Phone: 330.325.6848 email: clozapine@neomed.edu

By Erik Messamore, M.D., Ph.D., NEOMED Associate Professor of Psychiatry and Medical Director, Best Practices in Schizophrenia Treatment (BeST) Center

Q: Is clozapine a “miracle drug”?

A: I’m not a fan of labels like “miracle drug” for medications. The most successful outcomes are usually the result of a combination of multiple treatment approaches, including medication, psychotherapy, environmental modification, bolstering social support and helping people to reconnect to the things give them meaning, purpose and joy. Labeling a particular medication “miraculous” creates a risk of over-focusing on one approach when others are also valuable. On the other hand, clozapine does appear to have a higher level of treatment effectiveness than any other medication for schizophrenia and can be uniquely effective in cases where other medications have failed. The average patient will have spent several years dealing with inadequately effective medications before she/he is offered clozapine. To someone who has struggled with symptoms for so long, finally being on a medication that truly works certainly can feel miraculous.

Q: How do you know if someone has a high-dopamine or a normal-dopamine form of schizophrenia?

A: It is possible to measure dopamine signaling in humans, but the techniques are not available outside of research studies. Medication response patterns can be useful guides. If symptoms respond to dopamine signal adjusting medications, it is quite likely that the psychosis was of the high-dopamine type. On the other hand, if symptoms have not much improved despite adequately-dosed dopamine signal-adjusting medications, then a normal-dopamine psychosis is likely. Paying attention to medication response is an indirect method of finding out if someone has a high-dopamine schizophrenia or a normal-dopamine schizophrenia.

Q: What do you think makes clozapine effective in situations where other medications have not been?

A: There are multiple schizophrenias, each with similar outward appearance, but different underlying pathophysiology. Almost every medication approved for the treatment of schizophrenia works blocking a very specific subtype of receptor for the neurotransmitter dopamine. Dopamine-receptor blocking medications are very effective for about two-thirds of the schizophrenias. However, one-third of schizophrenias have little to do with dopamine over-activity; as a result, dopamine-blocking medications are not helpful. The reason clozapine succeeds where other medications fail is because clozapine works on other (non-dopamine) systems that contribute to persistent psychosis.

Q: What severe side effects have you seen in patients who take clozapine?

A: Many of clozapine’s side effects can be prevented by using the lowest effective doses, and by taking care to discontinue prescribing medications that will not be needed once clozapine reaches therapeutic levels. Knowing what to look for allows early detection of potentially serious side effects and early intervention to prevent harm.

Most people fear the possibility of suppressing the white blood cell count with clozapine. This is why patients who are on clozapine are required to have weekly blood draws to monitor their white cell counts for the first six months, and then, if no drops in counts occur, biweekly for six months and then monthly. Because white blood cells are a first line of defense against infection, a drastic reduction in their numbers can lead to very serious infections. Although patients having small dips in white blood cell count while on clozapine is relatively common, most are temporary and insignificant. Having a medically serious white blood cell suppression from clozapine is actually rare (less than 1 percent). Getting an infection from such white cell count suppression is even rarer because the white blood cell count is measured frequently.

Constipation is the most common medical serious complication from clozapine, and in its most severe forms, constipation can lead to a medical emergency. It is important for patients to pay attention to the frequency of bowel movements and to take medications to ensure regular bowel movements if necessary.

Weight gain is a risk with clozapine, but can be minimized or prevented by diet and exercise, possibly combined with medications like metformin or liraglutide that promote weight loss.

Q: What tips would you like to offer to others who prescribe clozapine?

A: A lot of people hate having their blood drawn often and may refuse to consider clozapine because of this. Topical anesthetic cream, to numb the skin at the blood draw site, can be really helpful to someone who might not consider clozapine because of the white blood cell testing requirements.

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