Can Vrylar (cariprazine) be used to treat depression?

Vrylar (Cariprazine) for Depression

Yes, Vrylar is FDA-approved for depression, but specifically as adjunctive therapy to antidepressants for major depressive disorder (MDD) and for bipolar I depression—it is not approved as monotherapy for unipolar depression. 1

FDA-Approved Indications for Depression

Vrylar has two distinct FDA-approved uses for depressive disorders 1:

• Adjunctive therapy to antidepressants for major depressive disorder (MDD) in adults who have inadequate response to antidepressant monotherapy 1
• Treatment of depressive episodes associated with bipolar I disorder (bipolar depression) as monotherapy 1

Efficacy for Major Depressive Disorder (Adjunctive Use)

For MDD, cariprazine 1.5 mg/day as adjunctive therapy is the evidence-based dose that demonstrates significant benefit. 2

• In a phase 3 randomized controlled trial, cariprazine 1.5 mg/day added to ongoing antidepressants significantly reduced MADRS scores compared to placebo (mean difference -2.6 points) at week 6 2
• The 1.5 mg/day dose showed significant improvement as early as week 2 and maintained superiority through week 6 2
• Response rates (≥50% MADRS reduction) were significantly higher with cariprazine 1.5 mg/day versus placebo (44.0% vs 34.9%, NNT=11) 2
• The 3.0 mg/day dose did not separate from placebo in the primary endpoint, making 1.5 mg/day the preferred dose for MDD 2

Efficacy for Bipolar I Depression

For bipolar depression, both 1.5 mg/day and 3.0 mg/day doses demonstrate efficacy as monotherapy. 3

• Both doses significantly reduced MADRS scores versus placebo (1.5 mg: -2.5 points; 3.0 mg: -3.0 points) at week 6 3
• Pooled response rates across trials were 46.3% versus 35.9% for placebo (NNT=10), and remission rates were 30.2% versus 20.9% (NNT=11) 4
• The likelihood of experiencing benefit substantially exceeds the likelihood of discontinuation due to adverse events 4

Clinical Algorithm for Use

For Unipolar Major Depressive Disorder:

• First-line treatment remains second-generation antidepressants (SSRIs, SNRIs, bupropion, mirtazapine) selected based on adverse effect profile, cost, and patient preference 5, 6
• Assess response within 6-8 weeks of antidepressant initiation 5
• If inadequate response after 6-8 weeks of adequate antidepressant trial, consider adding cariprazine 1.5 mg/day as adjunctive therapy 2
• Do not use cariprazine 3.0 mg/day for MDD augmentation given lack of efficacy separation from placebo 2

For Bipolar I Depression:

• Cariprazine can be used as monotherapy at either 1.5 mg/day or 3.0 mg/day 1, 3
• Start with 1.5 mg/day given better tolerability profile; the 3.0 mg/day dose has higher rates of adverse events and discontinuation 4
• Cariprazine represents the fourth FDA-approved agent for bipolar depression and offers an alternative to mood stabilizers like lithium, valproate, and lamotrigine 7

Tolerability and Safety Profile

Common adverse events include akathisia, nausea, restlessness, and extrapyramidal symptoms. 1, 2

• Discontinuation rates due to adverse events are relatively low: 6.7% for cariprazine versus 4.8% for placebo (NNH=51, not significant) 4
• The 3.0 mg/day dose has higher rates of adverse events and discontinuation compared to 1.5 mg/day 4
• Metabolic effects are minimal, with relatively small and comparable changes in weight and metabolic parameters across treatment groups 3
• All adverse events in clinical trials were mild to moderate in severity 8

Monitoring Requirements

• Begin monitoring within 1-2 weeks of initiation, assessing for treatment response, adverse effects, and emergence of suicidal thoughts or behaviors 5, 7
• Continue regular monitoring throughout treatment, particularly during the first 1-2 months when suicide risk is highest 5
• Assess for akathisia and extrapyramidal symptoms at each visit given the dopaminergic mechanism of action 2, 3

Important Caveats

• Cariprazine is NOT approved as monotherapy for unipolar depression—it must be used adjunctively with an antidepressant 1
• The drug has a very long half-life (1-3 weeks for the active metabolite didesmethyl-cariprazine), meaning steady state takes weeks to achieve and adverse effects may persist after discontinuation 4
• Treatment should continue for at least 4-9 months after satisfactory response, with longer duration for patients with recurrent episodes 7