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Clozaril Withdrawal Symptoms, Clozapine Side Effects, Treatment Help

Last Updated on February 2, 2024 by Carol Gillette

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

Careful Clozaril withdrawal can minimize the potential for rebound psychosis and cholinergic, dopaminergic, serotonergic, and other crises. Clozaril® (clozapine) belongs to a class of drugs called SGA’s or second-generation antipsychotics.

Used in the treatment of certain mental conditions such as schizophrenia and psychosis, Clozaril is often prescribed only after other antipsychotics did not work or caused severe side effects.

Do Your Symptoms Require Clozaril?

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Clozaril Withdrawal Symptoms

In the vast majority of cases, abrupt Clozaril withdrawal is not recommended as it will produce the most severe withdrawal responses. Gradual cessation is recommended to help alleviate this phenomenon.

Clozaril withdrawal symptoms can include:
  • Seizure-like reactions* 11
  • Newly emerging psychosis in persons with no psychiatric history of such symptoms 10
  • Rapid onset agitation 6,7
  • Severe, abnormal movements such as lurching gait, muscle spasms 7
  • Return of psychotic symptoms, high risk of relapse if withdrawal is abrupt 6,9
  • Gagging while eating or drinking 7
  • Nausea, vomiting, diarrhea 1,8
  • Irregular WBC (white blood cell) count, must be monitored while taking Clozaril and for at least 4 weeks after discontinuation 1,15
  • Cardiovascular issues (i.e., tachycardia, blood pressure fluctuations) 1,15
  • Excessive salivation (placing a towel on the pillow is recommended at night) 1
  • Headache 1,8
  • Serotonin syndrome can result during Clozapine withdrawal (see below for symptoms of serotonin syndrome in detail) 11,12,13,14,24
  • Catatonia is associated with abrupt Clozaril withdrawal.19

*Skelly et al.’s 2019 study on abrupt withdrawal from high dose Clozaril, describes the phenomenon of seizure-like activity and other severe reactions as a result of coming off too quickly. In Clozaril patients, multi-receptor influences make seizures of particular concern when compared to withdrawal from other antipsychotic medications where seizures can occur but are less prevalent.11

Clozaril Withdrawal Guidance

Clozaril can cause certain side effects and Clozaril withdrawal symptoms that may be difficult to navigate without assistance or guidance. The drug is not usually a first-line treatment choice but is more often used as an alternative choice where other prescriptions did not work or were not well tolerated due to severe reactions.

There are many important health reasons why it would be wise to research a drug before either starting or stopping a prescription drug, especially one as potent as Clozaril. Regular blood testing is mandatory with the use of Clozaril as well as during Clozaril withdrawal.17 Below you will find information on these and other topics that may be helpful in understanding more about Clozaril and what to expect during Clozaril withdrawal.

SPECIAL NOTE:  As with all leftover, expired, or unused prescription medications, please remember not to flush them or place them in regular garbage containers, and do not otherwise allow them to enter the water system in your community. Ask your local friendly pharmacist about the best way to dispose of medications so you can help protect the environment and the health of people around you.

Serotonin Syndrome and Clozaril Withdrawal

Serotonin syndrome or toxicity is a cluster of potentially life-threatening symptoms that is drug-induced. The condition can present with single or multiple serotonergic medications, resulting in too much serotonin. It can also present when abruptly discontinuing a drug such as Clozaril — this action can also flood the CNS with excessive serotonin. Serotonin syndrome can range from mild to severe requiring hospitalization to avert fatality. Symptoms can escalate quite rapidly, over one to six hours, in 30% and 60% of patients, respectively. Symptoms are classified into three main categories outlined below.12,13,14

Mental Status:  anxiety, elevated mood, hypomania, confusion, impaired consciousness, restlessness, insomnia.

