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Rexulti Withdrawal | Tips on How to Navigate Safely

Last Updated on December 12, 2023 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

While Rexulti is classed as an antipsychotic medication, Rexulti withdrawal can involve a somewhat nuanced approach to the neurotransmitter pathways to consider, compared to other antipsychotic medications and types of medications used to treat depression or schizophrenia.

Strategies exist that can safely guide the process without undue recoil or return of symptoms. Please read further to learn more about techniques that can help you navigate the Rexulti withdrawal process, under the care of medical professionals and caregivers.

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What is Rexulti?

Rexulti (generic brexpiprazole) is classed as an atypical antipsychotic medication. In the past, antipsychotic drugs were limited in use to treat schizophrenia or schizophrenia-like symptoms. There are many drugs that fall under the atypical or second-generation category. However, Rexulti differs from some other antipsychotics because it targets serotonin receptors as well as dopamine receptors, to a lesser degree. All antipsychotic drugs target dopamine to get a reduction in mania, psychosis, or other symptoms associated with schizophrenia-like disorders.

However, doctors commonly prescribe an add-on medication like Rexulti when a patient is labeled “TRD,” meaning they are manifesting treatment-resistant depression. About half of depressed patients do not respond favorably to antidepressants.1

That means there are a lot of patients for whom doctors might decide to prescribe Rexulti when other antidepressants have not worked.4

How Does Rexulti Work?

Although the exact mechanisms of how Rexulti works are unknown, the manufacturer has stated that this antipsychotic blocks serotonin primarily, and dopamine to a lesser degree. There are many different ways in which drugs classed as antidepressants work. For instance, bupropion targets both dopamine and norepinephrine (adrenaline), but not serotonin. Prozac targets serotonin but not dopamine. 2

Today, all of the drugs classed as typical antipsychotics target dopamine receptors. The newer, or “atypical” antipsychotics such as Rexulti, Risperidone, Asenapine, and others, target dopamine plus other types of neurotransmitters which may include choline, histamine, and/or certain serotonin receptors.3

Why Prescribe an Antipsychotic Drug for Depression?

As mentioned above, about half of all depressed patients get a positive response to antidepressant medication. And, about 2/3 of patients do not achieve remission of depression using antidepressant medications. So, as is so common in pharmaceutical treatment, the typical answer is to switch to another drug, or to add another drug or several, to see if doing so will lead to a better outcome for the patient. The FDA approved Rexulti for this purpose when it was first brought to market, as well as to treat schizophrenia for patients aged 13 and up.

How to Withdraw Safely from Rexulti

The following guidelines are intended for discussion with your prescriber. It is NOT recommended to try to quit Rexulti without medical oversight. The best route is to find an inpatient center with staff who understand the mechanics of safe withdrawal, and who can provide ample support nutritionally and psychologically to ease the process. Even when inpatient care is not available to you, follow the gradual method very closely, working with your prescriber. And, practicing patience with the process is safer than trying to rush it.5

Helpful tips for safe Rexulti withdrawal can include:
  • rexulti withdrawal helpful tipsArrange to work with your prescriber to gradually reduce the dosage over an adequate period of time.
  • Bear in mind that dosages should decrease more gradually over time. To start with, your prescriber may initiate something like a 10-25% decrease of the last dose taken, followed by smaller and smaller increments as time goes forward.
  • Near the end of your withdrawal, dosages of 1/40th may be required to avoid rebound or relapse phenomena.
  • At each step-down, allow time for reactions to settle out, perhaps a week or longer will be needed.
  • Before you begin dosage reduction, have a family member or close friend stay with you if possible. You may want to call on others to help with managing chores, shopping, meal prep, driving you to the doctor, etc. while you give yourself time to rest, relax, and recuperate.
  • Before the dosage reduction commences, ensure you are sleeping and eating well.
  • Taking time off work is advisable for some weeks, or longer in some cases.
  • Follow your prescriber’s directions. Keeping a daily log of dosages and results can be helpful.
  • Stay in touch with caregivers regularly, especially if symptoms arise that concern you.
  • Research the kinds of foods and supplements that will support the body throughout the process and afterward, and have these on hand. More information is given on recommendations below.

How Important is Nutrition in Rexulti Withdrawal?

According to research published in the 2021 World Journal of Clinical Cases, the importance of proper nutrition in relation to schizophrenia and other mental health concerns cannot be overstated.6 For example, the condition of schizophrenia is associated with deficiencies in B1, 6, 9, and 12. Therefore, it is especially important in managing Rexulti withdrawal that the diet should include supplementation and foods high in these nutrients which include leafy greens, animal proteins, beans, vegetables, and dairy products.12

Fermented foods support a healthy gut microbiome. In turn, a healthy microbiome supports mental health in ways that are becoming increasingly important according to clinical trials. Therefore, it is recommended to add foods to the daily diet like yogurt and sauerkraut, and supplement with probiotics to promote and maintain a healthy gut.13 These actions can support success with Rexulti withdrawal.

