Atypical Antipsychotic Drug to an Selective Serotonin Reuptake Inhibitor or Serotonin Norepinephrine Reuptake Inhibitor and the Brain-Derived Neurotrophic Factor (Val66Met) Polymorphism in Refracto

  • 1Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.
  • 2Department of Psychiatry Research, The Zucker Hillside Hospital, New York, USA.
  • 3Department of Psychiatry, Fujita Health University, School of Medicine, Toyoake, Japan.


OBJECTIVE: This study examined the association between the brain-derived neurotrophic factor (BDNF) (Val66Met) polymorphism and the response to the addition of an atypical antipsychotic drug to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in treatment-refractory depression.
The study enrolled 64 patients meeting the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depressive disorder who were treated with at least two courses of a single antidepressant, but who had Hamilton Depression Rating Scale (HAMD-17) scores > or =15 points that were reduced less than 50% over at least a 4-week treatment period. There were 24 males and 40 females (age range 27-68 years; mean+/-SD, 48+/-13 years). The patients' clinical improvement was evaluated using the HAMD-17. Patients with at least a 50% decrease in the HAMD-17 score were defined as responders. Serum BDNF levels were assayed using enzyme-linked immunosorbent assays and the presence of the BDNF (Val66Met) polymorphism was determined using the TaqMan genotyping assay.
No correlation was found between the BDNF (Val66Met) polymorphism and a positive response to adding an atypical antipsychotic drug. No differences were observed in the changes in the serum BDNF levels and HAMD-17 scores between Val66Val and Met-carriers. In addition, in patients who experienced remission, the atypical antipsychotic drug was discontinued after at least 3 months of treatment and the patients were then followed for 1 year; 14 of 27 patients (52%) relapsed within 1 year.
These results suggest that the BDNF (Val66Met) polymorphism is not associated with the response to the augmentation of a SSRI or SNRI with an atypical antipsychotic drug, and that the combination of an atypical antipsychotic drug and a SSRI or SNRI should be continued for 3 months or more in refractory depressed patients in the Japanese population.


Brain-derived neurotrophic factor; Treatment-resistant depressive disorder; Antipsychotic drug; Polymorphism; Selective Serotonin Reuptake Inhibitor; Serotonin Norepinephrine Reuptake Inhibitor
Full Text Links
  • CPN
  • Twitter
  • Facebook
Copyright © 2020 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: