The Effect of S-ketamine for Patients Undergoing Electroconvulsive Therapy (ECT)

Major Depressive Disorder Clinical Trial

— ECT  

Official title:

Effect of S-ketamine on Depressed Patients Undergoing Electroconvulsive Therapy-a Randomized, Double-blind, Controlled Clinical Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04399070
• Other study ID #: West China Hospital Anes
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2020
• Est. completion date: January 31, 2021

Study information

• Verified date: July 2020
• Source: West China Hospital
• Contact: Yan Qiu, Doctor
• Phone: +8618980606269
• Email: qiuyan_mz[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will determine the effectiveness and safety of S-Ketamine in depression patients undergoing electroconvulsive therapy.

Description:

Nowadays, depression has become one of the serious mental diseases that affect human's life. With the acceleration of life pace and social pressure, the incidence of depression is increasing year-on-year. According to the statistics of the WHO, by 2017, there were more than 300 million people suffering from depression, accounting for 4.4% of the global population. Depression is highly related to suicide, which is an important reason for suicidal intention and attempt. It has been demonstrated that the incidence of suicide associated with major depression was as high as 15%. The main characteristic of depression is significant and lasting depression, which is caused by the decrease of monoamine transmitters (including dopamine, 5-HT, et al.) related to mood. In the past, antidepressants mainly relied on increasing or reducing the metabolism of transmitters, but these drugs usually took weeks or even months to take effect, and although the symptoms of depression were relieved within weeks after the start of treatment, they were still not ideal in the long term. Therefore, the drug treatment of depression is not optimistic.

Electroconvulsive therapy (ECT), as the first biological therapy introduced into psychiatry, has been improving with the progress of technology and equipment. More studies show that ECT is a safe and effective treatment, and the treatment of severe depression is the first choice in some cases. However, cognitive dysfunction, relapse tendency and related safety after ECT need further study.

Short acting sedatives and muscle relaxants before ECT can minimize the fear and muscle pain caused by ECT induced seizures. Previous sedatives used include propofol, mesaclopidol, thiopental and ketamine. Ketamine can be used for ECT anesthesia in patients with depression because of its good epileptic characteristics and prevention of cognitive dysfunction after ECT. More evidences reveal ketamine has strong antidepressant effect and reduces suicide of patients with treatment-resistant depression or mania. The low dose of ketamine can take effect within one hour, produce rapid antidepressant effect, and can play a role in more than 70% of patients with refractory depression. In addition, even a single intravenous injection of ketamine can effectively reduce the symptoms of depression within 24-72 hours, and may have synergistic antidepressant effect when combined with ECT. Although ketamine is considered to have a significant antidepressant effect in patients with depression, its application in mental disorders remains to be further explored because it may aggravate mental symptoms. However, some studies also found that ketamine did not significantly improve the effect of ECT on depression compared with other anesthetics.

Esketamine is the isomer of ketamine, which mainly acts on NMDA receptor of glutamate and its affinity to the receptor is 3-4 times that of ketamine, therefore it has stronger effect. Evidence suggests that esketamine can regulate NMDA receptor, increase the release of various neurotransmitters, improve the depression of patients, and repair the damaged neurons to improve the neuronal connections in the brain. As an anesthetic, the potency of esketamine is two times higher than ketamine, three times higher than R-ketamine, and its drug metabolism time is shorter, and the related side effects are also significantly reduced. Conseuqently, it has been widely used as an anesthetic in some countries. The efficacy and safety of esketamine nasal spray as a rapid and effective antidepressant in the treatment of patients with refractory depression have been confirmed. However the effect of intravenous esketamine as an anesthetic in ECT anesthesia on patients who are depressed remains unknown. The aim of this study is to evaluate the short-term effect and safety of esketamine as a adjunctive anesthetic in routine ECT anesthesia for patients with depression.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: January 31, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) Physical Status I-II

• diagnose depressive disorders with DSM-IV

• Without cognitive impairment

• Without ECT in past 6 months

Exclusion Criteria:

• had other comorbid psychiatric diagnoses, including schizophrenia, mania

• organic heart diseases, severe hypertension and arrhythmia

• severe hepatic and renal diseases

• severe cerebrovascular disorder or malformation, intracranial mass lesions and seizure

• glaucoma or high intraocular pressure and intra-ocular pathology

• severe haematological disease, fracture and obesity, pregnancy

• severe respiratory tract disease or difficult ventilation or incubation

• had pre-existing neurological disease or cognitive impairment

• allergy to anesthetics

• drugs abuse or alcohol addiction

• family history of malignant hyperthemia

• refuse to participate in this trial, had taken part in other clinical trial and with less education and couldn't understand the content of questionnaire

