Episode 28
The SP Care Project on Clozapine
Clozapine Program Notes:
In today’s episode of the podcast, HOPE: On the Other Side of the Door, there’s a book review on a very special and important medication for the treatment of psychosis in those folks living with schizophrenia. Please recommend this to your loved one’s doctor if there are months or a few years of poor response of the psychotic symptoms to the medicines or persistent suicidal thinking.
Schizophrenia, is a condition, which is called a major mental illness, and it is an odd type of medical diagnosis. In the brief report available on my website, many of you have already read that schizophrenia is called a disorder, and not called a disease. It is a diagnosis made by physicians specializing in the field of psychiatry. It is identified when a person has at least 6 months of a set of conditions, and the doctor can find no other cause for the troubles seen in thought, speech, behavior and social relations and functioning. That is to say that nothing is found on the ordinary readily available tests in the medical office or hospital. However, there are things which can be found in some special exams done on test subjects at a University or at a Medical research facility. Those tests can show that schizophrenia is a physical medical condition.
Briefly, to review, Schizophrenia is defined at psychosis, with no known medical / physical / or drug cause on those ordinary tests, and a decline in the person’s functioning in life, over 6 months of time, less if treated successfully. The anti-psychotic medicines are a part of the treatment and care of those living with schizophrenia. The anti-psychotics are like aspirin or Tylenol for a fever, they reduce the symptoms, but they are not a cure. That is to say, not a cure in the same way that penicillin can kill-off the bacteria that are causing an infection. Psychosis is defined as 5 things: hallucinations, delusions, disorganized thought and speech, disorganized behaviors and the lack of ambition / planning ability called “negativism.” It is not defined by suicidal, dangerous or aggressive behavior.
Furthermore, there is a range or a grading the severity, from the mild to moderate and then the severe cases. Today’s episode is about a medication used in the severe cases. A part of those people with very mild to moderate cases can be treated with lower medication doses or even no medication, but with lots of social, family and psychological support. This has been seen around the world in non-standard treatment. One of those non-standard forms of care is the Soteria approach talked about in other podcasts.
So what is Clozapine? It is the generic name for this compound first made 60 years ago in 1958. Then in 1961 it was developed as a medicine, and finally by 1965-66 there were successful tests in patients. Since 1988 it has been documented to be the most effective medicine for psychosis in those living with schizophrenia whose symptoms are not reduced adequately by the other antipsychotic medicines. Later on a second and third use was found for those living with schizophrenia. The second reason is those with persistent suicidal thoughts / attempts get better relief, and the third reason is those with persistently aggressive behavior also get better relief when compared to treatment with the regular anti-psychotic medications.
Why is clozapine not used very much? Fear. Fear is the main reason. Back in 1975 there was a scare when several patients in Finland has bone marrow problems resulting in a severe blood disorder, low white cells were being made. The drug company took clozapine off the market for a while, and it fell into disfavor for about 10 years.
So, again, there are three reasons to use clozapine in those living with schizophrenia because it is better and more effective than the standard medicines for psychosis. The reasons are 1) the person’s symptoms simply do not respond to regular antipsychotics; 2) the person is persistently suicidal; and 3) the person is persistently aggressive while on the regular medicines.
For today’s episode, it is my hope that as listeners, as interested people and many of you are the caregivers of a person living with schizophrenia, that you will learn a bit about clozapine. Clozapine is the most effective medication for schizophrenia. The aim of this podcast episode includes the hope that you can then help the prescribing doctor who is caring for your loved one, to be more comfortable using clozapine because of your family-based and social support for using that medicine. You, dear listeners, may want to get into some political action with your local county’s mental health department to provide support for the clinics, the doctors and the patients using this amazingly helpful medicine.
WHY USE CLOZAPINE?
