Randomized controlled trials support the antidepressant efficacy of transcranial magnetic stimulation (TMS); however, there is individual variability in the magnitude of response. Examination of response predictors has been hampered by methodological limitations such as small sample sizes and single-site study designs. Data from a multisite sham-controlled trial of the antidepressant efficacy of TMS provided an opportunity to examine predictors of acute outcome. An open-label extension for patients who failed to improve provided the opportunity for confirmatory analysis. Treatment was administered to the left dorsolateral prefrontal cortex at 10 pulses per second, 120% of motor threshold, for a total of 3000 pulses per day. Change on the Montgomery-Asberg Depression Rating Scale after 4 weeks was the primary efficacy outcome. A total of 301 patients with nonpsychotic unipolar major depression at 23 centers were randomized to active or sham TMS. Univariate predictor analyses showed that the degree of prior treatment resistance in the current episode was a predictor of positive treatment outcome in both the controlled study and the open-label extension trial. In the randomized trial, shorter duration of current episode was also associated with a better outcome. In the open-label extension study, absence of anxiety disorder comorbidity was associated with an improved outcome, but duration of current episode was not. The number of prior treatment failures was the strongest predictor for positive response to acute treatment with TMS. Shorter duration of current illness and lack of anxiety comorbidity may also confer an increased likelihood of good antidepressant response to TMS.

Longer depressive episodes and medication failure at baseline are robust predictors of poor response to ECT, with effect sizes that are modest but clinically relevant. Patient characteristics used traditionally such as age, psychosis, and melancholic features are less likely to be clinically useful. More robust clinical and biological predictors are needed for management of depressed patients considering ECT.

For US patients with treatment-resistant depression, ECT may be an effective and cost-effective treatment option. Although many factors influence the decision to proceed with ECT, these data suggest that, from a health-economic standpoint, ECT should be considered after failure of 2 or more lines of pharmacotherapy/psychotherapy.

sgACC connectivity reduces along with depressive symptoms, not specific to rTMS therapy. Altered connectivity of DMN with anterior insula may reflect a type of patient less likely to respond to an intervention.

PSYCHIATRIST.COM studies. 1-6 More recently, a large, multisite trial of TMS administered to patients with treatment-resistant depression demonstrated superiority for TMS over a sham condition in a randomized controlled trial. 7 A unique feature of that trial design allowed nonresponders (defined by prespecified criteria) who had received at least 4 weeks of double-blind treatment the opportunity to enroll in a second extension trial and receive 6 weeks of openlabel TMS. The enrollment of patients who had failed to respond during the blinded, randomized sham-controlled trial into an open-label extension provides additional insights into TMS treatment effectiveness. Specifically, for the subgroup of patients who had received the sham intervention during the previous double-blind study, this second, open-label study represents a partial crossover trial. Furthermore, for the patients who had not responded