Which is better, Caplyta or Vraylar? A 2025 Medical Review

An estimated 2.8% of U.S. adults experienced bipolar disorder in the past year, and up to 0.64% live with schizophrenia [1.8.2, 1.8.3]. For these individuals, the question of 'Which is better, Caplyta or Vraylar?' is critical for effective treatment.

Quick Summary

Caplyta and Vraylar are atypical antipsychotics for schizophrenia and bipolar disorder. Caplyta has a lower risk of movement and metabolic side effects, while Vraylar treats a broader range of bipolar I episodes and serves as an add-on for MDD.

Key Points

• Indications: Caplyta treats schizophrenia and bipolar I & II depression, while Vraylar treats schizophrenia, bipolar I (manic, mixed, depressive episodes), and is an add-on for MDD [1.2.3, 1.4.2].

• Side Effects: Caplyta's most common side effects are sleepiness and nausea, while Vraylar is more associated with restlessness (akathisia) and movement disorders [1.2.1].

• Metabolic Profile: Caplyta is noted for having a lower risk of metabolic side effects like weight gain and cholesterol changes compared to many other antipsychotics [1.5.1, 1.3.7].

• Tolerability: In an indirect comparison, Caplyta was rated as having better overall tolerability than Vraylar, which was ranked last among several drugs reviewed due to its side effect profile [1.5.1].

• Dosing & Half-Life: Caplyta has a simple once-daily 42mg dose, whereas Vraylar dosing is variable. Vraylar also has a much longer half-life, meaning it stays in the system for weeks [1.2.1, 1.4.6].

• Cost: Both are expensive brand-name drugs, but manufacturers offer savings programs that can significantly lower costs for eligible, commercially insured patients [1.6.1, 1.7.1].

• Patient-Specific Choice: The 'better' medication depends entirely on the patient's specific diagnosis, side effect sensitivity, and treatment goals, a decision that must be made with a doctor [1.2.2].

Understanding Atypical Antipsychotics: Caplyta and Vraylar

Choosing a medication for schizophrenia or bipolar disorder is a significant decision made between a patient and their healthcare provider. Caplyta (lumateperone) and Vraylar (cariprazine) are two prominent second-generation, or atypical, antipsychotics prescribed for these conditions [1.2.2]. Both are effective treatments, but they have distinct differences in their approved uses, mechanisms of action, side effect profiles, and dosing that may make one a more suitable option than the other for an individual patient [1.2.1]. Both are brand-name-only medications, meaning no generic versions are currently available [1.2.1].

What is Caplyta (Lumateperone)?

Caplyta is FDA-approved for the treatment of schizophrenia in adults and for depressive episodes associated with both bipolar I and bipolar II disorder in adults [1.2.3]. Its mechanism is complex, primarily acting as an antagonist at serotonin 5-HT2A receptors and a postsynaptic antagonist at dopamine D2 receptors [1.3.6]. This unique profile is thought to contribute to its efficacy with a lower risk of certain side effects compared to other antipsychotics [1.3.6].

One of Caplyta's notable features is its generally favorable metabolic profile. Clinical trials have shown that it is associated with minimal changes in weight, cholesterol, and blood sugar for many patients [1.3.2, 1.3.7]. The most common side effects are sleepiness, dizziness, nausea, and dry mouth [1.3.2]. It is taken as a single 42 mg capsule once daily with food [1.3.6].

What is Vraylar (Cariprazine)?

Vraylar has a broader range of FDA-approved indications. It is used to treat schizophrenia, acute manic or mixed episodes of bipolar I disorder, depressive episodes of bipolar I disorder, and as an adjunctive (add-on) treatment for major depressive disorder (MDD) [1.4.2]. Vraylar works as a partial agonist at dopamine D2/D3 and serotonin 5-HT1A receptors, with a high preference for the D3 receptor [1.4.6].

Vraylar's side effect profile is different from Caplyta's. The most common side effects include extrapyramidal symptoms (EPS) like restlessness (akathisia), tremors, and uncontrolled muscle movements [1.4.4]. While often associated with minimal weight gain, it can still cause metabolic changes [1.2.1, 1.4.3]. A key characteristic of Vraylar is its very long half-life (up to 3 weeks for one of its active metabolites), meaning the drug stays in the body for an extended period, which can delay the onset of side effects and their resolution after discontinuation [1.4.6, 1.4.4]. Dosing is more variable than Caplyta, starting at 1.5 mg and adjusting up to 6 mg depending on the condition [1.2.1].

Head-to-Head Comparison: Caplyta vs. Vraylar

While no direct clinical trials have compared Caplyta and Vraylar head-to-head, we can compare their features based on available data from separate studies [1.5.1, 1.5.2].

