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Clozaril Tapering (generic clozapine)

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

Last Updated on August 8, 2022 by Carol Gillette

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

Virtually all antipsychotic drugs share challenging withdrawal phenomena, which can be even more pronounced in Clozaril tapering, weaning, and titration. These difficulties are most apparent where it is not done correctly.

Clozaril tapering treatment must be done using attentive medical oversight, and adequate support — in other words, the kind of treatment provided at Alternative to Meds Center.

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Clozaril tapering (generic name clozapine) has been studied for over 2 decades, and it has been shown that Clozaril is particularly subject to dramatic withdrawal phenomena, especially in comparison to some other antipsychotic medications.1

The particular risks associated with Clozaril have resulted in strict regulations for the prescribing of Clozaril called REMS, or the Clozaril Risk Evaluation and Mitigation Strategy program, due to potential adverse drug effects such as cancers, seizures, heart damage, and others.16,34

The inherent risks of antipsychotic medication and the process of Clozaril tapering, may at first seem daunting. This can be especially true for those who have experienced or witnessed the damage that mishandling these medications can inflict. Virtually all drugs carry risks. However, antipsychotic medications historically provide perhaps the most alarming and wide range of glaring examples of the double jeopardy of not just taking them, but trying to get off them. Each of these processes can be challenging, to say the least. We have refined our programs to respect these important elements in treatment.

Tapering Guidelines for Safe Clozaril Tapering

The bullet points below are expanded further in this article. It is important to realize that antipsychotics are considered to be one of the most arduous of all drug classes to taper, so please share this information with your caregiver. The information here is not intended to be acted on without support and medical oversight.

It is our stance at Alternative to Meds Center that unsupported Clozaril tapering done without proper oversight and support is highly likely to go off the rails and should not be attempted.

Clozaril Tapering Guidelines include:
  • clozaril tapering guidelinesBegin your taper when you are stable. This would mean sleeping well, eating well, and not experiencing episodes of anger, rage, or compulsive or unmanageable behaviors.
  • Part of the preparatory steps to seriously consider would be putting in place a “Ulysses contract” for safety. This is like making a pact with someone you trust and who is willing to help you if you become resistive or noncompliant, such as a family member or close associate. Consider this assurance for your own peace of mind and that of the loved ones around you.8,15
  • Arrange to work with a prescriber who is familiar with antipsychotic withdrawal phenomena, and who is sympathetic to your situation and willing to assist.
  • Caffeine or other stimulants should be totally restricted.7,8,20
  • Also restrict stimulating or repetitive music, television, or even stimulating religious material or the like, which may contribute to over-excitement associated with surging dopamine levels as the drug is weaned.14
  • Restrict the use of recreational marijuana.9,10,17,18,19
  • Do not ingest caffeine in drinks or other products including acetaminophen, aspirin, or Tylenol© as caffeine reduces Clozaril metabolism by 14%.34
  • Regular protein-based breakfast daily can help balance blood sugar along with frequent meals (but avoid sugars/refined carbs/glutamate/MSG) throughout the day.11,12,25, 28
  • Regular cardio exercise is physiologically therapeutic.13,33
  • Ask your doctor for the lowest dose (25mg pill) or oral liquid version of Clozaril available to help configure lower dosages during the taper. The pills may need to be cut, so ask your doctor to assist for accuracy.
  • IMPORTANT:  Advise your prescriber of any other medications you are also on to avoid unexpected drug interactions. The PDR published over 60,000 words on dangerous drug interactions between clozapine and benzodiazepines, opioids, antidepressants, and hundreds of other drugs, particularly noted for heart issues, seizures, and additive sedative effects that could be life-threatening.34
  • Based on our own observations at the center, one can expect the taper to last at least 1 month for every year on Clozaril.
  • Your prescriber can advise you on how much to reduce the medication and how long to wait between cuts. These adjustments need to be correlated to the intensity, duration, or frequency of withdrawal symptoms, as well as how long you have been taking Clozaril so discuss your reactions with your doctor. As reported in the American Journal of Medicine, there are no published guidelines for antipsychotic medication withdrawal so it is important to work with your caregiver to design the plan that works best for you.27
  • It is reasonable to expect to experience withdrawal symptoms even during a slow tapering process, and these can be helpful signposts to slow down further. Keep a log of details such as when they occurred, duration, intensity, etc., to discuss with your prescriber so that incremental adjustments can be made as timely and accurately as possible.21
  • Suddenly not sleeping or eating are red flags. Discuss any such changes with your doctor.
  • Do not expect the end of the taper to go fast. At Alternative to Meds, we have observed generally that the last cuts may be the most challenging.
  • The FDA stipulates that Clozapine withdrawal must be followed up by closely monitoring white blood cell counts. Discuss and plan for this process with your prescriber.16
  • Optional: Talk with your prescriber about possibly using bridge medications if needed to get through a point of impasse, such as Depakote.

