What are the management options for hyperkinetic movement disorders?

Management of Hyperkinetic Movement Disorders

For hyperkinetic movement disorders, VMAT2 inhibitors (tetrabenazine, deutetrabenazine, valbenazine) are first-line pharmacological agents, with tetrabenazine demonstrating marked improvement in 57-89% of patients across various hyperkinetic conditions, while specific movement disorder subtypes require tailored approaches including anticonvulsants for paroxysmal dyskinesias and dopamine agonists for certain secondary causes. 1, 2, 3

Pharmacological Management by Disorder Type

VMAT2 Inhibitors as Primary Therapy

Tetrabenazine is FDA-approved for Huntington's chorea and demonstrates efficacy across multiple hyperkinetic disorders:

• Tardive stereotypy: 89.2% marked improvement 3
• Huntington's disease chorea: 82.8% marked improvement 3
• Tardive dystonia: 80.5% marked improvement 3
• Idiopathic dystonia: 62.9% marked improvement 3
• Tourette's syndrome: 57.4% marked improvement 3
• Myoclonus: 83.3% marked improvement 3

Critical dosing considerations for tetrabenazine:

• Patients requiring >50 mg/day must undergo CYP2D6 genotyping before dose escalation 1
• Poor metabolizers (PMs) have 3-fold higher α-HTBZ and 9-fold higher β-HTBZ levels; maximum dose is 50 mg/day total with 25 mg maximum single dose 1
• Extensive metabolizers can be titrated higher based on response and tolerability 1

Paroxysmal Kinesigenic Dyskinesia (PKD)

Sodium channel blockers are the definitive treatment for PKD:

• Carbamazepine 50-200 mg/day or oxcarbazepine 75-300 mg/day achieve complete remission in >85% of patients 4
• Start carbamazepine at 50 mg (or 1 mg/kg in children) and titrate based on response 4
• Start oxcarbazepine at 75 mg and adjust as needed 4
• Approximately 97% of patients achieve complete or partial relief with these agents 4
• Take medication at bedtime to minimize dizziness side effects 4
• Screen for HLA-B*15:02 in Han Chinese populations before initiating carbamazepine to reduce Stevens-Johnson syndrome risk 4

Movement Disorders in Specific Populations

For 22q11.2 deletion syndrome with movement disorders:

• Parkinsonism responds to standard dopaminergic therapy (levodopa, dopamine agonists) similar to idiopathic Parkinson's disease 4
• Dystonia and other movement disorders may be exacerbated by hypocalcemia; correct metabolic abnormalities first 4
• Monitor for drug-induced movement disorders as this population has increased susceptibility 4

For restless legs syndrome (RLS) with hyperkinetic features:

• Dopamine agonists are first-line: ropinirole 0.25-4 mg or pramipexole 0.125-0.5 mg taken 1-3 hours before bedtime 4
• Start ropinirole at 0.25 mg, increase to 0.5 mg after 2-3 days, then 1 mg after 7 days, with weekly 0.5 mg increments to maximum 4 mg 4
• Start pramipexole at 0.125 mg, double every 4-7 days to maximum 0.5 mg 4

Monitoring and Safety Considerations

Common Adverse Effects of VMAT2 Inhibitors

Monitor for these dose-related side effects:

• Sedation/somnolence: Most common dose-limiting effect (31% in controlled trials, up to 57% in open-label studies) 1
• Parkinsonism: Bradykinesia, rigidity, hypertonia in 15% of patients 1
• Depression: Occurs in 15% of patients; screen regularly 1, 3
• Akathisia: Develops in 19% of patients; requires dose reduction or discontinuation 1
• Drowsiness: 36.5% of patients 3

Critical Safety Warnings

Neuroleptic Malignant Syndrome (NMS) risk:

• Presents with hyperpyrexia, muscle rigidity, altered mental status, autonomic instability 1
• Immediately discontinue tetrabenazine if NMS suspected 1
• Monitor for recurrence if restarting therapy after NMS recovery 1

Psychiatric monitoring:

• Assess for depression and suicidality at each visit, as tetrabenazine increases these risks 1
• Evaluate cognitive decline, which may be drug-induced versus disease progression 1

Functional assessment:

• Periodically re-evaluate need for therapy by assessing chorea control versus adverse effects 1
• Drug-induced parkinsonism may cause more functional disability than untreated chorea in some patients 1
• Reduce dose or discontinue if adverse effects outweigh benefits 1

Alternative and Adjunctive Therapies

When VMAT2 inhibitors are contraindicated or ineffective:

• Anticonvulsants (other than for PKD) may provide benefit in certain hyperkinetic disorders 2
• Avoid typical neuroleptics when possible, as tetrabenazine has not been demonstrated to cause tardive dyskinesia unlike neuroleptics 3
• Consider newer VMAT2 inhibitors (deutetrabenazine, valbenazine) with optimized pharmacology for improved tolerability 5

For drug-induced hyperkinetic disorders:

• Identify and discontinue offending agent when possible 6
• Antidepressants, antiepileptics, and over-the-counter medications can worsen hyperkinetic disorders 6

Treatment Algorithm

Step 1: Characterize the specific hyperkinetic disorder (chorea, dystonia, myoclonus, tics, ballism) through clinical examination 7

Step 2: Identify and treat reversible causes:

• Metabolic abnormalities (hypocalcemia, hypomagnesemia) 4
• Drug-induced causes (discontinue offending agents) 6
• Secondary causes requiring etiological treatment 4

Step 3: Initiate disorder-specific pharmacotherapy:

• Paroxysmal kinesigenic dyskinesia: Carbamazepine or oxcarbazepine 4
• Huntington's chorea, tardive dyskinesia, other choreiform disorders: Tetrabenazine (with CYP2D6 testing if >50 mg/day needed) 1, 2, 3
• RLS with hyperkinetic features: Dopamine agonists 4

Step 4: Titrate to lowest effective dose that controls symptoms without causing intolerable side effects 1, 3

Step 5: Monitor every 6 months for disease progression, medication efficacy, and adverse effects 4, 8