Clozapine (Clozaril)

What clozapine is

Clozapine is available as a generic medicine and under the brand names Clozaril and Versacloz. It works on dopamine and serotonin, two of the chemical messengers nerve cells use to communicate, helping to steady signals involved in thinking, mood, and how the brain filters experience. What sets it apart is that it can help some people when other medicines have not, and that it comes with regular blood tests as part of treatment. It comes as a tablet, a tablet that dissolves on the tongue, and a liquid.

What it treats

Your clinician might suggest clozapine for one of these, among other possible off-label uses:

• Schizophrenia that has not responded well enough to other medicines
• Lowering the risk of recurrent suicidal behavior in some people with schizophrenia or schizoaffective disorder who remain at risk

It is usually considered after a couple of other medicines have been tried. That is not a sign that things are hopeless; it is because clozapine can work when other options have not. It is not approved for behavior problems in older adults with dementia, where medicines in this group can carry serious risks. Whether it is a good fit for you depends on several factors, including your history and what you are working on. As with everything in psychiatry, that is decided case by case.

Who should not take clozapine. FDA labeling lists one firm exclusion: a past serious allergic reaction to clozapine, such as a severe skin reaction. Beyond that, the label says starting clozapine is not recommended when the infection-fighting white blood cell count is already below a set level, which is why a blood test comes before the first dose, and that people who have had a severe drop in that count on clozapine, or clozapine-related inflammation or weakening of the heart muscle, are generally not restarted on it. The label also calls for extra care with a history of seizures, serious constipation, trouble emptying the bladder, or an enlarged prostate. Those do not rule clozapine out, but your clinician needs to know about them first.

How it works

Honestly, no one knows with complete certainty how clozapine produces its benefit. What research suggests is that it works by steadying the activity of dopamine and serotonin, messengers involved in thinking, mood, and how the brain filters experience, and that for reasons not fully understood it can help some people who have not gotten enough relief from other medicines. The biology is only part of the picture: how much a medication helps, and how it feels, is individual. Two people on the same medication can have very different experiences.

How to take it

There is no single right way to take clozapine; it depends on you and your clinician. It is usually taken once or twice a day, with or without food, and the dose is built up slowly at the start to keep side effects like dizziness manageable. The regular blood tests are part of taking it: your clinician follows the results and uses them to decide whether to continue, adjust, or pause the dose. The plan you and your clinician make together is the one to follow, not a number you read online. A few general points apply broadly:

• Take it the way you and your clinician agreed, and keep up with the blood tests, even when you feel well.
• If you miss even one day of doses, do not restart at your usual dose; check with your clinician first, because clozapine has to be built back up after any interruption.
• Try not to stop on your own. Your clinician can guide any change, and stopping a medication like this is best done thoughtfully rather than all at once.
• Constipation is common with clozapine, so it helps to stay ahead of it with fluids, fiber, and movement; your clinician may suggest a stool softener. Let your clinician know promptly about constipation or any change in your usual bowel movements.
• Because clozapine can affect weight, blood sugar, and cholesterol over time, your clinician will usually check these along with your blood counts.

What to expect

This varies from person to person. Some effects can show up before the benefit does: things like drowsiness and dizziness often appear early and tend to ease as your body adjusts, while extra saliva can last longer, while the full benefit can take several weeks or more. The blood tests are most frequent at the beginning and usually spread out over time. If clozapine helps where other medicines did not, that can be worth the routine that comes with it. As always, this is case by case.

Side effects

Not everyone gets side effects, and some ease over the first weeks while others need active management. The lists below are possibilities, not certainties.

Possible more common side effects:

• Feeling drowsy or tired
• Dizziness or feeling lightheaded when standing up, especially early on
• More saliva than usual, including drooling at night
• Dry mouth
• Constipation
• A faster heartbeat
• Increased appetite and weight gain

If any of these stick around or bother you, they are worth raising. For mild effects that can wait, send a non-urgent message through the patient portal or bring it up at your next visit; often a small change helps. Constipation is the exception: report it promptly, so it can be managed before it becomes a bigger problem.

