Electroconvulsive Therapy in Clozapine Refractory Schizophrenia

• ClinicalTrials.gov Identifier: NCT00042224
• Recruitment Status: Completed
• First Posted: July 26, 2002
• Results First Posted: October 15, 2015
• Last Update Posted: May 15, 2017
• Sponsor: Northwell Health
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): George Petrides, Northwell Health

Study Description

Brief Summary:

This study will evaluate electroconvulsive therapy (ECT) in patients who have not responded adequately to clozapine.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Procedure: Electroconvulsive Therapy (ECT); Drug: Clozapine	Phase 1; Phase 2

Detailed Description:

ECT augmentation of clozapine will be compared to clozapine monotherapy in schizophrenic patients who continue to have psychotic symptoms despite optimal treatment with clozapine.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: ECT in Clozapine Refractory Schizophrenia
• Study Start Date: December 2000
• Actual Primary Completion Date: July 2008
• Actual Study Completion Date: July 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 ECT plus clozapine; Electroconvulsive therapy ECT plus clozapine for 8 weeks	Procedure: Electroconvulsive Therapy (ECT); ECT will be used to augment clozapine in schizophrenic patients who continue to have psychotic symptoms despite optimal treatment with clozapine.; Drug: Clozapine; Patients with psychotic symptoms will receive clozapine; Other Name: Clozaril
Active Comparator: 2 Clozapine; Clozapine for 8 weeks	Drug: Clozapine; Patients with psychotic symptoms will receive clozapine; Other Name: Clozaril

Outcome Measures

Primary Outcome Measures :

1. Response Rates in the ECT Plus Clozapine Group vs the Pharmacotherapy Group. [ Time Frame: 8 Weeks ]
   Response is defined as 40% reduction of symptoms in the psychotic symptom sub-scale (hallucinatory behavior, suspiciousness, conceptual disorganization, and unusual thought of content) of the Brief Psychiatric Rating Scale (BPRS) at the end of the 8-week study. BPRS assesses psychotic symptoms on a 18-item scale. The severity of each item is rated on a continuous scale from 1-7, with 1 being the least severe and 7 being most severe. Participants included in the study, at baseline had at least a moderate score of 4 on one of the four psychotic symptom sub-scale or a score of 12 on all four of these items combined (ranges 4 -28, with higher scores indicative of greater severity). A reduction of symptoms would be a sub-scale score which is 40% less than participants baseline score. If a participant enters the study with a sub-scale score of 15, to be considered a responder (at least a 40% reduction in symptoms score) his/her score must decrease by at least 6 points and be 9 or less.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Diagnosis of schizophrenia according to DSM-IV criteria
• Duration of illness 2 years or greater
• Resistance to at least 2 antipsychotics
• Clozapine resistance
• Capacity to give informed consent
• For women of childbearing capacity, a negative pregnancy test and patient agreement to use a medically accepted form of contraception
• Brief Psychiatric Rating Scale score of at least a 4 on one of the four psychotic items on the psychotic sub-scale or a score of 12 on these 4 items combined.
• Clinical Global Impressions (CGI) - severity rating of at least moderate (score of 4)
• Receiving at least two 400 mg doses of chlorpromazine equivalents for at least 4 weeks (may include newer antipsychotics)
• Having substantial psychotic symptoms despite at least 12 weeks of treatment (at least 8 weeks at a consistent dose)

Exclusion criteria

• schizoaffective disorder; bipolar disorder;
• current affective episode;
• Electroconvulsive Therapy (ECT) within the past 6 months
• history of epilepsy; severe neurological or systemic disorder that could significantly affect cognition, behavior, or mental status (other than tardive dyskinesia or neuroleptic-induced parkinsonism); psychoactive substance dependence (other than nicotine or caffeine) within 1 month prior to entering the study
• a score of less than 18 on the 24-item Hamilton Depression Rating Scale (HAM-D)
• clinical determination that mood stabilizers were necessary and therefore could not be discontinued.
• pregnancy.
• affective disorders and prominent depressive symptoms because ECT is well known to be effective in those situations, and we wanted to avoid contamination of our results by improvement solely driven by the treatment of the affective symptoms.

Contacts and Locations

Locations

United States, New York

Zucker Hillside Hospital

Glen Oaks, New York, United States, 11004

Sponsors and Collaborators

Northwell Health

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Georgios Petrides, MD; New Jersey Medical School

More Information

• Responsible Party: George Petrides, Associate Professor of Psychiatry, Northwell Health
• ClinicalTrials.gov Identifier: NCT00042224
• Other Study ID Numbers: R01MH060390 ( U.S. NIH Grant/Contract ); R01MH060390 ( U.S. NIH Grant/Contract ); DSIR AT-SO ( Other Identifier: NorthShore LIJ Health System )
• First Posted: July 26, 2002
• Results First Posted: October 15, 2015
• Last Update Posted: May 15, 2017
• Last Verified: April 2017

Keywords provided by George Petrides, Northwell Health:

Electroconvulsive Therapy

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Clozapine; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; GABA Antagonists; GABA Agents