Effect of Subanesthetic Dose of Ketamine Combined With Propofol on Cognitive Function in Depressive Patients Undergoing Electroconvulsive Therapy

NCT ID: NCT02305394

Last Updated: 2014-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

132 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2017-02-28

Brief Summary

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Electroconvulsive therapy (ECT) is an effective treatment for depression compared with the current antidepressant agents,but the most important side effect is cognitive dysfunction. The purpose of this study is to determine whether subanesthetic dose of ketamine combined with propofol is superior to propofol anesthesia alone in improving cognitive function in depressive patients undergoing ECT.

Detailed Description

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Depression is one of the most debilitating and widespread illnesses affecting up to 20% of individuals in their lifetime. However, the current antidepressant agents take weeks to work, and fail to help at least 40% of depressed patients. Electroconvulsive therapy (ECT) is a remarkably effective treatment for depression, but its use is limited by cognitive dysfunction.

As a result, it is becoming a clinical problem which need to be settled urgently. Previous clinical study showed that subanesthetic dose of ketamine could play a role in antidepressant effects with safety and minimal positive psychotic symptoms.The investigators also found that subanesthetic dose of ketamine combined with other anesthetics could improve cognitive function in depressive rats receiving electroconvulsive shock (a model for analogy with ECT). Few clinical researches concerned the effects of subanesthetic dose of ketamine combined with propofol anesthesia on cognitive function in patients after ECT, therefore the investigators conduct this randomized controlled double-blind trial. In this study, cognitive function will be rated by Mini-Mental State examination score.

Conditions

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Depressive Symptoms Impaired Cognition Electroconvulsive Therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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PK group (ketamine and propofol)

propofol 1.5 mg/kg and ketamine 0.3 mg/kg will be administered to participants separately by intravenous infusion.When patients become unconscious, succinylcholine 1 mg/kg (a muscle relaxant) will be administered intravenously. After 1 minute of succinylcholine infused, ECT will be performed with bitemporal electrode placement using a stimulus dose of 1.0-millisecond pulse width, 60-Hz frequency, 6.0-second stimulus duration, and 0.8-A maximal stimulus intensity.

Group Type EXPERIMENTAL

ketamine and propofol

Intervention Type DRUG

propofol 1.5 mg/kg and ketamine 0.3 mg/kg will be administered to participants separately by intravenous infusion.

P group (propofol group)

propofol 1.5 mg/kg and normal saline \[weight(kg)×0.3÷10\]ml will be administered to participants separately by intravenous infusion.When patients become unconscious, succinylcholine 1 mg/kg (a muscle relaxant) will be administered intravenously. After 1 minute of succinylcholine infused, ECT will be performed with bitemporal electrode placement using a stimulus dose of 1.0-millisecond pulse width, 60-Hz frequency, 6.0-second stimulus duration, and 0.8-A maximal stimulus intensity.

Group Type ACTIVE_COMPARATOR

propofol and normal saline

Intervention Type DRUG

propofol 1.5 mg/kg and normal saline \[weight(kg)×0.3÷10\]ml will be administered to participants separately by intravenous infusion.

Interventions

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ketamine and propofol

propofol 1.5 mg/kg and ketamine 0.3 mg/kg will be administered to participants separately by intravenous infusion.

Intervention Type DRUG

propofol and normal saline

propofol 1.5 mg/kg and normal saline \[weight(kg)×0.3÷10\]ml will be administered to participants separately by intravenous infusion.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. diagnosed with moderate or severe depression according to Diagnostic and Statistical Manual of Mental Disorders
2. aged from 18 to 65 years old

Exclusion Criteria

1. cerebrovascular malformation, arterial aneurysm, hypertension, or glaucoma;
2. classification of American Society of Anesthesiologists physical status score IV or V;
3. complications such as respiratory disease, cardiovascular disease, intracranial hypertension, cerebral vascular disorder;
4. presence of a foreign body such as pacemaker, intracranial electrode, and clips;
5. history of seizures;
6. history of drug abuse;
7. concomitant presence of a mental disorder;
8. pregnancy;
9. history of serious adverse effects related to anesthetics;
10. refusal to consent for the study, or refusal to undergo one single ECT during the first week of therapy.
11. hyperthyreosis
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role lead

Responsible Party

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Min Su

The Department of Anesthesia and Pain Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Su Min

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Chongqing Medical University

Locations

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China,Chongqing The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Site Status

Countries

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China

Central Contacts

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Qibin Chen, Master

Role: CONTACT

023-89011061

Facility Contacts

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Su Min, MD

Role: primary

+86-23-89011068

References

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Machado-Vieira R, Salvadore G, Diazgranados N, Zarate CA Jr. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther. 2009 Aug;123(2):143-50. doi: 10.1016/j.pharmthera.2009.02.010. Epub 2009 May 3.