After initial studies showing better effects, that is a greater reduction in psychotic symptoms compared to other anti-psychotics, there was a stronger study done in 1988. This included failure to respond to high doses of the other anti-psychotic medications. Other studies and even a collection of studies are weaker due to less strict definitions of the illness, the doses, and measures of the response of the symptoms to the medicines. So, the 1988 study by Dr Kane was a landmark. In the meantime, newer studies include blood level data. The blood levels of the clozapine are a more important and meaningful measure of treatment than the dose. Treatment resistance is when there is a very poor response of the psychotic symptoms even when the person takes over 80% of the medication doses. It is seen that even with good dosing of regular anti-psychotic medicines, that 20% or more of people with schizophrenia symptoms will not have adequate relief of those symptoms. This basic truth for most medicines is that a smaller group will not respond much at all when given that medication. Some studies report that after getting to the stage of “treatment resistance” that over half of those patients will get some relief of symptoms when started on high enough doses of clozapine.
WHEN TO START CLOZAPINE?
The goal here is for the patient and the doctor to see that there were at least 2 different times of using another anti-psychotic medication, in at least 2 different classes, and even the use one of long-acting injectable medication for at least 4 months. The person should have at least 6 weeks of treatment at a high enough blood level of the old medicine, too. Encourage your psychiatrist to look into this handbook. Encourage your loved one living with schizophrenia to be open to using this special medicine, too. Your psychiatrist may wish to consult with others in the area who are well versed in using clozapine to help him or her get started offering that medicine to your loved one. There is some data from around the world that if the doctor waits too long to begin clozapine then the response rate to the clozapine goes down dramatically. The time noted in the book is about 2 and a half years. If the person in your care is having high levels of disturbing symptoms over a few months, or a year, then think of staying in touch with your clinic staff and doctor. Please feel free to ask the doctor of your loved one to explore this medication and to make sure that the current medicines are at high enough blood levels. You can empower your psychiatrist to consider a medicine that very few in the USA are using.
Mortality can be a scary topic. Once a person living with schizophrenia starts taking clozapine various studies show a reduction in mortality. Mortality is either natural death or accidental death or death by suicide. Clozapine patients show a definite reduction in all causes of mortality. The benefit in reduced mortality lasts only as long as the person is actually taking the clozapine. Remember that this medicine is used in those cases with persistent strong symptoms which did not respond well to regular anti-psychotic medicines.
My personal opinion is that it is good to think of this situation like diabetes. In the case of diabetes, there are those people who can control the abnormally high blood sugar levels by changing their diet and doing gentle aerobic exercise for 15 minutes at a time on a near daily basis. Then there are those diabetes cases where the person needs blood sugar lowering medications, that is not insulin yet. Then there are those people with diabetes which is a little more severe, and they need insulin. Getting higher up on the severity scale, are those who need many doses a day of different types of insulin. Finally there are those with a more brittle case which may require surgically implanted blood sugar monitors and maybe even an insulin pump. So it is with schizophrenia. In Schizophrenia, there are mild, moderate and severe cases as defined by the course of the symptoms & condition over time, the frequency of hospitalizations, and response of the symptoms to medicines.
WHAT TO DO IN ORDER TO START CLOZAPINE
It is most important to begin with the person who is living with schizophrenia, and help them to understand the risks and benefits of clozapine as best as possible. Also, it is important to get their buy-in for using this medicine, and their cooperation with the weekly testing and monitoring needed in clozapine therapy. Common side effects are important to talk about and know about. Make sure that there is awareness of the importance of near daily aerobic exercise times and the importance of keeping a routine healthy diet. Make sure the person and the caregivers are aware to look for signs of infections, too.
Work with the psychiatrist and clinic team starting clozapine. A physical exam by the medical doctor is usually needed. Get a full set of common blood tests and an EKG for checking the heart. It is hard to measure the waist size reliably, thus the calculated number, the BMI, or Body Mass index is a better measure to follow. Next the patient (and of course the doctor) need to get registered with the national record keeping system. The pharmacist and pharmacy are also included in this system. Then begin to start and raise the dose depending on things like the severity of the psychosis, and the age of the person, and if they are in hospital or at home, other medicines and cigarette smoking are important, too. There may be other things that involve how fast the person’s liver will do it’s normal work. That normal work of the liver is to destroy the clozapine over time. This is called drug metabolism. It goes step by step and the compound is changed and broken down little by little. Sometimes the first or second break-down product of the medicine has the main effect or it may have a powerful side effect. The liver and or kidneys do this work to almost all medicines.
