Adding Electroconvulsive Therapy to Clozapine Improves Drug-Resistant Schizophrenia

June 23, 2010 (Boca Raton, Florida) — Adding electroconvulsive therapy (ECT) to clozapine is an effective treatment for patients with clozapine-resistant schizophrenia, researchers reported at the New Clinical Drug Evaluation Unit 50th Anniversary Meeting.

Clozapine is the drug of last resort for patients with treatment-resistant schizophrenia, but up to 70% of patients do not respond, said lead study author Georgios Petrides, MD, from the Zucker Hillside Hospital, Northshore-Long Island Jewish Health System, Glen Oaks, New York.

"We had nothing that works for these patients. They had failed every medication, and they were on clozapine and even then they had psychotic symptoms," Dr. Petrides told Medscape Psychiatry. "ECT worked before the advent of medications, but we really didn’t have good studies to prove that it did. This is the first ECT study to be done in this population."

The study, which was funded by the National Institute of Mental Health, randomized 20 patients to receive 8 weeks of ECT in addition to clozapine and 19 patients to continue with clozapine treatment for 8 weeks.

Patients in the clozapine arm who did not respond after 8 weeks crossed over to the ECT arm of the study and received combination treatment for another 8 weeks in an open trial.

All patients were taking a stable dose of clozapine with serum levels more than 350 mEq/mL for at least 8 weeks. All had psychotic symptoms rated greater than 12 on the Brief Psychiatric Rating Scale (BPRS) psychosis subscale but no current mood symptoms. Their mean age was 39 years, mean BPRS rating was 46.0, and mean rating for the psychosis subscale was 16.5.

Patients received up to 20 ECT treatments.

Using a 20% reduction in the psychosis subscale as a definition of response to treatment, the study found no responders in the clozapine-alone group. In contrast, 12 of 20 patients (60%) in the ECT plus clozapine group responded to treatment (P < .001).

When a 40% reduction in the psychosis subscale was used to define response to treatment, none of the clozapine-alone group responded, compared with 10 of 20 (50%) in the ECT plus clozapine group (P < .001).

In the open crossover trial, 11 of 15 patients (73%) responded to ECT plus clozapine when response was defined as a 20% reduction in the psychosis subscale and 6 of 15 patients (40%) when a 40% reduction was used to define response.

The combination of ECT and clozapine was well tolerated.

"ECT is a very safe treatment. It affects memory; people lose immediate memory but this is temporary," Dr. Petrides said. "But in our study, the patients really didn’t show this affect. Before and after the treatment, their cognitive function was exactly the same."

He added that ECT is feasible as long as it is available. This may not be the case for community and state hospitals, however. "This would be a practical treatment, but it is mostly available in university or teaching hospitals and private institutions. But it is very feasible. The question is, how long will the good effects last? It seems that most patients need maintenance treatment once every 2 weeks or once a month.

"Clozapine is the best of what we have in our toolbox for treatment-resistant patients, and the options after clozapine are not very well explored," commented Jean-Pierre Lindenmayer, MD, director of the Psychopharmacology Research Unit, Nathan Kline Institute for Psychiatric Research, Department of Psychiatry, New York University, New York City. "This study offers a possible treatment for patients who failed clozapine."

He added that the findings have to be placed in the context of a small sample size. Also, an important issue not addressed by the study is the maintenance of the response, Dr. Lindenmayer said. "In my experience, we do get a response. However, this response dissipates as soon as we start reducing the frequency of the ECT treatments."

This study was funded by the National Institutes of Health. Dr. Petrides has disclosed no relevant financial relationships. Dr. Lindenmayer has reported financial relationships with Janssen, Eli Lilly, Merck, Otsuka, Organon, Pfizer, Azur, and Astra Zeneca.

New Clinical Drug Evaluation Unit (NCDEU) 50th Anniversary Meeting: Abstract 57, Session I. Presented June 15, 2010.