News|Articles|September 17, 2026

What Low Doses of VRAYLAR® (Cariprazine) May Mean for Clinical Practice

PARTNER CONTENT

Sponsored by AbbVie

Public conversation around mental health has shifted from the margins to the mainstream,^1,2 reflecting a broader cultural reset in how mental health conditions are understood and prioritized. With awareness of mental health conditions increasing, more patients may be coming forward to ask about treatment, including for major depressive disorder (MDD) and bipolar I disorder (BP-I). VRAYLAR® (cariprazine) is indicated for adjunctive therapy to antidepressants for the treatment of MDD in adults, for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults, for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adult and pediatric patients 10 years of age and older, and for the treatment of schizophrenia in adult and pediatric patients 13 years of age and older. VRAYLAR is the #1 prescribed branded atypical antipsychotic*,^3,4has been prescribed by over 150,000 clinicians†⁴and used to treat over 1.8 million patients, since 2015, inclusive of all indications.† ^3,4VRAYLAR is available in 1.5 mg, 3 mg, 4.5 mg, and 6 mg capsules with two low-dosage strengths 0.5 and 0.75 mg approved for patients taking strong or moderate CYP3A4 inhibitors. VRAYLAR can be taken once a day.³

*#1 prescribed branded antipsychotic per April 2026 IQVIA data for both new-to-brand prescriptions and total prescriptions.⁴

IMPORTANT SAFETY INFORMATION

WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS AND SUICIDAL THOUGHTS AND BEHAVIORS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.

Please see additional Important Safety Information throughout.

Please also see full Prescribing Information, including Boxed Warnings, or visit https://www.rxabbvie.com/pdf/vraylar_pi.pdf

The Potential Impact and Consequences of MDD and Bipolar I Disorder

Two psychiatric disorders that impact millions of Americans each year are MDD (about 12.5% from 2020-2022) and BP-I (1.5% from 2012-2013).^5,6

Both conditions can have serious impacts on patients. Symptoms of MDD can include but are not limited to feelings of sadness, loss of interest or enjoyment, sleep disturbances, slowed thinking, and suicidal thoughts.⁷ MDD may present early in life and can follow a recurrent course, with many patients experiencing multiple episodes over time.⁸

Bipolar I disorder is characterized by a clinical course of recurring mood episodes of mania, depression, or mixed manic/depressive symptoms. Diagnosis of BP-I requires the occurrence of at least one manic episode, which may have been preceded or followed by hypomanic or major depressive episodes. Although the defining feature of BP-I is mania, patients with BP-I report spending about three times more time in depressive episodes than in manic or hypomanic episodes.^9-12 Symptoms of manic episodes can include mood elevation, increased energy, grandiosity, impulsivity, racing thoughts, reduced need for sleep, irritability, risk-taking behavior, restlessness, agitation, inflated self-confidence, increased productivity, and impaired judgement; and symptoms of depressive episodes can include depressed mood, anhedonia, changes in weight and/or sleep, fatigue, psychomotor agitation, feelings of worthlessness, diminished ability to concentrate, and suicidal ideation or behavior. These episodes can result in marked impairment in social or occupational functioning or may require hospitalization.¹³

Diagnostic Challenges in Psychiatry

Misdiagnosis remains common, particularly in BP-I, where depressive episodes may precede the first manic episode or where patients may not recognize or reveal a previous manic episode and only report their depressive symptoms.¹⁴

“Our ability to consistently and accurately diagnose these conditions is impacted by our reliance on subjective inputs, including patient-reported experiences and observable behaviors during clinical evaluation,¹⁵ and the absence of objective biological markers for psychiatric conditions,”¹⁶ explained Board-Certified Psychiatrist Dr. Greg Mattingly, who has over 30 years of experience in the field.

The days of relying on observation and subjective report alone,^17,18 however, may be coming to an end. Technology is advancing to the point where we are gaining a deeper understanding of how entire circuits function in the brain. “Mental health conditions, we are learning, are not driven by isolated cells, but by patterns of activity across connected systems that regulate mood, cognition, and behavior,”¹⁹ shared Dr. Mattingly.

