With this post, we continue our biweekly series on medications used to treat bipolar disorder and related symptoms. Over the past several weeks, we covered five commonly used atypical antipsychotics, including Zyprexa (olanzapine) and Seroquel (quetiapine). Because the Zyprexa post contains a great deal of information that applies to the atypical antipsychotics as a group, we encourage you to read it first.
Clozaril is a unique medication, even within the class of “atypical antipsychotics” and has been around for many years – it was first formulated in 1960 and studied in the 60’s and 70’s for the treatment of schizophrenia. In 1975, research was halted in the US and the UK due to a severe and frequent side effect causing reduction of white blood cell counts, leading to deadly infections.
Clozaril continued to be seen as quite effective for schizophrenia, especially treatment-resistant schizophrenia; therefore, it was ultimately re-introduced in the US and UK with a formal blood test monitoring system required for those who take it. It received approval in 1990, making it the first of the atypical antispsychotics to be prescribed.
Clozaril has FDA indications for schizophrenia, treatment-resistant schizophrenia, suicidal behavior in schizophrenia, and suicidal behavior in schizoaffective disorder. It does not have FDA indications for any phases of bipolar disorder. There are a number of clinical studies, however, that have found Clozaril to be effective in bipolar mania. It is not clear what benefits Clozaril has for bipolar depression or maintenance treatment of bipolar, but it has some clear benefits in the closely related schizoaffective disorder.
Clozaril was an exciting medication when it first came out because it can be effective in treating some people with schizophrenia who were unresponsive to many other antipsychotics. It was described as a miracle for some patients. Patients and prescribers were also pleased that Clozaril seemed to reduce negative symptoms in schizophrenia more effectively than other antipsychotics. Negative symptoms are things like withdrawal, inertia, and low motivation and energy, Clozaril has also been found to effectively reduce aggression in some patients with schizophrenia.
Clozaril can improve symptoms of schizophrenia and psychotic symptoms that may occur in bipolar, including the following:
It may also improve conditions such as social isolation, limited motivation, and reduced speech activity for some people.
Clozaril can also improve symptoms related specifically to mania, including the following:
Clozaril must be introduced very gradually because of the potential for severe “orthostatic hypotension” – meaning drop in blood pressure when someone stands up. It is also quite sedating. The typical goal dose is 500 mg per day, in divided doses, but starting dose is much lower – more like 25 mg per day. The range of therapeutic doses is 400-700 mg per day. At doses about 500 mg per day, the risk of seizures increases significantly.
In my practice, I have not used Clozaril much, since I do not work in a hospital or clinic setting. When I did prescribe it for schizophrenia or severe mood disturbances, it was often effective but poorly tolerated due to a number of side effects, including terrible weight gain, drooling, and sedation.
Clozaril can cause agranulocytosis – in which the bone marrow stops making white blood cells, which the body needs to fight off infection. To combat this side effect, patients taking Clozaril must have their blood drawn once a week to check white blood cell counts for the first year of treatment. Beyond the first year, the monitoring can go to every two weeks. Clozaril tends to have a limited scope of use because of this restriction. It tends to be used more in clinic and hospital settings than private practice. It is probably an underutilized medication because of concerns about this side effect and the intrusive blood draws required when someone is on Clozaril.
Other potentially serious side effects include the following:
For additional information about Clozaril, visit Novartis Pharmaceuticals’ Clozaril page.
If you’ve taken any form of Clozaril for bipolar disorder or are a doctor who has prescribed it, please share your experiences, insights, and observations.
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The Onset Of Bipolar Disorder Symptoms (January 24, 2009)
» Bipolar Disorder Medication Spotlight: Clozaril (Clozapine … « Bipolar Disorder (January 25, 2009)
Hi there. My name is Iulia and i suffer from OCD and had a psychotic episode as well. I have been taking zoloft and clozapine since i was 16, which means for almost 8 years and it worked great for me. unfortunately, the zoloft made me not think abotu what i was doing so i engaged in risky activities such as drinking a lot with the pills especially vodka and engaging in sexual activities, although protected. Moreover, in my last job i was under a lot of stress so i dranka lot of red bull and coffeee while on the pills. as if it wasn’t enough i also kept drinking vodka form time to time. then it culminated when i went to amsterdam and i smoked a joint of hashish by myself. since then i have been feeling horrible. i seem to have neurovegetative dystonia, i have tingling and burning in my amrs and leg, i can’t breathe, my heart beats strangely, i have pressure headaches and panic attacks. thus i decided with my psychiatrist to quit this treatment and go on fluvoxamine. i quit the clozapine bc with my new neurotic heartbeat it made it worse and the zoloft made me more agitated. the fluvoxamine works better, i havent touched vodka coffee or red bull in 2 months. i have done acupuncture, seena lot of doctors and my tests came out fine. however, i still have shortness of breath, muscle weakness a tense heart and terrible withdrawal symptoms from clozapine and zoloft. now i know i was wrong to mess with all this nervous excitants. i hope i will get better as time passes.
clozaril,works I’d say the best for my bipolar allthough I find the side effecs at times unberable.I’m currently at 250mg/day.I get like anxiaty attacks frequently both in sleep and awake.Its like a running out of breath and grasping for air attackI’ve also gained alot more weight over the last two years on it.I would like to know if there are any other meds That might be as effective for my bipolar that don’t put me through those side effects. I’ve tried many with the assistance of my psychiatrist but still haven’t found an ideal one yet. Please write if you can help or have any suggestions. Thanks, Ben.
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