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Canadian Journal of Anesthesia/Journal canadien d'anesthésie

Published in:

01-06-2018 | Reports of Original Investigations

Ketamine-based anesthesia improves electroconvulsive therapy outcomes: a randomized-controlled study

Authors: Jonathan J. Gamble, MD, Henry Bi, MD, Rudy Bowen, MD, Grahme Weisgerber, MD, Rohan Sanjanwala, MD, Renuka Prasad, MBBS, Lloyd Balbuena, PhD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 6/2018

Abstract

Background

Major depressive disorder (MDD) is a common and debilitating condition that can be challenging to treat. Electroconvulsive therapy (ECT) is currently the therapeutic gold standard for treatment-resistant MDD. We tested our hypothesis that ketamine-based anesthesia for ECT results in superior improvement in treatment-resistant MDD outcomes compared with propofol-based anesthesia.

Methods

Patients with treatment-resistant MDD were enrolled in a randomized clinical trial with assignment to ketamine- or propofol-based anesthesia arms. Using a modified intention-to-treat analysis, we compared the median number of ECT treatments required to achieve a 50% reduction (primary outcome) and a score ≤ 10 (secondary outcome) on the Montgomery-Asberg depression rating scale (MADRS) between anesthesia groups.

Results

The study was terminated as significant results were found after the first planned interim analysis with 12 patients in each of the ketamine (intervention) and propofol (control) groups. All ketamine patients achieved at least a 50% MADRS reduction after a median of two ECT treatments whereas ten propofol patients (83%) achieved the same outcome after a median of four ECT treatments. All ketamine patients and seven propofol patients (58%) achieved MDD remission (MADRS ≤ 10). Log rank tests showed that both time-to-50% reduction and remission differed significantly between groups. Adverse events and recovery time were similar between groups.

Conclusions

In this early-terminated small-sized study, ketamine-based anesthesia compared with propofol-based anesthesia provided response and remission after fewer ECT sessions.

Trial registration

www.clinicaltrials.gov (NCT01935115). Registered 4 September 2013.

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Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62: 593-602.CrossRefPubMed

World Health Organization. The global burden of disease: 2004 update. Geneva, Switzerland: World Health Organization; 2008. Available from URL: https://www.fda.gov/NewsEvents/Testimony/ucm113265.htm/https://www.fda.gov/NewsEvents/Testimony/ucm113265.htm (accessed January 2018).

Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008; 5: e45.

U.S. Department of Health and Human Services. U.S. Food and Drug Administration. Anti-depressant Drug Use in Pediatric Populations - 2004. Available from URL: https://wayback.archive-it.org/7993/20170723044254/https://www.fda.gov/NewsEvents/Testimony/ucm113265.htm (accessed January 2018).

Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry 2007; 52: 46-54.CrossRefPubMed

Uk ECT. Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361: 799-808.CrossRef

Sackeim HA, Prudic J, Devanand DP, et al. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. N Engl J Med 1993; 328: 839-46.CrossRefPubMed

Sackeim HA, Haskett RF, Mulsant BH, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA 2001; 285: 1299-307.CrossRefPubMed

Kellner CH, Fink M, Knapp R, et al. Relief of expressed suicidal intent by ECT: a consortium for research in ECT study. Am J Psychiatry 2005; 162: 977-82.CrossRefPubMedPubMedCentral

10.

Fond G, Loundou A, Rabu C, et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl) 2014; 231: 3663-76.CrossRef

11.

Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013; 170: 1134-42.CrossRefPubMedPubMedCentral

12.

Reinstatler L, Youssef NA. Ketamine as a potential treatment for suicidal ideation: a systematic review of the literature. Drugs R D 2015; 15: 37-43.CrossRefPubMedPubMedCentral

13.

Caddy C, Amit BH, McCloud TL, et al. Ketamine and other glutamate receptor modulators for depression in adults. Cochrane Database Syst Rev 2015: CD011612.

14.

McCloud TL, Caddy C, Jochim J, et al. Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults. Cochrane Database Syst Rev 2015; 9: CD011611.

15.

Lam RW, Michalak EE, Swinson RP. Assessment scales in depression, mania and anxiety. London, UK: Taylor and Francis; 2005 .

