Major Depressive Disorder Research Roundup

Research Roundup

In this Research Roundup, we explore new studies examining major depressive disorder (MDD) and approaches to treatment.

MDD Onset in At-Risk Adults Mitigated by Psychological Interventions

Adult patients experiencing subthreshold depression symptoms may be able to experience an improvement in their symptoms after receiving psychological interventions, according to a 2024 study.

Researchers evaluated the effectiveness of psychological interventions in preventing the onset of MDD in patients experiencing subthreshold depression symptoms in a systematic review. Individual participant data was collected from 7201 participants who received psychological interventions. Researchers collected data from participants post treatment after 6 months, 12 months, and 24 months.

Over half of the interventions used were based on cognitive behavioral therapy (CBT), and face-to-face was the most common delivery type. Patient symptoms were measured using standardized tools for depressive and anxiety symptoms, including the patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7). Findings revealed that psychological interventions significantly reduce the incidence of MDD by 43% post treatment, 42% within 6 months, and 33% within 12 months.

While factors like age did not have an impact on effectiveness, researchers found that preventative effects were stronger for individuals who had not previously had psychotherapy. Researchers also found that, while there is limited data, the efficacy of conference calls showed potential.

“Our findings support guidelines recommending psychological interventions as a treatment option in the management of subthreshold persistent depressive symptoms,” the authors wrote.

Reference

Buntrock C, Harrer M, Sprenger AA, et al. Psychological interventions to prevent the onset of major depression in adults: a systematic review and individual participant data meta-analysis. Lancet Psychiatry. 2024;11(12):990-1001.

Exercise Modalities as an Arm in the Treatment of MDD

Exercise is known to ease symptoms of depression by releasing endorphins, but what types of exercise are the most effective? A systematic review and network meta-analysis (NMA) study compared different kinds of exercise to determine the most effective modalities for patients experiencing MDD.

The 218 randomized studies yielded 14,170 participants with controls including usual care, placebo tablet, stretching, educational control, and social support. Participants met the criteria for MDD either by clinician diagnosis or scoring >13 on the Beck depression inventory-II. The studies included had interventions at least 1 week long.

Overall, results showed moderate reductions were found were found for walking, jogging, yoga, strength training, mixed aerobic exercises, tai chi or qigong. Researchers found that the intensity of exercise correlated with its effectiveness.

In isolation, it was found that walking, jogging, yoga, strength training and dancing were found the most effective. Women and young adults responded best to strength training; men experienced better outcomes with yoga or qigong. Yoga was somewhat more effective with older adults. Researchers found that giving participants autonomy in factors like frequency, intensity, or type yielded lower impact over participants. Benefits were equally effective for different weekly doses, patients with comorbidities, and different baseline levels of depression.

“Health systems may want to provide these treatments as alternatives or adjuvants to other established interventions (cognitive behavior therapy, SSRIs), while also attenuating risks to physical health associated with depression,” the authors concluded.

Reference

Noetel M, Sanders T, Gallardo-Gómez D, et al. Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2024;384. Published February 14, 2024.

Neuromodulatory Procedures Show Promise in Treating Treatment-Resistant Depression

Although treatments for MDD cover a wide range of modalities, researchers say nearly half of patients experiencing MDD meet the criteria for treatment-resistant depression (TRD). A 2024 systematic review and NMA study compiled and analyzed 69 randomized controlled trials to compare the efficacy of different antidepressant treatments for TRD.

The compiled studies included 10,285 participants who failed to respond to at least 2 antidepressants treatments. Researchers evaluated 25 therapies, categorized into mood stabilizers, antipsychotics, other pharmacological mechanisms, serotonergic psychedelics, N-methyl-_D-aspartate receptor (NMDAR) targets, and neuromodulatory treatments.

Researchers found that 6 of the 25 treatments were associated with significantly higher response rates than placebo: electroconvulsive therapy (ECT), minocycline, theta-burst stimulation (TBS), repetitive transcranial magnetic stimulation (rTMS), ketamine, and aripiprazole. Neuromodulatory treatments, although limited in study duration and lack of long-term effect evaluations, showed the strongest effects and had good tolerability. ECT, which the authors clarify that few randomized controlled trials exist for the treatment, showed the best odds ratio at 12.86.

The report authors noted that this is the first study to incorporate neuromodulatory treatments alongside established antidepressants and novel, rapid acting antidepressants. “The findings of this NMA underscore the efficacy of several available treatments for TRD, including ECT, rTMS, TBS, ketamine, aripiprazole, minocycline, and the combination of olanzapine/fluoxetine; the first four treatments demonstrated efficacy across all outcomes,” the report authors wrote.

Reference

Saelens J, Gramser A, Watzal V, et al. Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials. Neuropsychopharmacology. December 30, 2024. Accessed January 10, 2025. https://www.nature.com/articles/s41386-024-02044-5#citeas