Efficacy and quality of life after 6-9 years of deep brain stimulation for depression.

BACKGROUND: Given the invasiveness of deep brain stimulation (DBS), the effect should prove to be stable over the long-term and translate into an improvement of quality of life (QOL). OBJECTIVE: To study the effectiveness and QOL up to nine years after the DBS surgery. METHODS: We treated 25 adult patients with major depression with DBS of the ventral anterior limb of the internal capsule (vALIC). We followed them up naturalistically for 6-9 years after surgery (mean: 7.7 [SD:1.5] years), including a randomized crossover phase after the first year comparing sham with active DBS. Symptom severity was quantified using the Hamilton Depression Scale with response defined as a ≥50% decrease of the score compared to baseline. Quality of life was measured using the WHOQOL-BREF, assessing 5 domains (general, physical, psychological, social, environmental). RESULTS: Intention-to-treat response rates remained mostly stable from Year 3 to last follow-up (Year 3, 5 and 6: 40%; Year 4: 36%; Last observation: 44%). General, physical, psychological (all P < 0.001) and the environmental (P = 0.02) domain scores increased during DBS optimization and remained stable over the long term. No statistically significant changes were detected on the social domain. Patients scored significantly higher during active than sham DBS on the psychological, social and environmental domains, and trended towards a higher score on the general and physical domains. CONCLUSION: This study shows continued efficacy of vALIC DBS in depression, which translates into an improvement of QOL providing further support for DBS as a durable treatment for TRD.

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

OBJECTIVE: Deep 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. METHODS: Depression 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. RESULTS: Of 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. CONCLUSIONS: vALIC 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 NUMBER: NTR2118.

Cognitive Behavioral Therapy vs. Eye Movement Desensitization and Reprocessing for Treating Panic Disorder: A Randomized Controlled Trial.

Objective: Cognitive Behavioral Therapy (CBT) is an effective intervention for patients with panic disorder (PD). From a theoretical perspective, Eye Movement Desensitization and Reprocessing (EMDR) therapy could also be useful in the treatment of PD because: (1) panic attacks can be experienced as life threatening; (2) panic memories specific to PD resemble traumatic memories as seen in posttraumatic stress disorder (PTSD); and (3) PD often develops following a distressing life event. The primary objective of this Randomized Controlled Trial (RCT), was to compare EMDR therapy with CBT for PD and determine whether EMDR is not worse than CBT in reducing panic symptoms and improving Quality Of Life (QOL). Methods: Two-arm (CBT and EMDR) parallel RCT in patients with PD (N = 84). Patients were measured at baseline (T1), directly after the last therapy session (T2), and 3 months after ending therapy (T3). Non-inferiority testing (linear mixed model with intention-to-treat analysis) was applied. Patients were randomly assigned to 13 weekly 60-min sessions of CBT (N = 42) or EMDR therapy (N = 42). Standard protocols were used. The primary outcome measure was severity of PD at T3, as measured with the Agoraphobic Cognitions Questionnaire (ACQ), the Body Sensations Questionnaire (BSQ), and the Mobility Inventory (MI). The secondary outcome measure was QOL, as measured with the World Health Organization Quality of Life short version (WHOQOL-Bref), at T3. Results: The severity of PD variables ACQ and BSQ showed non-inferiority of EMDR to CBT, while MI was inconclusive (adjusted analyses). Overall QOL and general health, Psychological health, Social relationships, and Environment showed non-inferiority of EMDR to CBT, while Physical health was inconclusive. Conclusion: EMDR therapy proved to be as effective as CBT for treating PD patients. Trial Registration: Dutch Trial Register, Nr. 3134 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3134.

Episodic memory following deep brain stimulation of the ventral anterior limb of the internal capsule and electroconvulsive therapy.

