Emory University researchers provided information about two long-term, National Institute of Health–funded studies in which researchers sought to obtain a better understanding into which factors could aid clinicians in predicting how well three first-line therapies may work for adults diagnosed with major depressive disorder (MDD).
The objective of the PReDICT (Predictors of Remission in Depression to Individual and Combined Treatments) study was to better forecast which individuals who did not have a history of clinical depression treatment improve with the usage of either one of two antidepressant medications (ADM) or with cognitive behavior therapy (CBT).
The researchers indicated that a critical goal of the PreDICT study was to ascertain the mutual and unique modifications in brain resting-state functional connectivity (rsFC) between patients with MDD who improved with CBT versus with ADM.
The latest results focused on the changes in brain circuit connectivity correlated with depressive symptom changes and were recently published in the American Journal of Psychiatry. In this publication, researchers randomized 344 adults aged 18 to 65 years with treatment-naive MDD to 12 weeks of treatment with CBT (16 1-hour sessions) or medication (duloxetine 30-60 mg/day or escitalopram 10-20 mg/day). At baseline and at Week 12, resting-state functional (rsFC) MRI scans were completed. The primary outcome was variation in the whole-brain rsFC of four seeded brain networks among participants who achieved remission. Treatment in the study persisted for 2 years or until the participants elected to halt therapy in collaboration with a mental health professional.
The results revealed that 131 participants completed therapy and had usable MRI data at both baseline and Week 12. An estimated 56.5% (74 participants) were female, with an average age of 39.8 years. Among the patients who completed therapy, 45 of 91 (49.5%) patients treated with medication and 19 of 40 (47.5%) patients treated with CBT achieved remission. The healthy control subjects were demographically comparable to the patients with MDD; the average age was 36.7 years, and 60% were female.
The researchers indicated that there were no variances in the relative clinical outcomes among the three front-line treatments for never-treated depressed participants, though the level of remission (an estimated 47%) was somewhat greater than in those studies involving previously depressed patients (remission an estimated 30%). They also noted that overall, PReDICT observed that an estimated 25% to 30% of participants did not respond to either or both treatments and may require an alternative biological or psychological intervention.
The authors wrote, “Three patterns of connectivity changes were observed. First, those who remitted with either treatment shared a pattern of reduction in rsFC between the subcallosal cingulate cortex and the motor cortex. Second, reciprocal rsFC changes were observed across multiple networks, primarily increases in CBT remitters, and decreases in medication remitters. And third, in CBT remitters only, rsFC increased within the executive control network and between the executive control network and parietal attention regions.”
The researchers concluded, “Remission from major depression via treatment with CBT or medication is associated with changes in rsFC that are mostly specific to the treatment modality, providing biological support for the clinical practice of switching between or combining these treatment approaches.”
They also indicated that medication is correlated with predominantly inhibitory effects, and with regard to CBT remitters, the rise in rsFC strength between networks implicated in cognitive control and attention provides biological reinforcement for the theorized mechanism of CBT.
They added, “Reducing affective network connectivity with motor systems is a shared process important for remission with both CBT and medication.”
One of the PReDICT principal researchers, W. Edward Craighead, PhD, J. Rex Fuqua professor of psychiatry and behavioral sciences, Emory University School of Medicine, stated, “Clinical depression is the leading cause of disability and loss of enjoyment of life among psychiatric disorders. Despite advances in personalized medicine for other diseases like cancer, treatment for depression remains largely based on trial and error and the preferences of the treating mental health professional. PReDICT is helping us better understand how different regions of the brain connect and respond to different treatments, so we can develop critically needed methods for a more personalized approach to treating depression.”
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