Call Mon-Sun:
1 (800) 301-3753
Alternative to Meds News & Blog Articles

Long-term Effects Rexulti (brexpiprazole) | What You Need to Know

This entry was posted in Antipsychotic and tagged on by .
Medically Reviewed Fact Checked

Last Updated on August 29, 2023 by Carol Gillette

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

Since Rexulti is a relatively new antipsychotic drug, the long-term effects of Rexulti are not yet fully understood. For nearly 20 years, Alternative to Meds Center has provided a retreat-style healing experience for anyone looking for relief using much less unpredictable measures.

Often, prescribers turned to Rexulti when other medications did not attain the results that were desired, or simply as a hopeful experiment. Alternative to Meds Center uses a much more measured and practical approach to treatment, without focusing on drugs, to eliminate unwanted symptoms.

Do Your Symptoms Require Rexulti?
rexulti long-term effects

Our long history of successful treatment has been documented in independent research which we invite you to review. Below we’ll cover an overview of the long-term effects of Rexulti and also describe the methods used at the center that have led to so much success using holistic treatments to address mental health concerns.
15 Years Experience by Professionals Who Understand Your Journey.
Up to 87 ½% Long-Term Success Rate.
Click to Call7 Days a Week

  • By completing this form, you will be added to our mailing list. You may opt out at any time.
  • Hidden
  • This field is for validation purposes and should be left unchanged.

The Clinical Trials — What is Known About the Long-Term Effects of Rexulti?

negative results rexulti clinical trialsAlthough it is classified as an antipsychotic drug, one of the common uses of Rexulti is to prescribe it on top of antidepressant medications when the antidepressants that were being used failed to get a positive change in the person. The majority of drug trials on Rexulti have been to study efficacy in treating major depressive disorder. The FDA granted approval for this use when Rexulti first appeared on the market. Notably, much research shows that only a percentage of persons with MDD adequately respond to antidepressant medications, according to a mammoth review of medical literature published in 2015 in the Journal of Psychiatry and Neuroscience.1

This body of research showed that about half of all controlled antidepressant drug trials ended up with negative results. And, that completed and attempted suicide rates actually doubled compared to the placebo group in drug trials.

Other published research has similarly shown that antidepressants are significantly associated with worsened depression and suicidality. Some researchers whose studies are funded by drug companies protest when others vilify antidepressants as too dangerous. Yet, other independent researchers claim that antidepressants should not be prescribed to anyone as their risk-to-benefit ratio is too high. Perhaps these problems inspired drug companies to look for a solution by combining an antipsychotic drug with traditional antidepressants for a better outcome.2-5

What about Rexulti Long-Term Effects in Schizophrenia Trials?

There have been numerous short-term but only a few long-term studies on Rexulti for the treatment of schizophrenia. Research published in the 2018 Journal of the Mental Health Clinician, describes 2 short-term (6-week) trials that were then extended to 52 weeks of monotherapeutic (Rexulti) schizophrenia treatment. Participants were all diagnosed with exacerbated schizophrenia, requiring hospitalization.

In the BEACON 6-week trial, 657 participants were divided into 4 groups:

  • 184 placebo
  • 120 were given 1 mg Rexulti daily
  • 186 were given 2 mg Rexulti daily
  • 184 were given 4 mg Rexulti daily

In the VECTOR 6-week trial, 623 participants were divided similarly:

  • 184 placebo
  • 90 were given .25 mg Rexulti daily
  • 182 were given 2 mg Rexulti daily
  • 180 were given 4 mg Rexulti daily

Trial results were remarkably similar. In both trials, participants reported Akathisia most frequently at 2mg and 4mg doses. Also in both of these short-term trials, weight gain doubled or tripled in all the Rexulti groups, compared to the placebo groups.

The extended 52-week study used variable dosages from 1 mg to 6 mg daily. At the end of the trial, researchers reported that only 34% of the participants completed the trial and that 58.6% of participants experienced at least one adverse event.6

The FDA drug label also describes two 6-week Rexulti schizophrenia trials reported by drug makers, with similar results to the above.

Rexulti Clinical Trials as an Adjunct to Antidepressant Medications

long-term rexulti serious risksThe FDA drug label cites a total of two 6-week-long studies combining Rexulti with antidepressant medications in patients who did not respond well to antidepressants alone. About 600 participants were treated with combined Rexulti (at varying dosages) plus an unspecified antidepressant, compared to approximately 400 participants (the study was double-blind) who were given a placebo plus their regular antidepressant medication.7

Surprisingly, a searching review of the drug label lists no positive results supporting this protocol for the treatment of depression. In addition, the antidepressant trials found that there was a greater shift from “normal” to “abnormal” for extrapyramidal and akathisia symptoms in the Rexulti group, compared to the placebo group.