Feature	Caplyta (Lumateperone)	Vraylar (Cariprazine)
Schizophrenia	Approved [1.2.2]	Approved [1.2.2]
Bipolar I Depression	Approved [1.2.3]	Approved [1.4.2]
Bipolar II Depression	Approved [1.2.3]	Not approved (failed to show effect in trials) [1.5.5]
Bipolar Mania	Not approved	Approved [1.4.2]
MDD (Add-On)	Not approved	Approved [1.4.2]
Common Side Effects	Sleepiness, dizziness, nausea, dry mouth [1.3.2]	Restlessness (akathisia), tremors, indigestion, insomnia [1.4.4, 1.2.1]
Metabolic Risk	Lower risk of weight gain and metabolic changes [1.5.1, 1.3.7]	Moderate risk of metabolic changes and weight gain [1.4.3]
Movement Disorders	Lower risk of extrapyramidal symptoms (EPS) [1.2.3]	Higher risk of akathisia and EPS [1.2.1]
Dosing	Once daily 42 mg with food [1.3.6]	Once daily 1.5 mg to 6 mg [1.2.1]
Half-Life	Shorter (18 hours) [1.2.4]	Very long (up to 3 weeks for active metabolite) [1.4.6]

Efficacy, Safety, and Tolerability

Both medications carry a boxed warning, the most serious warning from the FDA, regarding increased mortality in elderly patients with dementia-related psychosis and an increased risk of suicidal thoughts and behaviors in young adults [1.2.2, 1.3.3, 1.4.3].

In a review that analyzed data from several antipsychotic studies, Caplyta was rated second for overall tolerability, while Vraylar was rated the least tolerable, largely due to side effects like akathisia [1.5.1]. In terms of efficacy in that same review, Caplyta was ranked higher than Vraylar [1.5.1]. However, both have been proven to be more effective than a placebo in their respective clinical trials [1.5.1]. The choice often comes down to balancing efficacy for a specific condition against the patient's sensitivity to potential side effects.

For a patient highly concerned about metabolic side effects like weight gain or diabetes, Caplyta may present a better option [1.5.1]. For a patient who needs treatment for bipolar mania or requires an add-on for depression, Vraylar is the indicated choice [1.2.2].

Cost and Accessibility

Both Caplyta and Vraylar are expensive brand-name drugs [1.2.2]. Without insurance, a one-month supply of either can cost over $1,500 [1.2.2, 1.7.3]. However, both manufacturers offer patient assistance programs and savings cards for commercially insured patients, which can significantly reduce out-of-pocket costs [1.6.1, 1.7.1]. For eligible patients, a Vraylar savings card may lower the cost to as little as $5 per month, while a Caplyta card may bring it to $15 after the first two fills [1.6.1, 1.7.1]. Coverage through Medicare and Medicaid is generally available but may require prior authorization [1.6.2, 1.7.2].

Conclusion: Which is Better?

The determination of whether Caplyta or Vraylar is "better" is entirely dependent on the individual patient's diagnosis, symptom profile, medical history, and tolerance for specific side effects. There is no universally superior option.

Caplyta may be preferred for individuals with bipolar II depression or for those where metabolic side effects and movement disorders are a primary concern [1.2.3, 1.5.1]. Vraylar offers versatility with its approval for bipolar mania and as an add-on for major depression, making it a valuable tool for a different set of clinical needs [1.4.2].

The most critical step is a thorough discussion with a healthcare provider who can weigh these factors and monitor the patient's response to treatment. For more information on these conditions, consult an authoritative source like the National Institute of Mental Health (NIMH).

Frequently Asked Questions

Can I take Vraylar for bipolar II depression?

Vraylar is not FDA-approved for bipolar II depression. In clinical trials, it failed to show a significant effect for this condition [1.5.5]. Caplyta, however, is approved for depressive episodes in both bipolar I and II disorder [1.2.3].

Which medication is more likely to cause weight gain, Caplyta or Vraylar?

While both can cause weight gain, Caplyta is generally associated with a lower risk of weight gain and other metabolic changes compared to many other antipsychotics, including Vraylar [1.5.1, 1.3.2].

What is akathisia and which drug is more likely to cause it?

Akathisia is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion. Vraylar has a higher reported incidence of akathisia compared to Caplyta [1.2.1, 1.2.2].

Do I need to titrate the dose for Caplyta or Vraylar?

Caplyta is typically prescribed at its target dose of 42 mg once daily without the need for titration (gradual dose increase) [1.3.6]. Vraylar's dose is variable, usually starting at 1.5 mg and potentially increasing up to 6 mg, requiring adjustments based on efficacy and tolerability [1.2.1].

How long does it take for Vraylar to leave my system after I stop taking it?

Vraylar has a very long half-life. Its active metabolites can remain in the body for several weeks after you stop taking the medication [1.4.4, 1.4.6]. This means side effects can persist for a while after discontinuation.

Are there generic versions of Caplyta or Vraylar?

No, as of late 2025, both Caplyta and Vraylar are only available as brand-name medications. There are no generic equivalents on the market [1.2.1].

Can I use a savings card for Caplyta or Vraylar if I have Medicare?

No, the manufacturer savings cards (like VRAYPAY or the Caplyta Savings Card) are generally for patients with private commercial insurance and cannot be used by those enrolled in federal or state programs like Medicare or Medicaid [1.6.2, 1.7.2].