ECT as augmentation for clozapine

In 1937, Cerletti conceived electroconvulsive therapy (ECT) as a treatment for schizophrenia, a safer way than injecting a drug to induce seizures, which by a still-unknown mechanism has an antipsychotic effect. For patients who are acutely suicidal or catatonic, ECT is often life-saving, but for chronic schizophrenia, it is overlooked as a treatment option perhaps because of lingering stigma. The combination of ECT and antipsychotics including clozapine is reported to be safe, but controlled trials of ECT are rare.

A team from New York has published the first single-blind trial of clozapine and ECT. Patients with DSM-IV schizophrenia who had failed to respond to 12 weeks of clozapine therapy despite adequate serum levels were randomly assigned to either continue clozapine alone or to a course of bilateral ECT under general anesthesia, 3 times weekly for 4 weeks, then twice weekly for 4 more weeks. The patients who continued clozapine but remained unwell after 8 weeks were given a course of ECT with the same parameters. In both treatment groups, the dose of clozapine on which the patient entered the study remained unchanged. Patients with significant depression or non-nicotine substance-use disorder were excluded.

The outcome measures, performed by masked raters at outset and weekly, were the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression-Severity scale (CGI). Patients also underwent a neuropsychologic battery at baseline and at treatment completion. Response was defined as a 40% or greater improvement in the psychotic subscale of the BPRS and a CGI of 3 (mildly ill) or less. The investigators note that these are stringent response criteria.

The ECT group comprised 20 patients of whom 17 completed the 8-week course; the clozapine-only group comprised 19 patients of whom 16 completed the trial. Ten of the patients receiving clozapine and ECT met response criteria whereas none of the clozapine-only patients did. In the crossover phase, 9 of 19, or 47% of the patients responded to the combined treatment.

The cognitive evaluations showed reduction in mean speed of processing in the ECT-treated group, whereas executive function and episodic memory showed inconsistent effects across patients. The collective global neurocognitive values did not change significantly in either group. As for other adverse effects, no patients had spontaneous seizures, but 2 ECT patients had transient confusion.

At the BC Psychosis Program, we frequently offer ECT to patients who have not had adequate response to other treatments. This study provides high-quality evidence that clozapine-resistant patients can benefit from this approach, and cognitive impairment, while not absent, is typically quite mild.

Petrides G, Malur C, Braga RJ et al. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: A prospective, randomized study. Am J Psychiatry. Published online Aug 26, 2014. Abstract

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