Diet and Nutrition During Clozaril Tapering

Diet and nutrition are powerful healing tools and can be extremely useful during antipsychotic tapering. Stick to a number of small meals over the day that supply adequate protein to keep blood sugar level. Regular protein-based breakfast is a good start to the day as well. Keep the refined carbs and white sugar and flour products to a minimum and use an organic, whole foods meal and snack plan that doesn’t contain glutamates or other chemicals that can be neurotoxic.11,12,24,25,28

Contracting For Safety

contracting for safetyDuring antipsychotic withdrawal, it is not uncommon for feelings of exuberance, newfound freedom, and resistance to following instructions to emerge, particularly if the taper has progressed too quickly. A super-surge of dopamine could make taking disciplined, controlled steps forward extremely difficult. Abruptly stopping the medication, even if it seems like the most logical thing you should do, could have dire consequences.8 Putting a contract for your own safety (sometimes called a Ulysses contract) in writing, signing it, and giving it to your trusted caregiver or family member before the tapering begins is a simple but effective strategy to help keep things on track. The agreement might stipulate that if you suddenly become unwilling to follow the doctor’s advice, or become bent on booking a midnight flight to Tibet, etc., you would have agreed to hospitalization or other measures to compensate and keep you safe until you can stabilize and resume the taper. Consider this an option that will help ensure your success in the long run.15,21

Restrict Stimulants and Recreational Use of Marijuana

Research is ongoing concerning psychosis associated with marijuana use. One study on animals published in the British Journal of Medicine observes that regular cannabis use depletes levels of a brain lipid called anandamide. When anandamide levels are low, the risk of persisting symptoms of psychosis increases. This would suggest that continuing marijuana use would not be recommended for a person recovering from symptoms of psychosis.9.10.17

For some time research suggested that some marijuana smokers may have certain genetic variants in their profile that likely play a role in dopamine release and dysregulation, which increases the risk of psychosis.18 Other studies have now confirmed this effect according to Di Forti et al in their report on 489 first-episode psychosis patients compared with 278 control subjects.18,19

Stimulants can also induce psychosis, including amphetamines, ADHD drugs, and even caffeine. Caffeine is normally associated with coffee consumption but is also a component of over-the-counter aspirin and other analgesics. Caffeine reduces clozapine metabolism by 14%. Avoid these and other types of stimulants during a Clozaril taper, as the effects will magnify opening up the dopamine floodgates and this is why the taper must be very slow and controlled. Adding stimulants to the mix will unnecessarily set a person up for a disaster.20,34

Reasons to Consider Safe Clozaril Tapering

As far back as 1973, we have researchers disclosing the brain damage caused by the class of drugs known as antipsychotic medications. In one example, the Menninger Clinic case, reports showed that a patient died from damage as a result of participating in an antipsychotic drug trial. The family was awarded millions of dollars as compensation in the court case. As a result, the clinic was fined, and that particular medication never received FDA approval.2 Antipsychotic drugs are well known for unpredictable side effects and concerns have been raised about their long-term effect vs benefit ratio for some individuals, who may in fact do better off antipsychotics than continuing on them for the rest of their life.6

For guidance, we also can look at research that delineates the outcomes of long-term antipsychotic treatment compared with the benefits of short-term antipsychotic treatment.29,30,31,32

Concern over Side Effects of Antipsychotics such as Clozaril

clozaril side effectsDrug-induced conditions like TD (tardive dyskinesia) and tardive dystonia, are linked directly to antipsychotic medications. And, the risk increases, according to published research,3 according to how long they were taken and at what dosage. TD (repetitive spasmodic involuntary muscle motion or painful twisting and contortions of the muscles) is almost always incurable once it develops. Tardive means slow or late-onset, pointing to the risk for development that increases with the length of time taking antipsychotic drugs such as Clozaril, Zyprexa, Abilify, and many many others.

