Neurostimulation involves the delivery of a physical intervention either through electric current or a magnetic field to target selective or generalized brain regions. ECT represents the prototypic form of neurostimulation, that has been used since the 1930s although it only received the Food and Drug Administration’s (FDA) approval in 1979. Despite favourable rates of response and remission, limitations include failure to sustain antidepressant response and adverse cognitive effects. Repetitive Transcranial Magnetic Stimulation (rTMS) relies on electromagnetic induction to generate a superficial current in the dorsolateral prefrontal cortex (DLPFC) which may be of high intensity or low intensity. This treatment is not associated with adverse neurocognitive effects and continues to be refined in the treatment of MDD.

Vagus Nerve Stimulation (VNS) and Deep Brain Stimulation (DBS) are more invasive forms of neurostimulation that have been approved for the treatment of neurological disorders (such as Parkinson’s Disease) prior to being investigated for treatment resistant depression (TRD). The VNS device received approval for adjunctive long-term use for chronic or recurrent MDD and relays a mild electrical pulsed stimulus to the left vagus nerve which activates limbic structures. The efficacy of this procedure is still being evaluated, although it has a good safety profile. DBS is the most invasive form of neurostimulation and requires direct neurosurgical implantation of electrodes to targeted brain regions. In both VNS and DBS, patients require an implantable pulse generator (IPG), usually inserted subclavicularly to maintain pulsatile or continuous current. Although early reports suggest promising results in open-label trials, DBS requires more evidence before it can be recommended in routine clinical practice. A summary of evidence and recommendations is contained in Table 1. However, the recommendations are presented as guidance for clinicians who should consider them in the context of individual patients, and not as standards of care.

There have been important advances in neuromodulation techniques since the previous CANMAT guideline publication for MDD in 2001. These changes reflect advances in theoretical models for depression, paired with emerging technologies to deliver continuous or intermittent electrical stimulation and experience from the application of these techniques in other disease states. At this stage, only ECT has a robust evidence base for its recommendation.