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Objective To assess the efficacy of increasing the number of fast left repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to achieve remission in treatment resistant depression (TRD). And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MT over the right DLPFC). Method Patients were part of a multicenter sham controlled trial investigating the efficacy of fast left rTMS 1. Patients who failed to meet minimal response criteria in the sham controlled study could enroll in this open fast left rTMS study for an additional 3- 6 weeks. Patients who failed to remit to fast left could switch to slow right rTMS for up to four additional weeks. The final outcome measure was remission, defined as a HAM-D score of ≤ 3 or two consecutive HAM-D scores less than 10. Results Forty-three of 141 (30.5%) patients who enrolled in the open phase study eventually met criteria for remission. Patients who remitted during fast left treatment received a mean of 26 active treatments (90,000 pulses). 26% of patients who failed fast left remitted during slow right treatment. Conclusion The total number of rTMS stimulations needed to achieve remission in TRD may be higher than is used in most studies. TRD patients who do not respond to fast left rTMS may remit to slow right rTMS or additional rTMS stimulations.

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IntroductionDeep brain stimulation (DBS) has recently emerged as a viable option for treatment-resistant depression (TRD). Among several neuroanatomical targets (subcallosal cingulate, nucleus accumbens, ventral capsule/ventral striatum, inferior thalamic peduncle and habenula), 1 DBS of the subcallosal cingulate (SCC) has been the most investigated. Four open-label studies of SCC-DBS involving a total of 66 patients with TRD (major depressive disorder and bipolar depression) showed efficacy and safety.2-7 Although these results are encouraging, about 40%-50% of patients did not respond and 70%-80% did not achieve clinical remission with SCC-DBS. 3,4,7 Adjusting stimulus parameters in patients with poor or suboptimal response may improve outcomes in Parkinson disease and TRD. 5,8 However, the selection of optimal stimulation parameters (frequency, pulse width, amplitude) can be time-consuming, even when studying movement disorders for which there are immediate objective motor outcomes to measure.9 At present, there is no evidence-based approach for the selection of optimal stimulus parameters for TRD. The optimization of stimulation settings for individual patients is guided by the experience and preference of the clinician and by adapting DBS parameters used for movement disorders. To establish an evidence-based standardized algorithm for optimal DBS for TRD, we need double-blind, controlled studies Background: Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD. Methods: Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression . In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes. Results: Longer pulse widths (270-450 µs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded. Limitations: Limitations include small sample size, weekly changes in stimu lus parameters, and fixed-order and carry-forward effects. Conclusion: Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using differen...