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Venlafaxine XR treatment for older patients with major depressive disorder: decision trees for when to change treatment
  1. Helena Kyunghee Kim1,
  2. Daniel M Blumberger1,2,
  3. Jordan F Karp3,
  4. Eric Lenze4,
  5. Charles F Reynolds5,
  6. Benoit H Mulsant1,2
  1. 1 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  2. 2 Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  3. 3 Department of Psychiatry, University of Arizona, Tucson, Arizona, USA
  4. 4 Department of Psychiatry, University of Washington, St. Louis, Missouri, USA
  5. 5 Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Professor Benoit H Mulsant, Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada; benoit.mulsant{at}


Background Predictors of antidepressant response in older patients with major depressive disorder (MDD) need to be confirmed before they can guide treatment.

Objective To create decision trees for early identification of older patients with MDD who are unlikely to respond to 12 weeks of antidepressant treatment, we analysed data from 454 older participants treated with venlafaxine XR (150–300 mg/day) for up to 12 weeks in the Incomplete Response in Late-Life Depression: Getting to Remission study.

Methods We selected the earliest decision point when we could detect participants who had not yet responded (defined as >50% symptom improvement) but would do so after 12 weeks of treatment. Using receiver operating characteristic models, we created two decision trees to minimise either false identification of future responders (false positives) or false identification of future non-responders (false negatives). These decision trees integrated baseline characteristics and treatment response at the early decision point as predictors.

Finding We selected week 4 as the optimal early decision point. Both decision trees shared minimal symptom reduction at week 4, longer episode duration and not having responded to an antidepressant previously as predictors of non-response. Test negative predictive values of the leftmost terminal node of the two trees were 77.4% and 76.6%, respectively.

Conclusion Our decision trees have the potential to guide treatment in older patients with MDD but they require to be validated in other larger samples.

Clinical implications Once confirmed, our findings may be used to guide changes in antidepressant treatment in older patients with poor early response.

  • Depression & mood disorders
  • Adult psychiatry

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Contributors BHM contributed to conducting the study, planning, acquisition of the data, data analysis and reporting of the study. BHM is guarantor. HKK contributed to planning, data analysis and reporting of the study. DMB, JFK, EL and CFR contributed to conduct the study, data acquisition and reporting.

  • Funding The IRL-GRey study was supported primarily by the National Institute of Mental Health (R01 MH083660 and P30 MH90333 to University of Pittsburgh, R01 MH083648 to Washington University, and R01 MH083643 to University of Toronto). Additional funding was provided by the UPMC Endowment in Geriatric Psychiatry, the Taylor Family Institute for Innovative Psychiatric Research (at Washington University), the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Centre for Advancing Translational Sciences (NCATS), and the Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto. Pfizer contributed venlafaxine extended-release capsules for this study and Bristol-Myers Squibb contributed aripiprazole and matching placebo tablets for the randomised phase of the study.

  • Competing interests HKK has no competing interests to disclose. DMB has received research support from Canadian Institutes of Health Research (CIHR), US National Institute of Health (NIH), Brain Canada, and the Temerty Family through the CAMH Foundation and the Campbell Family Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway. He is the site principal investigator for three sponsor-initiated studies for Brainsway. He also receives in-kind equipment support from Magventure for two investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. JFK received medication supplies from Pfizer and Indivor for investigator-initiated studies. He is also on the scientific advisory board of Aifred Health. EL has received funding from Takeda, Lundbeck, Janssen, Alkermes, Aptynx, and Patient-Centered Outcomes Research Institute (PCORI). He is also a consultant for Janssen and Jazz Pharmaceuticals. CFR received research support from NIH, PCORI, American foundation for suicide prevention, center for Medicare and Medicaid services, commonwealth of Pennsylvania, and the Brain and behavior research foundation. His work is also sponsored by pharmaceutical supplies from Bristol Meyers Squib and Pfizer. BHM receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He receives research support from Brain Canada, CIHR, the CAMH Foundation, PCORI, NIH, Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). He has been an unpaid consultant to Myriad Neuroscience.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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