Torticollis Medication

The goals of pharmacotherapy in the treatment of torticollis are to reduce morbidity and prevent complications. Medication categories are as follows: (1) dystonia reducing (eg, trihexyphenidyl, pramipexole, glutamate release inhibitors and receptor blockers, botulinum toxin) and (2) selective adjunctive (eg, clonazepam for blepharospasm, baclofen for oromandibular dystonia, propranolol or primidone for prominent tremor).

Class Summary

Anticholinergic agents reduce dystonia.

Trihexyphenidyl

Central cholinergic blockade is often an effective treatment strategy in dystonias in all categories, not just torticollis. Doses used in nontorticollis dystonias are often much higher than those suggested here. Anticholinergic agents should be tried initially and may be more effective in children than in adults. Children tend to tolerate much higher doses than adults.

Class Summary

Agents with high potency at the D2 receptor, relative to lower potency at the D1 receptor, can be used to enhance activity in the indirect pallidal outflow pathway (see the following image). This is especially useful in treating the cervical dystonias.

Pramipexole hydrochloride (Mirapex)

Pramipexole is an especially appropriate agent in treatment of torticollis, because its D2 specificity fits single photon emission computed tomography (SPECT) and positron emission tomography (PET) scanning evidence of D2 underactivity in the indirect pallidal outflow pathway. In addition, antidepressant properties are most appropriate to this group of patients and stem from the additional specificity of pramipexole for D3 receptors. Because of the tedium of regular painful injections that are required in botulinum toxin use, try administration of pramipexole before using the toxin.

Ropinirole hydrochloride (Requip)

Ropinirole is a nonergot dopamine agonist that has high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. This agent has moderate affinity for opioid receptors. The precise mechanism of action of ropinirole as treatment for torticollis is unknown. However, it is possibly related to the stimulation of dopamine receptors in the striatum.

To avoid malignant hyperthermic complications when stopping the drug, discontinue ropinirole gradually over a 7-day period. Decrease the frequency of administration from tid to bid for 4 days. For the remaining 3 days, decrease the frequency to once daily before complete withdrawal.

Ropinirole serves as an alternative agent to pramipexole if that drug has objectionable adverse effects. Its dopamine receptor profile is similar to that of pramipexole.

Class Summary

Glutamate release inhibition and glutamate receptor blockade are alternatives to potentiating D2 receptors in the indirect pallidal outflow pathway by reducing the glutamate-related excitatory circuit in this outflow pathway (see the following image).

Riluzole (Rilutek)

Riluzole appears to block glutamatergic neurotransmission in the central nervous system (CNS) through indirect mechanisms. This agent may inactivate voltage-dependent sodium channels; it may also activate guanosine triphosphate-binding signal transduction proteins (G-proteins), which may cause inhibition of glutamate release.

This agent has the least adverse effects of the 3 drugs mentioned for glutamate release inhibition, but its expense is prohibitive unless the insurance carrier has a low copay. Because riluzole is classified as an orphan drug, the carrier is required to make payment by law (Federal Orphan Drug Act). Amantadine must be dosed above a threshold amount (usually 300 mg) to provide release inhibition above and beyond the dopamine receptor agonism. Lamotrigine is an acceptable alternative, but its effective dosing is not as clear and ranges from 25 to 100 mg tid. Memantine can also be tried as 10 mg bid.

Nevertheless, if riluzole is not covered by the insurance carrier, one can try amantadine, lamotrigine, or possibly memantine.

Amantadine

Amantadine inhibits N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine release in rat striatum. This agent may enhance dopamine release, inhibit dopamine reuptake, stimulate postsynaptic dopamine receptors, or enhance dopamine receptor sensitivity. Glutamate receptor inhibition occurs at high doses only. Use amantadine only at 100 mg orally (PO) tid (lower doses or frequencies only provide dopamine agonism).

Memantine (Namenda)

Memantine is an N-methyl-D-aspartate (NMDA) antagonist.

Lamotrigine (Lamictal)

Lamotrigine blocks glutamate receptors and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane. This drug is a back-up alternative to amantadine.

