Is it safe to start Vraylar (cariprazine) in a 61-year-old female with a history of seizures and severe anhedonia?

Vraylar Can Be Started with Caution in This Patient

Vraylar (cariprazine) may be initiated in this 61-year-old female with a history of seizures and severe anhedonia, but requires careful monitoring and seizure control optimization before starting, as the FDA label explicitly warns that cariprazine may cause seizures with greatest risk in patients with a history of seizure disorders. 1

Seizure Risk Considerations

FDA-Mandated Warnings

• The FDA label for Vraylar clearly states that "like other antipsychotic drugs, VRAYLAR may cause seizures" with the risk being "greatest in patients with a history of seizures or with conditions that lower the seizure threshold" 1
• This is a formal warning rather than an absolute contraindication, distinguishing it from medications like metronidazole which are contraindicated in seizure patients 2

Pre-Treatment Requirements

• Ensure adequate seizure control with anticonvulsants before initiating cariprazine, following the principle established for other medications with seizure risk 3
• Verify the patient is on an appropriate anticonvulsant regimen and has stable seizure control (no recent breakthrough seizures) 4
• Consider obtaining baseline EEG if seizure control is uncertain or if there have been recent changes in seizure pattern 4

Anhedonia Treatment Rationale

Strong Evidence for Anti-Anhedonic Effects

• Cariprazine demonstrates specific anti-anhedonic effects in patients with bipolar depression, with both 1.5 mg/day and 3 mg/day doses showing significant reductions in anhedonia factor scores compared to placebo 5
• These anti-anhedonic effects persist even after adjusting for other depressive symptoms, indicating a direct rather than pseudospecific effect 5
• The unique D3-preferring partial agonist pharmacology of cariprazine provides advantages for treating negative symptoms and anhedonia that are challenging to address with other agents 6, 7

Dosing Strategy for This Patient

Start Low, Go Slow Approach

• Initiate at the lowest effective dose (1.5 mg/day) given the seizure history 3, 1
• The 1.5 mg/day dose has demonstrated efficacy for anhedonia while potentially minimizing seizure risk 5
• Avoid rapid dose escalation; cariprazine has a long half-life requiring gradual titration 7

Age-Related Considerations

• At 61 years old, this patient falls into the category where "conditions that lower the seizure threshold may be more prevalent in older patients" 1
• Monitor closely for somnolence (reported in 7-11% of patients), which could increase fall risk in this age group 1

Monitoring Protocol

Seizure Surveillance

• Monitor closely for breakthrough seizure activity during initiation and dose adjustments, similar to recommendations for other medications with seizure risk 3
• Maintain regular communication with the patient's neurologist if one is involved in seizure management 4
• Educate the patient and caregivers on recognizing seizure activity and when to seek immediate care 4

Safety Monitoring

• Assess for akathisia, nausea, and insomnia (the most common adverse events occurring in ≥5% of patients at twice the rate of placebo) 8
• Monitor for orthostatic hypotension, particularly during initial dose titration, given age-related vulnerability 1
• Cariprazine has a neutral metabolic profile with mean weight increase <1 kg, reducing concerns about metabolic complications 8

Common Pitfalls to Avoid

• Do not start cariprazine if seizures are poorly controlled or if there have been recent breakthrough seizures - optimize anticonvulsant therapy first 3, 1
• Avoid combining with other medications that lower seizure threshold without careful consideration 1
• Do not use enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) as they may interact with cariprazine metabolism; levetiracetam or lamotrigine are preferred anticonvulsants 4
• Recognize that cariprazine's long half-life means adverse effects may take time to resolve if discontinuation becomes necessary 7

Overall Safety Profile

• Cariprazine has demonstrated good tolerability with high study completion rates (90%) and low discontinuation rates due to adverse events (4.3%) in clinical trials 8
• The medication shows broad-spectrum efficacy advantages including effects against difficult-to-treat negative symptoms and anhedonia 7
• No new safety signals have been identified with longer-duration treatment 7