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depression, Bipolar
• Depression, Unipolar
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Manic-Depressive - Now Depressed

Intervention

Drug:
• S-ketamine
The depression patients received propofol and S-ketamine before ECT
• ketamine
The depression patients received propofol and ketamine before ECT
• saline
The depression patients received propofol and saline before ECT

Locations

Country	Name	City	State
China	West China Hospital of Sichuan University, Department of Anesthesiology	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Yan Qiu

Country where clinical trial is conducted

China, 

References & Publications (18)

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Carspecken CW, Borisovskaya A, Lan ST, Heller K, Buchholz J, Ruskin D, Rozet I. Ketamine Anesthesia Does Not Improve Depression Scores in Electroconvulsive Therapy: A Randomized Clinical Trial. J Neurosurg Anesthesiol. 2018 Oct;30(4):305-313. doi: 10.1097/ANA.0000000000000511. — View Citation

Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):139-148. doi: 10.1001/jamapsychiatry.2017.3739. — View Citation

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Fond G, Bennabi D, Haffen E, Brunel L, Micoulaud-Franchi JA, Loundou A, Lançon C, Llorca PM, Auquier P, Boyer L. A Bayesian framework systematic review and meta-analysis of anesthetic agents effectiveness/tolerability profile in electroconvulsive therapy for major depression. Sci Rep. 2016 Jan 25;6:19847. doi: 10.1038/srep19847. Review. — View Citation

Hashimoto K. Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective. Psychiatry Clin Neurosci. 2019 Oct;73(10):613-627. doi: 10.1111/pcn.12902. Epub 2019 Jul 11. Review. — View Citation

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Kellner CH, Husain MM, Knapp RG, McCall WV, Petrides G, Rudorfer MV, Young RC, Sampson S, McClintock SM, Mueller M, Prudic J, Greenberg RM, Weiner RD, Bailine SH, Rosenquist PB, Raza A, Kaliora S, Latoussakis V, Tobias KG, Briggs MC, Liebman LS, Geduldig ET, Teklehaimanot AA, Lisanby SH; CORE/PRIDE Work Group. Right Unilateral Ultrabrief Pulse ECT in Geriatric Depression: Phase 1 of the PRIDE Study. Am J Psychiatry. 2016 Nov 1;173(11):1101-1109. Epub 2016 Jul 15. — View Citation

Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med. 2016 May;46(7):1459-72. doi: 10.1017/S0033291716000064. Epub 2016 Feb 12. — View Citation

Li DJ, Wang FC, Chu CS, Chen TY, Tang CH, Yang WC, Chow PC, Wu CK, Tseng PT, Lin PY. Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis. Eur Neuropsychopharmacol. 2017 Jan;27(1):29-41. doi: 10.1016/j.euroneuro.2016.11.008. Epub 2016 Nov 28. Review. — View Citation

Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, Mazzucco C, Hough D, Thase ME, Shelton RC, Molero P, Vieta E, Bajbouj M, Manji H, Drevets WC, Singh JB. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry. 2019 Jun 1;176(6):428-438. doi: 10.1176/appi.ajp.2019.19020172. Epub 2019 May 21. Erratum in: Am J Psychiatry. 2019 Aug 1;176(8):669. — View Citation

Ribeiro JD, Huang X, Fox KR, Franklin JC. Depression and hopelessness as risk factors for suicide ideation, attempts and death: meta-analysis of longitudinal studies. Br J Psychiatry. 2018 May;212(5):279-286. doi: 10.1192/bjp.2018.27. Epub 2018 Mar 28. — View Citation

Rong C, Park C, Rosenblat JD, Subramaniapillai M, Zuckerman H, Fus D, Lee YL, Pan Z, Brietzke E, Mansur RB, Cha DS, Lui LMW, McIntyre RS. Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder. Int J Environ Res Public Health. 2018 Apr 17;15(4). pii: E771. doi: 10.3390/ijerph15040771. Review. — View Citation

Sackeim HA. Modern Electroconvulsive Therapy: Vastly Improved yet Greatly Underused. JAMA Psychiatry. 2017 Aug 1;74(8):779-780. doi: 10.1001/jamapsychiatry.2017.1670. — View Citation

Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, Sos P, Wang G, Zarate CA Jr, Sanacora G. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry. 2018 Feb 1;175(2):150-158. doi: 10.1176/appi.ajp.2017.17040472. Epub 2017 Oct 3. Review. — View Citation

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Zhang K, Hashimoto K. An update on ketamine and its two enantiomers as rapid-acting antidepressants. Expert Rev Neurother. 2019 Jan;19(1):83-92. doi: 10.1080/14737175.2019.1554434. Epub 2018 Dec 4. — View Citation