The brain requires a lot of energy for its ongoing operation, neuronal integrity, and repair. But, the brain has a low storage capacity. Low-glycemic carbohydrates are recommended to provide long-lasting energy for optimum brain function. Additionally, avoiding glucose (sugars) and other fast-burning fuels will prevent the overproduction of cortisol, which is a stress-response hormone. Cortisol has a high affinity for fat, and at high levels, is a red flag for psychosis, and other mental health symptoms.

Healthy Diet and a Healthy Brain

mental emotional wellbeing requires healthy dietWhen it comes to a healthy brain, remember that this organ is composed mostly of fat. High cortisol levels will hamper Rexulti withdrawal because it is well-associated with worsening mental health symptoms.7,9 However, a diet that is rich in Omega-3 fatty acids robustly supports brain function. The body does not make its own, so adequate intake has come from foods or supplements.

Essential amino acids are proteins that act as building blocks essential for mental and physical health. Food sources and supplements are good sources of these important nutrients.

Sensitivity to wheat or other grain-based gluten is associated with psychiatric symptoms and schizophrenia and hence should be avoided. Cut out grain-based products or switch to gluten-free products to avoid possible negative reactions that may complicate your Rexulti withdrawal.7,14

If your doctor prescribed Rexulti as part of a treatment regimen for depression, you will be interested to know that deficiency in vitamin D is strongly associated with depression. Vitamin D is a fat-soluble vitamin found in fish, liver, and egg yolks. Also, vitamin D3 is available in supplement form. Exposure to sunlight is another excellent and often overlooked source of this nutrient.8,10

In this short piece, we cannot possibly cover all nutritional aspects that can support or hamper your Rexulti withdrawal, but we do encourage you to study the subject and modify the diet to your best advantage.

Will Original Symptoms Return After Rexulti Withdrawal?

Alternative to Meds Center is a holistic mental health facility. We focus on finding and addressing the root causes of mental health symptoms, rather than simply numbing the unwanted symptoms. Addressing deficiencies in nutrition, repairing a dysfunctional gut microbiome, cleansing the body of neurotoxic elements, and psychotherapy to address mental health issues such as trauma are some avenues that observably reduce and even eliminate unwanted symptoms.

If these core issues are never addressed, yes it is likely that the symptoms that a drug suppressed will return once the drug is simply stopped, with no other interventions.

Dopamine Supersensitivity and Rexulti Withdrawal

Antipsychotics suppress dopamine expression. So, when the drug is withdrawn, dopamine expression will elevate and if this occurs too rapidly, the withdrawal will be hampered by the sudden flood of dopamine. Dopamine supersensitivity is thought responsible for why many antipsychotic reduction attempts end up in a state of unmanageable chaos. Ensure your prescriber is aware of the potential consequences of dopamine supersensitivity, and will work closely with you to avoid this impediment to successful Rexulti withdrawal.14,15

Addressing root causes for symptoms is paramount in successful Rexulti withdrawal, and along with safe protocols for Rexulti withdrawal, this is our overarching mission at the center. While not every person will be able to withdraw from Rexulti 100%, the vast majority of our clients achieve success through this balanced approach to treatment.

Safety Concerns About Rexulti

While prescribing Rexulti may have been the correct medical intervention in many cases, longer-term use of heavy psychotropic drugs can cause associated safety liabilities and the drugs can stop working over time. These concerns can include significant drug side effects and impacts on health that are clinically documented.14-16

We recommend studying the FDA label for the potential problems associated with Rexulti, including suicidality, increased mortality, TD (tardive dyskinesia), NMS (neuroleptic malignant syndrome), pathological gambling and other compulsive disorders, weight gain, and many others of concern.1

Thus, these may be avoided by limiting the use of a drug like Rexulti. Safe Rexulti withdrawal is essential to avoid a cascade of problems that can worsen if Rexulti withdrawal is done too quickly or in a haphazard fashion.

Safe Rexulti Withdrawal at Alternative to Meds Center

If you are looking for inpatient treatment to safely manage your Rexulti withdrawal please take time to review all the services at the center that are provided for a safe journey to better mental health and drug-free life. We are insurance-friendly, and happy to help you research your insurance coverage and other important information that you may need in your decision-making and information-gathering process.

Please call us for any additional information that may help you in planning your safe and comfortable Rexulti withdrawal experience with us.


