Ketamine as an Augmentation Strategy for Electroconvulsive Therapy (ECT) in Depression

NCT01881763 | Completed Phase 4 Results

• 1 other identifier: 10-127
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to compare outcomes of Electroconvulsive Therapy (ECT) using ketamine versus methohexital anesthesia in depressed patients. The investigators hypothesize that patients who receive ketamine anesthesia during ECT will achieve remission status faster than those receiving methohexital anesthesia. Also, at the end of the ECT course subjects will display fewer cognitive side effects compared to those treated with methohexital anesthesia.

Conditions

Unipolar Depression; Bipolar Depression

Keywords

Electroconvulsive Therapy; Ketamine; anesthesia; depression; unipolar; bipolar

Outcome Measures

Primary Outcomes (1)

• Hamilton Rating Scale for Depression (HRSD) Improvement

  The items mostly range from a score of 0-4 but there are some questions that range from a score of 0-2. The maximum total score that can be reported is 76 and the lowest score is 0. Higher values represent a worse outcome. Items are summed together to compute the total score. Remission is defined as two consecutive Hamilton Rating Scale for Depression, 24 items (HRSD-24) scores \< 10, and HRSD-24 total score does not increase \> 3 points on the second consecutive HRSD-24, or remains \< 6 at the last two consecutive treatments. HRSD-24 scores are used to define remission.

  Days required to achieve remission (on average 3-4 weeks)

Secondary Outcomes (1)

• Cognitive Side Effects of ECT

  Neuropsychological Battery: Changes from baseline to the end of the ECT course (on average 3-4 weeks)

Other Outcomes (1)

• Resting Stated Functional Magnetic Resonance Imaging (rs fMRI)

  Changes from baseline to the end of ECT course (approximately 3-4 weeks)

Study Arms (2)

Ketamine

EXPERIMENTAL

Participants will be randomized 1:1 to either Ketamine (experimental condition) or Methohexital anesthesia (active comparator)

Drug: Ketamine

Methohexital

ACTIVE COMPARATOR

Participants will be randomized 1:1 to either Ketamine (experimental condition) or Methohexital anesthesia (active comparator)

Drug: Methohexital

Interventions

Ketamine DRUG

Ketamine 1-2 mgr/ kg IV

Also known as: Ketalar

Ketamine

Methohexital DRUG

Methohexital 0.5-1mg/kg IV

Also known as: Brevatol

Methohexital

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects 18 to 70 years of age
• Diagnostic Statistical Manual (DSM) IV diagnosis of Major Depression (296.3), unipolar without psychotic features or Bipolar I or Bipolar II Depression without psychotic features confirmed by Structured Clinical Interview for DSM-IV (SCID-IV) interview
• Pretreatment 24-item Hamilton Rating Scale for Depression score \> 21
• Subjects must have an initial score of at least 20 on the Montgomery-Asbergers Depression Rating Scale (MADRS) at screen
• ECT is clinically indicated
• Patient is competent to provide informed consent

You may not qualify if:

• Lifetime DSM-IV diagnosis of schizophrenia, schizoaffective disorder, psychotic depression or any other psychotic disorder as defined in the DSM-IV
• Current (within the last year) diagnosis of anxiety disorder, obsessive- compulsive disorder, or eating disorder that precedes the onset of the current episode of depression
• Current diagnosis of delirium, dementia, or amnestic amnesiac disorder
• Diagnosis of Mental Retardation
• Baseline Mini Mental State Exam (MMSE) score \< 21 or a total score falling two standard deviations below the age- and education-adjusted mean, whichever is less
• Any active general medical condition or central nervous system (CNS) disease which can affect cognition or response to treatment
• Current (within the past three months) diagnosis of active substance dependence, or active substance abuse within the past week
• Lifetime history of ketamine or phencyclidine (PCP) abuse or dependence
• ECT within three months
• The presence of any known or suspected contraindication to methohexital or ketamine including but not limited to known allergic reactions to these agents, uncontrolled hypertension, arrhythmia, severe coronary artery disease and porphyria
• Pregnancy
• Status 4 or greater according to the criteria of the American Society of Anesthesiologists
• MRI contraindications

Sponsors & Collaborators

• Northwell Health: lead
• National Alliance for Research on Schizophrenia and Depression: collaborator

Study Sites (1)

Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

Location

Related Publications (8)

• Kellner CH, Knapp RG, Petrides G, Rummans TA, Husain MM, Rasmussen K, Mueller M, Bernstein HJ, O'Connor K, Smith G, Biggs M, Bailine SH, Malur C, Yim E, McClintock S, Sampson S, Fink M. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry. 2006 Dec;63(12):1337-44. doi: 10.1001/archpsyc.63.12.1337.

  PMID: 17146008 BACKGROUND

• Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

  PMID: 10686270 BACKGROUND

• Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.

  PMID: 16894061 BACKGROUND

• 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 Sep;26(3):223-7. doi: 10.1097/YCT.0b013e3181c3b0aa.

  PMID: 19935085 BACKGROUND

• Gregory-Roberts EM, Naismith SL, Cullen KM, Hickie IB. Electroconvulsive therapy-induced persistent retrograde amnesia: could it be minimised by ketamine or other pharmacological approaches? J Affect Disord. 2010 Oct;126(1-2):39-45. doi: 10.1016/j.jad.2009.11.018. Epub 2010 Jan 8.

  PMID: 20060172 BACKGROUND

• Sanacora G, Rothman DL, Mason G, Krystal JH. Clinical studies implementing glutamate neurotransmission in mood disorders. Ann N Y Acad Sci. 2003 Nov;1003:292-308. doi: 10.1196/annals.1300.018.

  PMID: 14684453 BACKGROUND

• Ostroff R, Gonzales M, Sanacora G. Antidepressant effect of ketamine during ECT. Am J Psychiatry. 2005 Jul;162(7):1385-6. doi: 10.1176/appi.ajp.162.7.1385. No abstract available.

  PMID: 15994728 BACKGROUND

• Dean RL, Marquardt T, Hurducas C, Spyridi S, Barnes A, Smith R, Cowen PJ, McShane R, Hawton K, Malhi GS, Geddes J, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with bipolar disorder. Cochrane Database Syst Rev. 2021 Oct 8;10(10):CD011611. doi: 10.1002/14651858.CD011611.pub3.

  PMID: 34623633 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Bipolar Disorder; Depression

Interventions

Ketamine; Methohexital

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Bipolar and Related Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Georgios Petrides, MD, PI
• Organization: Northwell Health

gpetride@northwell.edu

718-470-8569

Study Officials

• Georgios Petrides, M.D.

  The Zucker Hillside Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2013
• First Posted: June 20, 2013
• Study Start: June 1, 2010
• Primary Completion: March 1, 2017
• Study Completion: July 1, 2017
• Last Updated: March 9, 2023
• Results First Posted: March 9, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)