A randomized double-blind crossover trial of deep brain stimulation of the subcallosal cingulate gyrus in patients with treatment-resistant depression: a pilot study of relapse prevention

Abstract

Background: To date, antidepressant drugs show limited efficacy, leaving a large number of patients experiencing severe and persistent symptoms of major depression. Previous open-label clinical trials have reported significant sustained improvements with deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) in patients with severe, chronic treatment-resistant depression (TRD). This study aimed to confirm the efficacy and measure the impact of discontinuation of the electrical stimulation.

Methods: We conducted a 6-month double-blind, randomized, sham-controlled crossover study in implanted patients with previous severe TRD who experienced full remission after chronic stimulation. After more than 3 months of stable remission, patients were randomly assigned to 2 treatment arms: the ON-OFF arm, which involved active electrode stimulation for 3 months followed by sham stimulation for 3 months, and the OFF-ON arm, which involved sham stimulation for 3 months followed by active stimulation for 3 months. The primary outcome measure was the difference in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score between sham and active stimulation.

Results: We enrolled 5 patients in our trial. A Friedman repeated-measures analysis of variance revealed a significant effect of treatment (χ(2)1 = 5.0, p = 0.025) in patients with higher depression scores during sham stimulation. At the end of active stimulation, depression was remitted in 4 of 5 patients and none of them had experienced a relapse, whereas at the end of sham stimulation, 2 patients remained in remission, 2 relapsed and 1 showed a progressive worsening without reaching relapse criteria.

Limitations: The small sample size limited the statistical power and external validity.

Conclusion: These preliminary findings indicate that DBS of the SCG is an effective and safe treatment for severe forms of TRD and that continuous electrical stimulation is required to maintain therapeutic effects.

Trial registration: NCT01268137 (ClinicalTrials.gov).

Figures

Fig. 1

Study selection for the randomized controlled clinical trial. LOCF = last observation carried forward; OFF–ON = 3 mo of sham stimulation followed by 3 mo of active stimulation; ON–OFF = 3 mo of active stimulations followed by 3 mo of sham stimulation.

Fig. 2

Location of electrode contacts on a sagittal view of the cingulate gyrus. Circles are schematic representations of electrode contacts (“+” indicates positive contacts and “−” indicates negative contacts). Numbers within circles correspond to each patient. Details of stimulating parameters are given in Table 2.

Fig. 3

Mean change in depression scores based on the 17-item Hamilton Rating Scale for Depression (HAMD-17) for the ON–OFF (3 mo active followed by 3 mo sham) group and the OFF–ON (3 mo sham followed by 3 mo active) group.

Fig. 4

Individual changes on th 17-item Hamilton Rating Scale for Depression (HAMD-17) scores during active stimulation (ON) and sham stimulation (OFF) periods. Scores on the dark grey background represent relapses; scores on the white background correspond to remissions.