Effectiveness study of venlafaxine-XR combined with aripiprazole for chronic or recurrent major depressive disorder

Andrew A. Nierenberg, Madhukar H. Trivedi, Bradley N. Gaynes, Jeff Mitchell, Lori L. Davis, Mustafa M. Husain, Stephen R. Wisniewski, Maurizio Fava, Diane Warden, James F. Luther, Adrienne O. Van Nieuwenhuizen, David W. Morris, Richard C. Shelton, A. John Rush

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9 Scopus citations


Objective: Although the second-generation antipsychotic, aripiprazole (ARI), has been approved as an adjunct for treatment-resistant major depressive disorder (MDD), neither ARI nor any second-generation antipsychotic has been assessed in combination with an antidepressant at the initiation of a treatment trial for non-treatment-resistant MDD. The aim of the present study was therefore to assess the safety, tolerability, and remission rate in the treatment of MDD using the specific combination of venlafaxine-XR (VEN-XR) and ARI in a generalizable, difficult-to-treat group with chronic or recurrent MDD. Methods: Self-declared participants in primary care or psychiatric settings who had chronic or recurrent MDD and a minimum score of 14 on the 17-item Hamilton Rating Scale for Depression were included. Up to 12 weeks of open treatment with the combination of VEN-XR and ARI was provided. Participants began with VEN-XR, and ARI was added at week 2. Maximum allowable doses were 300 mg day 1 for venlafaxine-XR and 30 mg day1 for ARI. Remission was defined as ≤ 5 on the 16-item Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR16). Results: Fifty outpatients with non-psychotic MDD were enrolled (mean age = 43±11 years; 38% male; QIDS-SR16=15±3). Mean exit dose of VEN-XR was 227±97 mg day1, and the mean exit dose of ARI was 11±7 mg day1. The combination was well tolerated; 16% of participants discontinued due to side-effects. Approximately 70% achieved remission at some point during the trial, and 66% achieved remission at study exit. Conclusions: To the best of the authors' knowledge this is the first study to combine an antidepressant and second-generation antipsychotic at the beginning of a treatment trial for chronic or recurrent non-treatment resistant MDD. VEN-XR and ARI combination appears to warrant further study in controlled trials.

Original languageEnglish (US)
Pages (from-to)956-967
Number of pages12
JournalAustralian and New Zealand Journal of Psychiatry
Issue number10
StatePublished - 2009


  • Aripiprazole
  • Major depressive disorder
  • Venlafazine-XR

ASJC Scopus subject areas

  • Psychiatry and Mental health


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