Adjunctive ECT Effective for Drug-Resistant Schizophrenia

Deborah Brauser

September 12, 2014

Adjunctive electroconvulsive therapy (ECT) is a safe and effective treatment option for drug-resistant schizophrenia, new research suggests.

Dr. John Kane

A small, randomized study of patients with clozapine-resistant schizophrenia showed that half of the group receiving ECT plus clozapine for 8 weeks had at least a 40% decrease in symptom scores vs none of the participants who received clozapine alone.

In addition, 47% of the latter group who received ECT in a crossover phase showed treatment response.

The researchers note that, to their knowledge, these are the highest response rates reported with any type of clozapine augmentation.

"This was what we were hoping to find, but we weren't really sure," coinvestigator John Kane, MD, chair of psychiatry at the Hofstra North Shore–Long Island Jewish School of Medicine in Glen Oaks, New York, and at the Zucker Hillside Hospital, told Medscape Medical News.

"Some of these patients are quite difficult to treat, so we were very pleased to see that 50% of those who received ECT plus clozapine met our response criteria," added Dr. Kane.

The study was published online August 26 in the American Journal of Psychiatry.

Low Response Rate to Clozapine

The investigators note that although clozapine is "the only medication shown to be effective in antipsychotic-refractory patients," up to 70% of these patients do not respond to it.

"The treatment of this subgroup of patients remains an enormous challenge, with significant public health implications," they write.

The researchers saw promising results from an earlier, open-label pilot study they conducted of 15 patients with schizophrenia who either did not respond or only partially responded to clozapine. A total of 9 of these patients met response criteria after receiving ECT augmentation.

For the current study, 30 patients with antipsychotic- and clozapine-resistant schizophrenia were randomly assigned to receive for 8 months either bilateral ECT plus clozapine (n = 20; 75% men; mean age, 35.7 years) or clozapine alone (n = 19; 68% men; mean age, 42.8 years).

The baseline mean dosage of clozapine for the first group was 525.0 mg/day, and for the latter group, 511.1 mg/day.

For the first 4 weeks, ECT was performed 3 times weekly. The therapy was then decreased to 2 times weekly during the last 4 weeks.

All nonresponders from the clozapine-only group participated in an additional 8-week open-trial crossover phase, where they also received ECT augmentation.

The primary outcome measure was treatment response, defined as a reduction by 40% or more on scores from the Brief Psychiatric Rating Scale (BPRS) psychotic symptom subscale.

"We chose to define response as a 40% reduction in symptoms, compared with the traditional 20% in medication studies, recognizing that ECT adds additional levels of complexity and requires increased effort by both clinicians and patients," explain the investigators.

Secondary measures included a rating of less than 3 on the Clinical Global Impressions (CGI)–severity scale.

High Rate of Symptom Reduction

Results showed that 50% of the ECT plus clozapine group achieved treatment response by the end of 8 weeks compared with none of those in the clozapine-only group.

However, 47.4% of the latter group achieved treatment response during the crossover phase, when ECT was added. This means that 19 of all participants (48.7%) had at least a 40% reduction in psychotic symptoms after receiving the ECT regimen.

In addition, 60% of the ECT augmentation group and 0% of the clozapine-only group (before the crossover phase) had a 20% reduction in symptoms on the BPRS.

When using stricter criteria, 9 members of the ECT augmentation group had a 50% reduction in symptoms, 6 had a 60% reduction, and 3 experienced a 70% reduction in symptoms.

The ECT plus clozapine group also had significantly lower rating scores on the BPRS-psychosis subscale by week 3 vs those who were receiving clozapine only, "and this significant difference persisted for the remainder of the 8-week trial."

They also showed significantly greater rating reductions on the CGI-severity scale.

There were no significant between-group differences in side effects, and there were only 2 treatment-related adverse events. "Two patients required the postponement of an ECT session because of mild confusion," report the investigators.

There were no "peculiarities" found in electroencephalography (EEG) or motor seizure expression, no prolonged seizures, and no spontaneous seizures for any of the participants.

In addition, there were no significant between-group differences in global neurocognitive measures, meaning potential concerns about the cognitive side effects of ECT were allayed.

Clinical Implications?

The investigators write that more research is now needed to determine the persistence of the results. However, Dr. Kane noted that the take-home message for clinicians is that ECT augmentation is a safe and effective treatment option ― and should be considered in this patient population.

"We do believe that this has clinical implications," said Dr. Kane.

He added that the researchers are now assessing brain imaging as a tool to potentially identify patients who might or might not respond well to clozapine.

"So, hopefully at some point in the future, we'll be better able to target treatment to appropriate individuals earlier in the course of their treatment."

As reported at the time by Medscape Medical News, preliminary findings from this study were first presented in 2010 at the New Clinical Drug Evaluation Unit 50th Anniversary Meeting, which was held in Boca Raton, Florida.

At that meeting, Jean-Pierre Lindenmayer, MD, director of the Psychopharmacology Research Unit at the Nathan Kline Institute for Psychiatric Research, Department of Psychiatry, at New York University, commented that clozapine "is the best of what we have in our toolbox" for treating this patient population.

"The options after clozapine are not very well explored," said Dr. Lindenmayer, who was not involved with this research. "This study offers a possible treatment for patients who failed clozapine."

However, he noted that the study limitations included the small sample size and that it did not assess maintenance of the treatment-related response.

The study authors have reported several financial relationships, which are fully listed in the original article.

Am J Psychiatry. Published online August 26, 2014. Abstract


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