These results were mirrored in the other trials in the schizophrenia population.

Of additional concern, the incidences of akathisia and restlessness increased when Rexulti dosages were increased. Below is a summary of the short-term and long-term effects of Rexulti that clinicians have reported in clinical trials.

Rexulti Long-Term Adverse Effects — Summary

The most common adverse effects that emerged in an extended 52-week-long trial that combined Rexulti with antidepressants to treat MDD were weight gain, headaches, tremors, somnolence, and akathisia. About 35% of the participants dropped out of the trial before its completion, due to these and other unspecified treatment-emergent adverse effects.

The common adverse effects of Rexulti in monotherapy closely mirror the above. In a 6-week-long trial, 58 % of the participants experienced at least one adverse effect. A summary of the known short-term and long-term effects of Rexulti is listed below.7

Short-Term and Long-Term Adverse Effects of Rexulti
  • serious long-term adverse effectsIncreased mortality including risk of stroke, cerebral adverse events, and death in elderly dementia patients
  • Worsened depression
  • Suicidality
  • Extrapyramidal side effects (EPS): tardive dyskinesia, dystonia, involuntary muscle movement
  • Neonates may suffer EPS and/or withdrawal symptoms if born to mothers taking Rexulti
  • Akathisia
  • Sedation
  • Insomnia
  • Psychosis
  • Urinary tract or other infections
  • Pathological gambling, sexual, binge eating, or other compulsive behaviors
  • Tremors
  • Somnolence
  • Headaches
  • Weight gain, metabolic dysfunction
  • Blurred vision
  • Restlessness
  • Abnormal dreams
  • Myalgia
  • Excessive salivation
  • Gastro-digestive disorders, nausea, flatulence, abdominal pain, diarrhea
  • Increase in blood prolactin
  • Seizure risk, especially in patients with a known low threshold
  • Low white blood cell count, can be fatal
  • Dizziness, and syncope (feeling faint after standing up), leading to falls and injuries
  • Body temperature dysregulation
  • Dysphagia (difficulty swallowing), choking, difficulty breathing, can be fatal
  • Cognitive and motor impairment

Rexulti Half-life

The half-life of Rexulti is reportedly 91 hours.

What is Known about Resulti’s Mechanisms of Action?

The drug label stipulates that the exact mechanics of how Rexulti works is not known. However, clinical data shows that Rexulti is more active with regard to serotonergic transmission and less so regarding its dampening effects on dopaminergic transmission. This is different than other antipsychotic medications which may only, or primarily, target (suppress) dopamine expression.1,8

A life-threatening condition known as NMS (neuro-malignant syndrome) has been reported with Rexulti as well as all other antipsychotics and medications that restrict or blockade dopamine transmission. NMS causes a rapid cascade of symptoms including sudden fever, severe muscle rigidity, disruption of mental functions, muscle dysregulation, elevated blood pressure, tachycardia (rapid heart rate), incontinence, and others.8

Can Holistic Treatment Help Avoid the Long-Term Effects of Rexulti?

A cautiously growing body of evidence and inquiry are developing that show promise for non-drug-based treatment of mental health issues such as depression and schizophrenia.

Examples include aerobic exercise, vitamin therapy, the use of probiotics to restore gut health, psychological counseling, improved social support systems, and many others.9-13

Treatment at Alternative to Meds Center

Alternative to Meds Center has focused for almost 2 decades on providing non-drug-based therapies and treatments for persons seeking relief from unwanted mental health symptoms such as depression and schizophrenia.14,15 Perhaps you are seeking holistic help to recover if the results from drug therapy were less than you had hoped. Possibly you are seeking relief from the long-term effects of Rexulti and/or other drugs.

tailored treatment sedona drug rehabWe tailor a treatment program that is highly individualized to fit the needs of the client. That will usually involve lab testing for genetic markers, and for discovering nutritional deficiencies, as well as determining any harmful accumulations over a lifetime of toxic exposures. Neurotoxicity is a prime culprit in many cases of mental distress, in our observation, and can be safely purged for relief and neurotransmitter rehabilitation. Once a person has achieved stabilization, safely eliminating the medications can then be initiated.

