Clozapine Side Effects

Risk of infection

The most infamous side effect of clozapine is the lowering of a certain type of white blood cell which fights infection. It results in a condition called neutropenia which can be deadly.

When this side effect was first discovered in 1975, clozapine was pulled from the market. In 1990, it was added onto the market in the US on the condition that prescribers conduct weekly blood tests on their patients and submit those results to a national database before a pharmacy could fill their prescription.

Since then, researchers and clinicians have found that the risk of neutropenia is rare: less than 1% of people who take clozapine are affected, and 90% of those cases occur within the first year of treatment.⁷ Given those findings, the federal government removed the mandated weekly blood test requirements.

It’s still important for clinicians to monitor their patients blood for neutropenia within the first 1-2 years of treatment, but doctors can use their discretion on how often that should be done for each person.

Heart Conditions

Clozapine can rarely lead to myocarditis, an inflammation of the heart, leading to irregular heartbeats or low blood pressure.¹⁰ Myocarditis is reported to affect between 0.06% and 3.88% of people who take clozapine.⁸ Risk of myocarditis increases when prescribers ramp up clozapine dosage too quickly in new patients.¹¹ A racing heartbeat, known as tachycardia, can be a symptom of inflammation of the heart. If myocarditis occurs, it typically shows up within the first two months of treatment and can be detected with blood testing. Researchers have created guidelines for managing clozapine use when these types of conditions are discovered.^12,13

Constipation

Constipation is a very common side effect of clozapine and can become a serious problem if it’s not addressed.⁹ Clozapine causes the muscles in the stomach to work more slowly, known as hypomotility. Bowel obstruction may also occur.

Tell your prescriber if you’re having abnormal bowel movements or missing bowel movements for more than two or three days.

Yes, we know this can be awkward for families who are supporting a loved one on clozapine. We’ve heard, “He won’t let me look in the toilet, what am I supposed to do?!” In these cases, it can be helpful to have a print out of the Bristol Myers stool chart that a loved one can point to.

Constipation can be well-managed with daily laxatives.³

Weight Gain

Weight gain is a common side effect across all antipsychotic medications, and it’s one of the top reasons people don’t stick to their prescription.⁴ It usually occurs rapidly within the first several weeks of treatment. But when it's managed early and proactively, overall weight gain can be limited. Researchers have found metformin, prescribed when clozapine treatment has started, can be effective at minimizing weight gain⁴, and GLP-1s are a newer class of medication that doctors may prescribe instead of, or along with, metformin.

Drooling

Drooling, especially at night time, is a common issue with clozapine. In some cases, it can lead to aspiration where too much liquid enters into your lungs which can lead to pneumonia. Research has found that atropine drops, ipratropium drops, and/or other oral medications can be effective at reducing drooling.⁵ To help manage drooling, we often recommend raising the head of your bed, placing a towel on your pillow, and reducing food and water consumption two hours before going to sleep at night.

Fatigue and Sleepiness

Another common complaint about clozapine are the feelings of fatigue and sleepiness felt especially during the first year of use. During this period, it’s common for people to sleep 10-14 hours per day. This can be frustrating for parents who are wondering why their loved one is sleeping all day, but this amount of sleep is normal – the brain is receiving much needed rest and recovery while adjusting to clozapine.

Fatigue will decrease as your prescriber works to find the minimally effective dose and tends to decline the longer you are on clozapine⁶. In some cases, they may prescribe additional medications to combat sleepiness.⁶ Ingesting clozapine at night can also relieve tiredness during the day.⁶ But, it’s important to contact your prescriber if you or your loved one are sleeping more than 14 hours per day, are very hard to wake up, or are unable to stay awake during the day.

Other Common Side Effects

At high doses, risk of seizure increases.¹⁴ Nausea and vomiting, bed wetting, and blurry vision are commonly reported. See the clozapine label for a full list of known side effects.

Warnings

While using clozapine, inform your provider if you experience any of the side effects listed above. Reach out to them as soon as possible if you experience signs of illness like fever, chills, prolonged vomiting, inability to keep water down, or you haven’t had a bowel movement in 2-3 days.

Let your doctor know when you experience common illnesses like cold, flu, or upper respiratory infections. They may need to adjust your dose.

Also reach out to your provider if you’ve missed any doses. They should help you get back on track with the correct dosage amount which might need to be adjusted. Never adjust your prescription without clinical direction.

Go to the ER if your resting heart rate is above 130 beats-per-minute (bpm), a drop in blood pressure causes you to faint or almost faint, you have a high heart rate with chest pains, shortness of breath, or swelling of ankles or feet, you have symptoms of pneumonia, acute confusion, delirium, you’re unable to stay awake, or you have suicidal or homicidal intent.

The EASE Protocol

At Doro Mind, our Chief Medical Officer, Dr. Robert Laitman, pioneered the EASE protocol for effective management of clozapine. With the ease protocol, side effects are managed early and proactively rather than waiting for them to become severe issues, and clozapine dosages are increased gradually with careful monitoring. This “slow and steady” approach helps to prevent complications for new clozapine patients.

At a Glance

Clozapine is an effective medication for those dealing with psychosis, but it’s very underutilized usually because of concern for its side effects. But awareness of those side effects and early, proactive management with the EASE protocol can significantly reduce their impact.

Common questions