Is Vraylar (cariprazine) appropriate for use in children or adolescents, and what dosing and monitoring are recommended?

Vraylar (Cariprazine) Use in Pediatric Patients

Vraylar is NOT FDA-approved for use in children or adolescents, and the FDA label explicitly warns that safety and effectiveness have not been established in pediatric patients. 1

FDA Regulatory Status and Black Box Warnings

The FDA prescribing information carries a black box warning specifically stating that antidepressants (including atypical antipsychotics used for depression) increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients, and that safety and effectiveness of Vraylar have not been established in pediatric patients. 1

• Vraylar is only FDA-approved for adult indications: schizophrenia, bipolar I disorder (manic/mixed and depressive episodes), and adjunctive treatment of major depressive disorder 1
• The medication carries warnings about increased mortality in elderly patients with dementia-related psychosis, though this applies to a different vulnerable population 1

Emerging Research Evidence in Pediatric Populations

Despite the lack of FDA approval, preliminary research has explored cariprazine in youth:

Pharmacokinetic and Safety Data

A 2023 open-label study in 25 pediatric patients (ages 5-17) with autism spectrum disorder found that cariprazine was generally well tolerated, with dose-normalized exposures modestly higher in children ages 5-9 compared to older patients. 2

• Dosing in this study: 0.5-1.5 mg daily for ages 5-9,0.75-1.5 mg daily for ages 10-12, and 1.5-3 mg daily for ages 13-17 2
• Most frequent adverse events were increased weight, elevated liver enzymes, increased appetite, dizziness, agitation, and nasal congestion—all mild to moderate 2
• Two subjects experienced extrapyramidal symptoms that resolved without discontinuation 2
• Weight increases were not considered clinically meaningful 2

Retrospective Clinical Experience

A 2020 retrospective chart review of 16 patients ages 6-20 with bipolar and psychotic disorders found a 44% response rate, with responders requiring higher doses (median 6 mg/day versus 3 mg/day in non-responders), but doses ≤3 mg/day appeared more tolerable with less BMI increase. 3

• Initial dosing typically started at 1.5 mg/day, with endpoint doses ranging from 1.5-4.5 mg/day 3
• Patients receiving ≥4.5 mg/day had significantly greater BMI increases compared to those on ≤3 mg/day 3
• No serious adverse events were reported; most common side effect was weight gain (19% of patients) 3

Safety in Adolescents

A 2020 safety analysis of 49 adolescent patients (ages 13 to <18) found cariprazine generally safe and well tolerated in the adult dose range of 1.5-6 mg, with adverse events comparable to adults except for less insomnia. 4

Critical Clinical Considerations

Long Half-Life and Delayed Effects

Because cariprazine and its active metabolites (especially didesmethyl-cariprazine) have very long half-lives, adverse reactions may occur late and persist for weeks after dose changes or discontinuation. 1

• The FDA label specifically warns clinicians to monitor for adverse reactions and patient response for several weeks after starting treatment and with each dosage change 1
• This pharmacokinetic profile is particularly concerning in pediatric patients where rapid dose adjustments may be needed

Metabolic and Movement Disorder Risks

Monitor closely for extrapyramidal symptoms, akathisia, metabolic changes (hyperglycemia, dyslipidemia, weight gain), and tardive dyskinesia—risks that may be heightened in developing pediatric patients. 1

• The FDA label lists extrapyramidal symptoms and akathisia as the most common adverse reactions across all approved adult indications 1
• Neuroleptic malignant syndrome, though rare, requires immediate discontinuation if suspected 1

Drug Interactions

Cariprazine requires dose reduction when co-administered with strong or moderate CYP3A4 inhibitors, and concomitant use with CYP3A4 inducers is not recommended. 1

• This is particularly relevant in pediatric patients who may be on multiple medications for comorbid conditions 1

Clinical Bottom Line

Given the lack of FDA approval, absence of controlled pediatric trials, and significant safety concerns including suicidality warnings, Vraylar should not be used in children or adolescents outside of research settings or exceptional circumstances where FDA-approved alternatives have failed and the potential benefits clearly outweigh risks. 1 If considered in rare cases, start with the lowest possible dose (1.5 mg daily for adolescents), monitor intensively for suicidality and adverse effects for several weeks after each dose change, and maintain doses ≤3 mg/day to optimize tolerability based on available pediatric data. 2, 3