Zheng W, Li XH, Zhu XM, Cai DB, Yang XH, Ungvari GS, Ng CH, Ning YP, Hu YD, He SH, Wang G, Xiang YT. Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: A meta-analysis of randomized controlled trials. J Affect Disord. 2019 May 1;250:123-131. doi: 10.1016/j.jad.2019.02.044. Epub 2019 Feb 18. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Headache	adverse events	from emergency, assessed up to 24 hours after each ECT
Other	Nausea and vomiting	adverse events	from emergency, assessed up to 24 hours after each ECT
Other	Myalgia	adverse events	from emergency, assessed up to 24 hours after each ECT
Other	Agitation	adverse events	from emergency, assessed up to 1 hour after each ECT
Other	Hallucinations	adverse events	from emergency, assessed up to 3 hours after each ECT
Primary	Hamilton Depression Scale-17 scores	the patients' depression were evaluated with Hamilton Depression Scale with 17 questions after ECT. The scores ranged 0-68, and <7 were normal, the higher the score means more serious disease.	the 1 day after the last ECT
Primary	Montgomery-Asberg Depression Rating Scale scores	the patients' depression were evaluated with Montgomery-Asberg Depression Rating Scale scores after ECT. The scores ranged 0-60, and <17 were normal, the higher the score means more serious disease.	the 1 day after the last ECT
Secondary	Hamilton Depression Scale-17 scores	the patients' depression were evaluated with Hamilton Depression Scale with 17 questions before ECT. The scores ranged 0-68, and <7 were normal, the higher the score means more serious disease.	baseline (before first ECT)
Secondary	Hamilton Depression Scale-17 scores	the patients' depression were evaluated with Hamilton Depression Scale with 17 questions after ECT. The scores ranged 0-68, and <7 were normal, the higher the score means more serious disease.	one week after the first ECT
Secondary	Hamilton Depression Scale-17 scores	the patients' depression were evaluated with Hamilton Depression Scale with 17 questions after ECT. The scores ranged 0-68, and <7 were normal, the higher the score means more serious disease.	one month after the last ECT
Secondary	Montgomery-Asberg Depression Rating Scale scores	the patients' depression were evaluated with Montgomery-Asberg Depression Rating Scale scores before ECT. The scores ranged 0-60, and <17 were normal, the higher the score means more serious disease.	baseline (before first ECT)
Secondary	Montgomery-Asberg Depression Rating Scale scores	the patients' depression were evaluated with Montgomery-Asberg Depression Rating Scale scores after ECT. The scores ranged 0-60, and <17 were normal, the higher the score means more serious disease.	one week after the first ECT
Secondary	Montgomery-Asberg Depression Rating Scale scores	the patients' depression were evaluated with Montgomery-Asberg Depression Rating Scale scores after ECT. The scores ranged 0-60, and <17 were normal, the higher the score means more serious disease.	one month after the last ECT
Secondary	Mini-mental State Examination scores	the patients' cognitive function were evaluated with Mini-mental State Examination scores before ECT. The scores ranged 0-30, and 27-30 were normal, the lower the score means more serious disease.	baseline (before first ECT)
Secondary	Mini-mental State Examination scores	the patients' cognitive function were evaluated with Mini-mental State Examination scores after ECT. The scores ranged 0-30, and 27-30 were normal, the lower the score means more serious disease.	one week after the first ECT
Secondary	Mini-mental State Examination scores	the patients' cognitive function were evaluated with Mini-mental State Examination scores after ECT. The scores ranged 0-30, and 27-30 were normal, the lower the score means more serious disease.	the 1 day after the last ECT
Secondary	Mini-mental State Examination scores	the patients' cognitive function were evaluated with Mini-mental State Examination scores after ECT. The scores ranged 0-30, and 27-30 were normal, the lower the score means more serious disease.	one month after the last ECT
Secondary	suicide	adverse events	times of symptomatic episodes from first ECT up to one month after last ECT
Secondary	Mean heart rate before ECT	patients' vital sign	5 minutes before each ECT
Secondary	Mean heart rate after ECT	patients' vital sign	5 minutes after patients emergency from each ECT
Secondary	Mean Arterial Pressure before ECT	patients' vital sign	5 minutes before each ECT
Secondary	Mean Arterial Pressure after ECT	patients' vital sign	5 minutes after patients emergency from each ECT
Secondary	Mean time for return of spontaneous respiration after ECT	time for return of spontaneous respiration after ECT	from end of ECT to return of spontaneous respiration after each ECT
Secondary	Mean emergency time after ECT	patients' recovery time after ECT	from end of ECT to eye opening or following commands after each ECT
Secondary	Mean seizure duration during ECT	patients' seizure duration during ECT	from end of electrical stimulus to clonic movements in the right lower limb during each ECT