Biological Non-pharmacological Treatments for Depressive Disorder

Depressive disorder is highly prevalent and disabling. Despite the central role of pharmacotherapy and psychotherapy, many patients have incomplete response or intolerance. Biological non-pharmacological interventions have, therefore, become increasingly important as alternatives or adjuncts. This chapter reviews electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), bright light therapy (BLT), exercise, and selected nutraceuticals (e.g., omega-3 fatty acids, S-adenosyl-methionine). We summarize mechanisms, randomized and meta-analytic efficacy, safety, and guideline positions (APA, CANMAT, NICE) with a brief note on KMAP-DD 2025 integration. ECT retains the most robust acute efficacy for severe or psychotic depression, rTMS offers effective non-invasive neuromodulation, and tDCS provides modest benefits with excellent tolerability and portability. VNS is useful in chronic refractory depression with delayed but durable benefits in a subset. BLT, exercise, and nutraceuticals are accessible, generally safe adjuncts with clinically meaningful effects, particularly for specified phenotypes. Practical checklists and parameter tables are provided to facilitate implementation (Rush et al.‚ Am J Psychiatry 163(11):1905–1917‚ 2006; Gaynes et al.‚ Depress Anxiety;37(2):134–145‚ 2020; Fava‚ Biol Psychiatry 53(8):649–659‚ 2003; Kennedy et al.‚ Can J Psychiatry 68(2):80–134‚ 2023).