Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression

Abstract

ObjectiveDeep brain stimulation (DBS) reduces depressive symptoms in approximately 40%–60% of patients with treatment-resistant depression (TRD), but data on long-term efficacy and safety are scarce. Our objective was to assess the efficacy and safety of DBS targeted at the ventral anterior limb of the internal capsule (vALIC) in 25 patients with TRD during a 1-year, open-label, maintenance period, which followed a 1-year optimisation period.MethodsDepression severity was measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Montgomery-Asberg Depression Rating Scale (MADRS) and self-reported Inventory of Depressive Symptomatology (IDS-SR). Primary outcomes were response rate (≥50% HAM-D-17 score reduction) after the maintenance phase, approximately 2 years after DBS surgery, and changes in depression scores and occurrence of adverse events during the maintenance phase.ResultsOf 25 operated patients, 21 entered and 18 completed the maintenance phase. After the maintenance phase, eight patients were classified as responder (observed response rate: 44.4%; intention-to-treat: 32.0%). During the maintenance phase, HAM-D-17 and MADRS scores did not change, but the mean IDS-SR score decreased from 38.8 (95% CI 31.2 to 46.5) to 35.0 (95% CI 26.1 to 43.8) (p=0.008). Non-responders after optimisation did not improve during the maintenance phase. Four non-DBS-related serious adverse events occurred, including one suicide attempt.ConclusionsvALIC DBS for TRD showed continued efficacy 2 years after surgery, with symptoms remaining stable after optimisation as rated by clinicians and with patient ratings improving. This supports DBS as a viable treatment option for patients with TRD.Trial registration numberNTR2118.

Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression

“…Another important factor in trial design is the length of time that the patient undergoes therapy. Long-term open-label studies have demonstrated that the efficacy of DBS for TRD improves over time, so longer trials may be necessary [17,18,38,66,67]. Finally, depression severity waxes and wanes throughout a patient's disease course.…”

Deep brain stimulation (DBS) in resistant mental disorders

“…This event demonstrates that the sudden discontinuation of stimulation can result in a recurrence of depressive symptoms. The results of DBS therapy are satisfactory, which enables further support in research into this method of treatment for patients with drug-resistant depression [21].…”

Deep brain stimulation for treatment-resistant depression: current status and future perspectives

“…The study's primary outcome was a comparison between depression scores in the ON and OFF groups, which showed significantly better depression scores during active rather than sham stimulation. The overall response rate during the 12 months open-label phase was 10/25 (40%), and twoyear follow up data were recently published, with 8/25 (32%) meeting responder status [10]. This was the first example that DBS for TRD may require an adaptive trial design, with a prolonged optimization period to establish optimal stimulation settings and extinguish placebo responses.…”