Clonidine: Tourette Syndrome

Clonidine & Breath Holding Spells (BHS)
Treatment for cyanotic breathholders has been more difficult. Given our current understanding of the underlying pathophysiology, central sympathetic outflow modulators would be anticipated to provide potential benefit. In an uncontrolled study, the use of tetrabenazine (a centrally acting a-adrenergic antagonist) has been effective in preventing cyanotic BHSs in a group of 15 patients.  A dose of 1.0 mg/kg/d divided into 3 or 4 doses was used. The addition of clonidine to tetrabenazine was even more effective	(Dimario, 1999)
Multiple medications have been tried with variable success, including iron therapy for children with low hemoglobin levels, piracetam, and central sympathetic modulators such as tetrabenzamine and clonidine for cyanotic BHS .	(Legge, Kantoch, Seshia, & Soni, 2002)
Clonidine in Neurodevelopmental Disorder
α2-adrenoreceptor agonist; activates inhibitory neurons resulting in decreased sympathetic outflow and decreased vasomotor tone and heart rate Clinically, clonidine is often used in the setting of poor sleep in children with NDDs, particularly those who have associated behavioral symptoms. Indicated for neurodevelopmental disorder (autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, and Smith-Magenis syndrome)	(Blackmer & Feinstein, 2016)
Clonidine in Taurette Syndrome (Tics )
The alpha-2 adrenergic agonist clonidine inhibits the release of noradrenaline. Studies supporting the efficacy of this drug in ameliorating tics include a retrospective study which found clonidine was efficacious in 47% of patients treated and had few side effects Similar figures were reported by a single-blind, placebo-controlled trial conducted by Leckman and colleagues, where 46% of the patients treated responded well, exhibiting improved motor and phonic tics Treatment with clonidine was associated with a decrease in the mean total tics score from 25.2 to 21.8 and minor sedation-related side effects.	(Eddy, Rickards, & Cavanna, 2011)
Alpha-agonists include clonidine and guanfacine, and though they lessen CNS adrenergic outflow, their mechanism in reducing tic frequency is not clear at present  Clonidine is a central-acting, presynaptic, alpha2-adrenergic agonist prescribed two to four times a day with a daily dose range of 0.05–0.3 mg; sometimes it is given only at bedtime	(Patel, D.R., Greydanus, D.E., Omar, H.A., Merrick, 2011)
Clonidine in Taurette Syndrome (Sleep Paralysis )
Treatment approaches have not been evaluated. Some success treating isolated sleep paralysis with REM-suppressing agents such as low doses of tricyclic agents, clonidine, or clonazepam	Uptodate
Clonidine & Sleep Disturbance in Children with Neurodevelopmental Disabilities
Clonidine received notoriety for being prescribed as a sleep aid in children, but currently, there are no well-controlled studies that address the effects of clonidine in children with sleep problems. Administration of low doses of clonidine (range, 0.025–0.05 mg) has little effect on sleep and can either increase or decrease the duration of REM sleep. At medium-to-high doses (range, 0.1–0.3 mg), clonidine appears to have postsynaptic activity on the α2-adrenergic receptors, which results in decrease of acetylcholine, which increases REM latency, stage 2 sleep, and slow-wave sleep. Ingrassia Turk in a retrospective chart review found clonidine to be an effective therapeutic intervention for alleviating sleep disturbances in six children, whose ages ranged from 6 to 14 years. Dose titration began at 0.05 mg and was gradually titrated up to 0.1 mg at bedtime. No severe side effects were reported. In a recent open label retrospective review, 19 children with ASD were treated with oral clonidine (range, 0.1–0.2 mg) 30 minutes before bed-reduced sleep latency and lessened nocturnal awakenings; this is especially important in children with ASD who are overly aroused or mildly anxious at bedtime. Moreover, Hollway et al performed a vast literature search, and clonidine was reported to be effective in children who experienced sleep disturbances with comorbid ASD and other neurodevelopmental disorders with behavioral problems at doses ranging from 0.05 to 0.225 mg/d.	(Angriman, Caravale, Novelli, Ferri, & Bruni, 2015)

Reference:

1.       Angriman, M., Caravale, B., Novelli, L., Ferri, R., & Bruni, O. (2015). Sleep in Children with Neurodevelopmental Disabilities. Neuropediatrics, 46(03), 199–210. http://doi.org/10.1055/s-0035-1550151

2.       Blackmer, A. B., & Feinstein, J. A. (2016). Management of Sleep Disorders in Children With Neurodevelopmental Disorders: A Review.

3.       Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 36(1), 84–98. http://doi.org/10.1002/phar.1686

4.       Dimario, F. J. (1999). Breathholding Spells in Childhood.

5.       Eddy, C. M., Rickards, H. E., & Cavanna, A. E. (2011). Treatment strategies for tics in Tourette syndrome. Therapeutic Advances in Neurological Disorders, 4(1), 25–45. http://doi.org/10.1177/1756285610390261

6.       Legge, L. M., Kantoch, M. J., Seshia, S. S., & Soni, R. (2002). A pacemaker for asystole in breath-holding spells. Paediatrics & Child Health, 7(4), 251–4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20046299

7.       Patel, D.R., Greydanus, D.E., Omar, H.A., Merrick, J. (2011). Neurodevelopmental Disabilities. Neurodevelopmental Disabilities