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Oral Medications and Dystonia

John W. Roberts, MD
Virginia Mason Medical Center
Seattle, WA

Overview

This is a review of the oral medications that are used to treat dystonia and oral medications that should be avoided by individuals with dystonia including spasmodic torticollis.

Oral Medications to treat dystonia

Oral medications may be used together with botulinum toxin injections or they may be used alone. For example, oral medications may work well for mild dystonia. Oral medications may also be the best option if there is a lack of benefit from botulinum toxin. Oral medications may be used before botulinum toxin injections are approved by an individual’s insurance plan; or they can be used between scheduled botulinum toxin injections as needed for recurrent symptoms. Oral medications were the original treatment for spasmodic torticollis and most other forms of dystonia but now they are secondary treatments to botulinum toxin injections. Furthermore, various surgeries are quickly becoming the treatment of choice.

Anticholinergics are drugs that block the transmission of acetylcholine. Acetylcholine is a neurotransmitter found throughout the nervous system. It is important in the function of the basal ganglia, a part of the brain that controls movement. Anticholinergics are one of the oldest classes of medications and are based on belladonna alkaloids. They have dozens of other uses besides the treatment of dystonia. There are numerous different drugs available but there is no strong evidence that one is superior. Most dystonia research has been done with trihexyphenidyl, which is branded Artane®. It comes as 2 mg and 5 mg tablets and the dosage ranges from 1 mg three times a day to 10 mg three times a day or even higher. Another popular anticholinergic is benztropine (Cogentin®). It comes as 0.5 mg, 1 mg and 2 mg tablets and the dosage ranges from 0.25 mg twice a day to 4 mg twice a day. Other anticholinergics include biperiden (Akineton®), ethopropazine (Parsitane®, available only in Canada) and diphenhydramine (Benadryl®). There are many other anticholinergic drugs that are not commonly used for dystonia. Anticholinergics can be very effective for some individuals but high dosages are sometimes needed. They are not habit forming and they are very inexpensive. Anticholingerics have several side effects that can be recalled using these mnemonics: Hot as a hare (reduced ability to sweat); blind as a bat (affects vision); dry as a bone (dry mouth, eyes); red as a beet (skin may look reddish); and mad as a hatter (confusion, memory loss).

Muscle Relaxants are a very large group of medications but baclofen (Lioresal®) is the most popular for the treatment of dystonia. Baclofen enhances the effect of gamma-aminohydroxybutyric acid (GABA), which is an inhibitory neurotransmitter. It has fair benefits for the average dystonia patient. Oral baclofen dosing ranges from 5 mg to 30 mg three times a day. Baclofen side effects include sleepiness, dizziness, nausea, confusion and hallucinations. Sudden withdrawal may result in seizures or psychosis. Baclofen can be infused by an implantable pump into space around the spinal cord and this is termed intrathecal baclofen. This method has greater benefit and avoids some of the mental side effects of oral baclofen but is riskier since it is an invasive procedure.

Benzodiazepines are another large class of medications and clonazepam is the most popular for the treatment of dystonia. There are many others in this group and all are relatives of diazepam (Valium®). They enhance the effect of GABA but work differently in the nervous system than baclofen. They have fair benefits for the average dystonia patient. Clonazepam dosing ranges from 0.5 mg twice a day to 2 mg three times a day. Benzodiazepine side effects include sleepiness, depression, unsteady balance and confusion. Sudden withdrawal may result in seizures, anxiety and other complications. There is a risk of dependence.

Tetrabenazine is a dopamine depleter. It is occasionally effective for dystonia. It is not available in the US but can be obtained from Canada, Europe and other countries. In the US, it is typically used when other treatment options are exhausted.

Medications to Avoid

Some drugs can worsen existing dystonia. This is the most important fact to know for an individual who has dystonia such as spasmodic torticollis. But some drugs can cause dystonia. Dystonia can develop in different ways after exposure to medications. There are acute dystonic reactions which refer to sudden, sometimes severe muscle spasms induced by medication. The spasms commonly involve the neck, back, limbs and facial muscles which produces generalized dystonia. Thankfully, these acute reactions usually reverse on withdrawal of the offending medication. On the other hand, there is delayed or “tardive” dystonia. This may take weeks, months or years to develop. Delayed dystonic reactions may involve just one body area, like spasmodic torticollis, or may generalize to multiple parts of the body. Importantly, delayed dystonic reactions may not resolve after withdrawal of medication.

