BECAUSE OF A SIGNIFICANT RISK OF AGRANULOCYTOSIS, A POTENTIALLY LIFE-THREATENING ADVERSE EVENT, CLOZAPINE SHOULD BE RESERVED FOR USE IN (1) THE TREATMENT OF SEVERELY ILL PATIENTS WITH SCHIZOPHRENIA WHO FAIL TO SHOW AN ACCEPTABLE RESPONSE TO ADEQUATE COURSES OF STANDARD ANTIPSYCHOTIC DRUG TREATMENT, OR (2) FOR REDUCING THE RISK OF RECURRENT SUICIDAL BEHAVIOR IN PATIENTS WITH SCHIZOPHRENIA OR SCHIZOAFFECTIVE DISORDER WHO ARE JUDGED TO BE AT RISK OF REEXPERIENCING SUICIDAL BEHAVIOR.
PATIENTS BEING TREATED WITH CLOZAPINE MUST HAVE A BASELINE WHITE BLOOD CELL (WBC) COUNT AND ABSOLUTE NEUTROPHIL COUNT (ANC) BEFORE INITIATION OF TREATMENT AS WELL AS REGULAR WBC COUNTS AND ANCs DURING TREATMENT AND FOR AT LEAST 4 WEEKS AFTER DISCONTINUATION OF TREATMENT. (SEE WARNINGS.)
CLOZAPINE IS AVAILABLE ONLY THROUGH A DISTRIBUTION SYSTEM THAT ENSURES MONITORING OF WBC COUNT AND ANC ACCORDING TO THE SCHEDULE DESCRIBED BELOW PRIOR TO DELIVERY OF THE NEXT SUPPLY OF MEDICATION. (SEE WARNINGS.)
SEIZURES HAVE BEEN ASSOCIATED WITH THE USE OF CLOZAPINE. DOSE APPEARS TO BE AN IMPORTANT PREDICTOR OF SEIZURE, WITH A GREATER LIKELIHOOD AT HIGHER CLOZAPINE DOSES. CAUTION SHOULD BE USED WHEN ADMINISTERING CLOZAPINE TO PATIENTS HAVING A HISTORY OF SEIZURES OR OTHER PREDISPOSING FACTORS. PATIENTS SHOULD BE ADVISED NOT TO ENGAGE IN ANY ACTIVITY WHERE SUDDEN LOSS OF CONSCIOUSNESS COULD CAUSE SERIOUS RISK TO THEMSELVES OR OTHERS. (SEE WARNINGS.)
ANALYSES OF POST-MARKETING SAFETY DATABASES SUGGEST THAT CLOZAPINE IS ASSOCIATED WITH AN INCREASED RISK OF FATAL MYOCARDITIS, ESPECIALLY DURING, BUT NOT LIMITED TO, THE FIRST MONTH OF THERAPY. IN PATIENTS IN WHOM MYOCARDITIS IS SUSPECTED, CLOZAPINE TREATMENT SHOULD BE PROMPTLY DISCONTINUED. (SEE WARNINGS.)
4. OTHER ADVERSE CARDIOVASCULAR AND RESPIRATORY EFFECTS
ORTHOSTATIC HYPOTENSION, WITH OR WITHOUT SYNCOPE, CAN OCCUR WITH CLOZAPINE TREATMENT. RARELY, COLLAPSE CAN BE PROFOUND AND BE ACCOMPANIED BY RESPIRATORY AND/OR CARDIAC ARREST. ORTHOSTATIC HYPOTENSION IS MORE LIKELY TO OCCUR DURING INITIAL TITRATION IN ASSOCIATION WITH RAPID DOSE ESCALATION. IN PATIENTS WHO HAVE HAD EVEN A BRIEF INTERVAL OFF CLOZAPINE, i.e., 2 OR MORE DAYS SINCE THE LAST DOSE, TREATMENT SHOULD BE STARTED WITH 12.5 mg ONCE OR TWICE DAILY. (SEE WARNINGS and DOSAGE AND ADMINISTRATION.)
