Evidence-Based Reviews

Neuromodulatory options for treatment-resistant depression

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Sorting out the evidence

In the absence of head-to-head trials, it is difficult to establish a hierarchal algorithm for use of the 4 neuromodulatory treatments discussed in the article. If we were to base our decision solely on the current literature, ECT by far has the most evidence and highest remission rates.11 We can reduce the risk of cognitive deficits by using twice-weekly instead of thrice-weekly ECT, or by using unilateral instead of bilateral ECT.12 Another strategy for reducing adverse effects associated with long-term maintenance ECT is by using it in combination with VNS. ECT and VNS can be used safely concomitantly; ECT can be used to treat acutely worsening depression, and VNS for maintaining the antidepressant effect.62

Aside from ECT, rTMS is the only other treatment that has evidence from RCTs. Although the remission rates are not as high as ECT, its preferable adverse effects profile, noninvasive nature, and comparative low cost (compared with surgical procedures) make it a favorable choice. The Canadian Network for Mood and Anxiety Treatment guidelines suggest rTMS as the first-line treatment for patients who do not respond to pharmacologic treatments.63 ECT can be considered second-line treatment unless the patient has acute suicidal ideation, catatonia, psychotic features, greater treatment resistance, or physical deterioration, in which case ECT should be tried before TMS.63

Among the invasive options, VNS has more evidence and is FDA-approved for TRD. However, DBS has shown great promise in early studies, with remission rates as high as 35%.56 DBS has the advantage of being reversible, and the amount of stimulation can be adjusted easily. Despite early promise, more research is needed before DBS can be widely used in clinical settings.

Bottom Line

When considering neuromodulatory treatments for patients with TRD, current evidence suggests electroconvulsive therapy and repetitive transcranial magnetic stimulation are preferable options. Vagus nerve stimulation and deep brain stimulation have also shown promise.

Related Resource

  • Bewernick B, Schlaepfer TE. Update on neuromodulation for treatment-resistant depression. 2015;4. doi: 10.12688/f1000research.6633.1.

Drug Brand Names

Lithium Eskalith, Lithobid
Remifentanil Ultiva


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