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

Depressive Symptoms Clinical Trial

Official title:

Effect of Subanesthetic Dose of Ketamine Combined With Propofol on Cognitive Function in Depressive Patients Undergoing Electroconvulsive Therapy ---a Randomized Control Double-Blind Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02305394
• Other study ID #: CYYYMZ-006
• Status: Not yet recruiting
• Phase: Phase 4
• First received: November 19, 2014
• Last updated: December 1, 2014
• Start date: January 2015
• Est. completion date: February 2017

Study information

• Verified date: November 2014
• Source: First Affiliated Hospital of Chongqing Medical University
• Contact: Qibin Chen, Master
• Phone: 023-89011061
• Email: 403497559[@]qq.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 132
• Est. completion date: February 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depressive Symptoms
• Electroconvulsive Therapy
• Impaired Cognition

Intervention

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

Locations

Country	Name	City	State
China	China,Chongqing The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Chongqing Medical University

Country where clinical trial is conducted

China, 

References & Publications (15)

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. Epub . — View Citation

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. — View Citation

Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci. 2006 Feb;7(2):137-51. Review. — View Citation

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. — View Citation

Garcia LS, Comim CM, Valvassori SS, Réus 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. Epub 2007 Aug 8. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Mini-Mental State examination score	Mini-Mental State examination score will be measured at 24 hours before the first ECT and 24 hours after each ECT, except the sixth ECT.	at 24 hours before the first ECT and 24 hours after each ECT, except the sixth ECT.	No
Secondary	Effects on Antidepression (Hamilton Depression Rating Scale(HDRS)	Effect on antidepression will be measured by 24-item Hamilton Depression Rating Scale(HDRS)	at 24 hours before the first ECT and 24 hours after each ECT	No
Secondary	Seizure Duration and Seizure Energy Index	Seizure duration and Seizure energy index will be recorded by the ECT apparatus.	at 30 seconds after each ECT	No
Secondary	Brief Psychiatric Rating Scale(BPRS)	Brief Psychiatric Rating Scale is related to psychotomimetic side-effect.	60 minutes prior to the first ECT and at 40, 80, 110, and 230 minutes after each ECT	No
Secondary	Adverse Effects include nausea, vomit, headache, tachycardia and increased blood pressure.	Adverse effects include nausea, vomit, headache, tachycardia and increased blood pressure.	at 40 minutes after each ECT	Yes