In a safe and peaceful environment, staffed by over 50 medical professionals, we help our clients find a path to better mental wellness by using protocols that can safely reduce and often eliminate medication. Diet modification, specific IV treatments, and supplementation along with a wealth of therapies grounded in science, and supportive psychotherapy can all be blended together for effective ways to reduce and eliminate symptoms without relying on pharmaceuticals. Based on orthomolecular principles, our educational modules provide each person with the tools that are needed to continue to support a healthy lifestyle well after they return home. Please contact us for more information if you are looking for a safe solution to the long-term effects of Rexulti and we will be happy to answer any questions you may have for yourself or for your loved one. We are here to help.


1. Hobart, M., Zhang, P., Skuban, A., Brewer, C., Hefting, N., Sanchez, R., & McQuade, R. D. (2019). A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Adjunctive Therapy in Adults With Major Depressive Disorder. Journal of clinical psychopharmacology39(3), 203–209. [cited 2023 Aug 24]

2. Blier P. (2008). Do antidepressants really work?. Journal of psychiatry & neuroscience : JPN33(2), 89–90. [cited 2023 Aug 24]

3. Khan A, Warner HA, Brown WA. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database. Arch Gen Psychiatry. 2000 Apr;57(4):311-7. doi: 10.1001/archpsyc.57.4.311. PMID: 10768687. [cited 2023 Aug 24]

4. Howland RH. Antidepressants & suicide: putting the risk in perspective. J Psychosoc Nurs Ment Health Serv. 2007 Jul;45(7):15-9. doi: 10.3928/02793695-20070701-06. PMID: 17679311. [cited 2023 Aug 24]

5. Jakobsen JC, Gluud C, Kirsch I. Should antidepressants be used for major depressive disorder? BMJ Evid Based Med. 2020 Aug;25(4):130. doi: 10.1136/bmjebm-2019-111238. Epub 2019 Sep 25. PMID: 31554608; PMCID: PMC7418603. [cited 2023 Aug 24]

6. Diefenderfer, L. A., & Iuppa, C. (2018). Brexpiprazole: A review of a new treatment option for schizophrenia and major depressive disorder. The mental health clinician7(5), 207–212.  [cited 2023 Aug 24]

7. FDA drug label Rexulti (brexpiprazole) tablets for oral use, first approval 2015 [cited 2023 Aug 24]

8. Simon LV, Hashmi MF, Callahan AL. Neuroleptic Malignant Syndrome. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: [cited 2023 Aug 24]

9. Vogel JS, van der Gaag M, Slofstra C, Knegtering H, Bruins J, Castelein S. The effect of mind-body and aerobic exercise on negative symptoms in schizophrenia: A meta-analysis. Psychiatry Res. 2019 Sep;279:295-305. doi: 10.1016/j.psychres.2019.03.012. Epub 2019 Mar 15. PMID: 30879703. [cited 2023 Aug 24]

10. Kim M, Lee Y, Kang H. Effects of Exercise on Positive Symptoms, Negative Symptoms, and Depression in Patients with Schizophrenia: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2023 Feb 20;20(4):3719. doi: 10.3390/ijerph20043719. PMID: 36834415; PMCID: PMC9967614. [cited 2023 Aug 24]

11. Zhuang Z, Yang R, Wang W, Qi L, Huang T. Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia. J Neuroinflammation. 2020 Oct 2;17(1):288. doi: 10.1186/s12974-020-01961-8. PMID: 33008395; PMCID: PMC7532639. [cited 2023 Aug 24]

12. Hoffer LJ. Vitamin therapy in schizophrenia. Isr J Psychiatry Relat Sci. 2008;45(1):3-10. PMID: 18587164. [cited 2023 Aug 24]

13. Brown HE, Roffman JL. Vitamin supplementation in the treatment of schizophrenia. CNS Drugs. 2014 Jul;28(7):611-22. doi: 10.1007/s40263-014-0172-4. PMID: 24846474; PMCID: PMC4083629. [cited 2023 Aug 24]

14. APA authors, What is Schizophrenia? published online N.D. [cited 2023 Aug 24]

15. Lang UE, Beglinger C, Schweinfurth N, Walter M, Borgwardt S. Nutritional aspects of depression. Cell Physiol Biochem. 2015;37(3):1029-43. doi: 10.1159/000430229. Epub 2015 Sep 25. PMID: 26402520.

Originally Published August 24, 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.

Social Profile: LinkedIn

View Bio

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.

We Accept Most PPO Insurance Plans for Partial Coverage of Fees

Call Now to Verify BlueCross BlueShield Cigna Aetna

Our Success Stories

Medication Withdrawal Success Stories

Can you imagine being free from medications, addictive drugs, and alcohol? This is our goal and we are proving it is possible every day!

Read All StoriesView All Videos