Venlafaxine XR treatment for older patients with major depressive disorder: decision trees for when to change treatment.

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.
Competing Interests: 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.
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