How can akathisia caused by Abilify (aripiprazole) be managed?

Management of Aripiprazole-Induced Akathisia

The first-line approach to managing akathisia from Abilify (aripiprazole) is to reduce the dose or switch to a different antipsychotic with lower akathisia risk (such as quetiapine or olanzapine), or add propranolol 10-30 mg two to three times daily. 1

Immediate Action Steps

Dose Reduction or Medication Switch

• Lower the aripiprazole dose while staying within therapeutic range as the initial intervention 1
• If dose reduction is insufficient, switch to quetiapine or olanzapine, which have significantly lower rates of akathisia compared to aripiprazole 1, 2
• The FDA label confirms that akathisia occurs in 8% of adult patients on aripiprazole versus 4% on placebo, and in pediatric patients (13-17 years) at 9% versus 6% on placebo 3

Critical Diagnostic Consideration

• Do not misinterpret akathisia as worsening psychosis or anxiety, as this commonly leads clinicians to inappropriately increase the antipsychotic dose, which will worsen the akathisia 1
• The FDA specifically warns that patients should be monitored for "akathisia (psychomotor restlessness)" as part of clinical worsening 3

Pharmacological Treatment Algorithm

First-Line: Beta-Blockers

• Propranolol 10-30 mg two to three times daily is the most consistently effective treatment for akathisia 1, 4, 5
• Use lipophilic beta-blockers specifically, as they are most effective 4

Second-Line: Benzodiazepines

• If propranolol fails or subjective distress persists, add a benzodiazepine such as clonazepam 1, 4
• Benzodiazepines provide symptomatic relief and address the anxiety component of akathisia 1

Third-Line: Low-Dose Mirtazapine

• Mirtazapine at low doses is a well-studied option when first-line treatments fail 5
• This can be added to beta-blockers if needed 2

Fourth-Line: Alternative Agents

• Gabapentin or pregabalin (voltage-gated calcium channel blockers) may be effective 5
• Amantadine is considered a fourth-line option with limited evidence 1
• Anticholinergic agents like benztropine 1-4 mg once or twice daily are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed 1

Special Warnings and Monitoring

Suicide Risk

• SSRI-induced akathisia is associated with increased suicidality, and this risk extends to akathisia from other agents 1
• The FDA label specifically instructs clinicians to advise patients and families to watch for "akathisia (psychomotor restlessness)" as a warning sign that may be "associated with an increased risk for suicidal thinking and behavior" 3
• Systematically inquire about suicidal ideation before and after any treatment changes 1

High-Risk Populations

• Pediatric patients (13-17 years) have higher rates of akathisia (25% EPS-related events vs 7% placebo) compared to adults 3
• Young age and male gender are additional risk factors 1
• When starting aripiprazole in patients with mood disorders taking multiple medications (especially with lamotrigine and antidepressants), begin with low doses and monitor closely 6

Practical Pitfalls to Avoid

• Avoid antipsychotic polypharmacy, which increases side effect burden without improving akathisia 1
• Do not use anticholinergics as first-line treatment—they are ineffective for akathisia despite being effective for other extrapyramidal symptoms 1
• Monitor for the appearance of akathisia early in treatment (most cases occur within the first 49 days), as early recognition prevents complications including non-compliance and impulsive behavior 3, 7
• Be aware that even "atypical" antipsychotics like aripiprazole that cause minimal other extrapyramidal side effects can still cause significant akathisia 5