Neuromuscular excitation:  seizure, agitation, rigidity, lack of muscle control, hyperreflexia, uncontrolled twitching, jerking, spastic movements, akathisia, hyperkinesis, repeating twisting motions of the neck or other muscles, ocular clonus (roving eye movement), dorsiflexion of the ankle, toes, or foot, if prolonged may progress to muscle rigidity.

Autonomic nervous system dysfunction:  cardiac collapse leading to death, tachycardia, vomiting, diarrhea, dilated pupils, tremors, incoordination, shivering, sweating, fever, hypertension, renal failure, metabolic acidosis, acute respiratory distress.

The potential severity of these symptoms that should be watched for during Clozaril withdrawal has been sufficiently researched for educated medical personnel to be alert to serotonin syndrome and the need for hospitalization immediately should it present.

What Is Clozaril (clozapine) Used For?

Clozaril is used in the treatment of certain mental disorders, where other (usually at least two) other antipsychotic medications have not worked, or where the side effects were too harsh and could not be tolerated by the patient. A candidate for a prescription of Clozaril could be someone diagnosed with conditions such as:

  • Treatment-resistant schizophrenia 1,15
  • Treatment-resistant schizoaffective disorder with a known risk for suicide.1,15
  • Please note that elderly patients with dementia-related psychosis should NOT be prescribed Clozaril (or other antipsychotic medications) due to the increased risk of death.1,15

Clozaril (clozapine) Alternative Names and Slang

Clozaril is the brand name for the active ingredient, clozapine. Other brand names include Clopine©, Clozapine Synthon©, and FazaClo©. Although the names may be different, the Clozaril withdrawal symptoms are common to other brand name versions.

Clozaril (clozapine) Side Effects

There are hundreds of known side effects of antipsychotic medications. Some of these overlap the list of Clozaril withdrawal symptoms. We will list Clozaril-specific side effects both physiological and psychological or mixed adverse effects, with the caution that this is not a complete list, as follows:

  • antipsychotic side effectsRisk of death in elderly patients with dementia (clozapine is not approved for this population)1,15
  • Agranulocytosis:  a drug-induced, life-threatening lowering of white blood cell count often marked by lethargy, fever, weakness, or other signs of infection.1,15,16,23
  • Eosinophilia:  An abnormal increase in certain (two-lobed) white blood cells, often accompanied by asthma or other allergic symptoms resulting from toxic excretions of these immune cells as the Clozaril reaction turns these cells against their host, the patient. This condition may be more prevalent in women according to the research of Banov et al published in the Journal of Clinical Psychiatry in 1993.1,15,25
  • Seizures:  patients are advised not to drive or operate machinery, etc., due to the risk of losing consciousness due to seizures on Clozaril.1,15
  • Myocarditis:  inflammation of the heart muscle, negatively affecting the electrical action and ability of the heart to pump blood. Clots can form in and around the heart leading to heart failure and death. The rate of myocarditis has been documented from 17–322 times greater in patients on Clozaril than in the general population.1,15
  • Orthostatic hypotension:  drop in blood pressure associated with collapse and respiratory failure.1,15,16
  • Cardiac events:  such as tachycardia (elevated heart rate), ischemic changes (narrowing of the arteries), myocardial infarction (stoppage of blood flow within the heart), arrhythmias (irregular slowing or speeding up of heartbeat), congestive heart failure (progressive heart disease that weakens the heart), pericarditis (inflammation of the heart lining), pericardial effusions (collection of fluid in the lining of the heart), and sudden death.1,15,16
  • Hyperglycemia:  High blood sugar level that may emerge while on Clozaril.1,15
  • Diabetes Mellitus:  A condition where the body cannot utilize (metabolize) energy from food, resulting in fatigue, weight loss, headaches, tingling or numbness in the hands and feet, etc.1,15
  • Neuroleptic Malignant Syndrome or NMS:  A potentially fatal reaction to antipsychotic medications marked by irregular or racing heartbeat and diaphoresis (heavy sweating), hyperpyrexia (body temperature over 106°F or 41.1°C), rigid muscles, and altered mental state.1,15
  • Tardive dyskinesia:  A potentially irreversible condition linked to antipsychotic medications, involving involuntary dyskinetic (jerky, spasmodic) muscle motions. The hands and feet may appear to be thrashing in a quick or dance-like manner. Motions in the face and tongue appear as rolling or brief intermittent and irregular writhing or twisting characteristics.1,15
  • Cardiomyopathy:  Refers to heart disease resulting in thickened or rigid heart muscles.1,15
  • Pulmonary embolism:  potentially fatal clotting causing a blockage in the lung which results in blockage of blood flow.1,15
  • Hepatitis:  Clozaril is associated with hepatitis whether or not a patient has had a history of liver disease before starting the drug.1,15
  • Urinary incontinence.16
  • Cognitive and Physical Motor Impairment:  Due to the sedating effects of Clozaril patients can experience significant cognitive and physical movement impairment on the drug.1,15,16
  • clozaril pregnancy side effectsWarning regarding pregnancy and nursing mothers:  Clozaril can be excreted into breast milk and should not be taken while nursing. No human studies have been performed on harm to the fetus, but the drug is not FDA recommended for mothers nursing their infant.1,15
  • Impaired CNS:  Includes adverse side effects such as sedation, akathisia, vertigo, headache, tremor, nightmares, insomnia, agitation, convulsions, rigidity, slurred speech, etc.1,15
  • Gastrointestinal:  Constipation, nausea, heartburn, abdominal pain, vomiting, diarrhea, anorexia, etc.1,15,16
  • Other adverse effects:  Include fever, rash, sexual dysfunction, respiratory issues, shortness of breath, numbness in the tongue, weight gain, shortness of breath, nasal congestion, drooling, sweating, dry mouth, visual disturbances such as blurred vision, etc.1,15,16

