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Lybalvi Withdrawal and Natural Mental Health

Last Updated on January 22, 2024 by Carol Gillette

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

Below, we have summarized key points selected from numerous clinical studies on Lybalvi withdrawal. Lybalvi is a new kid on the block in the antipsychotic medication class. In the middle of a mental health crisis such as an episode of psychosis, or a diagnosis of Bipolar, there typically isn’t a lot of time to consider options outside of medication. After the crisis has passed, perhaps this is the time to re-evaluate treatment plans and strategies, especially where the use of Lybalvi is associated with the emergence of new and troubling symptoms.

Another potential problem is misdiagnosis which is notoriously common, about 69%, according to a survey published in the Journal of Psychiatry (Edgmont).6 While there may be a time and place for antipsychotics, that may not always necessitate a lifetime of heavy medication. But coming off medication has to be done properly or one might end up back in the soup.

You will want to locate a physician who has the familiarity and confidence in proper Lybalvi withdrawal and discuss if this is a viable option for you. Never abruptly stop taking Lybalvi. Seek help and guidance to come off safely.
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Lybalvi Withdrawal Symptoms — A Dual Set to Contend With

Lybalvi is a combination of olanzapine, an atypical antipsychotic medication sold under the brand name Zyprexa©, plus samidorphan, a potent opioid receptor antagonist, or blocker. So the symptoms experienced in Lybalvi withdrawal can be dual in nature:  one set of withdrawal symptoms similar to other antipsychotics, and a different set associated with withdrawal from opioid receptor antagonists like samidorphan.

Opioid receptor blockers are typically used short-term to reverse an opiate overdose. These medications are also used longer-term for opiate and alcohol dependency. Drugs such as naloxone and naltrexone are drugs sometimes used to block the effects of opioids or alcohol as part of a strategy for addiction recovery. According to Lybalvi`s drugmaker, samidorphan was combined with olanzapine to help prevent the substantial weight gain which is typical with olanzapine. Although Lybalvi’s opioid receptor blocking is thought to reduce fat accumulation, it is strongly contra-indicated in patients concurrently using opioids or while coming off opioids. Lybalvi can precipitate severe opioid cessation symptoms in persons dependent on opioids. Because it does not enhance the reward centers, Lybalvi is not considered a drug that is prone to abuse.7

lybalvi withdrawalOlanzapine and Lybalvi are similar in their efficacy and safety profiles in patients diagnosed with schizophrenia or BiPolar 1 disorder. Lybalvi is associated with excess sleepiness, dry mouth, and weight gain, which was found to be 2% less than olanzapine alone in drug trials. Lybalvi and olanzapine both increased appetite, but Lybalvi to a lesser degree. Olanzapine is structurally very similar to clozapine, and similarities in withdrawal have been cited in clinical case reports. Some Lybalvi withdrawals and drug adverse effects are quite similar. It is the timing of when these present that can help distinguish whether they are symptoms of the cessation process. The withdrawal symptoms (even after a slight reduction) are often misdiagnosed as relapse or some new mental illness that is emerging. The temporal relationship will help inform which it is. The following list of Lybalvi withdrawal symptoms may not be complete, as there are limited studies available at the current time.

Lybalvi withdrawal symptoms can include:
  • Patients taking opioids and interrupting or stopping Lybalvi are especially at risk for overdose and hospitalization if opioids are continued or resumed during Lybalvi withdrawal.8
  • Infants born to mothers taking Lybalvi in the third trimester are prone to agitation, tremors, breathing difficulties, stiffness in muscles, decreased muscle strength, feeding disorder, and excessive sleepiness. Some infants require lengthy hospitalization to recover.
  • Withdrawal-emergent psychosis, particularly if Lybalvi withdrawal is abrupt, can be more severe than pretreatment featuring illusions, hallucinations, and catatonia.9,11,17
  • Spasmodic movements of the eye, mostly upward but also downward or lateral, may last for minutes or hours.10
  • Spasmodic repetitive muscle movements (dystonias, dyskinesias, hyperkinesis) 12,16,18
  • Withdrawal-emergent tardive dyskinesia 16
  • Ataxia — weakness in muscles causing clumsy movements and poor control 12
  • Gastrointestinal:  nausea, vomiting, abdominal pain, diarrhea, anorexia 12,13
  • Insomnia
  • Physiological:  dry mucous membranes, sweating, headache, myalgia (muscle aches, soreness)
  • Paresthesia:  burning, prickling, itching, numbness, crawling feeling under the skin13
  • Cardio:  tachycardia
  • Agitation, anxiety, tension, restlessness 16,17
  • Akathisia 17
  • Withdrawal-emergent parkinsonism featuring unstable posture, gait impairment, shaking, tremors, rigidity, and other impairments believed associated with dopamine dysregulation.15,19

Consider a Holistic Approach to Lybalvi Withdrawal

science-based holistic substance withdrawalNo one, especially someone in a weakened and fragile state should have to maneuver through Lybalvi withdrawal alone. The withdrawal process must be done very slowly. That is of paramount importance. But utilizing holistic strategies can provide a multitude of ways to greatly ease the process and make it less arduous.

