Research Notes

Gerald A. Maguire, University of California, Riverside School of Medicine

Although no medication is FDA approved for stuttering, several studies have shown certain medications to have beneficial effects on reducing the severity of stuttering symptoms. Different classes of medications have been investigated, but those with dopamine blocking activity have been shown in numerous trials to have positive effects on stuttering. These medications are FDA approved in the United States (and hold similar approval in most countries) for other conditions and their safety profiles are well established in the relevant disorders.

The best studied medication in stuttering is olanzapine whose effectiveness has been established in replicated trials. Olanzapine acts as a dopamine antagonist to D2 receptors in the mesolimbic pathway, and inhibits similarly serotonin 5HT2A receptors in the frontal cortex.1 At doses between 2.5-5mg, olanzapine has been shown to be more effective than placebo at reducing stuttering symptoms2,3 Olanzapine has the most data supporting its efficacy however it can be associated with weight gain and metabolic agents (lipid elevations, diabetes) suggesting other more tolerable compounds may be considered earlier in treatment. 2

Risperidone (a 5HT2 and Dopamine D2 antagonist as well) and haloperidol (a strong Dopamine D2 antagonist and somewhat weaker on D1, neutral on 5HT2 receptors) have also shown effectiveness in the treatment of stuttering. However, haloperidol in particular results in poor long-term compliance due to concerning side effects such as movement disorders and prolactin elevation which can also occur to a lesser extent with risperidone.3,4

Other dopamine active medications reported to positively treat stuttering include aripiprazole, asenapine, lurasidone and the investigational compound, ecopipam.

Ecopipam is unique from other dopamine antagonists in that it acts on D1 receptors instead of D2. An open label study of ecopipam in adults demonstrated significantly improved stuttering symptoms with no reports of parkinsonian-like movement disorders typically seen with D2 antagonists.5 In addition, ecopipam had no reported weight gain, but instead reported weight loss.5 In a preliminary study, it was well-tolerated in subjects, effectively reduced stuttering severity and was even associated in this short-term study with improved quality of life in persons who stutter.5 Further research is still warranted, but this novel mechanism is showing promise in the pharmacologic treatment of stuttering.

One should always consult with a medical doctor before considering medication treatment of stuttering to review potential risks/benefits.


References:

1. Thomas, K., & Saadabadi, A. (2018). Olanzapine. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK532903/

2. Maguire, Gerald A., Glyndon D. Riley, David L. Franklin, Michael E. Maguire, Charles T. Nguyen, and Pedram H. Brojeni. "Olanzapine in the treatment of developmental stuttering: a double-blind, placebo-controlled trial." Annals of Clinical Psychiatry 16, no. 2 (2004): 63-67. https://www.ncbi.nlm.nih.gov/pubmed/15328899


3. Shaygannejad, V., Khatoonabadi, S. A., Shafiei, B., Ghasemi, M., Fatehi, F., Meamar, R., & Dehghani, L. (2013). Olanzapine versus haloperidol: which can control stuttering better?. International journal of preventive medicine, 4 (Suppl 2), S270. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678230/

4. Maguire, Gerald A., Glyndon D. Riley, David L. Franklin, and Louis A. Gottschalk. "Risperidone for the treatment of stuttering." Journal of clinical psychopharmacology 20, no. 4 (2000): 479-482. https://www.ncbi.nlm.nih.gov/pubmed/10917410

5. Charoensook J, Maguire G. A Case Series on the Effectiveness of Lurasidone in Patients with Stuttering. Annals of Clinical Psychiatry. 2017 August 29(3): 191-194. PMID 28738099 https://www.ncbi.nlm.nih.gov/pubmed/?term=charoensook+maguire

6. Maguire GA, LaSalle L, Hoffmeyer D, Lochhead J, Nelson M, Burris A, Davis K, Yaruss JS. Ecopipam as a Pharmacological Treatment of Stuttering. Annals of Clinical Psychiatry. 2019 Aug;31(3):164-168. PMID 31369655 https://escholarship.org/uc/item/8ct0028k

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