Additional Notes on Clozaril Withdrawal Symptoms

Several studies such as have suggested that women and the elderly are more at risk of withdrawal symptoms and certain adverse effects of Clozaril than other cohorts.21,25

Clinical research has shown that withdrawals may only emerge some weeks after abrupt Clozaril cessation, leaving some physicians unaware of the consequences for their patients of suddenly stopping Clozaril. In contrast, involuntary movement disorders, delirium, agitation, and other serious Clozaril withdrawal symptoms have been reported immediately after abruptly stopping Clozaril in some patients. These reactions are thought related to a surge in dopamine if Clozaril withdrawal is too abrupt.6

Studies published from the 1960s right up to current times all suggest that slow tapering is the very best route for easing Clozaril withdrawal.19-21

How Long does Clozaril Withdrawal Last?

A significant number of individuals stop Clozaril due to side effects that become intolerable and outweigh any perceived benefit. Compounding the problem, persons stopping Clozaril too quickly have often reported a rapid deterioration in their mental state, especially without proper guidance for gradual withdrawal. Sometimes these withdrawal symptoms are misdiagnosed as a relapse, leading to subsequent treatment errors. Clozaril is one of the most troublesome antipsychotic medications due to the severity of withdrawals that can emerge after abrupt discontinuation. This is why slow, gradual Clozaril withdrawal is the best approach.

Except in circumstances where a life-saving intervention indicates sudden cessation, as discussed in more detail below in the section entitled “Discontinuing/Quitting Clozaril—Can You Just Stop Taking Clozaril?,” the FDA advises never to abruptly stop taking an antipsychotic agent such as Clozaril.

Clozaril withdrawal symptoms can be mild or severe and may begin quite soon after forgetting a dose when tapering from Clozaril, but they can also happen after a considerable lapse of time has occurred post-discontinuation. There is no one-size-fits-all Clozaril withdrawal timeline. Constant monitoring and careful, gradual titration is considered the best practice for coming off Clozaril and other antipsychotic medications.19-21

Discontinuing/Quitting Clozaril — Can You Just Stop Taking Clozaril?