At Alternative to Meds Center, we assist Lybalvi withdrawal with an abundance of holistic therapies that can soften and ease what might otherwise be unwieldy and difficult to tolerate. Coming off antipsychotic medications must be done precisely and gradually to overcome the changes related to regaining dopaminergic stability. Done in the context of the natural restoration of balance, the process becomes much easier to tolerate and less subject to erratic or unpredictable events.

Dopamine hypersensitivity is the technical name for the wild reactions that can occur in antipsychotic withdrawal as the dampening effects of drug therapy begin to lift. Just as a driver needs to carefully descend a steep slippery slope by applying adequate braking, neurotransmitter rehabilitation can be the ‘brakes’ that provide safety and confidence. At Alternative to Meds Center, many strategies help to stabilize eating, sleeping, and general mood before any dose reductions are made so that stability is the focus right from the start. Orthomolecular medicine as well as many therapeutic and evidence-based holistic therapies are used in this process.

Tips for Planning Lybalvi Withdrawal

There may be a great need for time to rest and recuperate without the pressures of work or home life. Inpatient treatment affords this time and space. If possible, plan on inpatient treatment but choose a facility that understands your goals and that you feel confident in the approach that will be used. Ask questions freely before you begin, and it may help to ask someone you trust to guide you in selecting a program you feel is a right fit for you.

Coming off heavy medication needs a group effort. Before starting the process, one should consider the advantages of putting a contract for safety in place. This is sometimes called a Ulysses contract, where you and your care partners make an agreement, in writing, and signed by you, so that if you suddenly veer from your treatment goals or decide not to follow the doctor`s orders, you understand hospitalization or the police may need to be involved for your safety and those around you. Spiraling out of control can thus be prevented by the use of such a contract, to help you keep yourself safe.20

Cautions and Concerns About Lybalvi Withdrawal

One of the biggest concerns about coming off medication is going too fast. At Alternative to Meds Center, you have over 40 professionals to coordinate with and ensure that the process is going at a tolerable and comfortable rate. Daily consultations keep your progress well-monitored so that any microchanges can be implemented easily and without delay. A wide variety of therapeutic, relaxation, and recreational opportunities as well as peer support programs are in place during your stay.

It may be wise to consider a facility like Alternative to Meds Center, which has direct access to hospitalization in the rare case that it may be needed, for any unexpected medical situations that may arise.

Many persons can eventually eliminate antipsychotic drug therapy. It may not be possible for every person to entirely eliminate their medication in a few months. We understand this and aim to reduce the dosage as much as possible while maintaining a desirable quality of life, and will coordinate with your medical caregiver so that when you return home, you can continue your program under their care to reach your end goal.

What is Lybalvi Prescribed to Treat

According to the FDA drug label, Lybalvi is approved to treat schizophrenia in persons over the age of 13, and Bipolar 1 in adults. As with all medications, off-label uses of antipsychotics are not uncommon. Some known circumstances include eating disorders, cases of extreme agitation, chemo-induced nausea, and delirium. It should be noted that Lybalvi is contraindicated in persons who are elderly and suffer from dementia, and also for anyone currently using or dependent upon opioids.2,21

Best Holistic Help at Alternative to Meds Center

lybalvi withdrawal help sedona drug rehabWe have a profound understanding and appreciation of the effort that is required for successfully achieving natural mental health. The journey can be long. But it does not need to be unduly arduous. Many of our staff have personal experience in transitioning to drug-free mental wellness and this provides them with confidence and compassion to help others reach their health goals.

Alternative to Meds Center specializes in holistic psychiatric care and wellness. Lab testing is extensively used in programming. Some of the services provided include gentle noninvasive neurotoxin removal, colon hydrotherapy, relaxation and spa services, Equine assisted therapy, dual diagnosis programs, peer support, CBT and other modes of counseling, diet modification, acupuncture services, environmental medicine, IV therapy, Qi Gong, Yoga, holistic pain management, and a wealth of others you can learn much more about on our services overview pages.

We welcome your inquiries and questions, and we will do our very best to guide and help you as you are in the decision-making phase of your treatment planning. You may have an interest in finding out about insurance and other details which we are happy to assist with. We are here to help. Contact us today for all the information you would like to receive on our world-class, truly exceptional Lybalvi withdrawal programs.