Depression is thought to involve different pathophysiological mechanisms. Initial models emphasized neurochemical deficits, such as those proposed by the monoamine hypothesis, while more recent research has expanded this focus to include network and circuit-based models.²⁰

“Depression is becoming increasingly hypothesized as a condition of circuit dysfunction, and is thought to involve communication abnormalities between regions in the brain thought to be responsible for emotion, reward, and executive control.”²⁰

Advances in imaging and computational biology are also making these networks more visible and measurable.^20-22

Complexities in Managing MDD and BP-I

“In order to implement effective management of these conditions, we need treatment strategies that reflect the realities of clinical practice and individual patient needs,”^7,23,24 said Dr. Mattingly. “Another factor to consider is that patient responses to psychiatric medications are inherently variable. Differences in metabolism, symptom severity, disease course, and prior treatment history can all influence outcomes.”²⁵

VRAYLAR (cariprazine) Efficacy, Tolerability and Safety, and Dosing

VRAYLAR is proven to treat the most common forms of depression—adjunctive MDD and bipolar I depression^‡—and has a combined 10+ years of clinical and real-world experience across all approved indications.^{ll,‡,3,4,13}

While the mechanism of action of VRAYLAR is unknown, its efficacy is thought to be mediated through a combination of partial agonist activity at central dopamine D₂ and serotonin 5-HT_1A receptors and antagonist activity at serotonin 5-HT_2A receptors. It is the only partial agonist approved for MDD (adjunctive) and BP-I depressive and acute manic or mixed episodes in adults.³

The FDA-approved prescribing information for VRAYLAR includes two low doses (0.5 mg and 0.75 mg) for patients who are taking strong or moderate CYP3A4 inhibitors. The update is clinically meaningful because CYP3A4 inhibition increases exposure to VRAYLAR and its active metabolites. The low-dose options allow all VRAYLAR patients to have once-daily dosing, while giving prescribers recommended dosing to start or adjust therapy. For patients already on a stable dose of VRAYLAR, the label also provides dose modifications when a strong or moderate CYP3A4 inhibitor is introduced.³

“From a treatment-management standpoint, the low dose strengths provide once-daily dosing while expanding dose-modification flexibility,” said Dr. Mattingly. “That matters in psychiatry, where medication regimens can be complex and drug interactions can complicate care.”

Access to care is also important, and VRAYLAR is leading the way in unrestricted patient access. It has the #1 unrestricted combined coverage across all channels, inclusive of national commercial, Medicare Part D, and Medicaid, among branded oral atypical antipsychotics (excluding branded products that have available generics).^{4 ¶,#,**,††} Ninety-two percent of claims for a filled VRAYLAR prescription cost patients $10 or less. Lower out-of-pocket cost may mean patients are more likely to stay on track with their treatment.^4,26 ^{‡‡, §§}

For more information about VRAYLAR visit VraylarHCP.com.

AbbVie: Dedicated to Delivering Science that Impacts Psychiatric Disorders

Psychiatry remains one of medicine’s most complex and nuanced fields. It requires sustained research investment to better understand the biological underpinnings of psychiatric conditions. With more than three decades of experience in neuroscience, AbbVie continues to invest in research to address persistent unmet needs across psychiatric conditions.

† Since 2015. Inclusive of all indications.

^‡Most common forms of depression that include a major depressive episode (MDE) according to DSM-V

^§Starting dose is 1.5 mg/day. May increase dose to 3 mg/day on Day 15, depending on clinical response and tolerability.³

^llVRAYLAR (cariprazine) is approved in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD; approved 2022), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression; approved 2019), for the acute treatment of manic or mixed episodes associated with bipolar I disorder (approved 2015), and for the treatment of schizophrenia (approved 2015).^3,27,28

^¶Excluding branded products that have available generics.

^#Unrestricted implies no step edit.

^**Source: Managed Markets Insight and Technology, LLC, a trademark of MMIT. Database as of July 2026. Applicable to the atypical antipsychotic market basket.

