Nicotine potentiation of haloperidol in reducing tic frequency in Tourette's disorder
Division of Child and Adolescent Psychiatry, University of Cincinnati College of Medicine, OH 45267-0559. American Journal of Psychiatry
(Impact Factor: 12.3).
In an open, nonblind study, 10 patients with Tourette's disorder who were being treated with haloperidol were videotaped before, while, and after chewing nicotine gum. The frequency of tics was reduced significantly during the 30-minute gum-chewing period and during the 1 hour after gum chewing. Nicotine appears to potentiate haloperidol effects in patients with Tourette's disorder.
Available from: Benedikt Amann
- "The treatment we chose was nicotine. Several studies have suggested that nicotinic drugs, such as nicotine itself, the psychoactive alkaloid in tobacco, or mecylamine may influence tics particularly in conjunction with haloperidol (McConville et al., 1991, 1992; Silver et al., 2001a,b). In addition, nicotine is easy to apply and is absorbed rapidly when given as a chewing gum. "
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ABSTRACT: The pathophysiology underlying the involuntary tics of Gilles de la Tourette syndrome (GTS) remains unknown. Here we used transcranial magnetic stimulation (TMS) to examine the excitability of two different inhibitory systems in the human motor cortex: short interval intracortical inhibition (SICI) and short interval afferent inhibition (SAI) in 10 healthy non-smoking controls and eight untreated non-smoking patients with GTS. Compared with the healthy control group, both SICI (measured at a range of conditioning intensities) and SAI were reduced in patients. This is consistent with the suggestion that reduced excitability of cortical inhibition is one factor that contributes to the difficulty that patients have in suppressing involuntary tics. In addition, the reduced SAI indicates that impaired intracortical inhibition may not be limited to the motor cortex but also involves circuits linking sensory input and motor output. A single dose of nicotine reduced tic severity as assessed by blind video scoring in the majority of patients. In addition, it abolished the difference between patients and controls in SICI and SAI. There was no effect of nicotine, and no difference between controls and patients in measures of motor or SICI threshold. This indicates that cholinergic input can modulate the efficiency of SICI and SAI differently in GTS and healthy controls.
Available from: Tony P George
- "Several lines of evidence suggest the role of nAChRs in mediating Tourette's-related symptoms. McConville et al. (1991 (1992) studied the effect of TNP in TD patients currently treated with haloperidol, and the combination of TNP and haloperidol significantly reduced tics compared to haloperidol treatment alone. Silver et al. (2001a) extended this finding and confirmed that nicotine gum augments haloperidol treatment more effectively than placebo gum in reducing the symptoms of TD as measured by the Clinical and Parent Global Improvement Scales. "
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ABSTRACT: Cigarette smoking rates in the American population are approximately 23%, whereas rates of smoking in clinical and population studies of individuals with neuropsychiatric disorders are typically two- to four-fold higher. Studies conducted in a variety of neuropsychiatric populations [e.g. attention-deficit hyperactivity disorder (ADHD), Alzheimer's disease, schizophrenia] have collectively suggested that nicotine may be efficacious in remediating selected cognitive deficits associated with these disorders, thus providing a framework for understanding the specific vulnerability of these patients to smoking initiation and maintenance. However, the specific gain in cognitive performance produced by nicotine administration in healthy subjects with normal cognitive function is less clear. This article reviews our current understanding of central nicotinic acetylcholine receptor (nAChRs) systems in normal and neuropsychiatric disease states and, specifically, their role with respect to cognitive dysfunction and clinical symptoms in several specific neuropsychiatric populations, including ADHD, Alzheimer's disease, Parkinson's disease, Tourette's Disorder, schizophrenia and affective disorders. The potential benefits of nicotinic agents for therapeutic use in neuropsychiatric disorders is discussed, as well as directions for further research in this area.
Available from: Martine Anne Jaworski
- "A recent publication of a randomized, placebo-controlled clinical trial reported on the effects of 19 days of transdermally administered nicotine on motor and phonic tics in Tourette's syndrome (TS) patients receiving concurrent individualized optimal neuroleptic treatment with the dopamine (D 2 ) antagonist, haloperidol . The superior motor tic symptom reduction observed with nicotine over placebo supported earlier observations of nicotine augmentation of fluphenazine and haloperidol-induced cataplexy and reduced locomotor activity in rats     and buttressed findings of case reports and open-label trials observing immediate , short-lived (45–60 min) attenuation of tic frequency with nicotine gum      as well as persistent tic symptom reductions (lasting up to 10 days and 4 weeks) following application of one and two consecutive 7 mg 24-h transdermal nicotine patches [9–12,44–47]. Although the significant high incident nicotine-related adverse side effect profile was said to limit its widespread use as a daily adjunctive therapy in patients being treated with typical neuroleptics , particularly for the control of tic symptoms in TS children and adolescents, the suggested use of transdermal nicotine on an intermittent p.r.n. "
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ABSTRACT: Evidence from pre-clinical infrahuman investigations, open-label clinical trials, and a single controlled trial found acute nicotine treatment potentiated up to 4 weeks neuroleptic-induced reductions of dyskinetic symptoms characterizing Tourette's syndrome (TS). Given the attentional disturbances associated with this syndrome, and the improvements in attentional processes reported with nicotine, this randomized, double-blind, placebo-controlled trial examined the acute (4 h) and sustained (2 weeks) effects of a single dose of transdermal nicotine on clinical (i.e., tics), attentional (continuous performance task, event-related potential, patient and parental reports) and behavioral symptoms in 23 children and adolescents with TS receiving neuroleptic treatment. In the 14 evaluable patients with complete primary efficacy data, nicotine (compared to placebo) failed to alter symptoms at 4 h but counteracted ERP-P300 signs of diminished attention seen 2 weeks following placebo treatment. Secondary efficacy measures, including patient self-reports and parental ratings, found nicotine to reduce complex tics and improve behaviors related to inattention. Additional work with intermittent dosing schedules is required to characterize optimal clinical and cognitive effects with nicotine treatment.
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