Perhaps chilling to realize is that antipsychotic drug makers have consistently ranked in the top 10 for lawsuits relating to brain injury or death, as shown in statistics from 2004 through 2012. The fines meted out to these drugmakers are mountainous. Fines in the US alone amounted to $10 billion during this 8-year period,

To compare, Perdue was fined a relative pittance of $600 million in lawsuits due to the infamous tsunami of OxyContin injury and death cases. In the news media, the opiate crisis receives near-constant mainstream air time, (not a criticism), but the antipsychotic drug crisis receives comparative silence. Little to no coverage whatsoever. Currently, it is reported that 500,000 US citizens suffer from drug-induced tardive dyskinesia/dystonia. These conditions are only ever drug-induced and have no other cause than antipsychotic medications.4,5,6

Do Antipsychotic Medications Stop Working Over Time?

Yes over time, antipsychotic medications can become less able to suppress symptoms. These can include psychosis, schizophrenia, or major depressive episodes of Bipolar conditions. Unfortunately, when the drug stops being effective at dampening symptoms, a person’s original psychosis or other symptomology or mania may begin to surface again. This is not surprising — as effective as they are at dampening psychosis and other undesirable symptoms, antipsychotic medications are rarely thought of as curative.5,6

clozaril taperingWhat can also happen over time is that drug side effects can begin to intensify. Antipsychotics such as Clozaril cause a pretty long list of side effects. Some of these may be more intense than others, just as some persons may be more sensitive than others to certain sensations, aches, pains, etc. Side effects can include restlessness, tremor, stiffness, and other physical sensations. Emotional side effects also occur such as emotional blunting. This is where the person feels no joy or satisfaction or reward in life. Others can include a racing heartbeat, dizziness, akathisia, dry mouth, nausea, lack of appetite, drowsiness, low blood pressure, incontinence, and a host of other undesirable reactions. There are some rare but quite severe side effects that Clozaril can cause such as seizures, life-threatening allergic reactions, sudden cardiac death, strokes, and NMS. Neuroleptic malignant syndrome carries the risk of death and like TD is a drug-induced (neuroleptic means drug-induced) life-threatening condition. The symptoms of NMS to watch for are sudden fever, sweating, confusion, muscle rigidity, and rapid breathing. If not treated immediately this condition can lead to death. Originally it was thought that only 1st generation antipsychotics produced symptoms of NMS but further research has shown that 2nd generation antipsychotics can also put a person at risk of NMS and similar conditions.22,23

It may be helpful for a person to discuss with a trusted health advisor or caregiver the benefit-risk ratio of continuing to take a drug that no longer suppresses their original symptoms. This is especially pertinent where the drug is causing or could cause additional discomforts or risks to health from the side effects, such as are listed in the multiple black box warnings on Clozaril package inserts.16, 26

holistic treatments for clozaril weaningA well-planned. individually tailored holistic-based path of treatment may be a more effective choice over neuroleptic-based treatment, especially over the long term. Holistic treatments can include many therapies to help a person regain their abilities to reduce stress, comfortably socialize, interact with others in a safe and welcoming setting, increase coping skills, learn skills to manage their life well, as well as physical and emotional therapies to address and ease troubles whether mental, emotional or physical in nature.

To reduce or eliminate antipsychotics safely provides a very good first step to becoming free of the burden of pharmaceutical drugs. Then one can begin exploring non-drug-based mental health solutions (one example is orthomolecular medicine). These holistic treatments may be much more productive when the toxicity and medication issues have been reduced or eventually eliminated totally. A gentle, gradual transition is the best way to achieve natural mental health.

Alternative to Meds Center Provides Tools to Improve Natural Mental Health

natural clozaril taperingAlternative to Meds Center has been providing inpatient natural mental health services for over 15 years now with tremendous success. A wide variety of adjunctive therapies include the practice of clearing out the neurotoxic body burden. Even this single step can deliver profound change and confidence toward very tangible improvements in healthy neurochemistry. You can learn more about the amazing array of services provided inpatient for Clozaril tapering in our beautiful and accommodating facility. We are here, more than 40 qualified staff, to help you achieve your mental health goals.

