For individuals with treatment-resistant depression, further research is needed to improve the standard of care, as well as treatment outcomes. When a patient has failed several adequate antidepressant trials, what’s the next step? Should one switch to another antidepressant or augment with an atypical antipsychotic agent, or should one consider TMS or ECT? All of these are valid, evidence-based approaches, but which is the most likely to be successful?
In a recent article published in Molecular Psychiatry, researchers from the Clinical Trials Network and Institute, including George Papakostas, MD and Maurizio Fava, MD, present data that helps to answer this important clinical question. They report on the ASCERTAIN-TRD study comparing the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the SNRI antidepressant venlafaxine (or duloxetine for those not eligible to receive venlafaxine) in a cohort of patients with treatment-resistant depression.
In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years) with treatment-resistant depression were randomly assigned to one of the three interventions listed above. These three options were chosen due to their popularity and widespread use. A total of 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis.
- With all three interventions, patients experienced a reduction in the severity of depressive symptoms.
- Augmentation with rTMS was more effective than switching antidepressants or augmentation with aripiprazole (changes in MADRS scores)
- Augmentation with rTMS was associated with higher rates of response (52.2%) compared to aripiprazole augmentation (38.1%) or switching to venlafaxine/duloxetine (35.8%).
- Augmentation with rTMS was associated with higher rates of remission (34.2%) compared to aripiprazole augmentation (25.3%) or switching to venlafaxine/duloxetine (24.9%).
Clinical Implications
Patients with treatment-resistant depression are those who have experienced insufficient symptom improvement following treatment with two or more antidepressant therapies. An unanswered question is whether adding a treatment for these patients to their medications is superior to switching them to a new antidepressant altogether.
Data from the current study indicates that adding rTMS, but not adding aripiprazole was more effective than changing antidepressants in patients with treatment-resistnat depression. In addition, a smaller but statistically significant advantage was found for aripiprazole augmentation versus switching to venlafaxine on patient-rated symptoms of depression.
While we have an array of antidepressants to choose from, TRD remains a significant challenge for clinicians and patients alike, and further research is needed to help improve both the standard of care and outcomes for patients with TRD. The findings of the ASCERTAIN-TRD study suggest that rTMS should be considered early on as an addition to patients’ treatment regimens for this patient population.
Other contributors to this study include Madhukar H Trivedi, Richard C Shelton, Dan V Iosifescu, Michael E Thase, Manish K Jha, Sanjay J Mathew, Charles DeBattista, Mehmet E Dokucu, Olga Brawman-Mintzer 9, Glenn W Currier 10, William Vaughn McCall 11, Mandana Modirrousta 12, Matthew Macaluso, Alexander Bystritsky, Fidel Vila Rodriguez, Erik B Nelson, Albert S Yeung, Anna Feeney, Leslie C MacGregor, and Thomas Carmody.
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Papakostas GI, Trivedi MH, Shelton RC, Iosifescu DV, Thase ME, Jha MK, Mathew SJ, DeBattista C, Dokucu ME, Brawman-Mintzer O, Currier GW, McCall WV, Modirrousta M, Macaluso M, Bystritsky A, Rodriguez FV, Nelson EB, Yeung AS, Feeney A, MacGregor LC, Carmody T, Fava M. Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial. Mol Psychiatry. 2024 Mar 7.
