Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: An analysis from the randomised non-inferiority THREE-D trial.

Background: Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), treatment selection is still mainly a process of trial-and-error. The present study aimed to identify clinical predictors of remission after a course of rTMS delivered to the left DLPFC to improve patient selection.

Methods: Data from a large randomised non-inferiority trial comparing standard 10 Hz and intermittent theta burst stimulation (iTBS) for the treatment of MDD were used for the exploratory analyses. Individual variables were assessed for their association with remission and then included in a logistic regression model to determine odds ratios (OR) and corresponding 95% confidence intervals. Model discrimination (internal validation) was carried out to assess model optimism using the c-index. ClinicalTrials.gov identifier: NCT01887782.

Findings: 388 subjects were included in the analysis (199-iTBS and 189-10 Hz, respectively). Higher baseline severity of both depressive and anxiety symptoms were associated with a lower chance of achieving remission (OR=0.64, 95% CI 0.46-0.88; and 0.78, 95% CI 0·60-0.98, respectively). Current employment was a positive predictor for remission (OR=1.69, 95% CI 1.06-2.7), while greater number of treatment failures was associated with lower odds of achieving remission (OR=0.51, 95% CI 0.27-0.98). A non-linear effect of age and remission was observed. An analysis to allow an estimate of the probability of remission using all variables was assessed. The c-index for the fitted model was 0.687.

Interpretation: Our results suggest that measuring depression symptom severity, employment status, and refractoriness are important in prognosticating outcome to a course of rTMS in MDD.

Funding: Canadian Institutes of Health Research MOP-136801.