Study Shows Clozapine Can Result in Serious Gastrointestinal Complications

Over 22-years, 43,132 individuals were prescribed Clozapine, 160 of which developed serious gastrointestinal hypomotility


A large observational study published in CNS Drugs sheds light on serious adverse effects of the ‘gold standard’ antipsychotic Clozapine. Researchers reviewed reports submitted over a 22-year span of patients on Clozapine reporting Clozapine-induced gastrointestinal hypomotility (CIGH).

“Clozapine’s advantages come at a cost, with an array of problematic adverse effects of which CIGH is on of the most serious,” the researchers write.

Clozapine is currently the ‘gold-standard’ for people diagnosed with “treatment-resistant Schizophrenia.” However, this drug comes with numerous side-effects. Among many others, one side effect previously reported by MIA includes the development of a stutter, which can be eliminated with a reduction in dose of the drug or by increasing dosages in smaller increments. The authors of the present study focus on clozapine-induced gastrointestinal hypomotility (CIGH) defined as “. . . an acquired state of delayed transit through the gastrointestinal tract . . . Resulting from the drug’s pharmacological actions on the nervous system”.

Previous studies have demonstrated that clozapine “. . . Has potent effects on the mammalian colon, inhibiting neurogenic and, at higher concentrations, myogenic contractions, profoundly disrupting gastrointestinal motility.” Further, between 50-80% of clozapine-treated patients have unambiguous evidence of CIGH.

From the period of 1992-2013, all reports of CIGH were examined to identify demographics, risk factors, and outcomes related to serious of life-threatening CIGH and to calculate the proportion of clozapine prescribed patients reported as having CIGH-type adverse drug reaction (ADR). Data were extracted from the New Zealand Pharmacovigilance Centre and the Australian TGA.  The study aimed to identify cases where clozapine was the causal element impacting the development of severe gastrointestinal hypomotility events. Data were analyzed for the variables age, gender, clozapine dose at onset of symptoms, duration of clozapine treatment before onset of CIGH, symptom onset date, clinical details of presentation, outcome and treatment, and other medications.

A total of 160 patients were included and were categorized as non-fatal cases (n= 131) and fatal cases (n = 29). ADR’s reported included: constipation (non-fatal = 62, fatal = 8), gastrointestinal hypomotility (non-fatal = 4, fatal = 0), fecal impaction (non-fatal = 13, fatal = 3), Ileus (non-fatal = 5, fatal = 3), paralytic ileus (non-fatal = 14, fatal = 1), Ogilvie syndrome (non-fatal = 2, fatal = 0), small bowel obstruction (non-fatal = 9, fatal = 1), pseudo small bowel obstruction (non-fatal = 1, fatal = 0), large bowel obstruction (non-fatal = 0, fatal = 1), intestinal obstruction (non-fatal = 54, fatal = 8), intestinal ischemia (non-fatal = 5, fatal = 5), megacolon (non-fatal = 8, fatal = 3), bowel perforation (non-fatal = 5, fatal= 6). Moreover, 42 (26%) were reported as recovered and 89 (56%) were reported as “unknown” or “not yet recovered”, 29 (18%) died from suspected CIGH.

The authors highlight that from the time clozapine entered the New Zealand market, 7691 people were started on the drug, of which .47% developed serious CIGH, and in Australia 35,441 individuals were prescribed clozapine and .35% developed severe CIGH. The researchers point out that these are likely underestimated due to under-reporting. Moreover, information provided on CIGH was poor with little if any reference to CIGH monitoring or treatment. The prevalence of serious CIGH was found to be 37/10,000, and the authors call for regulators and manufacturers to update their guidance to reflect current knowledge and risk.


Every-Palmer, S., & Ellis, P. M. Clozapine-Induced Gastrointestinal Hypomotility: A 22-Year Bi-National Pharmacovigilance Study of Serious or Fatal ‘Slow Gut’Reactions, and Comparison with International Drug Safety Advice. CNS Drugs, 1-11. (Abstract)

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Bernalyn Ruiz
MIA Research News Team: Bernalyn Ruiz-Yu is a Postdoctoral Fellow in the Department of Psychiatry and Biobehavioral Sciences at the University of California, Los Angeles. She completed her Ph.D. in Counseling Psychology from the University of Massachusetts Boston. Dr. Ruiz-Yu has diverse clinical expertise working with individuals, families, children, and groups with a special focus on youth at risk for psychosis. Her research focuses on adolescent serious mental illness, psychosis, stigma, and the use of sport and physical activity in our mental health treatments.


  1. When any drug has side effects, these side effects should be thoroughly explained to the patient, and then the person should be asked if they want to take meds.

    I wasn’t on clozapine, they put me on geodon. But they never even mentioned side effects.

    That is all I want. Give me a choice and let me know the consequences I might experience.

    I know this will never happen, but wouldn’t it be nice if they had to show youtube videos of people with akathisia and tardive dyskinesia BEFORE they ask the personto decide whether they want take the meds.

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    • Epthe:

      I couldn’t agree with you more. Informed consent needs an overhaul, starting with an educational component, and it should be mandatory to watch a video of someone with tardive dyskinisia and the video should be produced by psych survivors and their allies, not the drug manufacturers. This should be mandatory. At least clozapine has a registry, unlike all the other typical and atypical neurloleptics. We need better long term tracking of the individuals who are forced to take these powerful drugs who haven’t had the benefit of learning the potential, long term harm they could suffer.

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    • Clozapine is a dibenzodiazepine
      Olanzapine (Zyprexhell) is classified as a thienobenzodiazepine.

