It is beyond the scope of this team to offer you any advice on medical treatment. However, several other advanced interventional treatments are described below.
Electroconvulsive therapy (ECT)
ECT is the first and most studied brain stimulation therapy to date. In fact, Cerletti and Bini, in 1938, conducted the first descriptions of using electric stimuli to induce therapeutic seizures. Although its mechanisms of action are still incompletely known, accumulated evidence points that its antidepressants effects are related to several mechanisms, such as restoring hemispheric balance, increasing BDNF serum levels, enhancing neurogenesis through a series of electrical shocks and, long-term up-regulation of serotonin activity and down-regulation of muscarinic activity. Nevertheless, several guidelines support the role of ECT as a first-line treatment of severe major depressive disorder, especially in psychotic and/or suicidal patients, or those with catatonia or treatment-resistant depression.
In recent years, several systematic reviews and meta-analyses of ECT efficacy have been published. The UK ECT Review Group reviewed the efficacy of ECT vs. (sham) ECT, drug therapy & other parameters. The pooled analysis of ECT comparisons against amitriptyline, imipramine, phenelzine or others favored ECT with a mean Hamilton difference of 5.2 (95% CI ranging between 1.4-8.9). Bilateral ECT was more effective than unilateral (mean Hamilton reduction of 3.6 points – 95% CI ranging between 2.2-5.2). Finally, treatment with high doses of ECT led to a greater reduction in depressive symptoms with a mean change of Hamilton scores of 4.1 (95% CI ranging between 2.4-5.9) when compared to placebo. They observed an important decrease in performance in almost all neuropsychological tests at post-ECT.
Repetitive transcranial magnetic stimulation (rTMS)
TMS uses the principle of electromagnetic induction to focus induced current in the brain. RTMS has been tested for several neurological and psychiatric conditions, but none has had the same number of studies and positive results than MDD. Recent meta-analyses published in 2007 and 2008 showed that rTMS had the same efficacy of pharmacological drugs for MDD with also similar rates of response and remission rates for TRD (25% and 17%), respectively, which interestingly is similar to the STAR*D results of 19% and 13%. Currently, rTMS has been approved for use in Brazil, Canada, Israel and some European countries and also in the US.
Vagus Nerve Stimulation (VNS)
Long-term studies have proven the good clinical outcome of VNS for MDD while it is well tolerated; a successful response have been described in half of the patients, with complete remission in one third. Immediately postoperatively and at short-term follow-up, VNS has shown a low effectiveness. However, its beneficial effect at long-term in a substantial amount of patients, together with its low number of unwanted side effects, make this method an attractive treatment for patients suffering from MDD.