ECT with Ketamine Anesthesia Vs High Intensity Ketamine with ECT Rescue for Treatment-Resistant Depression

Официальное название

A Prospective Randomized Controlled Trial of Electroconvulsive Therapy with Ketamine Anesthesia (Standard Therapy) and High Intensity Ketamine with Electroconvulsive Therapy Rescue for Treatment-Resistant Depression - EAST HIKER Trial

Обзор

To determine if an high intensity ketamine with ECT rescue (HIKER) approach for treatment resistant depression will: 1) reduce patient suffering by hastening disease remission, 2) have fewer side effects, 3) reduce the need for ECT, and 4) be preferred by most patients. Half of participants will be randomized to the HIKER arm and receive high intensity ketamine treatment for eight consecutive days, and the other half will be assigned to the ECT with ketamine anesthesia (EAST) arm and receive 8 ECT treatments (2-3 treatment/week)

Подробное описание

Major depressive disorder (MDD) is a common psychiatric illness that will affect at least 15% of the population. The burden of MDD is staggering, considered by the World Health Organization to be the leading cause of disability in developed countries for people aged 15-44.

Oral antidepressant therapy for MDD is notoriously ineffective. At least 3 weeks of treatment is usually required to achieve response rates that rarely exceed 40% (only 10% better than placebo); furthermore, treatment can be complicated by serious side effects serious (e.g. falls, weight gain) including increased suicidality. Up to 15% of patients will eventually be diagnosed as having treatment-resistant depressions (TRD), defined as the failure to respond to at least two antidepressants from different pharmacologic classes after adequate treatment duration at therapeutic dosages. The gold standard therapy for TRD is electroconvulsive therapy (ECT) with general anaesthesia (GA), which produces rapid antidepressant effects after only a few sessions. Propofol is the traditional anaesthetic agent used in GA for ECT, although recently this research group showed that ECT with ketamine as the primary anaesthetic produced faster depression remission compared to ECT with propofol.

Despite its efficacy, ECT is associated with considerable problems. More than 10% of patients will experience amnesia and confusion, which can persist for weeks. These cognitive side effects limit the frequency of ECT treatments to two or three times per week. There is also a risk of rare but devastating cardiorespiratory adverse events, at least part of which can be attributed to the need to induce chemical paralysis (for safety) and administer opioids (for pain control) during ECT with GA. Lastly, ECT requires specialized psychiatric expertise, dedicated resources, specially trained nurses, and an anaesthesiologist - requirements that are both costly and not readily available in many settings.

In contrast to ECT, daily short-acting anaesthesia, including ketamine, is well tolerated. A recent study found that only three treatments of intravenous ketamine produced a greater early improvement in depression scores compared to ECT under non-ketamine-based GA. This suggests a possibility of achieving early disease remission in TRD with ketamine-only infusions while avoiding the safety risks and treatment delays associated with ECT under GA.

The efficacy, feasibility, and improved side-effect profile of frequent successive ketamine treatments suggest it may be the preferred treatment for TRD compared to ECT with ketamine-based GA. There may, however, be a small subgroup of TRD patients who do not respond to ketamine alone and require ECT, although with a daily treatment regimen, ketamine non-responders could be quickly identified and given a standard course of ECT. The researchers propose that a treatment protocol of daily High Intensity Ketamine with ECT Rescue (HIKER) will be superior to ECT Therapy with ketamine anesthesia standard therapy (EAST) in facilitating early disease remission, while at the same time yielding similar overall remission rates by allowing ketamine non-responders to be quickly identified and given ECT.

Вмешательства

• Препарат Ketamine
  IV Ketamine 0.50 mg/kg
• Процедура ECT
  ECT with unilateral or bilateral electrode placement and monitoring of seizure threshold by the half-age method

Первичные конечные точки

• Number of treatments required to reach disease remission [Срок оценки: From date of randomization until the date of disease remission or after 8 treatments, assessed up to 4 weeks]

Вторичные конечные точки (5)

• Rate of rescue ECT in the HIKER arm [Срок оценки: From date of randomization up to 6 days]
• Suicidal ideation [Срок оценки: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks]
• Cognitive Impairment [Срок оценки: MMSE will be assessed at baseline, final treatment, and 30 day post-treatment follow-up]
• Self- and clinician rated improvement [Срок оценки: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks]
• Patient satisfaction with treatment [Срок оценки: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks]

Критерии участия

Критерии включения

• Montgomery Asberg Depression Rating Scale (MADRS) score of greater than 20) planned for ECT therapy.
• Subjects must meet clinical criteria for TRD defined as failure to respond to at least 2 standard-of-care drug therapies of adequate treatment duration.

Критерии исключения

• Subjects will be ineligible if they cannot provide informed consent
• American Society of Anesthesiology physical status score of four or greater
• Implanted medical device with electronic parts (e.g. pacemaker, defibrillator, intrathecal pump, spinal cord stimulator, deep brain stimulator)
• Schizoaffective disorder
• Women of child-bearing potential will be asked to undergo a commercial urine pregnancy screening test. Those who refuse or screen positive will be excluded.
• Allergic to any of the study drugs or their carrier components
• Any serious physical condition prior to randomization deemed by the attending psychiatrist or consulting anesthetist to be a contraindication to ECT such as cardiovascular disease (including untreated hypertension), respiratory disease, cerebrovascular disease, intracranial hypertension (including glaucoma), or seizures.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Royal University Hospital — Saskatoon

Публикации

• 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 Jun;62(6):593-602. doi: 10.1001/archpsyc.62.6.593. PMID 15939837
• Mathers C, Fat DM, Boerma JT. The global burden of disease: 2004 update: World Health Organization; 2008.
• 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 Feb;5(2):e45. doi: 10.1371/journal.pmed.0050045. PMID 18303940
• Skolnick P, Layer RT, Popik P, Nowak G, Paul IA, Trullas R. Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression. Pharmacopsychiatry. 1996 Jan;29(1):23-6. doi: 10.1055/s-2007-979537. PMID 8852530
• 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 Jan;52(1):46-54. doi: 10.1177/070674370705200108. PMID 17444078
• Fink M. Is Catatonia a Primary Indication for ECT? Convuls Ther. 1990;6(1):1-4. No abstract available. PMID 11941041
• Bundy BD, Hewer W, Andres FJ, Gass P, Sartorius A. Influence of anesthetic drugs and concurrent psychiatric medication on seizure adequacy during electroconvulsive therapy. J Clin Psychiatry. 2010 Jun;71(6):775-7. doi: 10.4088/JCP.08m04971gre. Epub 2009 Dec 29. PMID 20051218
• Comparing Ketamine and Propofol Anesthesia for Electroconvulsive Therapy [database on the Internet]. 2013 [cited 2017 Jan 1]

Идентификаторы

NCT: NCT03272698 · 123456

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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