Please contact us at the center for more information concerning our compassionate and welcoming inpatient Clozaril tapering program, get your insurance questions answered, and let us provide you with other hopeful, helpful information for you or for your loved one.

1. Stanilla, de Leon, Simpson “Clozapine withdrawal resulting in delirium with psychosis: a report of three cases.” NIMH, US National Library of Medicine [Internet] 1997 [cited 2022 July 21]

2. Breggin P “The Three Most Important Facts About Psychiatric Drugs” article, blog Mad In America [2017 Dec 14] [cited 2022 July 21]

3. Drug Lawsuit Source article, “List of largest Pharmaceutical Settlements in the US” [cited 2022 July 21]

4. Soumitra D, et al, “Clozapine-induced Tardive Dyskinesia.” Indian Journal of Psychological Medicine [Internet] 2017 July-Aug [cited 2022 July 21]

5. Montcrieff J “Antipsychotic Maintenance Treatment: Time to Rethink?” PLOS article, [cited 2022 July 21]

6. 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 2022 July 21]

7. Hedges DW, Woon FL, Hoopes SP. Caffeine-induced psychosis. CNS Spectr. 2009 Mar;14(3):127-9. doi: 10.1017/s1092852900020101. PMID: 19407709. [cited 2022 July 21]

8. Wang HR, Woo YS, Bahk WM. Caffeine-induced psychiatric manifestations: a review. Int Clin Psychopharmacol. 2015 Jul;30(4):179-82. doi: 10.1097/YIC.0000000000000076. PMID: 25856116.[cited 2022 July 21]

9. NIDA. 2020, May 28. Is there a link between marijuana use and psychiatric disorders? [cited 2022 July 21]

10. Henquet C, Di Forti M, Morrison P, Kuepper R, Murray RM. Gene-environment interplay between cannabis and psychosis. Schizophr Bull. 2008;34(6):1111-1121. doi:10.1093/schbul/sbn108. [cited 2022 July 21]

11. Sahoo S, Mehra A, Grover S. Acute Hyperglycemia Associated with Psychotic Symptoms in a Patient with Type 1 Diabetes Mellitus: A Case Report. Innov Clin Neurosci. 2016;13(11-12):25-27. Published 2016 Dec 1. [cited 2022 July 21]

12. Hormone Health Network Non-Diabetic Hypoglycemia EDITOR(S): Prof. Margaret Eckert-Norton, PHD, FNP-BC, CDE, Ramon Martinez, M.D., Susan Kirk, M.D. LAST UPDATED: July 2020. [cited 2022 July 21]

13. Herbert C, Meixner F, Wiebking C, Gilg V. Regular Physical Activity, Short-Term Exercise, Mental Health, and Well-Being Among University Students: The Results of an Online and a Laboratory Study. Front Psychol. 2020;11:509. Published 2020 May 26. doi:10.3389/fpsyg.2020.00509 [cited 2022 July 21]

14. Ashok AH, Marques TR, Jauhar S, Nour MM, Goodwin GM, Young AH, Howes OD. The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment. Mol Psychiatry. 2017 May;22(5):666-679. doi: 10.1038/mp.2017.16. Epub 2017 Mar 14. PMID: 28289283; PMCID: PMC5401767. [cited 2022 July 21]

15. Oxford Reference, “Overview – Ulysses contract” [published online 2022] [cited 2022 July 21]

16. Novartis FDA approved label, “Clozaril (clozapine) tablets.” [cited 2022 July 21]

17. Morgan CJ, Page E, Schaefer C, Chatten K, Manocha A, Gulati S, Curran HV, Brandner B, Leweke FM. Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms. Br J Psychiatry. 2013 May;202(5):381-2. doi: 10.1192/bjp.bp.112.121178. Epub 2013 Apr 11. PMID: 23580381. [cited 2022 July 21]

18. van Winkel R, van Beveren NJ, Simons C; Genetic Risk and Outcome of Psychosis (GROUP) Investigators. AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder. Neuropsychopharmacology. 2011 Nov;36(12):2529-37. doi: 10.1038/npp.2011.141. Epub 2011 Jul 20. PMID: 21775978; PMCID: PMC3194079. [cited 2022 July 21]

