Treatment Strategies for Dystonia: Medical and Surgical
Available Treatment Options: Oral Medications

Trihexyphenidyl

Trihexyphenidyl and related anti-cholinergics (benztropine, biperidin, procyclidine, scopolamine) block muscarinic acetylcholine receptors. Their mechanism of action is thought to involve an influence on the activity of cholinergic neurons of the basal ganglia. The anticholinergics are among the most widely prescribed oral agents for all types of dystonia. However, efficacy is limited and side effects are common because high doses are required. They seem to be most effective and best tolerated in childhood-onset dystonias where their use is supported by two small double-blind clinical trials. Although anticholinergics often are prescribed for adults with dystonia, their value is less clear and not substantiated by rigorous clinical trials. Some adults seem to find them to be useful, while many do not. Effective doses of trihexyphenidyl range from 6-120 mg daily in 3-4 divided doses. Common side effects include sedation, impaired mentation, constipation, urinary retention, restlessness, insomnia, burry vision, and dry mouth.

Levodopa

Levodopa is a precursor in dopamine synthesis, and serves to augment dopamine levels. Its mechanism is thought to involve augmentation of dopaminergic neurotransmission in the basal ganglia.Inchildren with dopa-responsive dystonia, the combination of levodopa with carbidopa is remarkably effective with almost complete elimination of symptoms at low doses. In this population, benefits may last for decades, with minimal side effects. Because of this dramatic response, a trial of levodopa is essential in all childhood-onset dystonias. Levodopa also can be effective in some adults with focal dystonias, particularly those involving the limbs. In some of these adults, limb dystonia may be a manifestation of late-onset dopa-responsive dystonia or early onset Parkinson’s disease. Unlike limb dystonias, the more common craniofacial and cervical dystonias of adults do not typically respond to levodopa. Children with dopa-responsive dystonia may respond to doses as low as ½ of a 25/100 mg levodopa/carbidopa tablet twice daily. However, some children and most adults require higher doses. An adequate trial for both children and adults requires reaching a levodopa dose of 20 mg/kg in 3-4 divided doses for at least one month. Common side effects include nausea and vomiting, immediate or delayed dyskinesias, sedation, orthostasis, and impaired mentation.

Tetrabenazine

Tetrabenazine depletes neuronal dopamine stores by displacing it from storage vesicles. It is thought to work by attenuating dopaminergic transmission in the basal ganglia. It is FDA-approved for the treatment of chorea in Huntington’s disease, but it appears capable of suppressing a variety of hyperkinetic movements. Its use in dystonia is supported by one small double-blind crossover trial, and several open or retrospective studies. Patients with idiopathic primary dystonia may respond, though best responses appear to occur in those with tardive dystonia. The effective dose range is 12.5-300 mg daily in 3-4 divided doses. Common side effects include sedation, Parkinsonism, impaired mentation, depression, orthostasis, and insomnia.

Dopamine receptor antagonists.

Dopamine receptor antagonists (fluphenazine, haloperidol, olanzepine, pimozide, risperdal, and others) block dopamine receptors. They are thought to work by attenuating dopaminergic transmission in the basal ganglia. They sometimes are advocated for the treatment of dystonia. However, these drugs carry a risk of causing tardive syndromes that may confound the dystonic disorder being treated, so the use of these drugs for the treatment of dystonia is generally discouraged. One exception may be clozapine, where the risk of tardive syndromes seems to be vanishingly small. However, this drug is associated with several problematic side effects including sedation, sialorrhea, and life-threatening agranulocytosis. Therefore it is used only rarely.

Baclofen

Baclofen is a GABA receptor agonist. There are no controlled studies to guide recommendations for its use, but retrospective studies and anecdotal experience suggest it is most often useful in childhood-onset dystonias, especially those with concomitant spasticity. Some adults also enjoy benefits, although most do not. Effective doses range from 30-120 mg daily in 3-4 divided doses. Common side effects include sedation, nausea, impaired mentation, dizziness, and loss of muscle tone. Abrupt discontinuation or rapid lowering of the dose can be associated with severe withdrawal reactions that include delirium and seizures.

