3 ‘next-step’ treatments appear effective for patients with MDD, comorbid PTSD
Patients with major depressive disorder and comorbid PTSD who were unresponsive to antidepressant treatment exhibited a positive response to three “next-step” treatments, according to a study published in Journal of Clinical Psychiatry.
“A recent randomized clinical trial of alternative next step treatments, the Veterans Administration (VA) Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, recruited veterans who had been unresponsive to previous antidepressant treatment and evaluated three next-step prescribing strategies,” Somaia Mohamed, MD, PhD, associate director of the VA Northeast Program Evaluation Center, and colleagues wrote. “Augmentation with the antipsychotic aripiprazole resulted in a significantly greater likelihood of remission compared [with] switching to bupropion monotherapy during a 12-week acute treatment phase and a greater likelihood of response (greater than 50% improvement) than either switching to bupropion or augmenting previous antidepressant therapy with bupropion during a 24-week extension phase for responders.”
In the current secondary analysis of data from the VAST-D study, Mohamed and colleagues aimed to determine whether concurrent PTSD should affect the decision of whether to switch or augment medications when MDD failed to respond to prior antidepressant treatment. The VAST-D study included 1,522 patients with nonpsychotic MDD across 35 VA medical centers from December 2012 to May 2015. These patients exhibited a suboptimal response to antidepressant treatment and were randomly assigned to three next-step treatments — a switch to bupropion, augmentation of the current antidepressant with bupropion and augmentation with the antipsychotic aripiprazole. Investigators determined 12-week response and remission, as well as relapse after remission, using blinded ratings with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated. They used survival analyses to compare treatment effects among 717 patients with concurrent PTSD and who were diagnosed with the Mini-International Neuropsychiatric Interview and 805 patients without PTSD.
Results showed those with PTSD exhibited more severe depressive symptoms at baseline and were less likely to achieve 12-week response or remission. Among patients with PTSD RR = 1.26; 95% CI, 1.01-1.59) and patients without PTSD (RR = 1.29; 95% CI, 1.05-1.97), augmentation with aripiprazole was linked to greater likelihood of achieving response (68.4%) than switching to bupropion (57.7%). The group that received augmentation with bupropion did not exhibit significant treatment comparisons, and the researchers observed no significant interaction between PTSD and treatment group on remission (P = .7), response (P = .98) or relapse (P = .15).
“VAST-D is the first randomized trial of next-step pharmacotherapy to our knowledge that directly allows evaluation of the potential impact of PTSD multimorbidity on the comparative effectiveness of MDD treatments and thus reflects a kind of secondary analysis that will be increasingly important in the interpretation of psychiatric effectiveness trials in the presence of potentially biasing concurrent disorders and comorbidities,” Mohamed and colleagues wrote.