Safety and Efficacy of RimabotulinumtoxinB for Treatment of Sialorrhea in Adults: A Randomized Clinical Trial

JAMA Neurol. 2020 Apr 1;77(4):461-469. doi: 10.1001/jamaneurol.2019.4565.


Importance: RimabotulinumtoxinB (RIMA) may be preferable as an anti-sialorrhea treatment compared with current oral anticholinergic drugs in people with neurological disorders.

Objective: To assess the safety, efficacy, and tolerability of RIMA injections for the treatment of sialorrhea in adults.

Design, setting, and participants: This randomized, parallel, double-blind, placebo-controlled clinical trial of RIMA 2500 U and 3500 U was conducted from November 14, 2013, to January 23, 2017. A total of 249 adult patients with troublesome sialorrhea secondary to any disorder or cause were screened. Of them, 13 refused further participation in the study or were lost to follow-up and 49 did not fulfill the criteria for participation; 187 were ultimately enrolled. Patients had to have a minimum unstimulated salivary flow rate (USFR) of 0.2 g/min and a minimum Drooling Frequency and Severity Scale score of 4.

Exposures: Patients were randomized 1:1:1 to RIMA, 2500 U (n = 63); RIMA, 3500 U (n = 64); or placebo (n = 60).

Main outcomes and measures: Primary outcomes were the change in USFR from baseline to week 4 and the Clinical Global Impression of Change (CGI-C) at week 4. The CGI-C scores were recorded on a 7-point scale ranging from very much improved to very much worse. Adverse events were recorded throughout the trial period.

Results: Of 187 patients enrolled (147 men [78.6%]; mean [SD] age, 63.9 [13.3] years), 122 patients had Parkinson disease (65.2%), 13 (7.0%) were stroke survivors, 12 had amyotrophic lateral sclerosis (6.4%), 6 had medication-induced sialorrhea (3.2%), 4 had adult cerebral palsy (2.1%), and 30 had sialorrhea owing to other causes (16.0%). A total of 176 completed the study. Treatment with both doses of RIMA significantly reduced USFR at week 4 vs placebo (mean treatment difference, -0.30 g/min [95% CI, -0.39 to -0.21] for both doses vs placebo, P < .001). The CGI-C scores were statistically significantly improved at week 4 for both treatment groups vs placebo (-1.21 [95% CI, -1.56 to -0.87] for 2500 U, -1.14 [95% CI, -1.49 to -0.80] for 3500 U, both P < .001). Treatment benefits were seen as early as 1 week after injection and were maintained over the treatment cycle of approximately 13 weeks. The RIMA injections were well tolerated compared with placebo. The most common adverse events were self-limited mild to moderate dry mouth, dysphagia, and dental caries.

Conclusions and relevance: Treatment with RIMA (2500 U and 3500 U) in adults was well tolerated and reduced sialorrhea, with the onset of the effect at 1 week after the injection. These data support the clinical use of RIMA in the management of sialorrhea in adults.

Trial registration: Identifier: NCT01994109.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine Release Inhibitors / adverse effects
  • Acetylcholine Release Inhibitors / therapeutic use*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Botulinum Toxins, Type A / adverse effects
  • Botulinum Toxins, Type A / therapeutic use*
  • Deglutition Disorders / chemically induced*
  • Dental Caries / chemically induced*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sialorrhea / drug therapy*
  • Treatment Outcome
  • Young Adult


  • Acetylcholine Release Inhibitors
  • rimabotulinumtoxinB
  • Botulinum Toxins, Type A

Associated data