SINCE COLLAPSE, RESPIRATORY ARREST AND CARDIAC ARREST DURING INITIAL TREATMENT HAS OCCURRED IN PATIENTS WHO WERE BEING ADMINISTERED BENZODIAZEPINES OR OTHER PSYCHOTROPIC DRUGS, CAUTION IS ADVISED WHEN CLOZAPINE IS INITIATED IN PATIENTS TAKING A BENZODIAZEPINE OR ANY OTHER PSYCHOTROPIC DRUG. (SEE WARNINGS.)
5. INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS TREATED WITH ANTIPSYCHOTIC DRUGS ARE AT AN INCREASED RISK OF DEATH COMPARED TO PLACEBO. ANALYSES OF SEVENTEEN PLACEBO-CONTROLLED TRIALS (MODAL DURATION OF 10 WEEKS), LARGELY IN PATIENTS TAKING ATYPICAL ANTIPSYCHOTIC DRUGS, REVEALED A RISK OF DEATH IN THE DRUG-TREATED PATIENTS OF BETWEEN 1.6 TO 1.7 TIMES THAT SEEN IN PLACEBO-TREATED PATIENTS. OVER THE COURSE OF A TYPICAL 10-WEEK CONTROLLED TRIAL, THE RATE OF DEATH IN DRUG-TREATED PATIENTS WAS ABOUT 4.5%, COMPARED TO A RATE OF ABOUT 2.6% IN THE PLACEBO GROUP. ALTHOUGH THE CAUSES OF DEATH WERE VARIED, MOST OF THE DEATHS APPEARED TO BE EITHER CARDIOVASCULAR (e.g., HEART FAILURE, SUDDEN DEATH) OR INFECTIOUS (e.g., PNEUMONIA) IN NATURE. OBSERVATIONAL STUDIES SUGGEST THAT, SIMILAR TO ATYPICAL ANTIPSYCHOTIC DRUGS, TREATMENT WITH CONVENTIONAL ANTIPSYCHOTIC DRUGS MAY INCREASE MORTALITY. THE EXTENT TO WHICH THE FINDINGS OF INCREASED MORTALITY IN OBSERVATIONAL STUDIES MAY BE ATTRIBUTED TO THE ANTIPSYCHOTIC DRUG AS OPPOSED TO SOME CHARACTERISTIC(S) OF THE PATIENTS IS NOT CLEAR. CLOZAPINE IS NOT APPROVED FOR THE TREATMENT OF PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS.
Clozapine, an atypical antipsychotic drug, is a tricyclic dibenzodiazepine derivative, 8-chloro-11-(4-methyl-1-piperazinyl)-5
] [1,4] diazepine.
Clozapine is indicated for the management of severely ill schizophrenic patients who fail to respond adequately to standard drug treatment for schizophrenia. Because of the significant risk of agranulocytosis and seizure associated with its use, clozapine should be used only in patients who have failed to respond adequately to treatment with appropriate courses of standard drug treatments for schizophrenia, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. (See WARNINGS.)
The effectiveness of clozapine in a treatment resistant schizophrenic population was demonstrated in a 6-week study comparing clozapine and chlorpromazine. Patients meeting DSM-III criteria for schizophrenia and having a mean BPRS total score of 61 were demonstrated to be treatment resistant by history and by open, prospective treatment with haloperidol before entering into the double-blind phase of the study. The superiority of clozapine to chlorpromazine was documented in statistical analyses employing both categorical and continuous measures of treatment effect.
Because of the significant risk of agranulocytosis and seizure, events which both present a continuing risk over time, the extended treatment of patients failing to show an acceptable level of clinical response should ordinarily be avoided. In addition, the need for continuing treatment in patients exhibiting beneficial clinical responses should be periodically re-evaluated.
Media Articles Related to Clozapine
Psychosis may be triggered by antibody reaction to brain protein
Source: Schizophrenia News From Medical News Today [2015.03.09]
New research further explores the links between autoimmune disorders and psychosis symptoms, identifying an antibody response unique to children with psychosis.
'Skunk' linked to increased risk of psychosis
Source: Schizophrenia News From Medical News Today [2015.02.17]
Researchers found that people who smoke a high-potency 'skunk-like' form of cannabis may be at much higher risk of psychosis than those who do not use the drug.
Psychedelic drug use 'does not increase risk for mental health problems'
Source: Mental Health News From Medical News Today [2015.03.08]
A new study suggests that the stereotype of LSD users developing psychosis is largely a myth, and that the drug may even have some beneficial properties.
