Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression: A Decade of Clinical Follow-Up

Frederick L. Hitti, MD, PhD^a ; Mario A. Cristancho, MD^b ; Andrew I. Yang, MD, MS^a ; Mahendra T. Bhati, MD^d,e ; Gordon H. Baltuch, MD, PhD^a

J Clin Psychiatry 2021;82(6):21m13973

ABSTRACT

Objective: Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant depression (TRD) that has shown variable efficacy. This report describes long-term outcomes of DBS for TRD.

Methods: A consecutive series of 8 patients with TRD were implanted with ventral capsule/ventral striatum (VC/VS) DBS systems as part of the Reclaim clinical trial. Outcomes from 2009 to 2020 were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Demographic information, MADRS scores, and data on adverse events were collected via retrospective chart review. MADRS scores were integrated over time using an area-under-the-curve technique.

Results: This cohort of patients had severe TRD—all had failed trials of ECT, and all had failed a minimum of 4 adequate medication trials. Mean ± SD follow-up for patients who continued to receive stimulation was 11.0 ± 0.4 years (7.8 ± 4.3 years for the entire cohort). At last follow-up, mean improvement in MADRS scores was 44.9% ± 42.7%. Response (≥ 50% improvement) and remission (MADRS score ≤ 10) rates at last follow-up were 50% and 25%, respectively. Two patients discontinued stimulation due to lack of efficacy, and another patient committed suicide after stimulation was discontinued due to recurrent mania. The majority of the cohort (63%) continued to receive stimulation through the end of the study.

Conclusions: While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this small open-label study demonstrates that some patients achieve meaningful and sustained clinical benefit. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including patient selection, integrative outcome measures, and long-term observation is essential for future trial design.

Trial Registration: ClinicalTrials.gov identifier: NCT00837486

Continue Reading...

Members enjoy unlimited free PDF downloads as part of their subscription! Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Buy PDF for $40

Please sign in or purchase this PDF for $40.

References (49)

