Table 2.

Major outcomes of clinical studies

Modality	Trial title	No. of participants	Year	Location	Trial outcome	Limitation/side effects	Reference
ECT and rTMS	A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression	46	2007	USA	ECT is more effective than rTMS for short-term treatment of depression	33% of patients reported substantial memory loss after ECT	[96]
tDCS	A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression	40	2007	Israel	Significant reduction in depression scores after DLPFC tDCS	–	[33]
tDCS	A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression	40	2009	Australia	Significant improvement in depression scores after 10 tDCS sessions	Minor side-effects	[39]
tDCS	Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study	11	2011	Spain, Australia	F-EX tDCS is safe and effective for depression treatment and may lead to more rapid improvement than bifrontal montage tDCS	Open label pilot study	[37]
rTMS	A controlled trial of daily left prefrontal cortex TMS for treating depression	30	2000	South Carolina, China	Significant reduction in depression symptoms at the end of two weeks	Occasional mild headache and discomfort at site of stimulation	[46]
rTMS	Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial	301	2007	USA, Australia	rTMS is effective in treating major depression with minimal side-effects	Eye disorder, gastrointestinal disorder, application site pain, muscle twitching, skin and subcutaneous tissue disorders	[49]
rTMS	Prefrontal rTMS for treating depression: Location and intensity results from the OPT-TMS multi-site clinical trial	185	2013	USA	Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances are safe for a broad range of patients.	–	[43]
VNS	Vagus nerve stimulation (VNS) for major depressive episodes: One year outcomes	30	2001	USA	Longer-term vagus nerve stimulation is effective in follow-up treatment of depression	Mild voice alteration (21%), dyspnea (7%), and neck pain (7%)	[60]
VNS	Vagus nerve stimulation for treatment-resistant depression: A randomized, controlled acute phase trial	235	2005	USA	No definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression	Voice alteration, increased cough, dysphagia, neck pain, palpitations, wound infection	[54]
VNS	P300 is enhanced in responders to vagus nerve stimulation for treatment of major depressive disorder	13	2006	Germany	Auditory ERP is a useful tool for investigating VNS-induced changes of information processing in major depressive disorder	Significant gender difference between groups; small sample size	[107]
VNS	Vagus nerve stimulation for treatment-resistant depression: behavioral and neural effects on encoding negative material	1	2007	England	VNS interferes with memory for negative information, an effect that may contribute to its antidepressant role	Throat tickling, decreased heart rate during VNS	[64]
DBS	A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle	1	2005	–	DBS of inferior thalamic relieves depressive symptoms in patient with TRD	Requires invasive electrode implantation. Long term safety and efficacy needs to be evaluated	[79]
DBS	Deep brain stimulation for treatment-resistant depression	6	2005	Canada	Positive behavioral changes time-locked to stimulation	No sustained antidepressant response in two of six patients after six months of treatment	[15]
DBS	Mood improvement after deep brain stimulation of the internal globus pallidus for tardive dyskinesia in a patient suffering from major depression	1	2007	Germany	Dyskinesia and symptoms of depression improve after 18 months of treatment. Depression declines significantly over the period of treatment and shows a sustained improvement in the last 3 months of treatment	Invasive, requires electrode implantation in brain	[71]
DBS	Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression	3	2008	USA, Germany	Immediate improvement in mood when DBS is on	No side-effects in any patients, but is invasive, requiring electrode implantation in brain	[73]
DBS	Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression	15	2009	USA	Significant improvement in depression symptoms; DBS of VC/VS is a promising strategy for treating refractory depression or TRD	DBS for long periods is more effective. Remission of symptoms and response rate to treatment increase with treatment duration	[82]
DBS	Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression	10	2010	Germany, USA	Nucleus accumbens region is a potential target for treating TRD with DBS	Invasive; requires electrode implantation in brain	[81]
DBS	Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years	20	2011	–	Progressive improvement of functional impairment related to social functioning and physical health. Supports long-term safety and efficacy of DBS	Requires electrode implantation in brain; however no significant adverse effects	[70]
DBS	A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression	21	2012	Canada	Reduction in depression along with significant enhancement in mood and improvement in severity of depression; suggests Cg 25 as an attractive target for implantation of DBS electrodes to treat depression and TRD	Invasive, requiring electrode implantation in brain; however no significant adverse effects	[80]