1. Dennis JA, Gittner LS, Payne JD, Nugent K. Characteristics of U.S. adults taking prescription antipsychotic medications, National Health and Nutrition Examination Survey 2013-2018. BMC Psychiatry. 2020 Oct 1;20(1):483. doi: 10.1186/s12888-020-02895-4. PMID: 33004022; PMCID: PMC7528276. [cited 2022 Oct 13]

2. FDA drug label Lybalvi (olanzapine and samidorphan) tablets for oral use [approval 2021) [cited 2022 Oct 13]

3. Chaudhary AMD, Khan MF, Dhillon SS, Naveed S. A Review of Samidorphan: A Novel Opioid Antagonist. Cureus. 2019 Jul 15;11(7):e5139. doi: 10.7759/cureus.5139. PMID: 31523568; PMCID: PMC6741386. [cited 2022 Oct 13]

4. Theriot J, Sabir S, Azadfard M. Opioid Antagonists. [Updated 2022 Jul 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Oct 13]

5. Correll CU, Newcomer JW, Silverman B, DiPetrillo L, Graham C, Jiang Y, Du Y, Simmons A, Hopkinson C, McDonnell D, Kahn RS. Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study. Am J Psychiatry. 2020 Dec 1;177(12):1168-1178. doi: 10.1176/appi.ajp.2020.19121279. Epub 2020 Aug 14. PMID: 32791894.[cited 2022 Oct 13]

6. Singh T, Rajput M. Misdiagnosis of bipolar disorder. Psychiatry (Edgmont). 2006 Oct;3(10):57-63. PMID: 20877548; PMCID: PMC2945875. [cited 2022 Oct 13]

7. Citrome L, Graham C, Simmons A, Jiang Y, Todtenkopf MS, Silverman B, DiPetrillo L, Cummings H, Sun L, McDonnell D. An Evidence-Based Review of OLZ/SAM for Treatment of Adults with Schizophrenia or Bipolar I Disorder. Neuropsychiatr Dis Treat. 2021 Sep 9;17:2885-2904. doi: 10.2147/NDT.S313840. Erratum in: Neuropsychiatr Dis Treat. 2021 Oct 15;17:3135-3136. PMID: 34526769; PMCID: PMC8437420. [cited 2022 Oct 13]

8. Alkermes Announces Commercial Availability of Lybalvi© [published online 2021] [cited 2022 Oct 13]

9. Moncrieff J. Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse. Acta Psychiatr Scand. 2006 Jul;114(1):3-13. doi: 10.1111/j.1600-0447.2006.00787.x. PMID: 16774655. [cited 2022 Oct 13]

10. Liuzzo K, Stutzman D, Murphy J. Olanzapine-Induced Withdrawal Oculogyric Crisis in an Adolescent With a Neurodevelopmental DisorderJ Pediatr Pharmacol Ther. 2020;25(5):455-458. doi:10.5863/1551-6776-25.5.455 [cited 2022 Oct 13]

11. Chouinard G, Samaha AN, Chouinard VA, Peretti CS, Kanahara N, Takase M, Iyo M. Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy. Psychother Psychosom. 2017;86(4):189-219. doi: 10.1159/000477313. Epub 2017 Jun 24. PMID: 28647739. [cited 2022 Oct 13]

12. Brandt L, Bschor T, Henssler J, et al. Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-AnalysisFront Psychiatry. 2020;11:569912. Published 2020 Sep 29. doi:10.3389/fpsyt.2020.569912 [cited 2022 Oct 13]

13. Dilsaver SC, Alessi NE. Antipsychotic withdrawal symptoms: phenomenology and pathophysiology. Acta Psychiatr Scand. 1988 Mar;77(3):241-6. doi: 10.1111/j.1600-0447.1988.tb05116.x. PMID: 2899377 [cited 2022 Oct 13]

14. Seeman P. All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2(high) receptors. CNS Neurosci Ther. 2011 Apr;17(2):118-32. doi: 10.1111/j.1755-5949.2010.00162.x. PMID: 20560996; PMCID: PMC6493870 [cited 2022 Oct 13]

15. Amore M, Zazzeri N,  Neuroleptic malignant syndrome after neuroleptic discontinuation  Elsevier Journal Vol. 19 Issue 8, Dec. 1995 p. 1323-1324 published online in Science Direct  [cited 2022 Oct 13]

16. Alblowi MA, Alosaimi FD. Tardive dyskinesia occurring in a young woman after withdrawal of an atypical antipsychotic drug. Neurosciences (Riyadh). 2015;20(4):376-379. doi:10.17712/nsj.2015.4.20150078 [cited 2022 Oct 13]

17. Keks N, Schwartz D, Hope J. Stopping and switching antipsychotic drugs. Aust Prescr. 2019 Oct;42(5):152-157. doi: 10.18773/austprescr.2019.052. Epub 2019 Oct 1. PMID: 31631928; PMCID: PMC6787301. [cited 2022 Oct 13]

18. NIH Dystonias Fact Sheet [published online ] [cited 2022 Oct 13]

19. Shrimanker I, Tadi P, Sánchez-Manso JC. Parkinsonism. [Updated 2022 Jun 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Oct 13]

20. Standing H, Lawlor R, Ulysses Contracts in psychiatric care: helping patients to prevent themselves from spiralling. [publishedéreviewed online c.2022] [cited 2022 Oct 13]

21. Thomas K, Saadabadi A. Olanzapine. [Updated 2022 May 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Oct 13]

Originally Published October 13, 2022 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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