Transdermal Nicotine and Haloperidol in Tourette's Disorder

Silver, Archie A.; Shytle, R. Douglas; Philipp, M K; Wilkinson, Berney J.; McConville, Brian J.; Sanberg, Paul R.

doi:10.4088/jcp.v62n0908

Cited by 109 publications

(54 citation statements)

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“…One study was a parallel trial where children treated with haloperidol (optimum dose titrated over 2 weeks before entering the trial) were randomised to nicotine patches (7 mg/day) or placebo for 19 days. 147 The dosage of haloperidol was reduced to 50% after 5 days and outcomes assessed 3 hours after patch application and at 5, 19 and 33 days. The other study was a crossover trial in which children being treated with an antipsychotic drug (96% of children) were given a single dose of transdermal nicotine (7 mg) or placebo in a randomised order and measurements made 7 days after treatment.…”

Section: Included Studiesmentioning

confidence: 99%

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis

Hollis

Pennant

Cuenca

et al. 2016

Health Technol Assess

127

109

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BackgroundTourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant distress and psychosocial impairment.ObjectiveTo conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2).Data SourcesFor the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013.Review/research methodsFor part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged < 18 years) with TS or chronic tic disorder were included. Mixed studies and studies in adults were considered as supporting evidence. Risk of bias associated with each study was evaluated using the Cochrane tool. When there was sufficient data, random-effects meta-analysis was used to synthesize the evidence and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. For part 2, qualitative studies and survey literature conducted in populations of children/young people with TS or their carers or in health professionals with experience of treating TS were included in the qualitative review. Results were synthesized narratively. In addition, a national parent/carer survey was conducted via the Tourettes Action website. Participants included parents of children and young people with TS aged under 18 years. Participants (young people with TS aged 10–17 years) for the in-depth interviews were recruited via a national survey and specialist Tourettes clinics in the UK.ResultsFor part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs [standardised mean difference (SMD) –0.74, 95% confidence interval (CI) –1.08 to –0.41;n = 75] and noradrenergic agents [clonidine (Dixarit®, Boehringer Ingelheim) and guanfacine: SMD –0.72, 95% CI –1.03 to –0.40;n = 164] are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD –0.64, 95% CI –0.99 to –0.29;n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects.LimitationsThe number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions.ConclusionsAntipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal®, Janssen), clonidine and aripiprazole (Abilify®, Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications (‘apps’) and video consultation.Study registrationThis study is registered as PROSPERO CRD42012002059.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Included Studiesmentioning

confidence: 99%

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis

Hollis

Pennant

Cuenca

et al. 2016

Health Technol Assess

127

109

View full text Add to dashboard Cite

show abstract

“…These studies provide unconvincing evidence that nicotine can provide an adjunctive benefit for tic suppression when added to ongoing treatment with an antipsychotic. [107][108][109] Mecamylamine, a nicotinic receptor antagonist, was no better than placebo in reducing tics. 110,111 The antiandrogen flutamide, which has theoretical appeal for the treatment of tics, showed little clinical benefit in the only placebo-controlled study.…”

mentioning

confidence: 99%

Contemporary assessment and pharmacotherapy of Tourette syndrome

et al. 2006

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Summary:To develop a guide to clinical assessment and pharmacotherapy for children and adults with Tourette syndrome (TS), we reviewed published literature over the past 25 years to identify original articles and reviews on the assessment and pharmacological treatment of Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD) and obsessivecompulsive disorder (OCD). The literature search also included a survey of reviews published in book chapters. The assessment section was compiled from several reviews. Pharmacological treatments were classified into those with strong empirical support (as evidenced by two positive placebo-controlled studies for tics, OCD, or ADHD in TS samples); modest empirical support (one positive placebo-controlled study), or minimal support (open-label data only). We conclude that accurate diagnosis, including identification of comorbid conditions, is an essential step toward appropriate treatment for patients with TS. In many patients with TS, symptom management requires pharmacotherapy for tics or coexisting conditions. The evidence supporting efficacy and safety for medications used in patients with TS varies. But this evidence offers the best guide to clinical practice.

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“…However, nicotine, mecamylamine, and varenicline specifically target nAChRs. Nicotine has demonstrated efficacy and safety in placebo-controlled trials in children with Tourette's disorder (Silver et al 2001a(Silver et al , 2001b, in placebo-controlled trials in adult attention-deficit/hyperactivity disorder (ADHD) (Conners et al, 1996) and in an open trial in adults age 20-30 years with Down syndrome (Bernert et al 2001). The efficacy of nicotine in reducing inattention, hyperactivity, and irritability in other chronic disorders beginning in childhood, such as Down syndrome (Seidl et al 2000;Bernert et al 2001) and Tourette's disorder, supports the strategy of testing a nicotinic cholinergic agent in autism.…”

mentioning

confidence: 99%

Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders

Arnold

Aman

Hollway

et al. 2012

Journal of Child and Adolescent Psychopharmacology

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Objective: To explore possible benefits of a nicotinic acetylcholine receptor (nAChR) agent for autistic symptoms based on postmortem observation of nAChR abnormalities (deficient a4b2 nAChRs, excess a7 nAChRs) in brains of patients with autism. Method: Mecamylamine, because of its safety record in children with other disorders, was chosen for this first exploration. Twenty children with autism spectrum disorder age 4-12 years were randomly assigned for 14 weeks to placebo (n = 8) or mecamylamine (n = 12) in ascending fixed doses: 0.5 mg/day for 6 weeks, 2.5 mg for 2 weeks, then 5 mg/day for 6 weeks. Improvement was rated by a blinded independent evaluator. Because of small sample, data analysis was descriptive. Results: Eighteen participants (10 mecamylamine, 8 placebo) completed the study. All doses were well tolerated; the only side effect of note was constipation (50% compared with 25% of placebo group). Three children had clinically nonsignificant electrocardiographic QT prolongation. Both groups showed modest to moderate improvement, but differences between groups were negligible. On the primary outcome measure, the Ohio Autism Clinical Impressions Scale, 90% of the active treatment group showed improvement at some point (but only 40% sustained it), compared with 62% on placebo. Of the four in active treatment that sustained improvement, three had a maximum dose of 0.13-0.15 mg/kg/day, while those who regressed had doses ‡ 0.18 mg/kg/day. Graphed means suggested better outcome with lower mg/kg and longer medication duration. Four parents spontaneously reported reduced hyperactivity and irritability and better verbalization and continued mecamylamine at their own expense. Conclusion: Mecamylamine appeared to be safe, but not very effective in autism. The suggestion of better results at lower doses and longer exposure warrants consideration for future trials. The next step would be exploration of a more specific a4b2 nAChR agonist, such as varenicline.

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Transdermal Nicotine and Haloperidol in Tourette's Disorder

Cited by 109 publications

References 0 publications

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis

Contemporary assessment and pharmacotherapy of Tourette syndrome

Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders

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