Zyprexa Withdrawal Symptoms, Olanzapine Side Effects, Treatment Help

Alternative to Meds Editorial Team
Medically Reviewed by Dr John Motl MD

Zyprexa (olanzapine) withdrawal symptoms

Zyprexa withdrawal is the set of physical and mental symptoms that can appear when olanzapine is lowered or stopped, especially if it’s done quickly or without support. The most common are nausea, vomiting, insomnia, headache, dizziness, sweating, a racing heart, and anxiety. The most serious is rebound psychosis or mania.

Zyprexa withdrawal symptoms may include:

• Rebound psychosis, mania, or hallucinations: caused by dopamine supersensitivity, and sometimes more intense than before treatment, notably after long-term use.^13,29
• Nausea, vomiting, and stomach pain: can persist for days or weeks.^18,19
• Insomnia: can last days, weeks, or longer.¹⁹
• Anxiety and panic: along with restlessness and tension.^18,29
• Heavy sweating (diaphoresis).^18,29
• Rapid heartbeat at rest (tachycardia).¹⁸
• Headache.¹⁹
• Dizziness and vertigo.¹⁸
• Diarrhea.^18,29
• Muscle and tissue soreness (myalgia) in ligaments and tendons.^18,29
• Dry mucous membranes.¹⁸
• Catatonia.²⁹
• Oculogyric crisis: the eyes involuntarily roll upward.^12,13,28

Who tends to have it harder: a large 2020 review of antipsychotic withdrawal studies in Frontiers in Psychiatry found withdrawal tended to be more severe in people over 50, and more severe in women than in men.¹⁸ Long-term treatment with these drugs raises its own concerns too.²²

Withdrawal or relapse? Withdrawal symptoms and drug side effects can look like a returning or new mental illness. Caregivers need to be careful not to mistake them for one. The timing of when symptoms appear can help tell a psychotic relapse apart from a withdrawal reaction.¹⁶

What happens if you stop olanzapine suddenly?

Stopping Zyprexa abruptly can be a severe shock to the body, and the symptoms can be intolerable. That’s why the well-known warning applies: never abruptly stop taking antipsychotic medication.

Abrupt withdrawal of this class of drugs has documented medical effects, including nausea, vomiting, headache, and insomnia.¹⁹ Even after only a few weeks on Zyprexa, lowering the dose, even gradually, can bring acute symptoms that affect the whole body. The biggest concern is the brain’s dopamine system, explained below. Without proper support, coming off can trigger the same kind of crisis the drug was first prescribed for.

Without help and a good plan, Zyprexa withdrawal can be harsh. Some people stay on the drug simply to avoid getting too sick to work and cope with daily life. A slow, carefully monitored taper with trained professionals is the safer path.

Why withdrawal happens: Zyprexa and dopamine

Zyprexa appears to block dopamine at the D2 receptor, which is likely what calms manic or agitated symptoms. To adapt, the brain builds more dopamine receptors. Studies have shown increased D2 receptor binding after long-term antipsychotic treatment.⁷

• While you take it: Zyprexa holds back dopamine’s effect.
• When the dose drops: dopamine comes back to a brain with extra receptors. Even small reductions can flood those receptors and set off rapid-onset mania.
• Beyond dopamine: Zyprexa affects many other brain chemicals, so similar disruptions can happen elsewhere in the nervous system, causing unusual and unpredictable reactions.

This is why tapering off Zyprexa or any dopamine blocker has to be conservative and very slow, giving the nervous system time to return to normal function.

How long does olanzapine withdrawal last?

There’s no single timeline. It depends on how long you took Zyprexa, how fast it was reduced, and how much support you had.

• Physical symptoms: nausea, vomiting, and stomach pain can persist for days or weeks; insomnia can last days, weeks, or longer.^18,19
• Without support: after long-term use, symptoms can last weeks, months, or even years, especially when the drug was withdrawn too fast.
• The brain’s recovery: receptors that adapted to the drug have no set return-to-normal time. It depends on genetics, how long you took Zyprexa, and diet (including caffeine and other stimulants), and can take months to years.⁷

How long does Zyprexa stay in your system? Its metabolites can show up in urine for about 4–10 days. That has little to do with how long it takes to fully adjust to being off it.

Coming off Zyprexa safely

A safe Zyprexa taper is slow, supervised, and built around the person, not a fixed schedule. We recommend inpatient antipsychotic withdrawal care. At Alternative to Meds Center, it happens in a comfortable residential setting in Sedona, Arizona.