19. Di Forti M, Iyegbe C, Sallis H, Kolliakou A, Falcone MA, Paparelli A, Sirianni M, La Cascia C, Stilo SA, Marques TR, Handley R, Mondelli V, Dazzan P, Pariante C, David AS, Morgan C, Powell J, Murray RM. Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biol Psychiatry. 2012 Nov 15;72(10):811-6. doi: 10.1016/j.biopsych.2012.06.020. Epub 2012 Jul 24. PMID: 22831980. [cited 2022 July 21]

20. Henning A, Kurtom M, Espiridion ED. A Case Study of Acute Stimulant-induced Psychosis. Cureus. 2019;11(2):e4126. Published 2019 Feb 23. doi:10.7759/cureus.4126 [cited 2022 July 21]

21. Greenberg LM, Roth S, Differential Effects of Abrupt Versus Gradual Withdrawal of Chlorpromazine in Hospitalized Chronic Schizophrenic Patients American Journal of Psychiatry, 1966;123(2):221-226 [cited 2022 July 21]

22. Belvederi Murri M, Guaglianone A, Bugliani M, Calcagno P, Respino M, Serafini G, Innamorati M, Pompili M, Amore M. Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs R D. 2015 Mar;15(1):45-62. doi: 10.1007/s40268-014-0078-0. PMID: 25578944; PMCID: PMC4359181. [cited 2022 July 21]

23. Moore TJ, Furberg CD. The Harms of Antipsychotic Drugs: Evidence from Key Studies. Drug Saf. 2017 Jan;40(1):3-14. doi: 10.1007/s40264-016-0475-0. PMID: 27864791. [cited 2022 July 21]

24. Kraft B, Westman E, “Schizophrenia, gluten, and low-carbohydrate diets – a case report and review of the literature.” Nutrition and Metabolism [INTERNET] 2009 Feb 26 [cited 2022 July 21]

25. Strassnig M, Brar JS, Ganguli R, “Dietary Intake of patients with Schizophrenia.” Psychiatry Journal [INTERNET] 2005 Feb 2 [cited 2022 July 21]

26. 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;27(11):2979-2986. doi:10.1523/JNEUROSCI.5416-06.2007. [cited 2022 July 21]

27. Horowitz MA, Murray RM, Taylor D. Tapering Antipsychotic Treatment. JAMA Psychiatry. Published online August 05, 2020. doi:10.1001/jamapsychiatry.2020.2166 [cited 2022 July 21]

28. Howes, Oliver & McCutcheon, Robert & Stone, James. (2015). Glutamate and dopamine in schizophrenia: An update for the 21st century. Journal of psychopharmacology (Oxford, England). 29. 10.1177/0269881114563634. [cited 2022 July 21]

29. Harrow M, Jobe TH. Long-term antipsychotic treatment of schizophrenia: does it help or hurt over a 20-year period?. World Psychiatry. 2018;17(2):162-163. doi:10.1002/wps.20518. [cited 2022 July 21]

30. Kirsch P, Ronshausen S, Mier D, Gallhofer B. The influence of antipsychotic treatment on brain reward system reactivity in schizophrenia patients. Pharmacopsychiatry. 2007 Sep;40(5):196-8. doi: 10.1055/s-2007-984463. PMID: 17874350. [cited 2022 July 21]

31. Schmitt, A., Zink, M., Müller, B. et al. Effects of Long-Term Antipsychotic Treatment on NMDA Receptor Binding and Gene Expression of Subunits. Neurochem Res 28, 235–241 (2003). [cited 2022 July 21]

32. Steingard, S. Five Year Outcomes of Tapering Antipsychotic Drug Doses in a Community Mental Health Center. Community Ment Health J 54, 1097–1100 (2018). [cited 2022 July 21]

33. Segura-Aguilar J., Paris I. (2014) Mechanisms of Dopamine Oxidation and Parkinson’s Disease. In: Kostrzewa R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. [cited 2022 July 21]

34.& PDR (Prescribers’ Digital Reference) Clozaril (clozapine) Drug Summary [internet] [cited 2022 July 21]

Originally Published Dec 14, 2019 by Lyle Murphy

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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Clozaril Tapering (generic clozapine)
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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