Oral Medications for Cervicle Dystonia

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Carlos Singer, MD
Director, Division of Movement Disorders.
Associate Professor of Neurology.
Miller School of Medicine
University of Miami.

I- Introduction.

What follows is not an exhaustive review on the subject of oral medications for cervical dystonia but is meant as basic information for patients suffering with cervical dystonia. It cannot substitute careful individual discussion of pros and cons of these and other medications between patients and their treating neurologists.

Although the centerpiece treatment of Cervical Dystonia (CD) is Botulinum toxin (BTX), whether type A (BOTOX) or type B (MYOBLOC), oral antidystonic agents (OAD’s) may be used either as a complement, occasional add-on or rarely as an alternative treatment.

As a complement: Some of my patients may use the oral medications on a continuous basis. They will frequently take one or more of these OAD’s at a low dose except at the time the effects of the Botulinum toxin start wearing off. They will then increase the dose, only to decrease it again once the effect of the subsequent injection kicks in.

As an ocassional add-on :I will use oral antidystonic agents while the patient is still waiting to experience the onset of the effect of the Botulinum toxin and I will take them off once the Botulinum toxin kicks in.

As an alternative: I will offer oral medications as an alternative only if there is a specific reason not to use Botulinum toxin. For example, while we wait for approval to administer BTX from the patient’s managed care company, or of the patient needs to overcome initial fears of injections, etc.

After all is said and done, my expectations from what I can get from the OAD’s is modest at best as compared to my expectations from Botulinum toxin, which are high. IN GENERAL THESE MEDICATIONS ARE OF LIMITED EFFECTIVENESS AND IT IS NECESSARY TO USE THEM WITH CAUTION AND UNDER MEDICAL SUPERVISION GIVEN THEIR POTENTIAL SIDE EFFECTS.

II- Types of OAD’s.

The three main types of medications which have become the standard treatment repeatedly mentioned in any review on the subject are:
The anticholinergics are medications that counteract the action of acetyl-choline which is one of the chemicals in the brain. This chemical is one of the chemicals that is represented within the movement-related centers of the brain. It is believed that by doing that, that is, by altering the chemical balance of this particular substance, we are able to diminish the dystonia.
Most frequently used anticholinergic: trihexyphenydil or trihexane
Brand name: Artane®.
Muscle Relaxants.
Baclofen is a muscle relaxant that enhances the action of another chemical in the brain named GABA (gamma-amino-hydroxy-butyric acid). GABA is considered a “calmer-downer” within the brain or – as I like to call it – “the neurotransmitter of tranquility”. It is believed that by promoting more of the GABA effect within the brain, we can counteract the dystonia.
Most frequently used muscle relaxant: baclofen
Brand name: Lioresal®
Clonazepam is a tranquilizer that belongs the so-called benzodiazepines, a group of medicines chemically related to Valium. There are actually receptors in the brain that respond to these drugs and that link their action to the same GABA function I explained with baclofen. In other words, the action would be similar as baclofen, in enhancing the action of GABA, the “neuro-transmitter of tranquility”.
Most frequently used: clonazepam
Brand name: Klonopin®.
Other benzodiazepines:
diazepam (Valium®)
chlordiazepoxide (Librium®)
chlorazepate (Tranxene®).

I usually only use one of these three drugs in my practice (with a fourth one kept in reserve).

III- Dosing of Anticholinergics:

Tablets of 2 mg and 5 mg tablets..
Starting dose: ½ tablet a day
Increase: 1/2 a tablet every 4-7 days
Usual dose: 1-2 tablets three times a day
Higher doses possible, if tolerated

In my experience most adults have difficulty tolerating doses higher than 4 mg three times a day of the the truhexyphenidyl.

If a physician wishes to try other anticholinergic drugs such as Cogentin® or Benadryl®, there are ways to calculate the equivalence between the different anticholinergics. For example, a tablet of 25 mg of Benadryl® is approximately equivalent to 2.5 mg of Artane®(one and a quarter tablet).

Equivalent anticholinergic doses

Benztropine (Cogentin®) 1 mg = 2.5 mg trihxyphenidyl (Artane®)
= 2.0 mg biperiden (Akineton®)
= 2.5 mg ethopropazine (Parsidol®)
= 25 mg diphenhydramine (Benadryl®)

Some of these anticholinergics, for example Parsidol®, are no longer available in the US, but may be available in Canada. In the specific case of Parsidol®, it is sold in Canada as Parsitane®. I should point out that there are no studies to suggest that any particular anticholinergic is superior to another. In general, most of the information on use of anticholinergics in dystonia has centered around the use of Artane®.

IV- Side Effects of the Anticholinergics.

One group of side effects of the anticholinergics are the so-called peripheral side effects. The list includes dry mouth, blurred vision, dry skin (anhidrosis), rapid heart rate (tachycardia), constipation, urinary retention and aggravation of pre-existent narrow angle glaucoma. These side effects have to do with effects these drugs have on the autonomic nervous system, that is, on the nerve-endings that go to the salivary glands, to the muscles that close and open the pupils, and to sweat glands, heart, gut, and bladder, respectively.

Dry mouth is very frequently present and to a certain extent accepted as a necessary evil.
It should also be noted that urinary retention, that is, the need for extra effort or straining to empty the bladder is more likely to occur in men with enlarged prostates. Finally those who have narrow angle glaucoma may experience an aggravation of this condition.

