What is the risk of Extrapyramidal Symptoms (EPS) with Aripiprazole (Abilify) and how can it be managed?

Aripiprazole and Extrapyramidal Symptoms: Risk and Management

Aripiprazole has a significant risk of extrapyramidal symptoms (EPS), with up to 25% of pediatric patients and 13% of adult patients experiencing EPS-related events excluding akathisia. 1 Despite being marketed as an atypical antipsychotic with lower EPS risk, clinical evidence shows that aripiprazole requires careful monitoring for movement disorders.

Risk of EPS with Aripiprazole

Incidence and Risk Factors

• In pediatric patients (13-17 years) with schizophrenia, EPS-related events occurred in 25% of aripiprazole-treated patients versus 7% for placebo 1
• Akathisia-related events occurred in 9% of aripiprazole-treated pediatric patients versus 6% for placebo 1
• In adults with schizophrenia, EPS-related events occurred in 13% of aripiprazole-treated patients versus 12% for placebo 1
• Higher doses correlate with increased EPS risk:
  • Extrapyramidal disorder: placebo (5%), 10mg (13%), 30mg (21.6%) 1
  • Somnolence: placebo (6%), 10mg (11%), 30mg (21.6%) 1
  • Tremor: placebo (2%), 10mg (2%), 30mg (11.8%) 1

Recent epidemiological research found that aripiprazole users had 5.38 times higher odds of developing EPS compared to non-users of antipsychotics, with risk increasing with longer duration of use 2. Even low doses (5mg) have been reported to cause EPS in children 3.

Types of EPS Associated with Aripiprazole

1. Akathisia - Most common EPS with aripiprazole

   • Characterized by restlessness, inability to sit still, pacing
   • Often misinterpreted as anxiety or psychotic agitation
   • Common reason for medication non-compliance

2. Dystonia

   • Sudden spastic contraction of muscle groups (neck, eyes, torso)
   • Risk factors include young age and male gender
   • Can be distressing and potentially life-threatening (laryngospasm)

3. Parkinsonism

   • Bradykinesia, tremors, and rigidity
   • May be difficult to differentiate from negative symptoms

4. Tardive Dyskinesia

   • Involuntary movements, typically of orofacial region
   • Can persist even after medication discontinuation
   • Has been reported with aripiprazole despite its atypical profile 4

Management of Aripiprazole-Induced EPS

Prevention Strategies

1. Start with lowest effective dose

   • Begin with 5-10mg for adults, lower for children and elderly
   • Titrate slowly to minimize EPS risk

2. Regular monitoring

   • Use standardized rating scales (Barnes Akathisia Scale, Simpson Angus Scale)
   • Assess for EPS at each visit, especially during initial weeks of treatment

3. Consider prophylactic antiparkinsonian agents

   • Particularly in patients with history of EPS or at high risk for dystonic reactions
   • Reevaluate need after acute phase of treatment 5

Treatment of EPS

1. Akathisia

   • Dose reduction if clinically feasible
   • Consider β-blockers or benzodiazepines if dose reduction ineffective 5

2. Dystonia

   • Anticholinergic medications (e.g., benztropine)
   • Antihistamines (e.g., diphenhydramine)
   • Prompt treatment essential, especially for laryngeal dystonia

3. Parkinsonism

   • Anticholinergic agents
   • Consider amantadine as alternative
   • Dose reduction when possible 5

4. Tardive Dyskinesia

   • If TD appears, consider drug discontinuation or maintaining lowest effective dose
   • Switch to an antipsychotic with lower EPS risk if symptoms persist 6
   • Regular monitoring using the Abnormal Involuntary Movement Scale every 3-6 months 5

Special Considerations

Mechanism of Aripiprazole-Induced EPS

Aripiprazole's unique partial agonism at D2 receptors was thought to reduce EPS risk, but research suggests it may also inhibit acetylcholinesterase activity, potentially contributing to EPS through cholinergic effects 7.

Age-Related Factors

• Children and adolescents appear more susceptible to aripiprazole-induced EPS than adults
• In older adults with depression, 26.7% developed akathisia with aripiprazole augmentation, with greater baseline depression severity predicting higher risk 8

Clinical Course

Most cases of akathisia improve over time, especially with dose reduction 8. However, vigilance for tardive dyskinesia is essential as it may persist even after medication discontinuation.

Practical Recommendations

1. Use the lowest effective dose of aripiprazole
2. Monitor regularly for early signs of EPS using standardized scales
3. Consider dose reduction as first-line management for EPS
4. Use anticholinergic agents judiciously for acute symptoms
5. Switch to an alternative antipsychotic if EPS persists despite interventions
6. Document baseline abnormal movements before initiating treatment
7. Provide thorough informed consent regarding EPS risks

Despite its reputation as an atypical antipsychotic with favorable side effect profile, aripiprazole carries a significant risk of EPS that requires vigilant monitoring and prompt management.