Class Summary

Adrenergic beta-blocking agents offer antitremor action when overt tremor complicates torticollis.

Propranolol (Inderal LA, InnoPran XL)

Propranolol is often the first choice for tremor control in essential tremor and can be used as adjunctive medical therapy when tremor complicates torticollis.

Class Summary

Primidone is an anticonvulsant drug used in low doses for its antitremor effect.

Primidone (Mysoline)

The low-dose form of primidone is the traditional second choice agent for treatment of essential tremor. This drug is also possibly effective as an adjunct in treatment of torticollis with prominent tremor.

Class Summary

The use of anticholinergics may improve morbidity.

Benztropine (Cogentin)

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

Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other possible mechanisms may include inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.

Aspirin (Ecotrin, Bayer Aspirin, Ascriptin)

Aspirin treats mild to moderately severe pain by inhibiting prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Ibuprofen (Motrin, I-Prin, Ultraprin)

Ibuprofen is the drug of choice (DOC) for patients with mild to moderately severe pain. This drug inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Class Summary

Paralysis of dystonic muscles by direct injection is used to reduce pain and abnormal posture. The various botulinum toxins possess individual potencies, and care is required to assure proper use and avoid medication errors. Changes to the established drug names by the US Food and Drug Administration (FDA) were intended to reinforce these differences and prevent medication errors. The products and their approved indications include the following:

• OnabotulinumtoxinA (Botox, Botox Cosmetic): Botox (cervical dystonia, blepharospasm)
• AbobotulinumtoxinA (Dysport): Cervical dystonia, moderate-to-severe glabellar lines
• IncobotulinumtoxinA (Xeomin): Cervical dystonia, blepharospasm
• RimabotulinummtoxinB (Myobloc): Cervical dystonia

OnabotulinumtoxinA (Botox)

Although botulinum toxin type A (Botox) is considered treatment of choice because of its degree of effectiveness, the duration of paralysis is limited to a few months, multiple sites must be injected, and electromyographic (EMG)–guided injections in neuromuscular junction are tedious and painful. On this basis, early oral (PO) medication trials with other drugs are desirable.

Alternatives to botulinum toxin type A (especially B and F) can be used if a patient develops resistance to type A by producing type A antibodies.

Botulinum toxin type A must be reconstituted from vacuum-dried toxin into 0.9% sterile saline without preservative according to manufacturer's instructions to provide an injection volume of 0.1 mL; this agent must be used within 4 hours of storage in a refrigerator at 2-8°C. Preconstituted dry powder must be stored in a freezer at less than 5°C.

IncobotulinumtoxinA (Xeomin)

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).

Class Summary

As an inhibitor of the neurotransmitter gamma-aminobutyric acid (GABA), baclofen can be used as an adjunctive medication when torticollis is complicated by oromandibular dystonia.

Baclofen (Lioresal, Gablofen)

Baclofen can be used to supplement other medications used to treat torticollis when oromandibular dystonia is present.

Class Summary

Benzodiazepine agents provide adjunctive treatment for patients with blepharospasm.

Clonazepam (Klonopin)

Clonazepam is the preferred benzodiazepine for movement disorders. This agent can be used alone or to supplement other medications used to treat torticollis that is complicated by blepharospasm.

Class Summary

Antipsychotic agents are useful for treating dystonia that is associated with torticollis.

Olanzapine (Zyprexa, Zyprexa Zydis)

Olanzapine may inhibit serotonin, muscarinic, and dopamine effects. This agent exerts dopamine receptor blockade in both striatal (D2 > D1 receptor blockade) and in nonstriatal sites (D3, D4).

Risperidone (Risperdal, Risperdal M-Tab, Risperdal Consta)

Risperidone is an atypical neuroleptic. This agent binds to dopamine D2-receptor with 20 times lower affinity than for serotonin subtype 2 (5-HT2)–receptor affinity. Has weak affinity for dopamine D1 receptors and no affinity for muscarinics or beta-1 and beta-2 receptors.