Taking Another Look a Too-Often-Forgotten Treatment for Schizophrenia

By Ken Duckworth, M.D. | Mar. 24, 2017

 

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.

Comments
Lynne
It seems the bigger cities have the best care givers. New York has so many doctors I guess there is competition. I wish more doctors would care as much as you. Giving a cell number and email is so helpful. In my town we would never see that happening. I don't know why. MH clinics....the same thing. No way to reach the doctor except during appointments.
6/10/2017 7:25:44 AM

lynne
Julie I'm so sorry for your loss. you said he was on abilify and Invega sustana shots and wondered if tests were supposed to be done (levels). Go to drugs.com and get all you need to know. I hope they were doing their jobs. Take care. Lynne
6/1/2017 9:24:58 PM

lynne
Julie I'm so sorry for your loss. you said he was on abilify and Invega sustana shots and wondered if tests were supposed to be done (levels). Go to drugs.com and get all you need to know. I hope they were doing their jobs. Take care. Lynne
6/1/2017 9:24:41 PM

Kathleen Cronin
This NAMI article sounds suspiciously like an ad for one medication. I am offended and worried, especially when the very serious side effects of this old drug are considered. The Dr. said NAMI does not prescribe, then spent hindreds of words doing just that. This is wrong and probably paid for by pharma.. I am shocked.
5/30/2017 12:16:31 AM

lynne
They aren't taking scitzophrenia seriously or they WOULD do brain scans like the AMEN clinic does. It's 'try this'. OK well my daughter is stable but still has symptoms! There are many diseases that mock this disease. No one has tested her. mmm
4/20/2017 5:47:46 PM

Terry Abate
I wish the best for you and your son.
4/20/2017 5:32:11 PM

Melissa Leisure
My child began at the age of 12 years with audio, visual, and tactile hallucinations. We tried antipsychotic med after antipsychotic med. Some work for a week some didn't help at all. Then they tried Haldol, that was the worse. She was so drugged up, and the hallucinations intensified. Finally after about 5 other meds they decided to try Clozapine. Slowly over weeks and months we finally settle on 650mg. Had we been able to try 2 med, they didn't work, we could have tried Clozapine and saved a lot of time! Our daughter spent her entire Freshman year in hospitals. Since then she goes in the hospital for a time-out about 3 times a year. She is now 19. She's put on about 80 pounds since starting this and going though puberty. Finally she is feeling in control of her life. She is now a he. He came out as transgender at 16, and is finally happy! The voices come occassionally with sever anxiety or depression. He's excited about possible starting college this fall.
4/16/2017 9:27:04 PM

Mary
I have a boyfriend that is on this medication.
4/12/2017 5:39:00 PM

Bonnie Devito
I was on this medication for barely a month. It helped my symptoms a little bit. I would like to try it as prescribed. I would like to participate in your study. I am diagnosed and suffer from schizophrenia. Thank you, Bonnie Devito
4/10/2017 11:18:09 AM

gloria
Where in Cook County Illinois do I find an involved Dr. like you. All they do is throw meds at people. You are involved from the bottom up. I have a 53 year old with schizophrenia and he id the most wonderful peaceful man. I need direction. He was diagnosed at UIC hospital. Through a sequence of events he lost his subscription and won't go to the Dr. He experiences peranoia.
4/5/2017 1:54:44 PM

Terry Abate
Took clozapine for six years and it worked well for me. I was on 600 mg daily. But then my psychiatrist called me and told me my white blood count was dangerously low and he need to take me off of the clozapine. I didn't know what I was going to do. Now on Abilify 30mg It working ok with some symptoms. Just have to keep on keeping on. Terry
4/5/2017 5:29:34 AM

Tanya Johnson
I'm the youngest sibling of four older siblings all with some form of mental illness. One of the siblings now 63. Needless to say there is no real family support. We currently live in Ga. My plan is to find a comfortable,compatible stable place for her. Since the state of Ga , decided to close all their mental instituition some years ago, leaving this group of people with the only option of PCH, which are not regulated...I'. willing to move there with her to be close by however 41 years of my 57 years has taken a toll on every area of my life,. physical, menta; amd emotional. I reall need some assisisant. a.s.a.p. I'm taken two weeks from work to try to start this process if possible, if not.... I don't know.
4/3/2017 8:35:59 AM

Kathleen Bernard
My daughter is 30 years old and has tried clozapine. She had the shakes so bad she couldn't continue the medication. The doctor wants to do ECT on her next. I am very skeptical of this therapy. Any suggestions? She has paranoid schizophrenia and anxiety disorder with depression.
4/2/2017 4:05:09 PM

