Can Vraylar (cariprazine) cause akathisia?

Vraylar (Cariprazine) and Akathisia

Yes, Vraylar (cariprazine) can cause akathisia, and this is one of its most common side effects, occurring significantly more frequently than with placebo across all approved indications. 1

Incidence Rates by Indication

The FDA label provides clear data on akathisia occurrence with Vraylar:

• Schizophrenia (6-week trials): Akathisia occurred in 11% of Vraylar-treated patients versus 4% on placebo, leading to discontinuation in 0.5% of patients 1

• Bipolar Mania (3-week trials): Akathisia occurred in 20% of Vraylar-treated patients versus 5% on placebo, with 2% discontinuing treatment 1

• Bipolar Depression (6-8 week trials): Akathisia occurred in 8% of Vraylar-treated patients versus 2% on placebo, leading to discontinuation in 1.5% of patients 1

• Major Depressive Disorder (adjunctive treatment): Combined akathisia and restlessness occurred in 12-22% of Vraylar-treated patients versus 4-6% on placebo, with 2-3% discontinuing 1

Dose-Dependent Relationship

Lower doses of cariprazine are associated with lower incidences of akathisia. In bipolar depression studies, akathisia occurred in 5.5% of patients on 1.5 mg/day versus 9.6% on 3 mg/day 2. This dose-response relationship is critical for clinical management.

Temporal Pattern and Severity

• Time to onset: Most akathisia events occur during the first 3 weeks of cariprazine initiation or dose increase 2

• Severity: Over 95% of akathisia cases are mild to moderate in severity 2

• Resolution: Median time to resolution after the last dose of cariprazine is approximately 1 week 2

• Rescue medication use: Less than 3% of patients required rescue medication to manage akathisia 2

Clinical Management Strategy

The primary strategy to minimize cariprazine-related akathisia is conservative dosing and slow titration. 2

If akathisia develops during treatment:

1. First-line intervention: Reduce the dose or discontinue the medication if clinically feasible 3

2. Pharmacological management: Propranolol 10-30 mg two to three times daily is the most consistently effective treatment for acute akathisia 3

3. Alternative options: Beta-blockers and benzodiazepines may provide relief 4

Comparative Context

Akathisia is the most common side effect of cariprazine, more frequent than other extrapyramidal symptoms 5, 6. While cariprazine shows higher risk of akathisia compared to placebo and some other second-generation antipsychotics like olanzapine, it does not cause weight gain, metabolic abnormalities, or prolactin elevation 7, 8.

Important Clinical Caveat

Akathisia can be frequently misinterpreted as psychotic agitation or anxiety, which may lead to inappropriate dose increases rather than decreases 4. Clinicians must maintain high clinical suspicion and use objective assessment tools like the Barnes Akathisia Rating Scale (BARS) to distinguish akathisia from psychiatric symptoms 1.