There are circumstances where immediate withdrawal of Clozaril is medically needed as a life-saving intervention. These include potentially life-threatening adverse reactions to the drug which are delineated in detail under the adverse effects section, for instance, cardiovascular compromise, risk of stroke, signs of tardive dyskinesia, and other severe reactions.

In the vast majority of cases, gradual Clozaril tapering methods are recommended for coming off Clozaril in the safest way.

Always seek medical guidance and direction from your doctor before making changes to medications.

Clozaril (clozapine) FAQs

Below you will find information concerning some of the most asked questions about Clozaril and Clozaril withdrawal. It is always recommended where possible, to research any medication as thoroughly as possible before starting or stopping. Ask your doctor for more information about any questions you may have that may be pertinent to your own unique health and medication history as well.

What does Clozaril do to the brain?

As with all psychoactive medications, there is much more that is yet to be discovered about their mechanisms of action and how they work.

clozaril impacts your primary command centerIt has been found that Clozaril binds to certain receptors in the brain and central nervous system (CNS) and that this action alters the way the body and brain receive and transmit messages and commands along nerve channels.

There are various hypotheses concerning the kinds of receptors influenced by antipsychotics such as Clozaril, and how strong or weak the reactions and interactions can be. It is proposed that Clozaril affects dopaminergic and serotonergic receptors. Adrenergic and histamine receptors are also thought to be affected. What is clear is that more research is needed in this area.1,2,15,19

Regarding the low and high moods of bipolar disorder, a potential theory to explain this phenomenon relates to the way that biological pathways of catecholamines function. Catecholamines include dopamine, norepinephrine, and adrenaline, otherwise known as excitatory neurotransmitters.

Dopamine is associated with reward, and a person experiencing an elevated sense of reward might be described as manic.

If something is present that impairs the breakdown of dopamine, it follows that an excess of dopamine would result, and subsequently, a manic state. One such impairment may stem from certain enzymes not working efficiently, as stated in a study published by the National Institute of Mental Health.3

Psychosis, schizophrenia, and other psychiatric symptoms are generally thought to be related to dopaminergic dysfunction,4,5 but other types of receptors may be likely involved such as histamine and adrenergic, for example. More research and clinical studies are needed to increase the medical community’s more exact understanding of mental disorders — their causes and best treatments.

How long does Clozapine stay In your system?

how long does clozaril stay in your systemThe drug stays in the system and can be tested as present in the urine for approximately 15 days, or around 360 hours. Based on the neuroadaptive effect and synaptic receptors that may have downregulated themselves as a result of the drug, the recalibrating time period back to premedicated states may be difficult to predict exactly. Other drugs taken simultaneously can affect the metabolism rate, as can certain genetic factors.18

When factoring in “How long does Clozaril stay in your system?” it may lead to a more pertinent question, which is, “How long are these neuroadaptive effects going to last?” There is no real obvious answer because there are several things that need to be considered, namely, individual genetics as well as external factors such as diet, duration of drug use, dosage, and similar. But it can be reasonably framed into months or even years. With the correct methods of treatment, this time dilation can be accelerated considerably. More information on this topic is given below in the “treatment” section of this article.

Treatment for Clozaril withdrawal?

Alternative to Meds Center inpatient program specializes in using holistic and natural methods for improving mental health. Where prescription drugs have not provided all the answers, or have caused unwanted adverse effects, we can help a person to safely and gently taper from them, or at least reduce them to a point of improved quality of life. Orthomolecular medicine and environmental medicine can provide practical, nutritional, and supplemental aids that can help with symptoms such as depression and can help reduce various presentations of mental disorders, mania, and psychosis, in a safe and effective way.