1. FDA Label Rexulti (brexpiprazole) tablets, for oral use [approval 2015] [cited 2023 Aug 30]

2. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:  [cited 2023 Aug 30]

3. Vinkers CH. Antipsychotica zonder dopaminereceptorblokkade [Antipsychotics with no dopamine receptor blockade; promise or hype?]. Ned Tijdschr Geneeskd. 2020 Dec 3;164:D5325. Dutch. PMID: 33332053.  [cited 2023 Aug 30]

4. Zhou, X., Keitner, G. I., Qin, B., Ravindran, A. V., Bauer, M., Del Giovane, C., Zhao, J., Liu, Y., Fang, Y., Zhang, Y., & Xie, P. (2015). Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis. The international journal of neuropsychopharmacology18(11), pyv060.  [cited 2023 Aug 30]

5. Horowitz, M. A., Jauhar, S., Natesan, S., Murray, R. M., & Taylor, D. (2021). A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse. Schizophrenia bulletin47(4), 1116–1129.  [cited 2023 Aug 30] 

6. Onaolapo, O. J., & Onaolapo, A. Y. (2021). Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment. World journal of clinical cases9(28), 8295–8311.  [cited 2023 Aug 30]

7. Raju M. S. V. K. (2017). Medical nutrition in mental health and disordersIndian journal of psychiatry59(2), 143–148.  [cited 2023 Aug 30]

8. Penckofer, S., Kouba, J., Byrn, M., & Estwing Ferrans, C. (2010). Vitamin D and depression: where is all the sunshine?Issues in mental health nursing31(6), 385–393.  [cited 2023 Aug 30]

9. Dziurkowska E, Wesolowski M. Cortisol as a Biomarker of Mental Disorder Severity. J Clin Med. 2021 Nov 8;10(21):5204. doi: 10.3390/jcm10215204. PMID: 34768724; PMCID: PMC8584322. [cited 2023 Aug 30]

10. Lamberg-Allardt C. Vitamin D in foods and as supplements. Prog Biophys Mol Biol. 2006 Sep;92(1):33-8. doi: 10.1016/j.pbiomolbio.2006.02.017. Epub 2006 Feb 28. PMID: 16618499. [cited 2023 Aug 30]

11. Jackson, J., Eaton, W., Cascella, N., Fasano, A., Santora, D., Sullivan, K., Feldman, S., Raley, H., McMahon, R. P., Carpenter, W. T., Jr, Demyanovich, H., & Kelly, D. L. (2014). Gluten sensitivity and relationship to psychiatric symptoms in people with schizophreniaSchizophrenia research159(2-3), 539–542. [cited 2023 Aug 30]

12. Hanna M, Jaqua E, Nguyen V, Clay J. B Vitamins: Functions and Uses in Medicine. Perm J. 2022 Jun 29;26(2):89-97. doi: 10.7812/TPP/21.204. Epub 2022 Jun 17. PMID: 35933667; PMCID: PMC9662251. [cited 2023 Aug 30]

13. Bell V, Ferrão J, Pimentel L, Pintado M, Fernandes T. One Health, Fermented Foods, and Gut Microbiota. Foods. 2018 Dec 3;7(12):195. doi: 10.3390/foods7120195. PMID: 30513869; PMCID: PMC6306734. [cited 2023 Aug 30]

14. Samaha AN, Seeman P, Stewart J, Rajabi H, Kapur S. “Breakthrough” dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci. 2007 Mar 14;27(11):2979-86. doi: 10.1523/JNEUROSCI.5416-06.2007. PMID: 17360921; PMCID: PMC6672560. [cited 2023 Aug 30]

15. El Hage C, Bédard AM, Samaha AN. Antipsychotic treatment leading to dopamine supersensitivity persistently alters nucleus accumbens function. Neuropharmacology. 2015 Dec;99:715-25. doi: 10.1016/j.neuropharm.2015.03.012. Epub 2015 Mar 27. PMID: 25823912. [cited 2023 Aug 30]

16. Divac N, Prostran M, Jakovcevski I, Cerovac N. Second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int. 2014;2014:656370. doi: 10.1155/2014/656370. Epub 2014 Jun 3. PMID: 24995318; PMCID: PMC4065707. [cited 2023 Aug 30]

Originally Published August 30, 2023 by Diane Ridaeus

This content has been reviewed and approved by a licensed physician.

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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Medical Disclaimer:
Nothing on this Website is intended to be taken as medical advice. The information provided on the website is intended to encourage, not replace, direct patient-health professional relationships. Always consult with your doctor before altering your medications. Adding nutritional supplements may alter the effect of medication. Any medication changes should be done only after proper evaluation and under medical supervision.

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