      A study has established that olanzapine and clozapine disturb the metabolism by making the body take preferentially its energy from fat (instead of privileging carbohydrates). Levels of carbohydrates remaining high, the body develops insulin resistance (causing diabetes).

      I was reading the fine print of the first Zyprexa sample pack and the doctor told me “don’t worry its safe” exact words.

      Meanwhile if I put some lead or mercury in some cookies and said try one “don’t worry its safe” and that guy got half as sick as I did from Zyprexa I would still be in prison for poisoning him.

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    • I think it’s playing word games to refer to the bad effects of a drug as “side” effects. This is an attempt to downplay how bad many of the effects are. Anything that a drug does is an effect, period, whether it’s the effect you desire or all the other things that will happen when you give the drug.

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  2. My daughter is on this drug and thankfully her doctor has incrementally tapered her dose to about 1/4 of the dosage she was originally prescribed. She is doing much better now physically and dealing with a lot of the repressed emotions that she couldn’t experience while being emotionally lobotomized.

    I hope she can be safely weaned off this drug completely without having to deal with lingering, protracted withdrawal effects or suffer a major relapse. She has worked so hard to get here.

    Thankfully, severe constipation wasn’t one of her side effects. But she had other horrible side effects, including incontinence, recurrent boils on her skin, jaw pain, vomiting, drooling, pin prick pains which I assume is called neuropathy, emotional numbing, extreme sedation (sleeping for sixteen hours a day) and headaches.

    I would give this drug and many others in the same category a big thumbs down. Hearing voices support group, liberty, employment, swimming, yoga, and mindfulness training have been much more helpful than these drugs with zero side effects.

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  3. Hi!

    I Took it for only 6 months (150 mg), am now off it for almost a year and Can say that It permanently destroys the Basis of all bodily emotions (and with that a lot of Other Things too). It is a very Strong drug and Personally i think that It is inhumane to use It. If you are a Patient, try to avoid It and Keep looking for alternatives.

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  4. LD50 test are tests to determine the lethality of a subsctance, you can find them in the Material Safety Data Sheet that a manufaturer needs to publish if it want to transport it’s product. Clozapine has a LD50 of 200 mg per kilogram bodyweight, which makes it a poison when using the Stern and Hodges scale (everything < 500 mg/kg bodyweight is a poison).

    Admistering poison is a crime and should be prosecuted, the doctor is not treating a patient, he is abusing the patient with poison. These days the lawsuits against manufaturers is about not properly informing the patient. Tomorrow's lawsuits will be about the torture the doctors practise on their patients.

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  5. MY BOYFRIEND DIED in 2003 AND HE WAS ON THIS DRUG. Sorry for the caps but I have known (and have written about it) deep in my heart that the drug did much of the damage. We’d been dating 17 years when he died.

    They couldn’t court-order him in MA, but they did it anyway via guardianship. His family got around the court-appointed guardian bit, but unfortunately he was put on the Clozaril at McLean. I hold myself fully responsible for supporting the idea of the Clozaril as well. I had been on it, too, as a Clozaril guinea pig, years previously.

    His time in the hospital in 1998 was just awful, many human rights violations. I was going to school at the time, a fiction class. I went to see him daily when he was there. The hospital should be ashamed of the disrespectful and outright cruel way they treated him. I hope McLean is reading this right now. I heard the stuff they said, too, when I went to visit….

    Anyway, he got out, got out of the halfway house too. He was still on Clozaril. That and Trilafon and Prozac from my recollection. It was August. We had tickets for the game, the Lowell Spinners where we often went. Two days before, on a Tuesday afternoon he collapsed in his own elevator and died. They said it was around 4:30 and I am guessing he was headed out to buy cigarettes.

    The drugs are responsible for making it impossible for him to quit smoking. Lithium, which he had taken in his 30’s was responsible for diabetes insipidus, and I don’t think he was even aware he had it. I remember when he first got on Clozaril he was vomiting a lot. He threw up right outside De Marneff. Served those assholes right. Then they put him on some purple pill. That and Ditropan. We used to joke about the cup of coffee ending up in his lap (the dropsies) and fishing for words. Not actually all that funny, but we had to make the best of things.

    I didn’t expect him to die. I never knew if he saw it coming. I tried to think back and remember. But I just don’t know. I loved him so much.

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  6. I read somewhere that, in psychiatry, drugs are often perceived as more “effective” when they cause the person/”patient” more suffering. Thus, now, the older neuroleptics/tranquilizers are considered “very effective, but can cause more “side effects,” and clozapine is regarded as the “gold standard” in neuroleptic/tranquilizers. This drug actually kills people often enough–or can, anyway– that there’s all kinds of red tape in most nations (I’ve read that China has dispensed with a lot of these regulations…). Instead of looking at the horrible adverse effects of this drug and looking elsewhere, it seems that psychiatrists have chosen instead to look at the pain inflicted upon the people/”patients” as some sort of “proof” that clozapine is some sort of wonder drug.

    I think this clearly shows that psychiatry is about control and punishment, especially when one starts dealing with those labeled with the more “severe mental illnesses,” especially Schizophrenia. The very label of “Schizophrenia,” in and of itself, is a tool psychiatry uses to invalidate, dehumanize, and control people.

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  7. My relative is on Clozaril . It is a very expensive drug that has over 100 known side effects, including seizures. My family member has seizures, pinpoint pupils, night-blindness, tartive dylexia, teeth grinding, night sweating, excessive drooling, severe constipation,excessive sedation and recurring for fungal infections from the excessive sweating and drooling. This is an awful drug.

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