GV
I have not taken clozapine. I have been diagnosed with schizprohenia for more than 20 years and have been taking medications. I changed medication a few times (Cogentin, Abilify, Risperdal, and others) and only Latuda finally worked for me. I have been taking it since 2014. I am highly functional since I have the same type of job for the last 25 years. Stressful at times and needs concentration most of the time. I returned to regular exercise and have lost some weight. I try to have a healthy diet, involved in church, strong faith in God and independent. It is by God's grace that I have support of family and close friends. Yes, there are side effects such as rapid blinking of my eyes, enhanced appetite etc. I am encouraging others that taking proper medication, healthy diet, exercise, church involvement, support of family and friends have helped me cope up. Today I when I hear voices or hallucinate, I remind myself of the reality. And yes, the strong Christian faith has played a vital role in my life.
4/2/2017 11:36:37 AM

Julie
My son pAssed away at 36 years old.he was one abilify and Invega sustana shots .just wondering if blood tests are required for either shot?
4/1/2017 6:22:52 PM

Tamara Lamb
My daughter is 20 and has been suffering with schizoaffective disorder for the past 3 years at least. Literally today she was just released from her 7th hospitalization. She has been on Abilify, Latuda, gained over 100 lbs on Zyprexa and now is on the brand new Vraylar. She has been hospitalized during the use of each of these medications - even the new one. I feel like we are running out of medication options. She is doing a round of ECT right now as well. Maybe clozapine will be helpful to her. Thinking about Amen clinics with the SPECT scans as well. Anyone have experience with them and these disorders?
3/31/2017 8:25:01 PM

lynne thomas
I understand how you feel when a family member is better when on a medication. Let me suggest that every brain is different and each needs something different. My daughter was on Zyprexa then they added prolixin. My fear is that she will lose her ability to go to her current mh center and a new place will deny her her regular antipsychotics and she will be hurt by it. The governor wants to push to a clinic environment where all care is given (saves govt. money they THINK but when you disturb a severly mentally ill person's meds they will end up in an institution and that will cost MORE. You tell them but politicians think they know everything. No reply or comment back to me. Ever. Federal or State. All I can do is pray. I'm glad your family member was helped by the meds she is on. I hope mine gets to keep her meds.
3/30/2017 1:26:18 PM

Mark
Anecdotal evidence is not science.
3/30/2017 12:07:21 AM

Donna spence
I have done better on this for schizoaffective/ schizophrenia than anything else. Thank you!
3/29/2017 7:29:59 PM

Martha Christensen
This has been a life saver for my daughter whom is now 18. Been on this medication for about one year now and has made such a difference. It wasn't recommended until the 5th failed medication. My daughter is on 400 mgs per day which is lots but I just have to keep her healthy. She still has her bad days but for the most part, doing wonderful. I just hope I just hope she wont need more than 400. She is on a couple of others as well.
3/29/2017 6:50:32 PM

Gary carman
My son takes this medication and it works well. The only draw back is a lack of concentration which effects his desires for higher education.
3/29/2017 6:44:33 PM

Alan White
Interesting article that hits close to home for me. My daughter spent 25 plus years being misdiagnosed and was on just about every anti-psychotic imaginable, suffering break after break with all the accompanying brain and personal damage until she was involuntarily placed into a center where she was finally put on clozapine which finally allowed her to recover her mind. She has been stable for well over ten years now but of course has lost her youth and life as we all formerly imagined it. I wish she had been able to benefit from the drug, nasty as it is, much earlier in life. Thanks for a very informative article Dr. Duckworth which I hope will save other mental illness sufferers who have been treatment resistant from similar years of pain and trouble.
3/29/2017 5:53:53 PM

Jewell McKenzie
My son (51 years) had 85% of the side effects. Drooling, high cholesterol, weight gain and voices did not go away. He has also been on 2 other meds with really bad side effects, .......(convulsions). I'm 75. Don't know what is going to happen to him when I die. Took the Nani family course. Nothing came out of it to help me. He is not violent, no vices and does not have anyone except me. We live in a very rural area... so not very good for doing anything that's helpful. He doesn't drive. Any advise?
3/29/2017 4:25:41 PM