BACKGROUND: Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are effective treatments for patients with treatment-resistant depression (TRD). However, a common side effect of ECT is autobiographical memory loss (e.g., personal experiences), whereas the impact of DBS on autobiographical memories has never been established. OBJECTIVE: Comparing autobiographical memories following DBS and ECT. METHODS: In two hospitals in The Netherlands, we interviewed 25 TRD patients treated with DBS of the ventral anterior limb of the internal capsule (vALIC), 14 TRD patients treated with ECT and 22 healthy controls (HC) with the Autobiographical Memory Inventory - Short Form (AMI-SF) in a prospective, longitudinal study between March 2010 and August 2016. Patients treated with DBS were interviewed before surgery, after surgery, and twice during treatment over 122.7 (SD: ±22.2) weeks. Patients treated with ECT were tested before ECT, after six right unilateral (RUL) ECT sessions and twice following ECT over 65.1 (±9.3) weeks. Controls were tested four times over 81.5 (±15.6) weeks. RESULTS: Compared to HC, the AMI-SF score decreased faster in both TRD groups (P < 0.001). More specifically, AMI-SF score decreased in a comparable rate as HC after DBS surgery, but decreased more during treatment. The AMI-SF decrease in the ECT group was larger than both the DBS and HC groups. CONCLUSIONS: Both ECT and vALIC DBS result in a faster autobiographical memory decline compared to HC. DBS might have a negative impact on autobiographical memories, although less so than ECT. Future work should dissect whether DBS or characteristics of TRD cause this decline.

Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial.

IMPORTANCE: Patients with treatment-resistant depression (TRD) do not respond sufficiently to several consecutive treatments for major depressive disorder. Deep brain stimulation (DBS) is a promising treatment for these patients, but presently placebo effects cannot be ruled out. OBJECTIVE: To assess the efficacy of DBS of the ventral anterior limb of the internal capsule (vALIC), controlling for placebo effects with active and sham stimulation phases. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five patients with TRD from 2 hospitals in the Netherlands were enrolled between March 22, 2010, and May 8, 2014. Patients first entered a 52-week open-label trial during which they received bilateral implants of 4 contact electrodes followed by optimization of DBS until a stable response was achieved. A randomized, double-blind, 12-week crossover phase was then conducted with patients receiving active treatment followed by sham or vice versa. Response and nonresponse to treatment were determined using intention-to-treat analyses. INTERVENTIONS: Deep brain stimulation targeted to the vALIC. MAIN OUTCOMES AND MEASURES: The change in the investigator-rated score of the 17-item Hamilton Depression Rating Scale (HAM-D-17) was the main outcome used in analysis of the optimization phase. The primary outcome of the crossover phase was the difference in the HAM-D-17 scores between active and sham DBS. The score range of this tool is 0 to 52, with higher scores representing more severe symptoms. Patients were classified as responders to treatment (≥50% decrease of the HAM-D-17 score compared with baseline) and partial responders (≥25 but <50% decrease of the HAM-D-17 score). RESULTS: Of 25 patients included in the study, 8 (32%) were men; the mean (SD) age at inclusion was 53.2 (8.4) years. Mean HAM-D-17 scores decreased from 22.2 (95% CI, 20.3-24.1) at baseline to 15.9 (95% CI, 12.3-19.5) (P = .001), Montgomery-Åsberg Depression Rating Scale scores from 34.0 (95% CI, 31.8-36.3) to 23.8 (95% CI, 18.4-29.1) (P < .001), and Inventory of Depressive Symptomatology-Self-report scores from from 49.3 (95% CI, 45.4-53.2) to 38.8 (95% CI, 31.6-46.0) (P = .005) in the optimization phase. Following the optimization phase, which lasted 51.6 (22.0) weeks, 10 patients (40%) were classified as responders and 15 individuals (60%) as nonresponders. Sixteen patients entered the randomized crossover phase (9 responders [56%], 7 nonresponders [44%]). During active DBS, patients scored significantly lower on the HAM-D-17 scale (13.6 [95% CI, 9.8-17.4]) than during sham DBS (23.1 [95% CI, 20.6-25.6]) (P < .001). Serious adverse events included severe nausea during surgery (1 patient), suicide attempt (4 patients), and suicidal ideation (2 patients). CONCLUSIONS AND RELEVANCE: Deep brain stimulation of the vALIC resulted in a significant decrease of depressive symptoms in 10 of 25 patients and was tolerated well. The randomized crossover design corroborates that vALIC DBS causes symptom reduction rather than sham. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2118.