Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study

Abstract

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...

A systematic review and meta-analysis of deep brain stimulation for depression

“…Ten publications from nine studies met inclusion criteria (Bergfeld et al., ; Dougherty et al., ; Kubu et al., ; Merkl et al., ; Holtzheimer et al., , ; Puigdemont et al., ; Ramasubbu, Anderson, Haffenden, Chavda, & Kiss, ; Schlaepfer, Bewernick, Braeuer, & Coenen, ; Fenoy et al., ). Table gives details of those studies that were excluded at the full‐text level.…”

Deep brain stimulation (DBS) at the interface of neurology and psychiatry

“…The long-term response rate for SCC DBS was approximately 60% (94). In addition to appropriate electrode placement, programming parameters within this node have not been fully explored (95) and optimized (96). Future trials, such as the ongoing multi- site randomized control trial (BROADEN), may potentially utilize parameters described above to optimize treatment delivery.…”

“…DBS studies targeting the SCC (21), internal capsule (97), and the reward circuitry (28, 101) have shown efficacy in not only severe unipolar depression, but also in individuals with bipolar disorder that were in an extended depressive episode (88). It is also clear that efficacy will increase when programming settings (96), the lead position in relation to the relevant circuitry (106), and the exact microstructural targets of modulation (93) are optimized. Ultimately, the DBS target choice for an individual's depression may be selected using the nature of the depressive symptoms (91) coupled with the side-effect profile and relevant comorbidities (107).…”

A Review of Brain Stimulation Treatments for Late-Life Depression

“…More recent studies have begun to investigate the relationship between stimulus parameters and clinical efficacy. A small double blind pilot study [74] ( n =4) randomly changed frequency and pulse widths weekly in TRD patients who underwent DBS (aged 46–56). They found that longer pulse widths (270–450 μs) were associated with more robust antidepressant effects.…”