Clonazepam

Clonazepam and related benzodiazepines (chlordiazepoxide, diazepam, lorazepam, and others) are often used in dystonia. There are no controlled trials to guide recommendations for their use, but experience suggests they may be most useful for blepharospasm and dystonias with a jerky or tremulous quality. Effective doses of clonazepam range from 0.5-6 mg daily in 3-4 divided doses. Common side effects include sedation, impaired mentation or coordination, and depression. There also is a risk for dependency and tachyphylaxis. Abrupt discontinuation or rapid lowering of the dose can be associated with severe withdrawal reactions that include delirium and seizures.

Muscle relaxants

Many patients request “muscle relaxants”, a broad category of medications with diverse actions that includes baclofen and benzodiazepines, as well as carisoprodol, cyclobenzeprine, metaxolone, methocarbamol, tizanidine, and others. There are no formal studies to guide recommendations for their use and responses vary widely, but children and adults with many different forms of dystonia often derive at least partial benefits. They may be particularly useful in patients who develop pain from uncontrolled muscle pulling.

Other drugs

Many other drugs sometimes are advocated for specific forms of dystonia, based on evidence from small and non-blinded studies, anecdotal reports, and personal experience. For example, carbamazepine and other anticonvulsants seem effective in paroxysmal kinesigenic dyskinesia, mexilitine and intravenous lidocaine may be useful in some focal dystonias, and alcohol seems to be of benefit in myoclonus dystonia. Among many other drugs sometimes advocated are amphetamines, cannabidiol, cyproheptidine, gabapentin, nabilone, and riluzole. Further studies are needed to delineate the potential usefulness of these drugs in different populations.

Drug: Indications: Titration: Typical doses: Main side effects:
Levodopa childhood-onset dystonias, adult-onset limb dystonias

start with ½ - 1 tablet of 25/100 mg levodopa/carbidopa daily and increase by ½ - 1 tablet every 3-7 days to a maximum dose of 20 mg/kg

100-1200 mg total levodopa per day, divided into 3-4 daily doses

nausea/vomiting, immediate or delayed dyskinesias, sedation, orthostasis, impaired mentation
Trihexyphenidyl generalized, segmental, or focal dystonia

start with 1-2 mg QHS, and increase by 1-2 mg every 3-7 days to a maximum dose of 120 mg daily.

4-120 mg total per day, divided into 3-4 daily doses

sedation, impaired mentation, constipation, urinary retention, restlessness, insomnia, burry vision, dry mouth
Tetrabenazine

tardive dystonia, generalized or segmental dystonia

start with 12.5 – 25 mg QHS, and increase by 1-2 mg every 3-7 days to a maximum dose of 300 mg daily. 12.5-300 mg total per day, divided into 3-4 daily doses

sedation, Parkinsonism, impaired mentation, depression, orthostatis, insomnia

Clonazepam any dystonia, especially blepharospasm or when co-occurring with prominent tremor start with 0.5-1.0 mg QHS, and increase by 0.5-1 mg every 3-7 days to a maximum dose of 8 mg daily.

0.5-8 mg total per day, divided into 3-4 daily doses

sedation, impaired mentation or coordination, depression, drug dependency, severe withdrawal reactions
Baclofen

any dystonia, especially childhood-onset

start with 5-10 mg TID, and increase by 5-10 mg at each dose every 3-7 days to a maximum dose of 120 mg daily.

30-120 mg total per day, divided into 3-4 daily doses sedation, nausea, impaired mentation, dizziness, impaired muscle tone, severe withdrawal reactions

H. A. Jinnah, MD PhD
Emory University School of Medicine
Atlanta, GA 30307