Cariprazine: Add-On Use in Major Depression and Bipolar Depression

What cariprazine is

Cariprazine is a capsule in a class called atypical antipsychotics. Vraylar is the brand name on the current FDA label. The word antipsychotic names the class, and having one discussed for depression does not mean a person has psychosis.

One feature sets it apart in the label: cariprazine and its active breakdown products last a long time in the body, which shapes how side effects are watched for.

Exactly what the label approves

The full list of approved uses is below, and there is a difference within depression. For major depressive disorder, approval is only as an add-on to an antidepressant, not on its own. The label's depression studies included adults who had an inadequate response to 1 to 3 courses of prior antidepressant treatment. Bipolar depression is a separate approval and a separate diagnosis.

NIMH says atypical antipsychotics are sometimes used to treat bipolar depression or depression in people who have not responded to an antidepressant alone. MedlinePlus says cariprazine may be prescribed for other uses but names none, so we list no off-label uses here. To see how add-ons fit into broader care, read our overview of depression medications.

• Adjunctive therapy to antidepressants for major depressive disorder in adults.
• Depressive episodes of bipolar I disorder (bipolar depression) in adults.
• Acute treatment of manic or mixed episodes of bipolar I disorder, in adults and in young people 10 and older.
• Schizophrenia, in adults and in young people 13 and older.

How it is thought to work

The label says the mechanism is unknown. Its effect could come from acting as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and blocking serotonin 5-HT2A receptors. The label also notes it binds strongly to dopamine D3 receptors. MedlinePlus says it works by changing the activity of certain natural substances in the brain.

What taking it can be like

Time is the main thing to understand. The label says that because of the long half-life of cariprazine and its active products, changes in dose are not fully reflected in the blood for several weeks. It tells prescribers to keep watching for side effects and response for several weeks after starting and after each change.

In practice, a side effect may not appear in the first days, and you may need to stay alert to changes after a visit has passed. MedlinePlus says it may take several weeks or longer to feel the full benefit, and says not to stop taking it without talking to your doctor, even if you feel well.

In adults using it as an add-on for major depressive disorder, the label lists akathisia (a restless need to move), restlessness, fatigue, constipation, nausea, insomnia, increased appetite, dizziness and extrapyramidal symptoms, which are movement effects such as stiffness or shaking.

Boxed warnings

The label has two boxed warnings, the FDA's strongest kind.

• Older people with dementia: older adults with dementia-related psychosis treated with antipsychotic medicines are at an increased risk of death. Cariprazine is not approved for this use.
• Suicidal thoughts and behaviors: antidepressants increased these risks in children, teens and young adults in short-term studies. The label calls for close monitoring of everyone on antidepressant treatment for worsening and for new suicidal thoughts and behaviors. If you are in crisis, call or text 988, or call 911. Locascio Wellness does not provide emergency services.

Other side effects and warnings

The label also describes these risks. Tell your prescriber right away about anything new, including when it shows up weeks later.

• Neuroleptic malignant syndrome: a rare, dangerous reaction with fever, severe muscle stiffness, confusion and fast or irregular heartbeat.
• Tardive dyskinesia: movements of the face or body that a person cannot control, which can be irreversible.
• Metabolic changes: high blood sugar, changes in blood fats, and weight gain.
• Blood counts: low white blood cell counts. Report fever or signs of infection.
• Also on the label: dizziness or fainting on standing, falls, seizures, sleepiness that can affect judgment and driving, trouble cooling down in heat and trouble swallowing.
• Allergy: it is contraindicated after a hypersensitivity reaction to cariprazine. Reactions have included rash, itching, hives and swelling of the tongue, lips or face.
• Pregnancy: if you are pregnant, planning a pregnancy or breastfeeding, tell your prescriber.

Can cariprazine be managed online in Pennsylvania and New York

Reporting changes over several weeks can happen by video. Blood sugar, blood fats, weight and blood counts have to be measured outside the visit, so ask how those would be arranged. Whether it is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help, using our medication inquiry form.

A licensed psychiatrist on our team treats depression by secure video for people physically located in Pennsylvania or New York during each visit. See online depression treatment, online psychiatry in Pennsylvania and our medicines list. Our therapists do not prescribe, and they see clients in Pennsylvania, West Virginia, Arizona, Colorado and Florida, not New York. Ask us about fees and insurance.