Evidence-Based Reviews

Neuromodulatory options for treatment-resistant depression

Current Psychiatry. 2018 March;17(3):26-28,33-37

References

1. Berlim MT, Turecki G. What is the meaning of treatment resistant/refractory major depression (TRD)? A systematic review of current randomized trials. Eur Neuropsychopharmacol. 2007;17(11):696-707.
2. Thase ME, Rush AJ. When at first you don’t succeed: sequential strategies for antidepressant nonresponders. J Clin Psychiatry. 1997;58(suppl 13):23-29.
3. Petersen T, Papakostas GI, Posternak MA, et al. Empirical testing of two models for staging antidepressant treatment resistance. J Clin Psychopharmacol. 2005;25(4):336-341.
4. Souery D, Papakostas GI, Trivedi MH. Treatment-resistant depression. J Clin Psychiatry. 2006;67(suppl 6):16-22.
5. Souery D, Amsterdam J, de Montigny C, et al. Treatment resistant depression: methodological overview and operational criteria. Eur Neuropsychopharmacol. 1999;9(1-2):83-91.
6. Evans DL, Charney DS. Mood disorders and medical illness: a major public health problem. Biol. Psychiatry. 2003;54(3):177-180.
7. Sanacora G, Mason GF, Rothman DL, et al. Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry. 2003;160(3):577-579.
8. Merkl A, Heuser I, Bajbouj M. Antidepressant electroconvulsive therapy: mechanism of action, recent advances and limitations. Exp Neurol. 2009;219(1):20-26.
9. Perera TD, Coplan JD, Lisanby SH, et al. Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J. Neurosci. 2007;27(18):4894-4901.
10. Abbott CC, Gallegos P, Rediske N et al. A review of longitudinal electroconvulsive therapy: neuroimaging investigations. J Geriatr Psychiatry Neurol. 2014;27(1):33-46.
11. Heijnen WT, Birkenhäger TK, Wierdsma AI, et al. Antidepressant pharmacotherapy failure and response to subsequent electroconvulsive therapy: a meta-analysis. J Clin Psychopharmacol. 2010;30(5):616-619.
12. UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet. 2003;361(9360):799-808.
13. Semkovska M, Landau S, Dunne R et al. Bitemporal versus high-dose unilateral twice-weekly electroconvulsive therapy for depression (EFFECT-Dep): a pragmatic, randomized, non-inferiority trial. Am J Psychiatry. 2016;173(4):408-417.
14. Charlson F, Siskind D, Doi SA, et al. ECT efficacy and treatment course: a systematic review and meta-analysis of twice vs thrice weekly schedules. J Affect Disord. 2012;138(1-2):1-8.
15. Loo CK, Kaill A, Paton P, et al. The difficult-to-treat electroconvulsive therapy patient—strategies for augmenting outcomes. J Affect Disord. 2010;124(3):219-227.
16. de Vreede IM, Burger H, van Vliet IM. Prediction of response to ECT with routinely collected data in major depression. J Affect Disord. 2005;86(2-3):323-327.
17. Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biol Psychiatry. 2010;68(6):568-577.
18. Baghai TC, Marcuse A, Brosch M, et al. The influence of concomitant antidepressant medication on safety, tolerability and clinical effectiveness of electroconvulsive therapy. World J Biol Psychiatry. 2006;7(2):82-90.
19. Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, et al. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994;35(3):616-626.
20. Nemeroff CB, Mayberg HS, Krahl SE, et al. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology. 2006;31(7):1345-1355.
21. Matthews K, Eljamel MS. Vagus nerve stimulation and refractory depression: please can you switch me on doctor? Br J Psychiatry. 2003;183:181-183.
22. George MS, Rush AJ, Sackeim HA, et al. Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders. Int J Neuropsychopharmacol. 2003;6(1):73-83.
23. Harden CL, Pulver MC, Ravdin LD, et al. A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy Behav. 2000;1(2):93-99.
24. Elger G, Hoppe C, Falkai P, et al. Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res. 2000;42(2-3):203-210.
25. Krahl SE, Clark KB, Smith DC, et al. Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia. 1998;39(7):709-714.
26. Ben-Menachem E, Hamberger A, Hedner T, et al. Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 1995;20(3):221-227.
27. Henry TR, Bakay RA, Votaw JR, et al. Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation. Epilepsia. 1998;39(9):983-990.
28. O’Keane V, Dinan TG, Scott L, et al. Changes in hypothalamic-pituitary-adrenal axis measures after vagus nerve stimulation therapy in chronic depression. Biol Psychiatry. 2005;58(12):963-968.
29. Rush AJ, George MS, Sackeim HA, et al. Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study. Biol Psychiatry. 2000;47(4):276-286.
30. Sackeim HA, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology. 2001;25(5):713-728.
31. Armitage R, Husain M, Hoffmann R, et al. The effects of vagus nerve stimulation on sleep EEG in depression: a preliminary report. J Psychosom Res. 2003;54(5):475-482.
