What are the treatment options for a patient with dyskinesia, possibly related to Parkinson's disease or antipsychotic medication use?

Treatment of Dyskinesia

Immediate Priority: Identify the Type of Dyskinesia

The treatment approach fundamentally differs based on whether you are dealing with drug-induced tardive dyskinesia (TD) or levodopa-induced dyskinesia (LID) in Parkinson's disease—these require opposite management strategies.

Drug-Induced Tardive Dyskinesia

For drug-induced TD, discontinue or reduce the offending antipsychotic medication as the first-line intervention, and if antipsychotic therapy must continue, switch to an atypical antipsychotic with lower TD risk. 1

First-Line Management for TD:

• Discontinue the causative dopamine receptor-blocking agent (antipsychotics, metoclopramide) if clinically feasible 1, 2
• If antipsychotic therapy cannot be stopped, switch to atypical antipsychotics with lower D2 receptor affinity 1, 2
  • Clozapine has the lowest risk profile for movement disorders among all antipsychotics and should be the preferred switch option 2, 3
  • Quetiapine carries risk but is less likely to worsen TD than risperidone or olanzapine 2, 4
  • Avoid risperidone, which has the highest TD risk among atypicals, especially at doses >6 mg/day 2

Pharmacologic Treatment for Established TD:

For moderate to severe or disabling TD, treat with VMAT2 inhibitors (valbenazine or deutetrabenazine) as first-line pharmacotherapy. 1, 2

• These are the first FDA-approved medications specifically for TD 2
• Deutetrabenazine demonstrates efficacy in class 1 studies 2
• Do NOT use anticholinergic medications for TD—they are indicated for acute dystonia and parkinsonism, not TD, and may worsen the condition 1, 2

Critical Monitoring:

• Perform baseline assessment using the Abnormal Involuntary Movement Scale (AIMS) before starting any antipsychotic 1, 2
• Monitor for dyskinesias every 3-6 months 1, 2
• TD may persist indefinitely even after medication discontinuation, making prevention paramount 1, 2, 3
• Up to 50% of youth receiving neuroleptics may experience some form of TD 1, 5

High-Risk Medications to Avoid:

• First-generation antipsychotics (haloperidol, chlorpromazine, fluphenazine, perphenazine) carry the highest TD risk with 12-month incidence of 12.3% in first-episode psychosis 2
• Metoclopramide should be avoided for long-term use due to potentially irreversible TD risk, particularly in elderly patients 2

Levodopa-Induced Dyskinesia in Parkinson's Disease

For LID in Parkinson's disease, globus pallidus interna deep brain stimulation (GPi-DBS) is the most effective intervention, with immediate-release amantadine ranking highest among oral medications. 6

Treatment Hierarchy for LID (Based on 2025 Network Meta-Analysis):

1. GPi-DBS (SUCRA = 97.4%, most effective) 6
2. Levodopa-carbidopa intestinal gel infusion (SUCRA = 89.7%) 6
3. STN-DBS (SUCRA = 89%, but GPi-DBS is superior) 6
4. Immediate-release amantadine (SUCRA = 86.5%, highest-ranking oral medication) 6
5. Pallidotomy (SUCRA = 84.9%, ranks higher than subthalamotomy) 6
6. ADS-5102 (SUCRA = 82.9%, but higher adverse event rates) 6
7. Clozapine (SUCRA = 77.2%) 6

Important Considerations for PD-Related Dyskinesia:

• Clozapine has beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias in PD patients 4
• Clozapine does not worsen motor function significantly at low doses 4
• Continuous drug delivery (CDD) dramatically reduces dyskinesia induction compared to pulsatile administration 7
• Novel anti-dyskinetic medications (ADS-5102, OS320) are associated with less-favorable tolerance profiles 6

Distinguishing TD from Acute Extrapyramidal Symptoms (EPS)

Acute EPS occur early in treatment (within days to weeks) and respond to anticholinergics or dose reduction, while TD develops after long-term exposure (≥3 months) and requires VMAT2 inhibitors or medication discontinuation. 1

Acute Dystonia:

• Sudden spastic muscle contractions within days of starting treatment 1
• Treat immediately with anticholinergic medications or antihistamines—laryngospasm can be life-threatening 1

Akathisia:

• Severe restlessness with subjective inner tension and semi-voluntary movements (pacing, inability to sit still) 1
• Often misinterpreted as psychotic agitation, leading to inappropriate dose increases 1
• Manage by lowering antipsychotic dose, or trial β-blockers or benzodiazepines 1
• Anticholinergic agents are not consistently helpful 1

Parkinsonism:

• Bradykinesia, tremors, and rigidity mimicking Parkinson's disease 1
• Responds to anticholinergic agents or amantadine 1, 8

Special Consideration: Paroxysmal Kinesigenic Dyskinesia (PKD)

PKD is a distinct entity triggered by sudden voluntary movements, lasting <1 minute in >98% of cases, and responds to sodium channel blockers (carbamazepine 50-200 mg/day). 9, 5

• Do not confuse PKD with TD—PKD patients can sometimes modify attacks through movement slowing when experiencing aura, while TD has no voluntary control 5
• Approximately 78-82% of PKD patients experience aura (numbness, tingling, muscle weakness) 9, 5
• Age of onset typically 7-15 years, with male predominance (2:1 to 4:1 ratio) 9

Critical Warnings

• Tardive dyskinesia may be potentially irreversible and can develop after relatively brief treatment periods at low doses 3
• Anticholinergic medications worsen TD despite being effective for acute dystonia 1, 2
• Abrupt clozapine discontinuation can cause cholinergic rebound (profuse sweating, headache, nausea, vomiting, diarrhea) and recurrence of psychosis 3
• Adequate informed consent regarding TD risk is necessary when prescribing antipsychotics 1, 2