16.

Bremner JD, Krystal JH, Putnam FW, et al. Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). J Trauma Stress 1998; 11: 125-36.CrossRefPubMed

17.

Oliver MNI, Simons JS. The affective lability scales: Development of a short-form measure. Pers Indiv Differ 2004; 37: 1279-88.CrossRef

18.

Jarventausta K, Chrapek W, Kampman O, et al. Effects of S-ketamine as an anesthetic adjuvant to propofol on treatment response to electroconvulsive therapy in treatment-resistant depression: a randomized pilot study. J ECT 2013; 29: 158-61.CrossRefPubMed

19.

Pagnin D, de Queiroz V, Pini S, Cassano GB. Efficacy of ECT in Depression: A Meta-Analytic Review. Journal of ECT 2004; 20: 13-20.CrossRefPubMed

20.

Singh JB, Fedgchin M, Daly EJ, et al. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry 2016; 173: 816-26.CrossRefPubMed

21.

Zimmerman M, Posternak MA, Chelminski I. Derivation of a definition of remission on the Montgomery-Asberg depression rating scale corresponding to the definition of remission on the Hamilton rating scale for depression. J Psychiatr Res 2004; 38: 577-82.CrossRefPubMed

22.

Shelton RC, Osuntokun O, Heinloth AN, Corya SA. Therapeutic options for treatment-resistant depression. CNS Drugs 2010; 24: 131-61.CrossRefPubMed

23.

Okamoto N, Nakai T, Sakamoto K, Nagafusa Y, Higuchi T, Nishikawa T. Rapid antidepressant effect of ketamine anesthesia during electroconvulsive therapy of treatment-resistant depression: comparing ketamine and propofol anesthesia. J ECT 2010; 26: 223-7.CrossRefPubMed

24.

Wang X, Chen Y, Zhou X, Liu F, Zhang T, Zhang C. Effects of propofol and ketamine as combined anesthesia for electroconvulsive therapy in patients with depressive disorder. J ECT 2012; 28: 128-32.CrossRefPubMed

25.

Pocock SJ. Clinical Trials - A Practical Approach. Chichester: John Wiley & Sons; 1983 .

26.

Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006; 63: 856-64.CrossRefPubMed

27.

Ghasemi M, Kazemi MH, Yoosefi A, et al. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Res 2014; 215: 355-61.CrossRefPubMed

28.

McGirr A, Berlim MT, Bond DJ, et al. A systematic review and meta-analysis of randomized controlled trials of adjunctive ketamine in electroconvulsive therapy: efficacy and tolerability. J Psychiatr Res 2015; 62: 23-30.CrossRefPubMed

29.

Yoosefi A, Sepehri AS, Kargar M, et al. Comparing effects of ketamine and thiopental administration during electroconvulsive therapy in patients with major depressive disorder: a randomized, double-blind study. J ECT 2014; 30: 15-21.CrossRefPubMed

30.

Zhong X, He H, Zhang C, et al. Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression. J Affect Disord 2016; 201: 124-30.CrossRefPubMed

31.

Fernie G, Currie J, Perrin JS, et al. Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial. Br J Psychiatry 2017; 210: 422-8.CrossRefPubMedPubMedCentral

32.

Fosse R, Read J. Electroconvulsive treatment: hypotheses about mechanisms of action. Front Psychiatry 2013; 4: 94.CrossRefPubMedPubMedCentral

33.

Shah A, Mosdossy G, McLeod S, Lehnhardt K, Peddle M, Rieder M. A blinded, randomized controlled trial to evaluate ketamine/propofol versus ketamine alone for procedural sedation in children. Ann Emerg Med 2011; 57(425-33): e2.

34.

Lalla FR, Milroy T. The current status of seizure duration in the practice of electroconvulsive therapy. Can J Psychiatry 1996; 41: 299-304.CrossRefPubMed

35.

Newport DJ, Carpenter LL, McDonald WM, et al. Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. Am J Psychiatry 2015; 172: 950-66.CrossRefPubMed

36.

Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 2016; 533: 481-6.CrossRefPubMedPubMedCentral

37.