Ferrari AJ, Charlson FJ, Norman RE, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013;10(11):e1001547. PubMed CrossRef
Steel Z, Marnane C, Iranpour C, et al. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980–2013. Int J Epidemiol. 2014;43(2):476–493. PubMed CrossRef
Bailine SH, Rifkin A, Kayne E, et al. Comparison of bifrontal and bitemporal ECT for major depression. Am J Psychiatry. 2000;157(1):121–123. PubMed CrossRef
Fava M, Rush AJ, Wisniewski SR, et al. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry. 2006;163(7):1161–1172. PubMed CrossRef
Hollon SD, Jarrett RB, Nierenberg AA, et al. Psychotherapy and medication in the treatment of adult and geriatric depression: which monotherapy or combined treatment? J Clin Psychiatry. 2005;66(4):455–468. PubMed CrossRef
Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163(9):1519–1530, quiz 1665. PubMed CrossRef
Rush AJ, Trivedi MH, Wisniewski SR, et al; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006;354(12):1231–1242. PubMed CrossRef
Thase ME, Friedman ES, Biggs MM, et al. Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry. 2007;164(5):739–752. PubMed CrossRef
Trivedi MH, Rush AJ, Wisniewski SR, et al; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28–40. PubMed CrossRef
Souery D, Papakostas GI, Trivedi MH. Treatment-resistant depression. J Clin Psychiatry. 2006;67(suppl 6):16–22. PubMed
Greden JF. The burden of disease for treatment-resistant depression. J Clin Psychiatry. 2001;62(suppl 16):26–31. PubMed
Taipale H, Reutfors J, Tanskanen A, et al. Risk and risk factors for disability pension among patients with treatment resistant depression- a matched cohort study. BMC Psychiatry. 2020;20(1):232. PubMed CrossRef
Hitti FL, Ramayya AG, McShane BJ, et al. Long-term outcomes following deep brain stimulation for Parkinson’s disease. J Neurosurg. 2019;1–6. PubMed
Miocinovic S, Somayajula S, Chitnis S, et al. History, applications, and mechanisms of deep brain stimulation. JAMA Neurol. 2013;70(2):163–171. PubMed CrossRef
Garnaat SL, Greenberg BD, Sibrava NJ, et al. Who qualifies for deep brain stimulation for OCD? data from a naturalistic clinical sample. J Neuropsychiatry Clin Neurosci. 2014;26(1):81–86. PubMed CrossRef
Raymaekers S, Luyten L, Bervoets C, et al. Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up. Transl Psychiatry. 2017;7(10):e1251. PubMed CrossRef
Sartorius A, Kiening KL, Kirsch P, et al. Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry. 2010;67(2):e9–e11. PubMed CrossRef
Coenen VA, Bewernick BH, Kayser S, et al. Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial. Neuropsychopharmacology. 2019;44(7):1224–1232. PubMed CrossRef
Fenoy AJ, Schulz PE, Selvaraj S, et al. A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression. Transl Psychiatry. 2018;8(1):111. PubMed CrossRef
Holtzheimer PE, Husain MM, Lisanby SH, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry. 2017;4(11):839–849. PubMed CrossRef
Holtzheimer PE, Kelley ME, Gross RE, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry. 2012;69(2):150–158. PubMed CrossRef
Merkl A, Schneider G-H, Schönecker T, et al. Antidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression. Exp Neurol. 2013;249:160–168. PubMed CrossRef
Merkl A, Aust S, Schneider G-H, et al. Deep brain stimulation of the subcallosal cingulate gyrus in patients with treatment-resistant depression: a double-blinded randomized controlled study and long-term follow-up in eight patients. J Affect Disord. 2018;227:521–529. PubMed CrossRef
Puigdemont D, Portella M, Pérez-Egea R, et al. 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. J Psychiatry Neurosci. 2015;40(4):224–231. PubMed CrossRef
Ramasubbu R, Anderson S, Haffenden A, et al. Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study. J Psychiatry Neurosci. 2013;38(5):325–332. PubMed CrossRef
Bergfeld IO, Mantione M, Hoogendoorn MLC, et al. Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2016;73(5):456–464. PubMed CrossRef
Dougherty DD, Rezai AR, Carpenter LL, et al. A randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression. Biol Psychiatry. 2015;78(4):240–248. PubMed CrossRef
Malone DAJ Jr, Dougherty DD, Rezai AR, et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry. 2009;65(4):267–275. PubMed CrossRef
Mayberg HS, Lozano AM, Voon V, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45(5):651–660. PubMed CrossRef
Zhou C, Zhang H, Qin Y, et al. A systematic review and meta-analysis of deep brain stimulation in treatment-resistant depression. Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:224–232. PubMed CrossRef
Kisely S, Li A, Warren N, et al. A systematic review and meta-analysis of deep brain stimulation for depression. Depress Anxiety. 2018;35(5):468–480. PubMed CrossRef
Berlim MT, McGirr A, Van den Eynde F, et al. Effectiveness and acceptability of deep brain stimulation (DBS) of the subgenual cingulate cortex for treatment-resistant depression: a systematic review and exploratory meta-analysis. J Affect Disord. 2014;159:31–38. PubMed CrossRef
Hitti FL, Yang AI, Cristancho MA, et al. Deep brain stimulation is effective for treatment-resistant depression: a meta-analysis and meta-regression. J Clin Med. 2020;9(9):2796. PubMed CrossRef
Crowell AL, Riva-Posse P, Holtzheimer PE, et al. Long-term outcomes of subcallosal cingulate deep brain stimulation for treatment-resistant depression. Am J Psychiatry. 2019;176(11):949–956. PubMed CrossRef
van der Wal JM, Bergfeld IO, Lok A, et al. Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression. J Neurol Neurosurg Psychiatry. 2020;91(2):189–195. PubMed CrossRef
Bewernick BH, Kayser S, Gippert SM, et al. Deep brain stimulation to the medial forebrain bundle for depression—long-term outcomes and a novel data analysis strategy. Brain Stimul. 2017;10(3):664–671. PubMed CrossRef
Kelley ME, Franco AR, Mayberg HS, et al. The Illness Density Index (IDI): a longitudinal measure of treatment efficacy. Clin Trials. 2012;9(5):596–604. PubMed CrossRef
Aaronson ST, Sears P, Ruvuna F, et al. A 5-year observational study of patients with treatment-resistant depression treated with vagus nerve stimulation or treatment as usual: comparison of response, remission, and suicidality. Am J Psychiatry. 2017;174(7):640–648. PubMed CrossRef
Ramasubbu R, Lang S, Kiss ZHT. Dosing of electrical parameters in deep brain stimulation (DBS) for intractable depression: a review of clinical studies. Front Psychiatry. 2018;9:302. PubMed CrossRef
Reitz SC, Luger S, Lapa S, et al. Comparing programming sessions of vim-DBS. Front Neurol. 2020;11:987. PubMed CrossRef
Wagle Shukla A, Zeilman P, Fernandez H, et al. DBS programming: an evolving approach for patients with Parkinson’s disease. Parkinsons Dis. 2017;2017:8492619. PubMed CrossRef
Ramasubbu R, Clark DL, Golding S, et al. Long versus short pulse width subcallosal cingulate stimulation for treatment-resistant depression: a randomised, double-blind, crossover trial. Lancet Psychiatry. 2020;7(1):29–40. PubMed CrossRef
Cogan SF, Ludwig KA, Welle CG, et al. Tissue damage thresholds during therapeutic electrical stimulation. J Neural Eng. 2016;13(2):021001. PubMed CrossRef
Hitti FL, Vaughan KA, Ramayya AG, et al. Reduced long-term cost and increased patient satisfaction with rechargeable implantable pulse generators for deep brain stimulation. J Neurosurg. 2018;131(3):799–806. PubMed CrossRef
De Vloo P, Raymaekers S, van Kuyck K, et al. Rechargeable stimulators in deep brain stimulation for obsessive-compulsive disorder: a prospective interventional cohort study. Neuromodulation. 2018;21(2):203–210. PubMed CrossRef
Bergfeld IO, Mantione M, Figee M, et al. Treatment-resistant depression and suicidality. J Affect Disord. 2018;235:362–367. PubMed CrossRef
Seo H-J, Jung Y-E, Jeong S, et al. Persistence and resolution of suicidal ideation during treatment of depression in patients with significant suicidality at the beginning of treatment: the CRESCEND study. J Affect Disord. 2014;155:208–215. PubMed CrossRef
Wulsin LR, Vaillant GE, Wells VE. A systematic review of the mortality of depression. Psychosom Med. 1999;61(1):6–17. PubMed CrossRef
Bari AA, Mikell CB, Abosch A, et al. Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders. J Neurol Neurosurg Psychiatry. 2018;89(8):886–896. PubMed CrossRef