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Transcranial magnetic stimulation a potential answer to treatment-resistant depression

Tristan Manalac
08 Jul 2018

Repetitive transcranial magnetic stimulation (rTMS) seems to be effective in improving remission rates in patients with treatment-resistant major depression (TRMD), a recent US study has shown.

However, the approach does not appear to have significant benefits over a sham treatment, highlighting the “importance of close clinical surveillance, rigorous monitoring of concomitant medication and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population,” said researchers.

The study included 164 veterans (mean age 55.2±12.4 years; 80.5 percent male) who were randomized to undergo either active rTMS (n=81; mean age 55.6±12.2 years; 82.7 percent male) or sham treatment (n=83; mean age 54.8±12.6 years; 78.3 percent male). [JAMA Psychiatry 2018;doi:10.1001/jamapsychiatry.2018.1483]

At the end of the acute treatment phase, 39.0 percent (n=64) of the participants achieved remission. This rate was slightly higher in the active rTMS than in the sham group (40.7 percent vs 37.4 percent), but the difference did not reach statistical significance (adjusted effect estimate, 1.16; 95 percent CI, 0.59–2.26; p=0.67).

This nonsignificant trend persisted until the end of the 24-week follow-up phase (active vs sham: 19.8 percent vs 15.7 percent; p=0.35).

Similarly, rTMS led to improvements in the severity of depression symptoms but was not statistically better than the sham (Beck Depression Inventory score: adjusted effect estimate, 2.22; –0.64 to 5.08; p=0.12; Hamilton Rating Scale for Depression score: adjusted effect estimate, 1.28; –1.42 to 3.97; p=0.34).

The same was true for scores in the Beck Scale for Suicide Ideation (adjusted effect estimate, 0.08; –1.46 to 1.62; p=0.91), Post-traumatic Stress Disorder (PTSD) Checklist-Military (adjusted effect estimate, 2.68; –0.84 to 6.19; p=0.13) and clinician-administered PTSD Scale (adjusted effect estimate, 5.20; –0.49 to 10.89; p=0.07).

“This finding is consistent with the observation that placebo response has been increasing over time in clinical trials of antidepressant medication,” though the observed remission rates in the present study are higher than in other reports of veterans with TRMD, said researchers.

Notably, PTSD may have a potential moderating effect on rTMS treatment. The rate of remission in participants without PTSD was higher than the overall mean (48.8 percent), while those with both PTSD and major depressive disorder (MDD) showed a lower remission rate at 32.5 percent. This was also observed in the sham treatment participants with and without PTSD (31.7 percent vs 42.9 percent).

“These high remission rates suggest that veterans’ expectations of improvement and extensive attention provided by the rTMS treatment team may have played a large role in the significant clinical improvements they experienced,” said researchers, noting that unlike other rTMS trials, the present study included extensive follow-ups and regular contact with study staff.

“This added attention may have interacted with the fact that this study was, to our knowledge, the first large rTMS clinical trial in which medications were included and contributed to enhanced adherence to pharmacologic treatments,” they added.

Despite a nonsignificant difference compared with the sham, “[t]his study supports the clinical observation that a combination of interventions including rTMS is effective for achieving symptom remission in 39.0 percent of veterans with MDD who were previously treatment-resistant,” said researchers.

“Future work with rTMS may show an enhanced effect when newer coil models, better stimulus targeting, biological markers of response, higher frequency rates of stimulation and longer duration of treatment are implemented,” they added.

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