Ecopipam improves stuttering in proof-of-concept trial

The oral selective dopamine D1 receptor antagonist ecopipam reduces stuttering symptoms in adults with moderate developmental stuttering, according to a small study.

Although dopamine D2 antagonists have previously been shown to be effective in reducing stuttering symptoms, these compounds were associated with adverse effects such as metabolic abnormalities and movement disorders.

“Ecopipam was well tolerated by the study participants,” said lead author Dr Gerald Maguire, chair of psychiatry and neuroscience at the University of California, Riverside School of Medicine in Riverside, California, US.

“Ecopipam is an investigational medication that acts as a selective dopamine D1 receptor antagonist. It has little affinity for dopamine D2 receptors and no reports of parkinsonian-like extrapyramidal symptoms or metabolic concerns typically seen with D2 antagonists,” explained Maguire and co-authors.

In the open-label study, ten adults aged 18–65 years with at least moderate severity on the 4^th edition of Stuttering Severity Instrument (SSI-4) received ecopipam 50 mg/day for the initial 2 weeks. Those who were able to tolerate the regimen increased their dosage to 100 mg/day for the remaining 6 weeks. [Ann Clin Psychiatry 2019;31:164-168]

After 8 weeks, stuttering symptoms were improved across different measures as indicated by the OASES*, SSS**, and SSI-4 scores (Cohen’s d effect size, +1.918, +1.358, +0.785, respectively). Duration of stuttering events assessed on SSI-4 was also shortened from 10.4 seconds at baseline to 4.3 seconds at the end of the study.

In addition, ecopipam improved stuttering behaviours, as reflected in significant reduction in the percentage of syllables stuttered in the reading and speaking domains in SSI-4 (p<0.05).

In terms of severity of stuttering, all evaluable participants with moderate stuttering symptoms improved to mild or very mild on SSI-4, while the two participants with very severe stuttering at baseline showed minimal gains in severity.

Ecopipam was well tolerated, with the 100 mg/day dosage being tolerated by all participants. There were no reports of adverse events, and no evidence of increased depression symptoms on the MADRS*** or suicidal thoughts on the C-SSRS^#. Also, no adverse events of movement disorders were reported for the BARS, SAS, or AIMS^##.

“Stuttering usually begins in childhood and often persists throughout the lifetime,” said the researchers. “Unfortunately, current forms of speech therapy are associated with high rates of relapse and low response rates.”

According to Maguire, the positive preliminary findings warrant further investigation in a double-blind, randomized controlled trial, which is currently under way.

“If ecopipam is found at the end of this trial to be a potentially safe and effective treatment for stuttering, it would be a major step toward seeking FDA approval for the first-ever medication to treat stuttering, a significant development for the millions of people around the world who stutter, bringing them hope and empowerment," said Maguire, a person who stutters himself.

"It may help them function better in social and academic settings, being able to communicate more freely with a resultant improvement in their quality of life,” he added.