32. Rush AJ, Marangell LB, Sackeim HA, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005;58(5):347-354.
33. Martin JL, Martín-Sánchez E. Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs. Eur Psychiatry. 2012;27(3):147-155.
34. Shah A, Carreno FR, Frazer A. Therapeutic modalities for treatment resistant depression: focus on vagal nerve stimulation and ketamine. Clin Psychopharmacol Neurosci. 2014;12(2):83-93.
35. Aaronson ST, Carpenter LL, Conway CR, et al. Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects. Brain Stimul. 2013;6(4):631-640.
36. Daban C, Martinez-Aran A, Cruz N, et al. Safety and efficacy of vagus nerve stimulation in treatment-resistant depression. A systematic review. J Affect Disord. 2008;110(1-2):1-15.
37. Eitan R, Lerer B. Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities. Dialogues Clin Neurosci. 2006;8(2):241-258.
38. Lam RW, Chan P, Wilkins-Ho M, et al. Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and metaanalysis. Can J Psychiatry. 2008;53(9):621-631.
39. Fitzgerald PB, Fountain S, Daskalakis ZJ. A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol. 2006;117(12):2584-2596.
40. Fitzgerald PB, Oxley TJ, Laird AR, et al. An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression. Psychiatry Res. 2006;148(1):33-45.
41. Berlim MT, Van den Eynde F, Daskalakis ZJ. Clinically meaningful efficacy and acceptability of low-frequency repetitive transcranial magnetic stimulation (rTMS) for treating primary major depression: a meta-analysis of randomized, double-blind and sham-controlled trials. Neuropsychopharmacology. 2013;38(4):543-551.
42. Gaynes BN, Lloyd SW, Lux L, et al. Repetitive transcranial magnetic stimulation for treatment-resistant depression. J Clin Psychiatry. 2014;75(5):477-489; quiz 489.
43. Carpenter LL, Janicak PG, Aaronson ST, et al. Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depress Anxiety. 2012;29(7):587-596.
44. Dunner DL, Aaronson ST, Sackeim HA, et al. A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder. J Clin Psychiatry. 2014;75(12):1394-1401.
45. Fitzgerald PB, Hoy K, Daskalakis ZJ, et al. A randomized trial of the anti-depressant effects of low- and high-frequency transcranial magnetic stimulation in treatment-resistant depression. Depress Anxiety. 2009;26(3):229-234.
46. Dumas R, Padovani R, Richieri R, et al. Repetitive transcranial magnetic stimulation in major depression: response factor [in French]. Encephale. 2012;38(4):360-368.
47. Fregni F, Marcolin MA, Myczkowski M, et al. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int. J. Neuropsychopharmacol. 2006;9(6):641-654.
48. Kennedy SH, Giacobbe P, Rizvi SJ, et al. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry. 2011;168(5):502-510.
49. Taghva AS, Malone DA, Rezai AR. Deep brain stimulation for treatment-resistant depression. World Neurosurg. 2013;80(3-4):S27.e17-S27.e24.
50. Mayberg HS. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull. 2003;65:193-207.
51. Mayberg HS, Liotti M, Brannan SK, et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999;156(5):675-682.
52. Jiménez F, Velasco F, Salín-Pascual R, et al. Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder. Acta Neurochir Suppl. 2007;97(pt 2):393-398.
53. Jiménez F, Velasco F, Salin-Pascual R, et al. A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery. 2005;57(3):585-593; discussion 585-593.
54. Bewernick BH, Hurlemann R, Matusch A, et al. Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry. 2010;67(2):110-116.
55. Schlaepfer TE, Bewernick BH, Kayser S, et al. Deep brain stimulation of the human reward system for major depression—rationale, outcomes and outlook. Neuropsychopharmacology. 2014;39(6):1303-1314.
56. Malone DA 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.
57. 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.
58. Schlaepfer TE, Bewernick BH, Kayser S, et al. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry. 2013;73(12):1204-1212.
59. Gálvez JF, Keser Z, Mwangi B, et al. The medial forebrain bundle as a deep brain stimulation target for treatment resistant depression: a review of published data. Prog Neuropsychopharmacol Biol Psychiatry. 2015;58:59-70.
60. Fenoy AJ, Schulz P, Selvaraj. Deep brain stimulation of the medial forebrain bundle: distinctive responses in resistant depression. J Affect Disord. 2016;203:143-151.
61. Riva-Posse P, Choi KS, Holtzheimer PE, et al. Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2014;76(12):963-969.
62. Burke MJ, Husain MM. Concomitant use of vagus nerve stimulation and electroconvulsive therapy for treatment-resistant depression. J ECT. 2006;22(3):218-222.
63. Milev R V, Giacobbe P, Kennedy SH, et al; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: section 4. Neurostimulation treatments. Can J Psychiatry. 2016;61:561-575.