Frank D Hernandez Jr.
Around 2003 i experience my first episode of hullucinations and delusions, i thought my nieghbors were Nazis and trying to poison my dog, i was living in Fontana at the time. I had my whole family standing on chairs looking over the neighbors wall and no one was there. Next day i drank 2 40 ouncers and thought it would go away it got worse my parents took me the the E.R., is this going to get worse over time
3/28/2017 2:38:50 PM

Debbie Pegher
My brother did well with Clozapine although he suffered with seizures. Managing either issue was a burden on our family, desperate to help and stop the pain.
3/26/2017 7:44:57 PM

Robert Laitman
We quickly learned what a life changing drug clozapine could be. We also soon learned that there are no easy answers with severe persistent mental illness. It is very hard work. I will make no pretense; clozapine is not an easy medicine to use correctly. We were forewarned by many Psychiatrists of the many potential pitfalls. In fact, for Daniel clozapine was not the whole answer but just a component of a complex solution to a complex problem. It came as no surprise to us that what we needed was an integrated approach. Daniel improved as we became more and more involved in his care. We molded his therapeutic regimen with only 1 goal in mind. Daniel would have a robust recovery and a full life. Daniel our n of 1 is now living independently in NYC as he pursues his career in Standup Comedy and Mental Illness Advocacy. I am extraordinarily proud of him. He led the way.
Now I am presently treating over 100 patients with persistent severe mental illness (PSMI) and I have been involved with the management of over 70 individuals treated with clozapine over the last 9 years. As of 10/1/16 I am actively responsible for 31 patients on the clozapine registry. 18/31 patients were started in my office. Of these patients, 16 remain employed or are full time students. 2 patients have been hospitalized with the total combined length of hospitalization being 4 weeks. Weight gain has not been problematic. 17 patients lost weight, 9 patients weights were without change, and 5 patients gained weight as defined as greater than a 10 pound weight change. I have written clozapine over the last 9 years for 51 individuals. Of the 20 patients that are no longer active in my practice 6 patients remain on clozapine and are followed elsewhere. 2 elderly patients being treated for psychosis related to Parkinson’s disease expired. 4 patients started and stopped clozapine within the first 3 months of therapy because of excessive sedation. 8 patients have been lost to follow up. I have seen no suicide, no incarceration, no seizures, no agranulocytosis, and only 1 cardiomyopathy in 1 of my elderly patients. The cardiomyopathy resolved with clozapine withdrawal. Of the 31 patients as of 10/1/16 on REMS 28 of the patients and their families felt that the benefits of clozapine outweighed the burdens. Of the 3 patients who remained unsure 1 patient was being treated for a schizoid personality disorder and the other patient refuses to increase her dosage above 37.5 mg. The last patient the family has considered a failure. However, since being on clozapine he has worked and remains out of the hospital. Finally only 2/31 patients are on an additional anti-psychotic.
My goal in treatment is to provide a setting in which we can restore optimal health. I want to restore the body and the mind of the individual so that the patient has a sense of purpose and self. I want them able to have the ability to form relationships and become a productive member of their
immediate community and society. I want vital individuals with optimal physical functioning, pain free both physically and emotionally enjoying long and fulfilling lives. I try to restore hope.
How do I do it? The first step is getting to know the patient and their family, if available, at the same time. Forming this therapeutic relationship is the critical first step. Getting to intimately know the patient and the family allows me to help formulate a reasoned and reasonable plan with realistic explanations. For example if someone comes to me with a long history of borderline intellectual functioning as a prodrome to their psychotic illness my bar for success is a bit lower than the person who had a psychotic break after being at the “top of their class”. What is often the case is that they are in a lot of pain. I try to use Xavier’s Amador’s approach of listening, empathizing, agreeing, and finally partnering with the patient. Even with the most burdened patients, those with anosognosia, the unawareness of their illness, I ultimately have had success. I try to make the patient feel safe and accepted. I am an active cheerleader and recognize that the road to recovery will almost always have a few detours. What my son has taught me is humor often helps. Sometimes I succeed, and sometimes I do not. Even when I flail and I mean flail, my attempts often helps the patient and family relax. They know that even if “they screw up” you will never abandon them. Both the family and the patient need to know that they can always reach me in times of need. All of my patients get my cell # and e-mail. Compassion and Availability and Positive Psychiatry really go a long way. Optimism is essential, as hope must be restored. The next step is to use clozapine. As I have demonstrated over the last 9 years Clozapine can be managed so that side effects are quite tolerable, and certain other medicines (rational polypharmacy) and modalities can augment recovery.
3/24/2017 11:44:48 PM

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