Pharmacologic Agents

Only a few controlled studies have been conducted on the effects of antimyoclonic drugs. Although clonazepam and valproic acid are often used in the treatment of myoclonus, they have never been formally studied for this use. Expert opinion forms the basis for the use of most drugs in treating myoclonus.

The guiding principles in the pharmacologic treatment of myoclonus are to recognize that

• Therapy is targeted at symptom relief
• Treatment is usually begun with a single drug
• Eventually, several drugs may be used in combination

The choice of drugs is based upon the answers to questions identified in the diagnostic approach—the fundamental cause and origin of the movements—and the side-effect profile of the agents. The primary drugs used to treat myoclonus include levetiracetam (Keppra®), clonazepam (Klonopin®), valproic acid (Depakote®, Depakene®), primidone (Myidone®, Mysoline®), piracetam (Nootrypl®), and acetazolamide (AK-Zol®, Diamox®).

Primary Pharmacologic Agents: Levetiracetam

Levetiracetam (Keppra®) has been shown in clinical studies to have antimyoclonic activity. This drug is well tolerated and has no interaction with other drugs. It does not require multiple dose adjustments (titration) when beginning treatment. A trial of this drug is reasonable in most patients with myoclonus, particularly those with proven posthypoxic cortical myoclonus.

Types of myoclonus in which levetiracetam may be useful

• Cortical
  • Lance Adams syndrome
  • Postencephalitic myoclonus
  • PME
  • Creutzfeldt-Jakob disease
• Paraneoplastic
• Negative
• Spinal

Possible side effects

• Lack of energy or weakness
• Headache
• Daytime sleepiness
• Dizziness

Cautions

• Dosage should be adjusted based on kidney function
• Should be used with caution in the elderly

Primary Pharmacologic Agents: Clonazepam

Types of myoclonus in which clonazepam may be useful

• Essential and other types of myoclonus
• Lance Adams syndrome
• Subcortical action myoclonus
• Spinal myoclonus, nocturnal myoclonus (PLMS)
• Opsoclonus-myoclonus
• Myoclonus that occurs secondary to tetanus toxin and opiate therapy

Possible side effects

• Sedation (including excessive sedation in the elderly)
• Sensation of movement or revolving in space (vertigo)
• Behavioral changes
• Tolerance

Cautions
Clonazepam should not be used or should be used with caution in patients with

• Acute narrow-angle glaucoma
• Liver problems

In children, clonazepam should be used with caution because it may cause hyperactivity.

Adverse events often limit the use of this drug in the treatment of myoclonus.

Primary Pharmacologic Agents: Valproic Acid

Types of myoclonus in which valproic acid may be useful

• Cortical myoclonus
• Subcortical myoclonus
• Opsoclonus-myoclonus
• Juvenile myoclonic epilepsy
• Other forms of myoclonus

Possible side effects

• Nausea and vomiting
• Weight gain
• Increased appetite
• Sedation
• Drowsiness
• Tremor
• Hair loss (alopecia)

Valproic acid should not be used or should be used with caution in some patients.

• Not recommended in patients with liver problems (insufficiency) or failure.
• Used with extreme caution in children younger than 2 years of age, who are at risk for developing life-threatening liver function problems (hepatotoxicity) with the use of this drug
• Has the possibility of causing defects in a developing fetus (teratogenic)

Liver function must be monitored while patients are on valproic acid. In addition, gastrointestinal side effects, sedation, and the rare but life-threatening liver (hepatic) toxicity and inflammation of the pancreas (pancreatitis) may limit the use of this drug.

Primary Pharmacologic Agents: Piracetam

Types of myoclonus in which piracetam may be useful

• Lance Adams syndrome
• PME
• Other forms of cortical myoclonus

Possible side effects

• Gastrointestinal discomfort
• Abnormally low levels of circulating blood platelets (thrombocytopenia)
• An unusual state of excitement or well-being (euphoria)
• Excessive physical activity along with impulsive behavior and rapidly changing thoughts (mania)

Piracetam should not be used or should be used with caution in some patients, including those with

• Poor kidney function (renal insufficiency)
• Abnormal liver function (hepatic dysfunction)

Piracetam, which is typically used as an "add-on therapy," is not currently available in the United States.

Primary Pharmacologic Agents: Primidone

Types of myoclonus in which primidone may be useful include

• Cortical
• Subcortical

Possible side effects

• Inability to properly coordinate voluntary movement (ataxia)
• Sensation of movement or revolving in space (vertigo)
• Drowsiness
• Irritability
• Impairment of thought processes (cognitive impairment)

Primary Pharmacologic Agents: Acetazolamide

Types of myoclonus in which acetazolamide may be helpful include

• Cortical myoclonus

Possible side effects

• Difficulty in breathing (dyspnea)
• Seizures
• Sensation of movement or revolving in space (vertigo)
• Lightheadedness
• Ongoing loss of appetite (anorexia)
• Nausea
• Itching (pruritis)
• Headache

Patients who are taking acetazolamide need to have their potassium levels carefully monitored. This is done with a simple blood test.

Other Pharmacologic Agents

Additional drugs that have been used in the treatment of myoclonus include a variety of anticonvulsants, including zonisamide (Zonegran®), phenobarbital (Solfoton®), and lamotrigine (Lamictal®); drugs related to the action of the neurotransmitter serotonin (serotonergic agents) such as 5-hydroxytryptophan (which is not available in the United States), sumatriptan (Imitrex®), and fluoxetine (Prozac®, Sarafem®); and other agents such as tetrabenazine (Nitoman®, Xenazine®), trihexyphenidyl (Artane®, Trihexane®, Trihexy®), sumatriptan (Imitrex®), and melatonin. Caution is urged with the use of these drugs because many may actually make myoclonic symptoms worse or may cause myoclonus in some patients.

Immunosuppression

Opsoclonus-myoclonus in children is usually treated with inhibition of the immune system with certain drugs (immunosuppression). These drugs include adrenocorticotropic hormone (ACTH), azathioprine (Imuran®), corticosteroids, and immunoglobulin therapy (IVIg).

• Adverse reactions with the use of ACTH include "cushingoid" features, such as a characteristic "moon-shaped," broad facial appearance, fluid retention, psychological effects, cardiovascular effects, gastric ulcers, skin changes, increasingly fragile bones (osteoporosis), infection, diabetes mellitus, and growth suppression. ACTH is typically administered as injections in a muscle for 2 months, beginning twice a day, with slow downward tapering.
• Adverse reactions with the use of azathioprine and corticosteroids include abnormally low levels of circulating white blood cells (leucopenia) and/or platelets (thrombocytopenia) and nausea and vomiting.
• IVIg may be effective in treating parainfectious opsoclonus-myoclonus and idiopathic opsoclonus-myoclonus. Adverse reactions with the use of IVIg include headache, fever, and flu-like symptoms. The typical dosage is 1 to 2 grams per kg per day for 1 or more days.

	Chemodenervation