Evidence-Based Reviews

Neuromodulatory options for treatment-resistant depression

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Repetitive transcranial magnetic stimulation

rTMS is a noninvasive technique that uses high-intensity magnetic impulses to stimulate cortical neurons. A magnetic field is produced when current passes through a coil, which in turn causes electrical stimulation in the cortical neurons that results in transient changes in the excitability of the cortical neurons.37 Although many stimulation parameters exist for TMS, high-frequency stimulation to the left prefrontal cortex (HFL-rTMS) and low-frequency stimulation to the right prefrontal cortex (LFR-rTMS) have been shown most efficacious for treating depression.38 High-frequency (5 Hz to 20 Hz) stimulation using rTMS increases cortical neuron excitability, whereas low-frequency (approximately 1 Hz) is associated with reduced cortical neuron excitability.39 The choice of targeting the DLPFC stems from a large body of functional neuroimaging studies that have shown reduction in activity/blood flow in the left DLPFC and abnormal activity/blood flow in the right DLPFC.40

There is no dearth of RCTs evaluating the efficacy of rTMS vs sham rTMS (where no magnetic stimulation was provided). In a meta-analysis of 8 RCTs, low-frequency rTMS applied to the right DLPFC was associated with a remission rate of approximately 34.6%, compared with a 9.7% remission rate with sham rTMS.41 A response rate of approximately 38.2% was observed with HFL-rTMS, compared with a response rate of 15.1% for sham rTMS.41

Gaynes et al42 conducted a meta-analysis to determine the efficacy of rTMS in TRD. They found that for patients with TRD, rTMs produced a response rate of 29% and a remission rate of 30%. In long-term, naturalistic, observational studies, the response rates and remission rates were much higher (58% and 37.1%, respectively).43 Over a 1-year follow-up, almost two-thirds of patients continued to meet criteria for response to treatment.44 Trials comparing HFL-rTMS and LFR-rTMS have found no significant differences in efficacy.45

Advanced age, psychotic symptoms, and a longer duration of the current depressive episode predict poor response to rTMS. Also, imaging studies have shown that a lower metabolism in cerebellar, temporal, anterior cingulate, and occipital parts of the brain correlate with better response to HFL-rTMS.46,47

Adverse effects. The major adverse effect associated with rTMS is the risk of inducing seizures, which is more commonly associated with high-frequency rTMS. Other common adverse effects include headache, facial muscle twitching, and tinnitus.37

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