Findings presented at the Society for Neuroscience meeting by Johns Hopkins scientists
Source: Huntingtons Disease News From Medical News Today [2014.11.24]
A Blood Pressure Hormone Implicated in PsychosisIn an effort to find a marker that predicts psychosis, postdoctoral researcher Lindsay Hayes, Ph.D.
Published Studies Related to Clozapine
Efficacy of pimozide augmentation for clozapine partial responders with
INTRODUCTION: A substantial number of patients with treatment-resistant
schizophrenia respond only partially to clozapine... DISCUSSION: In this well controlled clinical trial of patients with
treatment-resistant schizophrenia currently receiving clozapine, pimozide
augmentation was not an effective strategy to maximize the benefit for better
control of positive and negative symptoms or improving neurocognitive function.
Choice of randomization to clozapine versus other second generation
antipsychotics in the CATIE schizophrenia trial. 
There is evidence to suggest that clozapine is underutilized in
treatment-refractory schizophrenia. Data from the Clinical Antipsychotic Trials
of Intervention Effectiveness (CATIE), a multi-phase, randomized comparative
effectiveness trial for schizophrenia, were used to identify factors associated
with choosing randomization to clozapine...
Effects of sertindole on cognition in clozapine-treated schizophrenia patients. 
CONCLUSION: The clozapine-treated patients displayed marked cognitive deficits at
Augmentation of clozapine with a second antipsychotic - a meta-analysis. 
CONCLUSION: Augmentation with a second antipsychotic is modestly beneficial in
Pharmacological augmentation strategies for schizophrenia patients with
insufficient response to clozapine: a quantitative literature review. 
treatment in schizophrenia spectrum disorder... CONCLUSIONS: Evidence for efficacy of clozapine augmentation is currently scarce.
Clinical Trials Related to Clozapine
A Study to Evaluate the Safety and Efficacy of Clozapine in Patients With Treatment-Resistant Schizophrenia [Active, not recruiting]
Clozapine is an antipsychotic. This 24-week study will evaluate the safety and efficacy of
clozapine in patients with treatment-resistant schizophrenia.
This study is not recruiting in the United States.
Treat Clozapine-Resistant Schizophrenia Comparing Between Clozapine + Haloperidol Versus Clozapine + Electroconvulsive Therapy (ECT) [Recruiting]
Clozapine treatment resistant schizophrenia is still prevalent. The effectiveness of
augmenting clozapine : one augmenting with haloperidol and the other with electroconvulsive
therapy should be determined. This study is a randomized control trial.
FazaClo Outcomes in the Control of Schizophrenia (FOCUS) Study Survey [Completed]
AZUR Pharma has received several reports from practicing psychiatrists prescribing FazaClo
showing that FazaClo patients start losing body weight instead of keep gaining it, after
being switched from other clozapine products or other atypical antipsychotics treatments.
Another important clinical observation reported by doctors is a considerable reduction in
hypersalivation when FazaClo administration is compared to other antipsychotic treatments.
Based on the findings described above, and on the real need for effective and safer
treatments for schizophrenia, AZUR Pharma has decided to design and conduct an observational
study in a large number of patients taking FazaClo to prove the received clinical reports
from physicians. Better understanding and evaluation of these beneficial findings are
necessary to provide physicians information for improved treatment decision.
A Long Term Study of Clozapine in Patients With Treatment-Resistant Schizophrenia [Active, not recruiting]
Clozapine is an antipsychotic. This open study will evaluate the safety and efficacy of long
term treatment of clozapine in patients with treatment-resistant schizophrenia.
Alcoholism and Schizophrenia: Effects of Clozapine [Terminated]
The purpose of this study is to examine the short – term effects of clozapine on alcohol use
in persons with schizophrenia and an alcohol use disorder. The hypothesis is that clozapine
will have greater efficacy in reducing alcohol use than other antipsychotic medications.
Reports of Suspected Clozapine Side Effects
White Blood Cell Count Decreased (116),
Drug Interaction (110),
White Blood Cell Count Increased (105),
Psychotic Disorder (101), more >>
Page last updated: 2015-03-09