What coming off Zyprexa looks like at ATMC:

• Stabilize first. When you’re stable, eating well, and sleeping well, the slow and gentle taper begins.
• Built around you. Your taper is individualized, never one-size-fits-all.
• Adjusted as you go. Our clinical team is on site, watches how you respond, and adjusts the pace.
• Precise doses. Our medical team plans each dose step, using half tablets or liquid preparations as needed, so each step is the right size.
• Supporting your brain chemistry. Nutrient therapy, targeted supplements, and neurotransmitter support help rebalance neurochemistry.
• Treating root causes. Testing early on looks for neurotoxins such as heavy metals, pesticides, and pollutants, which are gently removed. Diet, sleep, and other contributors are addressed too.

Learn more about antipsychotic tapering and how we treat medication withdrawal.

Tapering at home vs. at ATMC

Helping a loved one come off Zyprexa

Families are often hit hardest. A person in withdrawal may be mentally fatigued or confused and may resist direction, which can make things very hard to manage. It’s difficult to watch someone you love suffer. These steps can help:

• Know the symptoms. Withdrawal can look like relapse. Timing helps tell them apart, so note when changes start.¹⁶
• Don’t let them stop suddenly. Abrupt withdrawal risks severe symptoms, including rebound mania or psychosis.^13,29
• Agree on a plan in advance. A voluntary safety agreement, sometimes called a “Ulysses contract,” can keep a taper on track if your loved one later resists following medical guidance.²⁵
• Choose care that recognizes withdrawal. If inpatient care isn’t possible, work closely with a doctor who has hospital admitting privileges and knows drug tapering.
• Be ready to slow down. If things become unstable, the taper can resume later at a slower pace, with your loved one’s cooperation.

Why the right care matters

People have reported going to the hospital with severe antipsychotic withdrawal only to find the symptoms weren’t recognized. Some are told they’re imagining things and sent home. Medical training often doesn’t cover how to recognize withdrawal or help someone safely come off a potent drug like Zyprexa, and this appears to be a worldwide problem.^6,15 In one study of 448 psychiatric inpatients in Japan, 338 medication errors occurred. More than half of all adverse drug reactions came from antipsychotics like Zyprexa, and the authors called for better patient monitoring.^14,15

Zyprexa side effects

Zyprexa’s side effects have been controversial since 2006, when leaked Eli Lilly documents reported by the New York Times described illegal off-label marketing and the company downplaying side effects to protect sales.^{2,5,6,7,8,9,10,11} Side effects are a common reason people choose to come off the drug when the negatives outweigh the benefits.

Known side effects include:^{5,7,13,17,22,23,26-29}

• Everyday effects: weight gain, tiredness, drowsiness, headache, dizziness, dry mouth, stomach pain, weakness, restlessness, and aches, especially in the arms and legs.
• Metabolic: high blood sugar, which can lead to diabetes.
• Hormonal: raised prolactin, which can stop menstrual periods or cause lactation in women, and breast growth and impotence in men.
• Movement and nerves: involuntary facial movements (tongue rolling, grimacing, lip-smacking), akathisia (intense inner restlessness that can lead to suicidality), seizures, tremors, slurred speech, and pins and needles or numbness.
• Mood and mind: suicidal thoughts, mood swings, personality changes, and memory loss.
• Sleep: sleepwalking and other parasomnias, and night terrors.
• Mouth and throat: swollen gums, mouth sores, drooling, and difficult or painful swallowing.
• Severe reactions: a life-threatening reaction with high fever, rigid muscles, heavy sweating, and confusion; DRESS (a rare, potentially fatal multi-organ reaction); yellowing of the skin or eyes (possible liver damage); sudden flu-like symptoms; and loss of bladder control.

Long-term antipsychotic use is linked to many problems, including the drugs ceasing to work over time.²²

What is Zyprexa (olanzapine) used for?

Zyprexa (olanzapine) is a second-generation atypical antipsychotic. Antipsychotics quickly dampen emotions, hallucinations, and mania, so they can help bring a crisis under control. Exactly how Zyprexa works in the brain still isn’t fully understood.