Numerous medications are reported to worsen or cause dystonia. The list may seem overwhelming but the list can be pared down to a few categories of medication. All medications have desired benefits and possible risks. Medicines are not simply good or bad. The vast majority of medications are designed to reduce human suffering from a number of different medical conditions. All of the medications listed here have legitimate uses. Medications on the “avoid list” will not necessarily worsen dystonia. Ironically, some medications on the “avoid list” are sometimes used to treat dystonia and sometimes this use is justifiable. However, health care practitioners unfamiliar with spasmodic torticollis and other forms of dystonia may not be fully aware of the effects of these medications. Individuals with dystonia commonly know little about the side effects of their medications. Knowledge by both parties is the key to better health care.

Neuroleptics are a class of drugs normally used to treat mental illness such as psychosis, bipolar disease and depression. Many people with dystonia have depression and a few may be exposed to these drugs. Neuroleptics work by blocking the transmission of dopamine in the brain. There are several types of neuroleptics. “High potency” neuroleptics are the most likely to cause or worsen dystonia. They include:

Fluphenazine (Prolixin®)
Haloperidol (Haldol®)
Pimozide (Orap®)
Trifluoperazine (Stelazine®)
Thiothixene (Navane®)

Lower potency neuroleptics have a slightly lower risk of dystonia and include:

Chlorpromazine (Thorazine®)
Chlorprothizene (Taractan®)
Droperidol (Inapsine®)
Loxapine (Loxitane®)
Mesoridazine (Serentil®)
Molindone (Moban®)
Perphenazine (Trilafon®)
Thioridazine (Mellaril®)
Thiethylperazine (Torecan®)
Triflupromazine (Vesprin®)

“Atypical” neuroleptics are the newest subclass and are designed to have a lower risk of dystonia:

Risperidone (Risperdal®)
Olanzapine (Zyprexa®)

Certain atypical neuroleptics have a very low risk of dystonia:

Clozapine (Clozaril®)
Quetiapine (Seroquel®)

Some antinausea (also called antiemetic) medications are similar to neuroleptics and should be avoided by individuals with dystonia:

Metoclopramide (Reglan®)
Prochlorperazine (Compazine®)
Promethazine (Phenergan®)
Droperidol (Inapsine®)
Benzquinamide (Emete-Con®)

A few antidepressants possess a small risk of causing or worsening dystonia. Since many people with dystonia have depression, many take antidepressants. The newer generation antidepressants are generally safe for people with dystonia. The antidepressants associated with dystonia are mostly from the older generation of this drug class:

Amitriptyline (Elavil®)
Amoxapine (Asendin®)
Bupropion (Wellbutrin®)
Buspirone (Buspar®)
Clomipramine (Anafranil®)
Desipramine (Norpramin®)
Fluoxitine (Prozac®)
Imipramine (Tofranil®)
Nortriptyline (Pamelor®)
Protriptyline (Vivactil®)
Trazadone (Desyrel®)
Trimipramine (Surnomtil®)

Lithium (Eskalith®, Lithobid®) is an important medication to treat bipolar disease. It rarely causes or worsens dystonia.

Benzodiazepines are used to treat dystonia as outlined above. A few benzodiazepines are reported to cause or worsen dystonia:

Alprazolam (Xanax®)
Midazolam (Versed®)

Antiseizure (anticonvulsant) medications are used to treat epilepsy. Some anticonvulsants may rarely cause or worsen dystonia:

Carbamazepine (Tegretol®)
Phenytoin (Dilantin®)

Levodopa (Sinemet®, Stalevo®) is most commonly used to treat Parkinson disease. It works well for a special type of dystonia called dopa-responsive dystonia. Only rare individuals with spasmodic torticollis have this type of dystonia. Levodopa rarely causes dystonia or worsens other types of dystonia.

Calcium channel blockers are common medications used to treat high blood pressure and heart disease. A few types rarely cause or worsen dystonia including verapamil (Calan®, Isoptin®).

Summary

Several types of medications are used to treat dystonia. These include anticholinergics, muscle relaxants, benzodiazepines and tetrabenazine.

Some medications should be avoided by individuals with dystonia. These include most neuroleptics, some antinausea medications, some antidepressants and a few others.