Comparison of Maintenance ECT Versus Clozapine in Treatment-resistant Schizophrenia

Treatment Resistant Schizophrenia Clinical Trial

Official title:

Comparison of Maintenance ECT Versus Clozapine on Psychopathology and Cerebral Hemodynamics in Treatment-resistant Schizophrenia: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03807882
• Other study ID #: T/IM-F/18-19/08
• Status: Completed
• Phase: Phase 4
• Start date: February 1, 2019
• Est. completion date: June 30, 2020

Study information

• Verified date: June 2021
• Source: All India Institute of Medical Sciences, Bhubaneswar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proposed study will be conducted to compare the efficacy of maintenance ECT (M-ECT) vs Clozapine in treatment resistant schizophrenia (TRS) in terms of change in psychopathology measures and cerebral hemodynamics.

Description:

The proposed study is a prospective, randomized clinical trial in patients suffering from treatment-resistant schizophrenia (TRS) and will be conducted in the Department of Psychiatry, AIIMS, Bhubaneswar, over a period of 16 months. Sixty patients with TRS (TRRIP consensus criteria, 2017), fulfilling the inclusion and exclusion criteria will be recruited for the study. Written informed consent will be taken after explaining the objectives and procedure of the study in detail. The detailed history, relevant social-demographic and clinical data will be collected in a structured case record form (CRF). At baseline, PANSS will be administered to determine the severity of positive symptoms, negative symptoms, and general psychopathology, Global assessment of functioning (GAF), and CGI to determine the baseline severity of the illness and improvement with treatment and MoCA to assess change in cognitive impairment. Before starting the treatment, brain SPECT-CT will be done to measure baseline regional brain blood perfusion. The study cohort will be randomized into two treatment groups by computer-generated random numbers, each group comprising 30 patients. One group will receive maintenance ECT (M-ECT) following acute treatment of bilateral ECT of six sessions along with ongoing antipsychotic and the other group will be treated with Clozapine monotherapy. PANSS, GAF, CGI, MoCA will be re-administered at 6 weeks, 3 months, and 6 months follow-up visits to compare the changes within each group and between the groups. Post-treatment SPECT-CT of the brain will be done at the end of 6 months to document changes in the regional cerebral blood perfusion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 30, 2020
• Est. primary completion date: May 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients clinically diagnosed with treatment-resistant schizophrenia (TRS) (TRRIP consensus criteria).
• Patients aged 18-60 years of either sex.
• Patients giving voluntary written consent for participation in the study

Exclusion Criteria:

• Patient already on Clozapine or ECT.
• History of psychoactive substance abuse or dependence.
• Co-morbid psychiatric, major medical, or neurological disorders.
• History of organicity or significant head injury.
• Pacemaker or metal in any part of the body excluding the mouth.
• Pregnant and breastfeeding females.

Related Conditions & MeSH terms

• Schizophrenia
• Treatment Resistant Schizophrenia

Intervention

Other:
• Bilateral M-ECT
Following acute treatment with bilateral ECT of 6 sessions over a period of two weeks, Bilateral M-ECT will be administered at a frequency of 1 session/week for one month, then 1 session / 2 weeks for 2 months and then 1 session/month for next 3 months.

Drug:
• Clozapine
Clozapine will be given in accordance with Maudsley guideline: 12.5 mg on the first day, followed by 12.5mg twice daily on the second day, followed by 25mg twice daily for next two days and then increment of 25mg every two days till the target dose of 250-400 mg per day in two divided doses as per tolerability of the patients

Locations

Country	Name	City	State
India	Dept of Psychiatry, Aiims, Bhubaneswar	Bhubaneswar	Odisha

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, Bhubaneswar

Country where clinical trial is conducted

India, 

References & Publications (16)

Chanpattana W, Andrade C. ECT for treatment-resistant schizophrenia: a response from the far East to the UK. NICE report. J ECT. 2006 Mar;22(1):4-12. Review. — View Citation

Chanpattana W, Chakrabhand ML, Sackeim HA, Kitaroonchai W, Kongsakon R, Techakasem P, Buppanharun W, Tuntirungsee Y, Kirdcharoen N. Continuation ECT in treatment-resistant schizophrenia: a controlled study. J ECT. 1999 Sep;15(3):178-92. — View Citation

