Vraylar (Cariprazine) Approved as Antidepressant 'Add On' - Everyday Health

Many people with major depressive disorder don't get enough relief from their symptoms despite antidepressant medication. To potentially rectify the problem, the U.S. Food and Drug Administration (FDA) has approved Vraylar (cariprazine), a so-called "add-on" or adjunctive medication that might make an antidepressant work better.

According to a press release from the pharmaceutical company AbbVie, the FDA has already approved cariprazine for the acute treatment of manic or mixed episodes associated with bipolar I disorder, for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), and for the treatment of schizophrenia.

Vraylar is part of a class of drugs known as second-generation antipsychotics (SGA) or atypical antipsychotics.

About 1 in 5 U.S. Adults Will Experience Depression at Some Point in Their Life

"As many as one in five U.S. adults will experience major depressive disorder during their lifetime, making it one of the most common mental health disorders in the U.S.," says Arif Khan, MD, an adjunct professor of psychiatry at Duke University School of Medicine in Durham, North Carolina, and a primary and coordinating investigator for one of the trials involved in the recent approval.

Major depressive disorder is a serious mental illness that affects how a person feels, thinks, and goes about their daily life, according to the Substance Abuse and Mental Health Services Administration.

It is characterized by a major depressive episode, "a period of at least two weeks when a person experienced a depressed mood or loss of interest or pleasure in daily activities, and had a majority of specified symptoms, such as problems with sleep, eating, energy, concentration, or self-worth," as described in the 2020 National Survey on Drug Use and Health (NSDUH).

The survey found that an estimated 21 million individuals in the United States, or roughly 8.4 percent, had at least one major depressive episode in the prior year. About 1 in 10 women experienced a major depressive episode in 2020, compared with about 1 in 6 men.

Vraylar Offers an Alternative to Switching Antidepressants and Starting Over

"Unfortunately, many people with major depressive disorder — approximately 50 percent — may continue to suffer from depressive symptoms despite taking an antidepressant," says Dr. Khan. For these individuals, Vraylar or another add-on medication may improve symptoms and build on any progress instead of requiring the person to switch antidepressants and start over, he says.

In the two trials used for the major depressive disorder (MDD) adjunct approval, cariprazine was deemed to improve symptoms on the basis of the average reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 and week 8 in people with MDD treated with the drug and an antidepressant. The scale includes questions about symptoms such as sadness, reduced sleep, reduced appetite, concentration difficulties, and suicidal thoughts.

Findings from the first trial were published in March 2016 in the Journal of Clinical Psychiatry.

How Does Vraylar Work?

Cariprazine is the first and only dopamine and serotonin partial agonist approved for adjunctive therapy to antidepressants for the treatment of major depressive disorder.

Although the exact way cariprazine works is unknown, scientists believe the drug helps the brain respond better to dopamine and serotonin, two chemicals in the brain that affect mood, according to Khan.

In some cases, combining medications that have different mechanisms of action can help address mood symptoms in multiple ways, he adds.

"When we were in the early stages of development for cariprazine, we focused on designing a compound that covers a range of symptoms for mental health conditions and affects the dopamine D3 receptor," said István Greiner, PhD, the research and development director at Gedeon Richter (the company that partnered with AbbVie on the drug), in the press release.

"While schizophrenia and bipolar manic and mixed episodes were the first indications [uses] in the U.S. market, we are thrilled to see the full potential of cariprazine unlocked with approvals in bipolar I depression, and now, as an antidepressant adjunct in major depressive disorder," said Dr. Greiner.

Safety and Potential Side Effects of Vraylar

Although consistently strong evidence has shown improvement for patients who take atypical antipsychotics as an add-on treatment for major depressive disorder, many patients are hesitant to add another medication to their regimen, says Khan.

"Knowledge of a safe, effective add-on medication like Vraylar — which has also been approved to treat other mental health conditions such as schizophrenia and bipolar I — can help encourage patients and their doctors to discuss and pursue all treatment options that could help the patient feel better," he says.

The most common side effects of the medication include difficulty moving or slow movements, tremors, uncontrolled body movements, restlessness and feeling like you need to move around, sleepiness, nausea, vomiting, indigestion, constipation, feeling tired, trouble sleeping, increased appetite, and dizziness, according to the prescribing information. These are not all the possible side effects of cariprazine.

It's worth noting that cariprazine is a "significantly benign" medication compared with other atypical antipsychotics, says Khan. "Second, the dose to be prescribed/used is approximately half of what you would use for patients with schizophrenia," he says.

Typically, the major concerns with this class of medication is weight gain, induction of diabetes or high cholesterol, or sleep problems; but studies have shown these are not an issue with cariprazine, notes Khan.

But he says that physicians need to watch for symptoms such as restlessness and muscle stiffness and take action if needed.

In addition, the FDA requires cariprazine to carry a special warning regarding increased mortality in elderly patients with dementia and related psychosis.

How Much Does Vraylar Cost?

The list price for a 30-day supply of Vraylar is $1,312 as of January 2022, according to the company's website. The actual cost or copay will depend on insurance coverage.

The company offers a copay program that can reduce the out-of-pocket cost.

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