Reference Type BACKGROUND
PMID: 19397926 (View on PubMed)

Garcia LS, Comim CM, Valvassori SS, Reus GZ, Barbosa LM, Andreazza AC, Stertz L, Fries GR, Gavioli EC, Kapczinski F, Quevedo J. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jan 1;32(1):140-4. doi: 10.1016/j.pnpbp.2007.07.027. Epub 2007 Aug 8.

Reference Type BACKGROUND
PMID: 17884272 (View on PubMed)

Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci. 2006 Feb;7(2):137-51. doi: 10.1038/nrn1846.

Reference Type BACKGROUND
PMID: 16429123 (View on PubMed)

Pigot M, Andrade C, Loo C. Pharmacological attenuation of electroconvulsive therapy--induced cognitive deficits: theoretical background and clinical findings. J ECT. 2008 Mar;24(1):57-67. doi: 10.1097/YCT.0b013e3181616c14.

Reference Type BACKGROUND
PMID: 18379337 (View on PubMed)

aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, Mathew SJ. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):139-45. doi: 10.1016/j.biopsych.2009.08.038.

Reference Type BACKGROUND
PMID: 19897179 (View on PubMed)

Chen J, Peng LH, Luo J, Liu L, Lv F, Li P, Ao L, Hao XC, Min S. Effects of low-dose ketamine combined with propofol on phosphorylation of AMPA receptor GluR1 subunit and GABAA receptor in hippocampus of stressed rats receiving electroconvulsive shock. J ECT. 2015 Mar;31(1):50-6. doi: 10.1097/YCT.0000000000000148.

Reference Type BACKGROUND
PMID: 24831997 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10686270 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16894061 (View on PubMed)

Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry. 2009 Sep 1;66(5):522-6. doi: 10.1016/j.biopsych.2009.04.029. Epub 2009 Jul 9.

Reference Type BACKGROUND
PMID: 19545857 (View on PubMed)

Ibrahim L, Diazgranados N, Luckenbaugh DA, Machado-Vieira R, Baumann J, Mallinger AG, Zarate CA Jr. Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):1155-9. doi: 10.1016/j.pnpbp.2011.03.019. Epub 2011 Apr 3.

Reference Type BACKGROUND
PMID: 21466832 (View on PubMed)

McDaniel WW, Sahota AK, Vyas BV, Laguerta N, Hategan L, Oswald J. Ketamine appears associated with better word recall than etomidate after a course of 6 electroconvulsive therapies. J ECT. 2006 Jun;22(2):103-6. doi: 10.1097/00124509-200606000-00005.

Reference Type BACKGROUND
PMID: 16801824 (View on PubMed)

Krystal AD, Weiner RD, Dean MD, Lindahl VH, Tramontozzi LA 3rd, Falcone G, Coffey CE. Comparison of seizure duration, ictal EEG, and cognitive effects of ketamine and methohexital anesthesia with ECT. J Neuropsychiatry Clin Neurosci. 2003 Winter;15(1):27-34. doi: 10.1176/jnp.15.1.27.

Reference Type BACKGROUND
PMID: 12556568 (View on PubMed)

Kranaster L, Kammerer-Ciernioch J, Hoyer C, Sartorius A. Clinically favourable effects of ketamine as an anaesthetic for electroconvulsive therapy: a retrospective study. Eur Arch Psychiatry Clin Neurosci. 2011 Dec;261(8):575-82. doi: 10.1007/s00406-011-0205-7. Epub 2011 Mar 13.

Reference Type BACKGROUND
PMID: 21400226 (View on PubMed)

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 Jun;28(2):128-32. doi: 10.1097/YCT.0b013e31824d1d02.

Reference Type BACKGROUND
PMID: 22622291 (View on PubMed)

Kellner CH, Briggs MC, Pasculli RM, Bryson EO. Antidepressant effect of the first electroconvulsive therapy with ketamine and/or propofol. J ECT. 2013 Jun;29(2):149. doi: 10.1097/YCT.0b013e3182702980. No abstract available.

Reference Type BACKGROUND
PMID: 23703230 (View on PubMed)

Other Identifiers

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CYYYMZ-006

Identifier Type: -

Identifier Source: org_study_id