title: Drooling in Parkinson's disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins.
abstract: Botulinum toxins are a therapeutic option for drooling in Parkinson's Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD.
  
  
  
  1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models.
  
  
  
  1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: -0.194 ± 0.61, range: -1.28 to 0.97, 95% CI -0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen's d: -1.32, CI -1.86 to -0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands.
  
  
  
  This study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, BIDMC, 330 Brookline Ave, Boston, MA 02215, USA. Electronic address: pnarayan@bidmc.harvard.edu.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Narayanaswami
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, BIDMC, 330 Brookline Ave, Boston, MA 02215, USA. Electronic address: thomas.geisbush@my.rfums.org.
authors.forename: Thomas
authors.initials: T
authors.lastname: Geisbush
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, BIDMC, 330 Brookline Ave, Boston, MA 02215, USA. Electronic address: Andrew.Tarulli@atlantichealth.org.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tarulli
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, BIDMC, 330 Brookline Ave, Boston, MA 02215, USA. Electronic address: eraynor@bidmc.harvard.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Raynor
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, BIDMC, 330 Brookline Ave, Boston, MA 02215, USA. Electronic address: sgautam@bidmc.harvard.edu.
authors.forename: Shiva
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, BIDMC, 330 Brookline Ave, Boston, MA 02215, USA. Electronic address: dtarsy@bidmc.harvard.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tarsy
authors.affiliation: Department of Neurology, Kansas University Medical Center, 3901 Rainbow Blvd, Mail Stop 1033, Kansas City, KS 66160, USA. Electronic address: ggronseth@kumc.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Gronseth
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001905:Botulinum Toxins / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D010306:Parotid Gland / Q000378:metabolism; D012720:Severity of Illness Index; D012798:Sialorrhea / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D001905:Botulinum Toxins
keywords: Botulinum toxin; Clinical trials randomized controlled; Clinical trials systematic reviews/meta-analysis; Parkinson’s disease; Sialorrhea