Further supporting dopamine hyperactivity in the pathology of stuttering, Stager et al compared pimozide (n = 6), a selective dopamine (D2) antagonist, paroxetine (n = 5), a highly selective serotonin reuptake inhibitor, and placebo (n = 6). The researchers found a positive clinical response in those on pimozide compared with those taking placebo, whereas the paroxetine group exhibited no clinical response.16 Although small, such a study supports the hypothesis that dopamine may be a principal transmitter involved in stuttering pathology, and serotonin may play a minor role, if any.
Risperidone, a newer-generation dopamine antagonist with a side-effect profile more favorable than haloperidol, has been shown in a well-controlled, double-blind, placebo-controlled study to improve stuttering symptoms (0.5 mg to 2 mg/d). Although generally well tolerated, long-term compliance was hindered by prolactin-related side effects such as sexual dysfunction, galactorrhea, amenorrhea, and dysphoria.17 Dysphoria with risperidone has also recently been reported to occur with its use in Tourette disorder.18
Olanzapine is a novel psychotropic medication that possesses dopamine-blocking qualities but is not associated as much with prolactin-related side effects or dysphoria. A preliminary open-label study suggests that it too improves the symptoms of stuttering.19
A multicenter study of olanzapine in the treatment of adult developmental stuttering involved 23 adults in a 3-month, double-blind, placebo-controlled trial preceded by a 1-month baseline rating period. At the end of the double-blind phase, subjects were followed for 1 year. Olanzapine (2.5 mg titrated to 5 mg/d) was shown to exert a statistically significant improvement over placebo in multiple objective measures of stuttering severity. The medication was well tolerated without prolactin-associated side effects. Concerns of appetite increase and weight gain with olanzapine were minimized through simple education. The average weight gain was 4 lb in the treatment group, compared with 1 lb in the placebo group. Compliance was also high. All subjects elected to enter the open-label phase of the protocol.
In many patients in the study, stuttering symptoms have continued to improve over 6 months to 1 year or even longer, suggesting that an adequate treatment trial should be measured not in days or even weeks, but possibly months. Also, some individuals in the open-label phase have shown even further efficacy with dose escalation to 7.5 mg to 10 mg/d or higher of olanzapine.20
It is likely, however, that pharmacologic treatment will not be the total answer. In the studies cited earlier, the novel dopamine antagonists led to significant—yet only partial—reductions in stuttering symptoms. The future of optimal stuttering treatment will likely involve the active collaboration between a speech language pathologist and a psychiatrist, using speech therapy to enhance the positive benefits of the medication.
Related resources
- National Stuttering Association http://www.nsastutter.org
- University of California-Irvine Medical Center: Facts About Stuttering. http://www.ucihealth.com/News/UCI%20Health/stutter2.htm
- Hulstijn W, Peters HFM, Van Lieshout PHHM, eds. Speech Production: Motor Control, Brain Research and Fluency Disorders. International Congress Series 1146. Amsterdam, Netherlands: Excerpta Medica, 1997.
- Haloperidol • Haldol
- Nimodipine • Nimotop
- Olanzapine • Zyprexa
- Paroxetine • Paxil
- Pimozide • Orap
- Risperidone • Risperdal
Drs. Maguire and Franklin report that they receive grant/research support from, serve as consultants to, and are on the speaker’s bureau of Eli Lilly &Co.
Dr. Maguire also reports that he receives grant/research support from Johnson & Johnson, and serves on the speaker’s bureau of Pfizer Inc. and GlaxoSmithKline.
Dr. Yu reports that he serves on the speaker’s bureau of Cephalon Inc.
Drs. Riley and Ortiz report no financial relationship with any company whose products are mentioned in this article.