By Ken Duckworth, M.D.
At the NAMI National Convention each year, someone invariably comes up to me and says, “We took a look at clozapine like you said at last year’s convention, and it has made such a difference for my son/daughter.” I cannot give specific medical advice in my role as medical director, especially while standing in line for coffee, but when I am told about severe symptoms of psychosis for a person living with schizophrenia and that two antipsychotics have been unsuccessful, clozapine is my go-to recommendation.
This past year, I mentioned the annual “hug trend” following my Research Update on Schizophrenia session, and I told the attendees that I had gotten many hugs over the years for this simple suggestion: Take another look at clozapine. After this past year’s session, three more people came up to me and simply gave me a hug and a smile.
So what is clozapine, and why is it different? Well, it’s unique for two primary—and significant—reasons: One, it is the only FDA-approved medicine for people with schizophrenia who have not responded to two antipsychotics, and two, it is the only medication shown by the FDA to reduce the risk of suicide in people with schizophrenia and schizoaffective disorder.
We don’t endorse specific treatments at NAMI, but reminding people that this treatment has two special FDA indications is good to remember. The consensus in the medical community is that this is an underutilized treatment. I have personally seen many individuals thrive on this medication when no other treatments worked. It has been a part of some of my happiest moments as a doctor.
I am big on shared decision-making—and understanding clozapine’s unique qualities is important, both in its potential and in its risks. Clozapine does have important medical risks and is not an easy treatment to take. For example, clozapine requires mandatory, regular bloodwork to reduce the risk of one of its possible side effects, agranulocytosis, which is the potentially fatal loss of white blood cells. This begins as a weekly requirement and becomes less frequent over time, but it never stops.
Side effects of clozapine can also include weight gain, constipation that can become severe, the potential to develop diabetes, sedation and drooling. There are other less common side effects as well, like myocarditis (an inflammation of the heart) and seizures. A person should consider both the potential for better symptom control and how to plan for and deal with the medical risks.
Some people are able to cope with the side effects better than others. One of my patients once asked me, “What is with you guys? I can only have a mind or a body?” Despite responding well to clozapine, she could not use the medicine over the long term because of its side effects. Careful attention to diet and exercise for motivated people on atypical antipsychotics can reduce these risks, though (see the accompanying article by Jackie Feldman, M.D., on side effects.
In spite of these challenges, many of my patients have done quite well on clozapine. It has been a building block of recovery for many in my own experience, and this is borne out in the research literature. In the past decade, two large multisite studies, the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) in the U.S. and the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 2) in the U.K., compared multiple antipsychotics for people with schizophrenia, and both found clozapine to be the most effective medication. In the U.K. study, the focus was on quality-of-life measures, and those taking clozapine reported the highest scores.
Clozapine is also unusual in that blood levels are available, which can help to correlate a response to dosage. In addition, there is research that suggests that clozapine is a good mood stabilizer, may reduce substance cravings and may reduce aggression. These are not FDA-approved uses, but the literature can also inform discussions about when it could be considered. It is important to review all of the possible impacts of a treatment as part of shared decision-making between me and my patients.
I recently spoke with Dan Laitman, a senior at the State Univerity of New York-Purchase, who began hearing many voices at the age of 15 at a sleepaway camp. He hid his symptoms for a while, but they eventually became too strong to ignore. He didn’t do well on many other antipsychotic medicines, but then he tried clozapine. He reports that clozapine has made his voices softer and less intense. There are still “many people living inside my head,” he told me, but clozapine has made it much more tolerable for him.
To help ward off the weight gain, he runs to keep in shape. He is a writer and is currently working on a sitcom about college. He also dreams of being a standup comic and made me laugh several times during our interview. Little of this would have been possible without the combination of a loving family, cognitive behavioral therapy and clozapine, he says.
I spoke with Dan’s dad, Rob Laitman, an internist and marathon runner who passionately advocates for clozapine, in part based on his son’s successes. To help avoid some of the side effects, he gets his patients to join in his running. (I asked Dan if he ran with his dad, and Dan joked, “No, that would be sadistic.”)
Dr. Laitman agrees that integrated care to monitor and prevent side effects is essential. He shared an observation with me that I have also found in my years of working with people who have schizophrenia: While it can be a challenge on a person’s body, the improved thinking that comes with a reduction—or even an absence—of symptoms can help to foster a positive approach to the problem of weight-gain prevention.
The New York State Office of Mental Health has made a concerted and systematic effort to have doctors and patients who have failed two antipsychotics take another look at clozapine as well. Drs. Jay Carruthers and Lloyd Sederer are leading an educational and quality-improvement project to raise awareness of this unique treatment. They have pursued a statewide approach to educate patients about clozapine’s profile as a treatment, and to work with psychiatrists in state hospitals and community settings to reconsider this as a more active treatment option. This could become a model for other states to emulate, given the potential boost it can give to recovery for some individuals. Their initial findings show an increase in use.
Clozapine is a treatment option that requires thoughtful assessment. While I have seen many people do very well, a handful of my patients haven’t been able to get over the side effects, and a few have had serious medical complications. We still cannot predict in advance who will thrive on this treatment and who will have difficult or serious side effects. Yet it is a unique treatment that deserves a second look if you or a loved one has symptoms that do not respond to other antipsychotics.
Hopefully, we will get a return on the neuroscience and genetic fronts in terms of new treatments for the hard-to-treat symptoms of schizophrenia and schizoaffective disorder. These new treatments will need to be less difficult to tolerate and have fewer risks. In the meantime, if you aren’t getting the symptom control you want, I encourage you to take another look at clozapine with your doctor. While I cherish my annual convention clozapine hugs, I look forward to the day when we can give them all to the researchers who develop better treatments.
Note: This piece is a reprint from the Spring 2015 Advocate.
We’re always accepting submissions to the NAMI Blog! We feature the latest research, stories of recovery, ways to end stigma and strategies for living well with mental illness. Most importantly: We feature your voices.
Check out our Submission Guidelines for more information.
Find Your Local NAMI