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

NCT02305394 | Unknown Phase 4

• 1 other identifier: CYYYMZ-006
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depressive Symptoms; Impaired Cognition; Electroconvulsive Therapy

Keywords

ketamine; Electroconvulsive Therapy; Cognitive Function

Outcome Measures

Primary Outcomes (1)

• Mini-Mental State examination score

  Mini-Mental State examination score will be measured at 24 hours after the sixth ECT.

  at 24 hours after the sixth ECT

Secondary Outcomes (5)

• Mini-Mental State examination score

  at 24 hours before the first ECT and 24 hours after each ECT, except the sixth ECT.

• Effects on Antidepression (Hamilton Depression Rating Scale(HDRS)

  at 24 hours before the first ECT and 24 hours after each ECT

• Seizure Duration and Seizure Energy Index

  at 30 seconds after each ECT

• Brief Psychiatric Rating Scale（BPRS）

  60 minutes prior to the first ECT and at 40, 80, 110, and 230 minutes after each ECT

• Adverse Effects include nausea, vomit, headache, tachycardia and increased blood pressure.

  at 40 minutes after each ECT

Study Arms (2)

PK group (ketamine and propofol)

EXPERIMENTAL

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.

Drug: ketamine and propofol

P group (propofol group)

ACTIVE COMPARATOR

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.

Drug: propofol and normal saline

Interventions

ketamine and propofol DRUG

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

PK group (ketamine and propofol)

propofol and normal saline DRUG

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

P group (propofol group)

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• First Affiliated Hospital of Chongqing Medical University: lead

Study Sites (1)

China,Chongqing The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

Related Publications (15)

• 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.

  PMID: 19397926 BACKGROUND

• 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.

  PMID: 17884272 BACKGROUND

• 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.

  PMID: 16429123 BACKGROUND

• 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.

  PMID: 18379337 BACKGROUND

• 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.

  PMID: 19897179 BACKGROUND

• 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.

  PMID: 24831997 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

• 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.

  PMID: 19545857 BACKGROUND

• 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.

  PMID: 21466832 BACKGROUND

• 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.

  PMID: 16801824 BACKGROUND

• 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.

  PMID: 12556568 BACKGROUND

• 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.

  PMID: 21400226 BACKGROUND

• 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.

  PMID: 22622291 BACKGROUND

• 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.

  PMID: 23703230 BACKGROUND

MeSH Terms

Conditions

Depression; Cognition Disorders

Interventions

Ketamine; Propofol; Saline Solution

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Su Min

  First Affiliated Hospital of Chongqing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qibin Chen, Master

CONTACT

023-89011061; 403497559@qq.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The Department of Anesthesia and Pain Medicine

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: December 2, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: February 1, 2017
• Last Updated: December 2, 2014

Record last verified: 2014-11

Locations

CN (1)