Deep brain stimulation

DBS is an invasive stereotactic surgical procedure. It involves unilateral or bilateral placement of electrodes at neuroanatomical locations to deliver continuous stimulation from a subcutaneously implanted pulse generator.⁴⁸ In the past, destructive surgical procedures were used to treat intractable depression. Surgeries such as anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy have been shown to effectively reduce depressive symptoms.⁴⁹ The advantages of DBS over destructive procedures include the fact that DBS is reversible and that the stimulation levels can easily be adjusted, and the treatment can easily be stopped or restarted.

There is no consensus on the optimal anatomic locations for the electrode implantation in DBS. Electrodes have been implanted in the subcallosal cingulate gyrus, inferior thalamic peduncle, ventral capsule/ventral striatum, superolateral branch of the medial forebrain bundle (MFB), and nucleus accumbens.

The choice of anatomic locations stems from the large body of neuroimaging literature characterizing functional changes associated with acute depression and response to treatment. The electrode placement targets “nodes” that form an integral part of the affected neural circuits that are responsible for regulating depressive symptoms.⁵⁰ Increased metabolic activity and blood flow to the subgenual cingulate gyrus and reduction in the blood flow to the DLPFC and the striatum have been associated with active depressed states. Response to antidepressant treatment has been associated with reversal of these findings.⁵¹ Functional magnetic resonance imaging studies have consistently shown increased activity in the amygdala in response to negative stimuli among patients with depression.

Regardless of the site of electrode placement, studies have reported symptomatic improvement among patients with depression who are treated with DBS. In 2 case reports, the electrode was implanted in the inferior thalamic peduncle.^52,53 Each study had 1 participant, and each patient remitted.^52,53

Placement of the electrodes in the nucleus accumbens resulted in a response rate of 45% in 1 study,⁵⁴ whereas in a different study, all patients reported improvement in anhedonia.⁵⁵ A response rate of 71% and a remission rate of 35% were observed in a study in which the electrode was implanted in the ventral capsule/ventral striatum area.⁵⁶

Neuromodulatory options for treatment-resistant depression

References

Deep brain stimulation

Pages

Recommended Reading