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Stephen Padilla
05 Apr 2019
Uncertainties and skepticism surrounding such brain stimulation devices have raised eyebrows, especially among neuroscience experts. (Photo credit: Princeton Innovation)

Nonsurgical brain stimulation techniques may serve as alternative or add-on treatments for adults with major depressive episodes, suggest the results of a systematic review and network meta-analysis.

“Our findings also highlight important research priorities in the specialty of brain stimulation, such as the need to conduct further randomized controlled trials for novel treatment protocols,” as well as sham-controlled trials investigating magnetic seizure therapy, researchers said.

An electronic search of Embase, PubMed/Medline and PsycINFO was conducted through 8 May 2018, accompanied by manual searches of bibliographies of several reviews, published between 2009 and 2018, and included trials. Included were clinical trials with random allocation to electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive [rTMS], accelerated, priming, deep and synchronized), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS) or sham therapy.

A total of 113 trials, involving 262 treatment arms and randomizing 6,750 patients (mean age, 47.9 years; 59 percent women) with major depressive disorder or bipolar depression, met the eligibility criteria. Among treatments, high frequency left rTMS and tDCS vs sham therapy were the most studied comparisons, while recent treatments remain understudied. There was typically low quality of evidence or unclear risk of bias (94 out of 113 trials; 83 percent). In addition, the precision of summary estimates for treatment effect differed significantly.

Of the 18 treatment strategies, 10 correlated with greater response compared with sham therapy in network meta-analysis, namely bitemporal ECT (summary odds ratio [OR], 8.91; 95 percent CI, 2.57–30.91), high-dose right unilateral ECT (OR, 7.27; 1.90–27.78), priming transcranial magnetic stimulation (OR, 6.02; 2.21–16.38), magnetic seizure therapy (OR, 5.55; 1.06–28.99), bilateral rTMS (OR, 4.92; 2.93–8.25), bilateral theta burst stimulation (OR, 4.44; 1.47–13.41), low-frequency right rTMS (OR, 3.65; 2.13–6.24), intermittent theta burst stimulation (OR, 3.20; 1.45–7.08), high-frequency left rTMS (OR, 3.17; 2.29–4.37) and tDCS (OR, 2.65; 1.55–4.55). [BMJ 2019;364:l1079]

In comparisons of network meta-analytic estimates of active interventions with another active treatment, bitemporal ECT and high-dose right unilateral ECT were shown to be associated with higher response. All treatment strategies were at least as acceptable as sham therapy.

“Our findings provide further clarification about the antidepressant efficacy of different ECT protocols. Previous comparative analyses did not consistently favour bitemporal ECT or right unilateral ECT, and it has been suggested that right unilateral ECT needs to be delivered at multiples of seizure threshold to be effective,” researchers said. [N Engl J Med 1993;328:839-846; Arch Gen Psychiatry 2000;57:438-444]

Previous analyses also support the findings on the antidepressant efficacy of high-frequency left rTMS and low-frequency right rTMS. [JAMA Psychiatry 2017;74:143-152; Psychol Med 2009;39:65-75; Psychol Med 2014;44:225-239; Acta Psychiatr Scand 2014;130:326-341; Neuropsychopharmacology 2013;38:543-551]

“We found little evidence for differences in all-cause discontinuation between active treatments and sham therapy. The notable exception was priming transcranial magnetic stimulation for which lower drop-out rates were reported. However, we did not examine specific undesired and adverse effects in this review; and future research will systematically evaluate specific cognitive and adverse effects,” researchers said. [BMJ Open 2019;9:e023796]

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