Multicenter, Double-Blind, Placebo-Controlled Study of Mecamylamine Monotherapy for Tourette's Disorder

University of South Florida College of Medicine, Tampa 33613, USA.
Journal of the American Academy of Child & Adolescent Psychiatry (Impact Factor: 7.26). 10/2001; 40(9):1103-10. DOI: 10.1097/00004583-200109000-00020
Source: PubMed


The safety and efficacy of mecamylamine as a monotherapy in children and adolescents with Tourette's disorder (TD) was investigated in an 8-week multicenter, double-blind, placebo-controlled study.
Eligible subjects included subjects with TD (DSM-IV), with a naturalistic mix of comorbid diagnoses, nonsmokers, aged 8 to 17 years, whose behavioral and emotional symptoms (according to parents) were more disturbing than tics. After a washout period of all psychotropic medication, subjects were randomly assigned to either mecamylamine (n = 29) or placebo (n = 32). Mecamylamine doses ranged from 2.5 to 7.5 mg/day. Primary efficacy measures included the Tourette's Disorder Scale-Clinician Rated (TODS-CR) and 21-point Clinical Global Improvement scale; secondary efficacy measures included the Yale Global Tic Severity Scale and a rage-attack scale (RAScal).
Of the 61 subjects who were randomized, 50 (82%) completed at least 3 weeks on medication and 38 (62%) completed the full 8-week trial. Study withdrawals included 12/29 on mecamylamine and 11/32 on placebo. For the total sample, mecamylamine was no more effective than placebo on any of the outcome measures. However, an item analysis of the TODS-CR suggested that mecamylamine may have reduced sudden mood changes and depression in moderately to severely affected subjects. Except for a slight increase in heart rate during the 1st week in both the mecamylamine and the placebo groups, there where no significant mecamylamine-related changes in vital signs, electrocardiogram, complete blood cell count, or blood chemistry values.
Mecamylamine, in doses up to 7.5 mg/day, is well tolerated in children and adolescents, but as a monotherapy it does not appear to be an effective treatment for tics or for the total spectrum of symptoms associated with TD. However, further studies should be conducted to investigate its possible therapeutic effects in subjects with comorbid mood disorders and as an adjunct to neuroleptic medication.

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    • "Extensive preclinical studies, as well as some clinical work, also support a role for nAChRs in depression, mood, and anxiety (Hurst et al., 2013;Mineur & Picciotto, 2010;Philip et al., 2010;Picciotto et al., 2015;Zurkovsky, Taylor, & Newhouse, 2013). The nAChR antagonist mecamylamine improved depression in a double-blind, placebo-controlled study for Tourette's disorder (Silver et al., 2001), although the mecamylamine enantiomer TC-5214 failed to meet the primary endpoint in a more recent trial (Hurst et al., 2013). A small open-label trial with varenicline was also associated with significant improvement in mood in outpatient smokers with persistent depressive symptoms (Philip, Carpenter, Tyrka, Whiteley, & Price, 2009). "
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    • "This was spontaneously reported by parents, and was sufficiently convincing that treatment was continued in these cases. Clearly additional studies are needed to establish the validity of the findings in trials designed to assess ARBS-specific outcomes, as both nicotine and mecamylamine have been described as effective for aggression and agitation in studies where they had no effect on the primary outcome (D'Souza and Markou, 2012; Silver et al., 2001b). Finally, studies should include both nicotinic agonists and antagonists, which might identify a preferred agent for a given indication. "
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