†† Coverage requirements and benefit designs vary by payer and may change over time. Please consult with payers directly for the most current reimbursement policies.

^‡‡Based upon paid commercial, Medicare Part D, Medicaid, Cash/Savings Card, and Federal claims data from national providers for a filled 30-day VRAYLAR prescription for the period June 2025-May 2026. Patient’s actual out-of-pocket cost may vary depending on their insurance coverage and eligibility for support programs.

^§§The objective of the systematic literature review of 71 articles published between January 2010 and August 2020 was to assess the impact of patient drug cost-sharing on medication adherence, clinical outcomes, resource utilization, and healthcare costs. The analysis observed increased cost-sharing was associated with worse adherence (84% of studies), persistence (79% of studies), or discontinuation (58% of studies). Limitations include that the type (eg, deductible, coinsurance, and copay) and magnitude (eg, $5, $50, or >$5,000 deductible) of cost-sharing were not homogeneous and outcome definitions varied (eg, proportion of days covered, medication possession ratios, or specific thresholds for treatment adherence, etc), making comparisons across publications difficult.²⁶

IMPORTANT SAFETY INFORMATION

WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.

Contraindication: VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and reactions suggestive of angioedema.

Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic drugs, elderly patients with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities, vs placebo. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotic drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered.

Late-Occurring Adverse Reactions: Adverse reactions may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. As a result, the incidence of adverse reactions in short-term trials may not reflect the rates after longer-term exposures. Monitor for adverse reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug.

Metabolic Changes: Atypical antipsychotics, including VRAYLAR, have caused metabolic changes, such as:

Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Assess fasting glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment.
Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after starting an antipsychotic, obtain baseline fasting lipid profile and monitor periodically during treatment.
Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at baseline and frequently thereafter.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases.

Falls: VRAYLAR may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotics and recurrently for patients on long-term therapy.

Seizures: Use VRAYLAR with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle).

Body Temperature Dysregulation: Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration.

Drug Interactions: Strong and moderate CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended.

Adverse Reactions: The most common adverse reactions in adult clinical trials (≥5% and at least twice the rate of placebo) are listed below:

Adjunctive Treatment of Major Depressive Disorder:
- In 6-week, fixed-dose trials the incidences within the recommended doses (VRAYLAR 1.5 mg/day + antidepressant therapy [ADT] or 3 mg/day + ADT vs placebo + ADT) were akathisia (7%, 10% vs 2%), nausea (7%, 6% vs 3%), and insomnia (9%, 10% vs 5%).
- In one 8-week flexible-dose trial, incidences within the doses (VRAYLAR 1-2 mg/day + antidepressant therapy [ADT] or 2-4.5 mg/day + ADT vs placebo + ADT) were akathisia (8%, 23% vs 3%), restlessness (8%, 8% vs 3%), fatigue (7%, 10% vs 4%), constipation (2%, 5% vs 2%), nausea (7%, 13% vs 5%), increased appetite (2%, 5% vs 2%), dizziness (4%, 5% vs 2%), insomnia (14%, 16% vs 8%), and extrapyramidal symptoms (12%, 18% vs 5%).
Bipolar Mania: The incidences within the recommended dose range (VRAYLAR 3–6 mg/day vs placebo) were EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%), dyspepsia (7% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%).
Bipolar Depression: The incidences within the recommended doses (VRAYLAR 1.5 mg/day or 3 mg/day vs placebo) were nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%), restlessness (2%, 7% vs 3%), and EPS (4%, 6% vs 2%).
Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5–3 mg/day and 4.5–6 mg/day vs placebo) were EPS (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%).

VRAYLAR is available in 0.5 mg, 0.75 mg, 1.5 mg, 3 mg, 4.5 mg, and 6 mg capsules.

Please also see full Prescribing Information, including Boxed Warnings.

INDICATIONS AND USAGE

VRAYLAR (cariprazine) is indicated for adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults, for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults, for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adult and pediatric patients 10 years of age and older, and for the treatment of schizophrenia in adult and pediatric patients 13 years of age and older.

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