What is the most effective somatic therapy for treatment-resistant depression?

Electroconvulsive therapy (ECT) is currently considered the most effective option in severe and urgent cases, with response rates above 70%.

Can rTMS replace antidepressant medications?

rTMS is often used in combination with pharmacotherapy, but it can also be effective as monotherapy in patients with drug intolerance.

Is tDCS suitable for severe depression?

No, tDCS is recommended for mild or moderate depression, often as an adjunct therapy. In severe cases, ECT or rTMS is preferred.

What are the risks of VNS?

The main side effects of VNS include hoarseness, dry cough, and localized discomfort. It is a semi-invasive surgical procedure with a long latency of clinical effect.

Is DBS an approved therapy for depression?

No, deep brain stimulation (DBS) is considered experimental and is only used in highly selected cases under clinical protocols.

Neuromodulation Therapies for Depression: Comprehensive Comparative Table

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Summary Table of Somatic Neuromodulation Therapies for Depression

Therapy	Mechanism of Action	Indications	Contraindications	Advantages	Disadvantages
Electroconvulsive Therapy (ECT)	Induces a controlled seizure via electrical stimulation; modulates limbic and cortico-subcortical circuits.	Severe, catatonic or treatment-resistant depression; used as monotherapy or in combination with medication.	Patient refusal, unstable cardiovascular disease, increased intracranial pressure.	Rapid onset of action; highly effective in urgent or refractory cases.	Transient cognitive side effects (e.g., amnesia); requires anesthesia and specialized setting.
Repetitive Transcranial Magnetic Stimulation (rTMS)	Focal electromagnetic stimulation of the dorsolateral prefrontal cortex; enhances neuronal plasticity.	Treatment-resistant depression or drug intolerance; used in monotherapy or combination.	History of seizures, implanted metallic devices in the skull.	Non-invasive, well tolerated, outpatient procedure.	Requires multiple weekly sessions; gradual effect, limited durability.
Transcranial Direct Current Stimulation (tDCS)	Delivers low-intensity direct current to modulate cortical excitability.	Mild to moderate depression; mostly used in combination with psychotherapy or pharmacotherapy.	Electronic implants, uncontrolled epilepsy.	Simple, painless, non-invasive technique.	Limited clinical evidence; weaker response compared to other techniques.
Vagus Nerve Stimulation (VNS)	Implanted device provides periodic vagal stimulation; modulates limbic circuits.	Long-term treatment-resistant depression; used in combination with other therapies.	Contraindications to surgery, cardiac conduction disorders.	Potential long-term benefits; useful in refractory cases.	Requires surgery; delayed clinical response; high cost.
Deep Brain Stimulation (DBS)	Intracerebral electrodes stimulate limbic areas (e.g., subgenual cingulate, nucleus accumbens).	Severe refractory depression; experimental use only; always in combination with other treatments.	High surgical risk, unstable psychiatric comorbidity.	Promising for extreme refractory cases.	Highly invasive; reserved for specialized centers; efficacy still under investigation.

References

UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders. Lancet. 361(9360), 2003: 799–808.
Brunoni AR et al. Repetitive transcranial magnetic stimulation for the acute treatment of major depressive episodes. JAMA Psychiatry. 74(5), 2017: 487–495.
Bikson M et al. Transcranial direct current stimulation for major depression: a general system for quantitatively assessing risk and benefit. Brain Stimul. 9(4), 2016: 641–658.
Aaronson ST et al. Five-year outcome study of vagus nerve stimulation for treatment of major depressive disorder. Am J Psychiatry. 174(7), 2017: 640–648.
Mayberg HS et al. Deep brain stimulation for treatment-resistant depression. Neuron. 45(5), 2005: 651–660.
Holtzheimer PE et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression. Arch Gen Psychiatry. 69(2), 2012: 150–158.
George MS et al. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder. Arch Gen Psychiatry. 67(5), 2010: 507–516.
Kedzior KK et al. Repetitive transcranial magnetic stimulation (rTMS) for depression in older adults. Neuropsychiatr Dis Treat. 10, 2014: 2087–2097.
Fregni F et al. Transcranial direct current stimulation (tDCS) for depression: a systematic review and meta-analysis. Psychol Med. 36(9), 2006: 1161–1170.
Drevets WC et al. Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders. Mol Psychiatry. 13(9), 2008: 831–846.