Ertugrul A, Volkan-Salanci B, Basar K, Karli Oguz K, Demir B, Ergun EL, Senturk S, Erbas B, Cila A, Ulug B. The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: relationship with treatment response. Psychia — View Citation

Grover S, Hazari N, Kate N. Combined use of clozapine and ECT: a review. Acta Neuropsychiatr. 2015 Jun;27(3):131-42. doi: 10.1017/neu.2015.8. Epub 2015 Feb 20. Review. — View Citation

Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, Bloomfield MA, Bressan RA, Buchanan RW, Carpenter WT, Castle DJ, Citrome L, Daskalakis ZJ, Davidson M, Drake RJ, Dursun S, Ebdrup BH, Elkis H, Falkai P, Fleischacker WW, Gadelh — View Citation

Kane JM. Management strategies for the treatment of schizophrenia. J Clin Psychiatry. 1999;60 Suppl 12:13-7. Review. — View Citation

Kim HS, Kim SH, Lee NY, Youn T, Lee JH, Chung S, Kim YS, Chung IW. Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia. Psychiatry Investig. 2017 Jan;14(1):58-62. doi: 10.4306/pi.2017.14.1.58. Epub 2016 Dec 29. — View Citation

Lally J, Tully J, Robertson D, Stubbs B, Gaughran F, MacCabe JH. Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis. Schizophr Res. 2016 Mar;171(1-3):215-24. doi: 10.1016/j. — View Citation

Lieberman JA. Maximizing clozapine therapy: managing side effects. J Clin Psychiatry. 1998;59 Suppl 3:38-43. Review. — View Citation

Novak B, Milcinski M, Grmek M, Kocmur M. Early effects of treatment on regional cerebral blood flow in first episode schizophrenia patients evaluated with 99Tc-ECD-SPECT. Neuro Endocrinol Lett. 2005 Dec;26(6):685-9. — View Citation

Petrides G, Malur C, Braga RJ, Bailine SH, Schooler NR, Malhotra AK, Kane JM, Sanghani S, Goldberg TE, John M, Mendelowitz A. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study. Am J Psychiatry. 20 — View Citation

Rey JM, Walter G. Half a century of ECT use in young people. Am J Psychiatry. 1997 May;154(5):595-602. Review. — View Citation

Santra A, Kumar R. Brain perfusion single photon emission computed tomography in major psychiatric disorders: From basics to clinical practice. Indian J Nucl Med. 2014 Oct;29(4):210-21. doi: 10.4103/0972-3919.142622. Review. — View Citation

Sharafi M. Comparison of Classical and Clozapine Treatment on Schizophrenia Using Positive and Negative Syndrome Scale of Schizophrenia (PANSS) and SPECT Imaging. Int J Med Sci. 2005;2(2):79-86. Epub 2005 May 10. — View Citation

Shimizu E, Imai M, Fujisaki M, Shinoda N, Handa S, Watanabe H, Nakazato M, Hashimoto K, Iyo M. Maintenance electroconvulsive therapy (ECT) for treatment-resistant disorganized schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):571 — View Citation

Siskind DJ, Lee M, Ravindran A, Zhang Q, Ma E, Motamarri B, Kisely S. Augmentation strategies for clozapine refractory schizophrenia: A systematic review and meta-analysis. Aust N Z J Psychiatry. 2018 Aug;52(8):751-767. doi: 10.1177/0004867418772351. Epub — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in severity of psychopathology	Severity will be assessed by Positive and Negative Symptom Scale (PANSS) PANSS Score ranges from 30- 210. A higher score represents more severe psychopathology	24 weeks
Secondary	Change in illness severity, and global improvement with treatment	Assessed by change in Clinical Global Impression Schizophrenia (CGI-SCH) scores.	24 weeks
Secondary	Change in global functionality	Assessed by change in Global assessment of functioning (GAF) scores.	24 weeks
Secondary	Change in Cognitive impairment	Assessed by change in Montreal Cognitive Assessment (MoCA) scores.	24 weeks
Secondary	Number of patients receiving rescue medications.	Patients with "treatment relapse" or "treatment non-response" will receive rescue medications.	24 weeks
Secondary	Change in regional cerebral blood flow	Change in regional cerebral blood flow will be measured by SPECT-CT Brain	24 weeks