Once the clozapine has been started, in the treatment resistant or poor responders, then up to 40% of them will still not respond well to clozapine. They will not have adequately reduced symptoms. Then it is time to consider whether the person living with schizophrenia is taking the doses of clozapine or not. Also, the psychiatrist may need to check blood levels of the clozapine. Check adherence. Push the plasma levels as high as the person can tolerate in order to reduce the distressing symptoms.
Next, the doctor and patient can consider using an older anti-psychotic medicine added on. Also, ECT is a good add on, that is Electro-Convulsive Therapy. Reports show that persons living with this level of severe persistent symptoms of schizophrenia can handle the ECT add on, fairly well.
PARTICULAR ISSUES:
STOPPING THIS MED:
Sometimes this is required by the situation, and may need to be done quickly. A low white cell blood count can be a causes to stop suddenly. Then the doctor and the clinic and caregivers should manage a set of things called “cholinergic rebound.” The basic “fight or flight” part of a persons nervous system is really two systems. One of them is blunted by clozapine, and when you stop it, then the balance or set-point of the two systems is way off. And it is important to give temporary medicines to make up the difference. Some of the rebound can be anxiety, tension, restlessness, insomnia and vomiting. It is very uncomfortable, but can be treated & managed in advance.
BLOOD LEVELS:
The regular anti-psychotic medicines all block dopamine. Clozapine on the other hand is only a weak blocker of dopamine, and it blocks a set of other known neurotransmitters. It is the complex set of effects that are thought to be why clozapine is more effective than other medicines. Particularly important is it effects on NMDA, the glutamate system. Also, it causes less of the shuffling gait, and muscle spasms and extra-pyramidal symptoms which may be caused by other anti-psychotic meds. Blood levels of any medicine go up and down during the day, between doses. It is the usual low blood level, or trough, that is important for your doctor to test.
BLOOD TESTS, THE ANC
In the complete blood count, or CBC, there are red cells and white cells and platelets. Among the white cells (which are in the immune system) there is one type of cell called “neutrophils” by name. That is the N in ANC. Those letters stand for Absolute Neutrophil Count. This can go too low in clozapine treatment, especially at the beginning or after a period of time off of clozapine, and after it is re-started. At the beginning of treatment with clozapine the ANC is tested every week.
TAKING CARE OF SIDE EFFECTS:
Common and bothersome side effects are constipation, drooling and sleepiness. Less common is the worsening or start of seizures. Each of these things can be managed and treated well with cooperation and attention.
At any given time, the percent of people living with schizophrenia is less than ½ of 1% globally. The treatment resistant folks living with schizophrenia are a fraction of all living with schizophrenia; some 20% or more. Around 2015 there are estimated to be 21 million living with schizophrenia. However, the cost of hospitalization, emergency medical services, and overall medical costs are way out of proportion. In the USA, the total medical costs & resource utilization of treatment resistant schizophrenia is about 10 times that of those with schizophrenia who respond well to regular medications. Globally the World Health Organization, WHO, ranks the burden of schizophrenia at #12 out of 310 diseases or injuries, almost in the top 10. It is a sobering finding in the WHO’s burden of disease study that acute schizophrenia has the highest burden index weight of all the conditions studied.
Hidden and huge costs to society of schizophrenia are unemployment of the person, and productivity loss due to caregiving by family members.. Other costs and burdens include direct health care, hospitalization, clinic, medications. Indirect costs include law enforcement, court, prison, homeless shelters, health care training and research, premature mortality. The human costs are almost incalculable.
As a word of hope and optimism, even for those people living with schizophrenia who for many months or a few years have no good symptom relief from the regular anti-psychotic medicines, there is hope. That hope is clozapine. Although few are using it in the USA and around the world, folks in other some countries are using it far more that we are here in America. The benefits outweigh the risks by far, and the benefits are well demonstrated in vastly improved quality of life for that sub-set living with and suffering with the most troublesome symptoms of schizophrenia.
○ 2019 Dr. Ken
Links from This Episode
S-Project: https://www.facebook.com/groups/140778123234472/
Instagram: https://www.instagram.com/drkencampos/
Schizophrenia Care Project on Facebook: https://www.facebook.com/SchizophreniaCareProject
Book: “The Clozapine Handbook” Cambridge University Press
ISBN: 978-1-108-44746-1 Paperback