• FDA-approved uses: schizophrenia, mixed episodes of bipolar disorder, and psychosis, with age restrictions.
• Black Box warning: the FDA has issued Black Box warnings on Zyprexa, including the extended-release injectable and any product containing olanzapine. Elderly patients with dementia-related psychosis should not be prescribed olanzapine because of an increased risk of death.⁵ It should not be prescribed under age 13 due to an increased risk of suicidality.
• Lawsuits: Eli Lilly agreed to pay about $1.4 billion over off-label promotion of Zyprexa, one of the largest corporate fines in history.² Similar settlements followed for Abbott ($1.5 billion), Johnson & Johnson ($2.2 billion), Pfizer ($2.3 billion), and GlaxoSmithKline ($3 billion).^8-11

Off-label uses: Zyprexa and related products such as Zyprexa Zydis are sometimes prescribed for depression, OCD, PTSD, personality disorder, and Tourette’s syndrome in children or teens, as well as agitation and anxiety. Reviews warn there’s no strong evidence these uses work.^1,24

Other names: olanzapine is sold under many brand names worldwide, including Zyprexa Zydis, Olanzapina Arrowblue, Olanzapine Torrent, Jolyon, Dopin, Marathon, and Kozylex. It isn’t a known street drug, so it has no slang names.

Why families choose Alternative to Meds Center

Alternative to Meds Center has specialized in antipsychotic withdrawal for nearly 20 years, and our results are documented in published evidence. Many of our staff have been through similar challenges, which is why they chose this work.

We often find that other contributors to psychotic episodes were never addressed: poor diet, genetic differences, recreational drug use, poor sleep, and more. Many of these can be resolved holistically. Alongside the taper, clients receive:

• Detox support: nebulized glutathione, carefully managed sauna, colon hydrotherapy, and a clean diet free of chemicals and preservatives.
• Nutrition and testing: orthomolecular medicine, lab testing, food-grade supplements, and NAD+ IV therapy.
• Comfort and healing: counseling, acupuncture, Qi Gong, massage, Reiki, equine-assisted therapy, and art therapy. See all on our services overview.

A family’s story: this young man was labeled schizoaffective and nearly lost in the psychiatric system. His mom wouldn’t give up. At ATMC we identified food allergies, did a physiological reboot, and helped him come off antipsychotics.

Our program lasts about 60 days on average. Slow, guided tapering can help a person move to drug-free living, or to the lowest dose that still gives a satisfying quality of life.

Watch: did your prescriber tell you about Zyprexa withdrawal?

Zyprexa withdrawal FAQs

Sources:

1. Office of the Inspector General Report Medicare Atypical Antipsychotic Drug Claims for Elderly Nursing Home Residents [published online 05-04-2011] [cited 2022 Sept 15]

2. Dept. of Justice Release, Eli Lily and Company Agrees to Pay 1.415 Billion to Resolve Allegations of Off-label Promotion of Zyprexa 2009 Jan 15 [cited 2020 Jun 13]

3. Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM. Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999 Sep;37(3):177-93. doi: 10.2165/00003088-199937030-00001. PMID: 10511917. [cited 2021 May 12]

4. Mendonça FJB Júnior, Scotti L, Ishiki H, Botelho SPS, Da Silva MS, Scotti MT “Benzo- and thienobenzo- diazepines: multi-target drugs for CNS disorders” NCBI 2015 [cited 2020 Jun 13]

5. FDA drug label Zyprexa (olanzapine) [online 2009) [cited 2020 Dec 3]

6.  Bhana N, Foster RH, Olney R, Plosker GL. Olanzapine: an updated review of its use in the management of schizophrenia. Drugs. 2001;61(1):111-61. doi: 10.2165/00003495-200161010-00011. PMID: 11217867.

7. Silvestri S, Seeman MV, Negrete JC, Houle S, Shammi CM, Remington GJ, Kapur S, Zipursky RB, Wilson AA, Christensen BK, Seeman P. Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology (Berl). 2000 Oct;152(2):174-80. doi: 10.1007/s002130000532. PMID: 11057521.[cited 2022 Sept 15]

8. “GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data” justice.gov. 2012 July 2 [cited 2020 Jun 13]

9. “Justice Department Announces Largest Health Care Fraud Settlement in Its History” (PDF) justice.gov. 2009 Sep 2 [cited 2020 Jun 13]

10. “Johnson & Johnson to Pay More Than $2.2 Billion to Resolve Criminal and Civil Investigations” justice.gov. 2013 Nov 4 Nov [cited 2020 Jun 13]

