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Vraylar: A Diverse Tool for Mental Health

Written byDesiree Smith


Vraylar (cariprazine) was first approved by the FDA in 2015 to treat schizophrenia and bipolar disorder (Stewart, 2022). Subsequently, it received FDA approval for maintenance treatment of schizophrenia (APA, 2019), treatment of bipolar depression, and, most recently, as an adjunctive treatment for major depressive disorder. The National Institute of Mental Health (NIMH) estimates that in 2020, 21 million adults in the United States, or approximately 8.4 % of all U.S. adults, had at least one major depressive episode (National Alliance on Mental Health, 2022).

To qualify this information, this means at least 1 of 12 adults in your social circle has experienced a depressive episode in the last year. And, if you are reading this article, perhaps it was you. The purpose of this article is to have a basic understanding of how Vraylar works, review the previous indications, detail the latest indication for major depressive disorder, briefly describe common side effects, and highlight the expectations of adding Vraylar to a treatment plan.

How it Works:

If you Google “what does Vraylar do to the brain?”, Google will tell you it “helps balance the levels of neurotransmitters in your brain.” While being vaguely accurate, this explanation does not do much to expand on how it is able to address the symptoms of three significant mental disorders. To be more specific: Vraylar is categorized as an anti-manic agent or second-generation atypical antipsychotic (Stahl, 2017). The two main neurotransmitters (or chemicals) Vraylar regulates are dopamine and serotonin (Stahl, 2017).

Let's use a party as an analogy for what's happening in your brain. Any good feeling you have had in the past, present, or future can be associated with dopamine; in other words, it’s not a fun party unless you have at least one or two “dope” guests. And a well-rounded shin dig also needs serotonin, or some seriously good tunes, to set the mood, help the appetizers digest, and let the sexual (and wound) healing commence.

So now we know what we need at the party, and let’s consider our brain as the most exclusive, A-list gala. We can’t have too many Chris Farleys or young Robert Downey Jr.s in, or it will be sheer mania - so we hire a guy that looks like the Rock, but is named Vraylar, as our bouncer. Vraylar is a partial agonist, which means it works on the receptors of dopamine and serotonin in a selective, limited manner. So Vraylar is essentially at the door of your brain party, working to make sure you have the right mix of serotonin and dopamine.

Previous Indications:

As mentioned above, Vraylar was initially approved to treat schizophrenia and acute treatment of manic or mixed episodes with bipolar 1 disorder (APA, 2019). Clinical studies revealed Vraylar was superior to the placebo in treating patients with mania, negative and positive symptoms of schizophrenia, as well symptoms of severe depression (Cariprazine, 2023). "Negative" symptoms of schizophrenia (such as reduced emotional affect or trouble experiencing pleasure) may look similar to severe depression in that there is not enough dopamine or serotonin at the party.

Positive schizophrenia symptoms, including hallucinations and impulsive actions, and mania symptoms may look similar in that you are not sleeping well or potentially seeing or hearing things that no one else does. Subsequently, another study revealed Vraylar to be effective in long term treatment of schizophrenia in patients receiving 20 weeks of treatment (Stewart, 2022).

New Indication:

Since we have reviewed how Vraylar should work and previous FDA approved indications, let’s explore the latest approval for its use as an adjunct to antidepressants in major depressive disorder. Major depressive disorder, as defined by the DSM-V, is experiencing either depressed mood or loss of interest/pleasure, as well as experiencing other depressive symptoms including: unintentional weight loss or gain, insomnia/hypersomnia, psychomotor agitation/retardation, fatigue, feelings of guilt or worthlessness, decreased ability to concentrate, and/or recurrent thoughts of death (APA, 2013).

Let’s return to our big brain bonanza to see how Vraylar the Bouncer can work with others to make sure the mix of chemical guests is just right. The most popular antidepressants are selective serotonin reuptake inhibitors (SSRIs), and they perform to keep the serotonin that’s already in the party, at the party. Let’s assume the SSRIs have been inside performing their latest hit “The Blues that Won’t Quit”, and the party is just not able to get going full steam. Vraylar the Bouncer keeps the fun guests from leaving to help keep the party going.

In real life, this may look like your antidepressant is alleviating some symptoms, but you are still struggling with motivation and focus. Now, your provider suggests Vraylar to potentially address the lingering symptoms and add more chemical regulation to your brain's functioning.

Side Effects:

While additional help with lingering symptoms can be positive, no medication is without risk of side effects. Some common side effects of Vraylar (and many antipsychotics) are akathisia, restlessness, gastrointestinal distress, weight gain, sedation, tardive dyskinesia (involuntary movements), hyperglycemia (increased blood sugar), neuroleptic malignant syndrome (severe but rare), seizures (rare), and cardiovascular events in elderly people with dementia (Stewart, 2022). Akathisia, restlessness, or inability to sit still, is the most reported symptom. In comparison to other antipsychotics, weight gain (overall) is not as significant (Cariprazine, 2023). The side effects may occur over a period as Vraylar accumulates in the blood plasma (Stewart, 2022).


As with any treatment, communicate questions and concerns with your provider. Vraylar may work better for some than others, but your provider will help assess what's best for you. Vraylar does have a long half-life, meaning it stays in the system a longer time. Thus, missing a dose may not be as negatively impactful (bonus); however, if experiencing a negative side effect, it will take longer to get out of your system.

The expectation is for Vraylar to significantly reduce acute depressive symptoms and irritability. The new indication approval by the FDA creates a clearer path for your provider to offer evidence-based care to treat depression.


American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders. (5th ed.).

American Psychological Association (APA). (2019). Clinical practice guideline for the treatment of depression across three

age cohorts.

Cariprazine. UpToDate. (n.d.). Retrieved January 16, 2023, from

Keepers, G. A., Fochtmann, L. J., Anzia, J. M., Benjamin, S., Lyness, J. M., Mojtabai, R., ... & (Systematic Review). (2020). The

American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. American

Journal of Psychiatry, 177(9), 868-872.

National Alliance on Mental Illness. (2022). Mental Health by the Numbers. Retrieved January 6, 2023.


Sadock, B. J., Kaplan, H. I., & Ruiz, P. (2021). Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical

Psychiatry (12th ed.). Wolters Kluwer.

Stahl, S. (2017) The Prescriber’s Guide: Essential Psychopharmacology series. (6th ed.). Cambridge: University Press.

Stewart, J. (December 21, 2022). Vraylar FDA approval history.

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