Dependence on psychiatric medications is sometimes compared synonymously to addiction. While the treatments for these conditions can overlap, there are also differences that must be taken into account in treating dependence that has developed when taking an antipsychotic medication, versus drug abuse and addiction. One major problem with psychiatric drugs, in general, is tolerance, when the drug stops working. Then, the use of other treatments can be effective in one’s journey to bettered mental health without piling on more medications, that often bring with them intolerable side effects. The side effects can begin to outweigh the benefits in many cases.

clozaril holistic withdrawal sedona drug rehabWe understand that dependence on a potent antipsychotic drug must be treated with caution with respect to the risks that can accompany even a slow taper. We have helped clients overcome these formidable barriers utilizing gradual Clozaril withdrawal, supported by nutrition-based, individualized, compassionate treatment methods.

Cleansing the entire system of neurotoxins is essential to neurotransmitter rehabilitation. Colon hydrotherapy and other gentle remedies are available, which could be quite helpful where certain drugs, such as antipsychotics are prone to cause severe constipation. Constipation is not only uncomfortable, but it can also rob the body nutritionally. Once resolved, clients experience great relief as the body begins to return to normal function again.

One of the most helpful treatments available to clients at Alternative to Meds Center is called holistic neurotransmitter replacement therapy. Using lab testing to isolate neurotoxic accumulations in the body, these are then purged using a highly effective but extremely gentle process of elimination. Nutritional support is also of great importance, as it gives the body what it needs to restore the neurochemical balance in a natural way. In our beautiful treatment facility, clients enjoy a comfortable retreat-styled transformative experience. We offer spa services for comfort and relaxation, equine therapy, counseling, IV therapies, and a wealth of other therapeutic treatments you can review in more depth on our services page.

We invite you to discover more about the effective and healthy protocols in use at the center for the benefit of all our clients at Alternative to Meds Center with whom we share the goal of recovery of natural mental health. Call us today for more information that is freely available to you or your loved one on request regarding our cutting-edge, safe, comfortable Clozaril withdrawal programs.


1. Novartis Pharmaceuticals Corp Clozaril Prescribing Information, 2004 November [cited 2022 Aug 1]

2. Dziedzicka-Wasylewska M1, Faron-Górecka A, Górecki A, Kuśemider M Mechanism of action of clozapine in the context of dopamine D1-D2 receptor hetero-dimerization—a working hypothesis. Abstract, NCBI Pub Med, 2008 Sep-Oct [cited 2022 Aug 1]

3. Diamond A Consequences of Variations in Genes that affect Dopamine in Prefrontal Cortex NCBI 2007 Sep 17 [cited 2022 Aug 1]

4. Kesby, J., Eyles, D., McGrath, J. et al.Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience.” Transl Psychiatry 8, 30 (2018). [cited 2022 Aug 1]

5. Kegeles LS, Abi-Dargham A, Frankle WG, Gil R, Cooper TB, Slifstein M, Hwang DR, Huang Y, Haber SN, Laruelle M. “Increased synaptic dopamine function in associative regions of the striatum in schizophrenia.” Arch Gen Psychiatry. 2010 Mar;67(3):231-9. doi: 10.1001/archgenpsychiatry.2010.10. PMID: 20194823. [cited 2022 Aug 1]

6. Stanilla JK, de Leon J, Simpson GM. Clozapine withdrawal resulting in delirium with psychosis: a report of three cases. J Clin Psychiatry. 1997 Jun;58(6):252-5. doi: 10.4088/jcp.v58n0603. PMID: 9228890. [cited 2022 Aug 1]

7. Ahmed S, Chengappa KN, Naidu VR, Baker RW, Parepally H, Schooler NR. Clozapine withdrawal-emergent dystonias and dyskinesias: a case series. J Clin Psychiatry. 1998 Sep;59(9):472-7. doi: 10.4088/jcp.v59n0906. PMID: 9771818. [cited 2022 Aug 1]

8. Shiovitz TM, Welke TL, Tigel PD, Anand R, Hartman RD, Sramek JJ, Kurtz NM, Cutler NR. Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal. Schizophr Bull. 1996;22(4):591-5. doi: 10.1093/schbul/22.4.591. PMID: 8938913. [cited 2022 Aug 1]