Balbuena L, Baetz M, Bowen RC. The dimensional structure of cycling mood disorders. Psychiatry Res 2015; 228: 289-94.CrossRefPubMed

38.

Ding Z, White PF. Anesthesia for electroconvulsive therapy. Anesth Analg 2002; 94: 1351-64.CrossRefPubMed

39.

Geretsegger C, Nickel M, Judendorfer B, Rochowanski E, Novak E, Aichhorn W. Propofol and methohexital as anesthetic agents for electroconvulsive therapy: a randomized, double-blind comparison of electroconvulsive therapy seizure quality, therapeutic efficacy, and cognitive performance. J ECT 2007; 23: 239-43.CrossRefPubMed

40.

Kirkby KC, Beckett WG, Matters RM, King TE. Comparison of propofol and methohexitone in anaesthesia for ECT: effect on seizure duration and outcome. Aust N Z J Psychiatry 1995; 29: 299-303.CrossRefPubMed

41.

Vaidya PV, Anderson EL, Bobb A, Pulia K, Jayaram G, Reti I. A within-subject comparison of propofol and methohexital anesthesia for electroconvulsive therapy. J ECT 2012; 28: 14-9.CrossRefPubMed

42.

Andolfatto G, Willman E. A prospective case series of pediatric procedural sedation and analgesia in the emergency department using single-syringe ketamine-propofol combination (ketofol). Acad Emerg Med 2010; 17: 194-201.CrossRefPubMed

43.

Andolfatto G, Willman E. A prospective case series of single-syringe ketamine-propofol (ketofol) for emergency department procedural sedation and analgesia in adults. Acad Emerg Med 2011; 18: 237-45.CrossRefPubMed

44.

David H, Shipp J. A randomized controlled trial of ketamine/propofol versus propofol alone for emergency department procedural sedation. Ann Emerg Med 2011; 57: 435-41.CrossRefPubMed

45.

Jalili M, Bahreini M, Doosti-Irani A, Masoomi R, Arbab M, Mirfazaelian H. Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: systematic review and meta-analysis. Am J Emerg Med 2016; 34: 558-69.CrossRefPubMed

46.

Sharieff GQ, Trocinski DR, Kanegaye JT, Fisher B, Harley JR. Ketamine-propofol combination sedation for fracture reduction in the pediatric emergency department. Pediatr Emerg Care 2007; 23: 881-4.CrossRefPubMed

47.

Willman EV, Andolfatto G. A prospective evaluation of “ketofol” (ketamine/propofol combination) for procedural sedation and analgesia in the emergency department. Ann Emerg Med 2007; 49: 23-30.CrossRefPubMed

48.

Donnelly RF, Willman E, Andolfatto G. Stability of ketamine-propofol mixtures for procedural sedation and analgesia in the emergency department. Can J Hosp Pharm 2008; 61: 426-30.

49.

Mankad MV, Beyer JL, Weiner RD, Krystal AD. Clinical Manual of Electroconvulsive Therapy. 1st ed. Washington, DC: American Psychiatric Publighing; 2010 .

50.

Flood P, Rathmell JP, Shafer S. Stoelting’s Pharmacology and Physiology in Anesthetic Practice. 5th ed. Philadelphia: Wolters Kluwer Health; 2015 .

51.

Dobson G, Chong M, Chow L, et al. Guidelines to the practice of anesthesia - revised edition 2017. Can J Anesth 2017; 64: 65-91.

Title: Ketamine-based anesthesia improves electroconvulsive therapy outcomes: a randomized-controlled study
Authors: Jonathan J. Gamble, MD
Henry Bi, MD
Rudy Bowen, MD
Grahme Weisgerber, MD
Rohan Sanjanwala, MD
Renuka Prasad, MBBS
Lloyd Balbuena, PhD
Publication date: 01-06-2018
Publisher: Springer US
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 6/2018
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI: https://doi.org/10.1007/s12630-018-1088-0

At a glance: The STEP trials

Springer Medicine

Ketamine-based anesthesia improves electroconvulsive therapy outcomes: a randomized-controlled study

Abstract

Background

Methods

Results

Conclusions

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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