11. “Abbott Labs to Pay $1.5 Billion to Resolve Criminal & Civil Investigations of Off-label Promotion of Depakote” justice.gov. 2012 May 7 [cited 2020 Jun 13]

12. Liuzzo K, Stutzman D, Murphy J. Olanzapine-Induced Withdrawal Oculogyric Crisis in an Adolescent With a Neurodevelopmental Disorder. J Pediatr Pharmacol Ther. 2020;25(5):455-458. doi:10.5863/1551-6776-25.5.455 [cited 2021 May 12]

13. 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 2021 May 12]

14. Mann K, Rothschild JM, Keohane CA, Chu JA, Bates DW. Adverse drug events and medication errors in psychiatry: methodological issues regarding identification and classification. World J Biol Psychiatry. 2008;9(1):24-33. doi: 10.1080/15622970601178056. PMID: 17853253. [cited 2021 May 12]

15. Ayani N, Sakuma M, Morimoto T, Kikuchi T, Watanabe K, Narumoto J, Fukui K. The epidemiology of adverse drug events and medication errors among psychiatric inpatients in Japan: the JADE study. BMC Psychiatry. 2016 Aug 30;16(1):303. doi: 10.1186/s12888-016-1009-0. PMID: 27577925; PMCID: PMC5004271. [cited 2021 May 12]

16. 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 2021 May12]

17. 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 2021 May12]

18. Brandt L, Bschor T, Henssler J, et al. Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis. Front Psychiatry. 2020;11:569912. Published 2020 Sep 29. doi:10.3389/fpsyt.2020.569912 [cited 2021 May 12]

19. Lacoursiere R, Spohn H, Thompson K, “Medical effects of abrupt neuroleptic withdrawal.” Comprehensive Psychiatry Vol 17 Issue 2, Mar-April 1976 [cited 2021 May12]

20. 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 2021 May 12]

21. Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013 Jul 12;3:tre-03-161-4138-1. doi: 10.7916/D88P5Z71. PMID: 23858394; PMCID: PMC3709416. [cited 2021 May 12]

22. Vijayakumar D, Jankovic J. Drug-Induced Dyskinesia, Part 2: Treatment of Tardive Dyskinesia. Drugs. 2016 May;76(7):779-87. doi: 10.1007/s40265-016-0568-1. PMID: 27091214. [cited 2021 May 12]

23. Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia?. World Psychiatry. 2018;17(2):149-160. doi:10.1002/wps.20516 [cited 2021 May 12]

24. Eisenberg Center at Oregon Health & Science University. Off -Label Use of Atypical Antipsychotic Drugs: A Summary for Clinicians and Policymakers. 2007 Jul 12. In: Comparative Effectiveness Review Summary Guides for Clinicians [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK45281/ [cited 2021 May 12]

25. Example of Ulysses Agreement for voluntary use. [online] [cited 2021 May 12]

26. National Alliance on Mental Health fact sheet, “Olanzapine(Zyprexa)” [cited 2021 May 12]

27. Kane J. Olanzapine in the long-term treatment of schizophrenia. Br J Psychiatry Suppl. 1999;(37):26-9. PMID: 10211138. [cited 2021 May 12]

28. Liuzzo K, Stutzman D, Murphy J. Olanzapine-Induced Withdrawal Oculogyric Crisis in an Adolescent With a Neurodevelopmental Disorder. J Pediatr Pharmacol Ther. 2020;25(5):455-458. doi: 10.5863/1551-6776-25.5.455. PMID: 32641917; PMCID: PMC7337127.[cited 2022 Sept 15] 

29. 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 Sept 15]

30. Klawans HL, Tanner CM, Barr A. The reversibility of “permanent” tardive dyskinesia. Clin Neuropharmacol. 1984;7(2):153-9. doi: 10.1097/00002826-198406000-00006. PMID: 6145520. [cited 2022 Sept 15] 

Originally Published Sep 13, 2018 by Diane Ridaeus

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

Dr. John Motl, M.D.

Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona.  He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine.  Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.

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Diane Ridaeus

Diane is an avid supporter and researcher of natural mental health strategies. Diane received her medical writing and science communication certification through Stanford University and has published over 3 million words on the topics of holistic health, addiction, recovery, and alternative medicine. She has proudly worked with the Alternative to Meds Center since its inception and is grateful for the opportunity to help the founding members develop this world-class center that has helped so many thousands regain natural mental health.