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Medication

Medication Summary

Patients with dopamine-responsive dystonia (DRD) typically experience marked, long-term benefit with low-dose levodopa. The optimal dose differs among patients; while some respond magnificently to small doses, others require higher doses. De la Fuente-Fernández et al reported achieving adequate control with a mean daily dose of 250 mg of levodopa (range, 25-500 mg).^[48]Others have reported benefit with 20 mg/kg,^[49]100 mg/d,^[50]or 750 mg/d.^[40]Wang et al suggested an optimal dose of 10 mg/kg.^[51]

Other effective medications include the anticholinergic agents, such as trihexyphenidyl, carbamazepine, BH4, and 5-hydroxytryptophan. The use of botulinum toxin (BOTOX) injection for focal dystonia should be considered in resistant cases as it would be for any cause of focal dystonia; this recourse rarely is needed in true DRD.

Motor fluctuations (as may happen in Parkinson disease treated with levodopa) do not occur in patients with DRD.^[52]Choreic dyskinesias have been reported that disappeared on reduction of the levodopa dose.^[48]

Class Summary

In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine-receptor subtypes is currently unclear.

Levodopa/Carbidopa (Sinemet, Parcopa)

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The active component is an L-isomer of dopamine (ie, L-dopa). Carbidopa is a peripheral DOPA hydroxylase inhibitor; by preventing peripheral metabolism, it increases the concentration of dopamine in the central nervous system (CNS). The total L-dopa dose required varies from person to person.

Class Summary

These agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.

Trihexyphenidyl

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Trihexyphenidyl is a synthetic anticholinergic noted to have a marked benefit in muscle spasm conditions, such as dystonia.

Benztropine (Cogentin)

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By blocking striatal cholinergic receptors, benztropine may help balance cholinergic and dopaminergic activity in striatum. This agent can be used as an alternative to trihexyphenidyl.

Class Summary

These agents are used to treat severe muscle spasms.

Carbamazepine (Tegretol, Equetro, Carbatrol)

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Carbamazepine may reduce polysynaptic responses and block posttetanic potentiation.

Class Summary

Botulinum toxin causes presynaptic paralysis of the myoneural junction and reduces abnormal contractions. Its therapeutic effects may last 3-6 months.

OnabotulinumtoxinA (BOTOX)

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Botulinum toxin type A (BTA) is useful in reducing excessive, abnormal contractions associated with DRD. It binds to receptor sites on motor nerve terminals, and after uptake it inhibits the release of acetylcholine, blocking transmission of impulses in neuromuscular tissue. Reexamine patients 7-14 days after administering the initial dose to assess for satisfactory response. Double the previously administered dose for patients who experience incomplete paralysis of the target muscle. Do not exceed 50U when giving BTA as a single injection, or 400U as a cumulative dose in 30-day period.

IncobotulinumtoxinA (Xeomin)

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IncobotulinumtoxinA is botulinum toxin type A that is free of complexing proteins found in the natural toxin from Clostridium botulinum. This drug is an acetylcholine release inhibitor and neuromuscular blocking agent. IncobotulinumtoxinA is indicated in adults for cervical dystonia in botulinum toxin–naive patients, and it is also indicated for blepharospasm in adults previously treated with onabotulinumtoxinA (BOTOX).

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Author

Nirjal K Nikhar, MD, FRCP Private Practice

Nirjal K Nikhar, MD, FRCP is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Haresh Mani, MD Assistant Professor, Department of Pathology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Syed M S Ahmed, MD Neurologist and Sleep Specialist, Capital Neurology and Sleep Medicine; Staff Attending in Neurology and Sleep Medicine, Montgomery General Hospital; Staff Attending in Neurology and Sleep Medicine, Suburban Hospital

Syed M S Ahmed, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, Maryland State Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock (managed by a financial services company) in healthcare companies including Allergan, Cellectar Biosciences, CVS Health, Danaher Corp, Johnson & Johnson.

Acknowledgements

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Ann M Neumeyer, MD Clinic Director, Instructor, Departments of Neurology and Pediatrics, Massachusetts General Hospital, Harvard Medical School

Ann M Neumeyer, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Dopamine-Responsive Dystonia Medication

Medication Summary

Decarboxylase Inhibitors