To counteract dry mouth, simple measures such as frequent sips of water, sucking on ice chips, chewing sugarless or xylitol-containing gum or hard candy can be tried. A number of over the counter saliva substitutes (ie, Salivart) can be recommended. Patients may want to check with their local pharmacist for the locally available over-the-counter preparations for dry mouth.

If still unsuccessful or the physician also desires to counteract other peripheral anticholinergic side effects such as the blurred vision or the difficulty urinating, the cautious use of certain antidotes (so-called anticholinesterase agents) can be considered. For example, pyridostigmine in doses of 30- 60 mg every 4-6 hours may provide adequate relief with a minimum of side effects. In addition, pilocarpine eye drops can be used to counteract the blurry vision. However, with the exception of mild dry mouth, when I run into these side effects I prefer to cut back and add another medication such as baclofen or clonazepam.

Anticholinergic may also have central side effects of interfering with mental function such as concentration, memory and word-finding. The older the person the more likely he or she will develop this side effect, even become very confused at very low dose. In those case, the physician has to either decrease the dose or discontinue the drug altogether. There are also rare instances of anxiety or nervousness or restlessness triggered by a small dose of anticholinergic.

V- Dosing of Baclofen.

Tablets of 10 and 20 mg
Starting dose: ½ tablet BID, TID or QID
Increase: 1/2 a tablet every 4-7 days
Usual dose: 60-80 mg/day
Higher doses possible, if tolerated (120-180 mg/day)

VI- Side Effects of Baclofen.

Common: Sleepiness, Dizziness, Stomach Upset, Urinary Frequency
Ocassional: Confusion,Hallucinations
Less Common: Dry Mouth, Urinary retention.
Rare: Worsening of dystonia.

WARNING: Gradual withdrawal in order to avoid psychosis or seizures.

In spite of the above shown list, in my experience, baclofen is a relatively well tolerated medication and I am more likely to use it in the elderly where I have reservations with regards to the use of anticholinergics. Of all the side effects listed here, the ones I have seen on occasion are lethargy and dizziness in particular, if any. I have also seen a few cases with nausea and very rare instances of urinary complaints.


Tablets of 0.5 mg, 1 and 2 mg
Starting dose: 0.5 mg BID or TID
Increase: 0.5mg every 4-7 days
Usual dose: 1-2 tablets TID
Higher doses possible, if tolerated
The 2006 PDR (Physician’s Desk Reference) mentions a maximun dose of 20 mg/day

VIII- Side Effects of Clonazepam.

The most frequent side effects associated with clonazepam include somonolence, depression, unsteadiness (imbalance) and difficulties with concentration and other mental abilities. A review of the package insert, however, discloses many other side effects, although they are uncommon.

This medication has to be used cautiously because it has the potential for tolerance and dependence. However, in my experience, if the patient does not have a history of drug addiction, drug dependence or alcoholism, one can use it reasonably safely at low doses.
This medication should not be stopped abruptly because it may cause withdrawal symptoms or seizures.

IX-The Use of Tetrabenazine in CD.

In the case of patients with severe CD, who have failed to respond well to the preceding agents and especially, if – in addition – their response to Botulinum toxin is less than satisfactory, one can consider the use of tetrabenazine. Tetrabenazine is a so-called dopamine depleter. This means that its mechanism of action is to empty the storage of dopamine in the brain. This effect is not only responsible for their potential benefit but also for their potential side effects. These medications have to be used with a lot of caution and under strict medical supervision.

Tetrabenazine is a so-called dopamine depleter. It empties the nerve terminals within the brain of their stores of dopamine. It is believed that by acting as an anti-dopamine agent, it changes the behavior within the movement-related centers of the brain in such a way as to diminish dystonia.

X- Dosing of Tetrabenazine.

Not available in the US.
Tablets of 25 mg
Starting dose: Half a tablet (12.5 mg) once a day
Increase: 12.5 mg/1-4 days till 50 mg/day
after reaching 50mg/d, 12.5 mg/week
Usual dose: 1-2 tablets TID (75-150 mg/day)
Higher doses possible, if tolerated

Tetrabenazine is currently not available in the US. It has been available in Canada, Europe and other countries(i.e., the Bahamas) for many years. It is available in tablets of 25 mg. The initial dose is 12.5 mg and some recommend that the initial increase to the first 50 mg be done by going up by half a tablet a day so in four days you are up to 50 mg. The increase can be done slower, by about ½ tablet every 4 days. Once a dose of 50 mg a day is reached, the further optional increases are by ½ tablet/week, in order to avoid excessive sedation or excessive lowering of blood pressure. Eventually one or two tablets three times a day (TID) (that is 75-150 mg/day) can be achieved. Higher doses can also be attempted if tolerated up to 250 mg/day.

XI- Side Effects of Tetrabenazine.

Among the most important side effects we have are the lowering of blood pressure particularly when going from the lying down or sitting positions to the standing position (so-called orthostatic hypotension), sleepiness, slowing down of movements and/or tremors (very similar to what is seen in Parkinson’s disease) and depression.

For this reason, it is necessary to closely monitor patients who are taking this medication as well as increase the doses very slowly.


The use of oral medications for cervical dystonia is more likely to be complementary to the Botulinum toxin injections rather than the main treatment. The most frequently used medications are trihexyphenidyl , baclofen and clonazepam. A fourth medication, tetrabenazine, is reserved for difficult cases. They have limited efficacy and patients need to be monitored for side effects.

My mom and I wanted to thank you for hosting such a great symposium this year. This was our third year and we are looking forward to next years. E. Mathews