Electroconvulsive Therapy (ECT) in Patients With Super Refractory Schizophrenia

Study Overview
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Brief Summary
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Introduction: In spite of recent advances in schizophrenia treatment, 30% of patients still do not respond properly to antipsychotic therapy. These patients are considered treatment-resistant or refractory, and the best choice for them is clozapine. However, even supported by the literature as the best known antipsychotic in terms of efficacy and rates of response, a considerable number of patients will still not respond to this treatment, remaining symptomatic and dysfunctional. These patients are classified as super-refractory (clozapine-resistent). In these cases, augmenting strategies are necessary, and some have been in use: typical and atypical antipsychotics, mood stabilizers, antidepressants and electroconvulsive therapy (ECT). Some studies have favored ECT, but no definitive conclusion has been drawn. Objective: Test the electroconvulsive therapy efficacy and safety as augmenting strategy to clozapine-resistant patients, as compared to placebo (sham ECT). Methods: This is a pilot double blind, placebo controlled and randomized study to assess electroconvulsive therapy efficacy as augmenting strategy to clozapine in super-refractory schizophrenia. The ECT treatment will be delivered with either a MECTA SPECTRUM 5000Q or 4000Q device, and the procedure is under general anesthesia and monitorization, after informed consent. The Hospital will follow national protocols and regulations on ECT. Sham ECT consists in habitual patient preparation and sedation, without stimulation. Patients that fit inclusion criteria will have their clozapine blood levels dosed and undergo structured assessments at baseline, after 6 treatments and at the end of the cycle of 12 ECT sessions (thrice a week protocol). The assessments will be based on CGI (Clinical Global Impression) and PANSS (Positive and Negative Syndrome Scale) scales. All medication will be maintained, except lithium carbonate.

Official Title
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Pilot Double Blind, Placebo Controlled and Randomized Study to Assess Electroconvulsive Therapy Efficacy as Augmenting Strategy to Clozapine in Super-refractory Schizophrenia

Conditions
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Refractory Schizophrenia, Super Refractory Schizophrenia

Intervention / Treatment
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* Device: MECTA SPECTRUM 5000Q ECT
* Procedure: Sham ECT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of schizophrenia or schizoaffective disorder (DSM-IV-TR); Ages between 18 and 55 years old, both genders; Must be using adequate contraception if a fertile woman; Must be on clozapine treatment for at least 6 months, with or without augmenting strategies; Must be clozapine-resistent (super-refractory patient), defined by a CGI-severity ≥ 4, PANSS total score ≥ 60 and at least 4 items of the positive subscale ≥ 4 at baseline. Exclusion Criteria: Clinical somatic disease not stabilized in the three months preceding the study; Other Axis I disorders (DSM-IV-TR); Laboratory tests with significantly abnormal values that persist for more than two weeks; Lack of permanent residence during the study period; History of poor treatment adherence. History of ECT use in the past six months that precede the start of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Electroconvulsive Therapy<br>Patients in use of clozapine randomized to receive ECT treatment | Device: MECTA SPECTRUM 5000Q ECT<br> <br> * Other names: electroconvulsive therapy device;|
| Sham Comparator: SHAM ECT<br>Patients receiving clozapine randomized to sham ECT (placebo) | Procedure: Sham ECT<br>* Sedation using propofol or etomidate and usual ECT preparation (no stimulation)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS change from baseline | Structured assessments will be done at baseline, and at the end of the cycle of 12 ECT sessions (thrice a week protocol). The assessments will be based on PANSS (Positive and Negative Syndrome Scale). Changes from Baseline on this scale will be documented after a 4 weeks period. | 4 weeks | 
| PANSS change from baseline | Structured assessments will be done at baseline, and at the end of the cycle of 6 ECT sessions (thrice a week protocol). The assessments will be based on PANSS (Positive and Negative Syndrome Scale). Changes from Baseline on this scale will be documented after a 2 week period. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGI change from baseline | Clinical Global Impression will be assessed as well, along with PANSS scale, and changes compared to baseline. | 4 weeks | 
| CGI change from baseline | Clinical Global Impression will be assessed as well, along with PANSS scale, and changes compared to baseline. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, electroconvulsive therapy, refractory Schizophrenia, super refractory schizophrenia, clozapine