Less common, but concerning side effects that could require emergency care:

• Signs of an infection, such as fever, sore throat, mouth sores, chills, or a flu-like feeling. Clozapine can lower the cells that fight infection in a small number of people, which is what the blood tests watch for, so let your clinician know promptly if you feel these
• Signs of heart inflammation, such as chest pain, a fast or pounding heartbeat, trouble breathing, unusual tiredness, or fever, especially in the first weeks or months
• Constipation that is not improving, fewer bowel movements than usual, or a swollen, painful belly with nausea or vomiting, which can become serious if ignored
• Fainting, or a very slow or irregular heartbeat
• A seizure
• A high fever with stiff muscles, confusion, heavy sweating, and a fast or irregular heartbeat, which can be a serious reaction that needs prompt care
• Uncontrollable or unusual movements of the face, mouth, tongue, arms, or legs
• Signs of very high blood sugar, such as being very thirsty, urinating often, or feeling confused or unusually drowsy
• Any new or worsening thoughts of harming yourself, whether or not you think the medication is behind it

For any of these, use the help options at the top of this page: call 911 or go to the nearest emergency department for a medical emergency or severe reaction, or call or text 988 for a mental health crisis.

Pregnancy and breastfeeding

If you are pregnant, thinking about it, or breastfeeding, this is worth going through together rather than settling from a page. What follows is what FDA labeling and the research currently show. Tell your clinician before changing anything, and do not stop suddenly on your own.

In pregnancy

Clozapine has been used for decades, and FDA labeling states that the published studies over that time have not established a higher chance of major birth defects, miscarriage, or other harm to the mother or baby from clozapine. For scale, about 2 to 4 in 100 babies are born with a major birth defect, and about 15 to 20 in 100 recognized pregnancies end in miscarriage, before any particular exposure is considered.

Symptoms in the newborn. Babies exposed to medicines in this group during the last three months of pregnancy can have symptoms after delivery. These can include agitation, muscles that are unusually stiff or unusually floppy, trembling, sleepiness, trouble breathing, and trouble feeding. They vary in severity: some babies recover within hours or days without treatment, and others have needed a longer hospital stay. The useful thing you can do is make sure the delivery team knows about the medication ahead of time, so someone is watching for it.

While breastfeeding

Clozapine passes into breast milk. Very little is known beyond that: the published experience amounts to a small number of cases. Among them, one had drowsiness and one had a serious drop in white blood cells that was possibly caused by clozapine. One child had delayed speech, which may or may not have been related. The others had no problems noted.

Because so little is known, and because of those two reports, LactMed, the National Institutes of Health lactation database, says other medicines are preferred during breastfeeding. It also notes that breastfeeding is not ruled out, and that some sources recommend against it when clozapine is needed. FDA labeling does not advise for or against; it says the benefits of breastfeeding should be weighed along with your need for clozapine and any possible effects on the baby.

If you do breastfeed, both sources describe watching the baby closely for excessive sleepiness and checking the baby's white blood cell count from time to time, which means blood draws for the baby, arranged with the baby's clinician. If your baby is unusually hard to wake, is feeding poorly, or has a fever, call the baby's clinician promptly.

Registries

There is a national registry that follows pregnancy outcomes for people taking psychiatric medications, including medicines in clozapine's group, and you can enroll yourself rather than waiting to be asked. It is listed in the references at the bottom of this page.

When to reach out, and where

For routine questions, side effects that can wait, or how things are going, send your clinician a message through the patient portal. These are part of your ongoing care and are answered in the normal course of a few business days, so they are best for things that are not urgent. With clozapine, signs of an infection like a fever or sore throat, or constipation that is not easing, are worth flagging promptly rather than waiting, even if you are not sure they are urgent.

If something feels urgent, you do not need to wait for a reply. The help options at the top of this page are the fastest way to get care: 911 or the nearest emergency department for a medical emergency or severe reaction, or 988 any time for a mental health crisis or thoughts of self-harm.

Questions to ask your clinician

• What are you hoping clozapine will help with in my case?
• How often will I need blood tests, and how will that change over time?
• What symptoms should make me call right away?
• How should I prevent or manage constipation?
• Is there any other monitoring, like weight, heart, or lab work, we should plan on?
• How will we handle stopping it, if and when we get there?