9. Szafrański T, Gmurkowski K. Odstawienie klozapiny. Przeglad piśmiennictwa [Clozapine withdrawal. A review]. Psychiatr Pol. 1999 Jan-Feb;33(1):51-67. Polish. PMID: 10786215. [cited 2022 Aug 1]

10. 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 Aug 1]

11. Skelly MK, Demler TL, Lee C. High-dose Clozapine Withdrawal: A Case Report and Timeline of a Single Potential Withdrawal SeizureInnov Clin Neurosci. 2019;16(7-08):22-24. Published 2019 Jul 1. [cited 2022 Aug 1]

12. Stevenson E, Schembri F, Green DM, Burns JD. Serotonin Syndrome Associated With Clozapine WithdrawalJAMA Neurol. 2013;70(8):1054–1055. doi:10.1001/jamaneurol.2013.95 [cited 2022 Aug 1]

13. Francescangeli J, Karamchandani K, Powell M, Bonavia A. The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice. Int J Mol Sci. 2019;20(9):2288. Published 2019 May 9. doi:10.3390/ijms20092288 [cited 2022 Aug 1]

14. Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future DirectionsInt J Tryptophan Res. 2019;12:1178646919873925. Published 2019 Sep 9. doi:10.1177/1178646919873925 [cited 2022 Aug 1]

15. FDA label Clozaril (revised 2014) [cited 2022 Aug 1]

16. Miller DD. Review and management of clozapine side effects. J Clin Psychiatry. 2000;61 Suppl 8:14-7; discussion 18-9. PMID: 10811238. [cited 2022 Aug 1]

17. Alphs LD, Anand R. Clozapine: the commitment to patient safety. J Clin Psychiatry. 1999;60 Suppl 12:39-42. PMID: 10372610. [cited 2022 Aug 1]

18. Clozaril (clozapine) Fact Sheet [medically reviewed Dec 1, 2020] [cited 2022 Aug 1]

19. Blackman G, Oloyede E. Clozapine discontinuation withdrawal symptoms in schizophrenia. Ther Adv Psychopharmacol. 2021 Sep 18;11:20451253211032053. doi: 10.1177/20451253211032053. PMID: 34552710; PMCID: PMC8450618. [cited 2022 Aug 1]

20. Brandt Lasse, Bschor Tom, Henssler Jonathan, Müller Martin, Hasan Alkomiet, Heinz Andreas, Gutwinski Stefan, Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis published in the Journal Frontiers in Psychiatry, Vol 11 [2020] [cited 2022 Aug 1]

21. Battegay R. Drug dependence as a criterion for differentiation of psychotropic drugs. Compr Psychiatry (1966) 7:501–9. doi: 10.1016/S0010-440X(66)80030-5 [cited 2022 Aug 1]

22. Youngren, K., Inglis, F., Pivirotto, P. et al. Clozapine Preferentially Increases Dopamine Release in the Rhesus Monkey Prefrontal Cortex Compared with the Caudate Nucleus. Neuropsychopharmacol 20, 403–412 (1999). [cited 2022 Aug 1]

23. Sedhai YR, Lamichhane A, Gupta V. Agranulocytosis. [Updated 2021 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Aug 1]

24. Williams AM, Park SH. Seizure associated with clozapine: incidence, etiology, and management. CNS Drugs. 2015 Feb;29(2):101-11. doi: 10.1007/s40263-014-0222-y. PMID: 25537107. [cited 2022 Aug 1]

25. Banov MD, Tohen M, Friedberg J. High risk of eosinophilia in women treated with clozapine. J Clin Psychiatry. 1993 Dec;54(12):466-9. PMID: 8276737.[cited 2022 Aug 1]

Originally Published on: 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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Clozaril Withdrawal Symptoms, Clozapine Side Effects, Treatment Help
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