Tourette’s Syndrome: Drug Treatment

Author: Will Bowman

A diagram of the GABA receptor.

 

Several drugs are being used to treat Tourette’s Syndrome, their effects range from reducing stress induced tics, dopaminergic systems, and adrenergic receptors. These drugs are being tested in both animal models, and human trials.

D1CT-7 mice are one of the best validated model organisms for Tourette’s Syndrome, and were used as the model organism to test the role of neurosteroid synthesis inhibition in reducing stress induced tics. In this model, neuronal hormone allopregnanolone was shown to have a dose dependent effect on generating tic-like responses in response to a stressful trigger. Allopregnanolone is a positive allosteric modulator of GABA-A receptors. In the synthesis pathway of allopregnanolone, a critical enzyme (5alpha-reductase) was marked as a drug target using finasteride as an inhibitor. Stress was found to increase allopregnanolone levels in the prefrontal cortex of D1CT-7 mice, although this mouse strain already had elevated levels of allopregnanolone over their wild type counterparts. Increased tic expression corresponded with elevated levels of allopregnanolone, however this effect could be negated via a pretreatment with haloperidole (Mosher, L. et al. 2017).

Currently, Tourette’s Syndrome is treated with tetrabenazine, which inhibits vesicular monoamine transporter type 2 which causes presynaptic dopamine depletion, though replacement with deuterabenazine is forthcoming as it has a longer half life and greater absorption. This treatment for the condition is currently only available in the EU, as in US tetrabenazine can only be administered for use in treating Huntington’s Disease. As alternatives, many alpha-2 agonists, such as clonidine and guanfacine, or antipsychotics, such as pimozide, haloperidol, flupheazine, risperidone, aripiprazole, olanzapine, and quetiapine, can be used to treat symptomatic tics. Botulinum toxin is also used to treat hyperkinetic disorders, and therefore the motor tics caused by Tourette’s. A current issue in the administration and medicinal success of these drugs is their apparent low effectiveness. Apparent failed treatment in many cases is due to failed diagnoses of other kinetic disorders as motor tics. Alternative medication with adverse side effects are then administered, when an increase in original drug dose is sufficient (Paton, D. M. 2017).

General medical trials have been performed to rank the order in which medication should be tried in Tourette’s Syndrome patients. In general, alpha-2 adrenergic receptor agonists should be considered as first line treatments for the condition, followed by antipsychotics. Some evidence is emerging that Habit reversal therapy (HRT) and comprehensive behavioral intervention for tics (CBIT) can be effective, but not without other forms of treatment as well (Kious, B. et al. 2106).

 

References:

 

Kious, Brent M., Joohi Jimenez-Shahed, and David R. Shprecher. 2016. “Treatment-Refractory Tourette Syndrome.” Progress in Neuro-Psychopharmacology and Biological Psychiatry 70 (October): 227–36. https://doi.org/10.1016/j.pnpbp.2016.02.003.

 

Mosher, Laura J., Sean C. Godar, Marianela Nelson, Stephen C. Fowler, Graziano Pinna, and Marco Bortolato. 2017. “Allopregnanolone Mediates the Exacerbation of Tourette-like Responses by Acute Stress in Mouse Models.” Scientific Reports 7 (1): 3348. https://doi.org/10.1038/s41598-017-03649-1.

 

Paton, D. M. 2017. “Deutetrabenazine: Treatment of Hyperkinetic Aspects of Huntington’s Disease, Tardive Dyskinesia and Tourette Syndrome.” Drugs of Today (Barcelona, Spain: 1998) 53 (2): 89–102. https://doi.org/10.1358/dot.2017.53.2.2589164.

 

Trifiletti, R. R., and A. M. Packard. 1999. “Immune Mechanisms in Pediatric Neuropsychiatric Disorders. Tourette’s Syndrome, OCD, and PANDAS.” Child and Adolescent Psychiatric Clinics of North America 8 (4): 767–75.

 

Whittington Craig, Pennant Mary, Kendall Tim, Glazebrook Cristine, Trayner Penny, Groom Madeleine, Hedderly Tammy, et al. 2016. “Practitioner Review: Treatments for Tourette Syndrome in Children and Young People – a Systematic Review.” Journal of Child Psychology and Psychiatry 57 (9): 988–1004. https://doi.org/10.1111/jcpp.12556.

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