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

Rajamannar Ramasubbu, Susan Anderson, Angela Haffenden, Swati Chavda, Zelma H T Kiss, Rajamannar Ramasubbu, Susan Anderson, Angela Haffenden, Swati Chavda, Zelma H T Kiss

Abstract

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 (HAM-D-17). 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 stimulus 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 different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.

Figures

Fig. 1
Fig. 1
Visual analogue scale (VAS) of patient-reported happiness as a function of pulse width applied. Frequency was kept constant (130 Hz), and changes were made weekly to pulse width. Stimulus intensity was applied at 3–5 V but was reduced at higher pulse durations to keep the charge density within the maximum allowable limit (30 μC/cm2). A pulse width of 0 indicates that the stimulation was turned off. Each patient is shown as an individual line/symbol/colour.
Fig. 2
Fig. 2
Mean and individual scores on the 17-item Hamilton Rating Sale for Depression (HAM-D-17) over time in all 4 patients. The horizontal grey bar indicates the baseline HAM-D-17 scores with standard deviation (SD). Each patient is shown as an individual line/symbol/colour, and the black indicates mean HAM-D-17 scores and SD for the entire group.

Source: PubMed

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