The life-threatening side-effects of clozapine and mandatory requirement for white blood cell (WBC) counts may partly account for the less than optimal use of the drug in clinical practice.
Clozapine may cause drowsiness, blurred vision, convulsions (seizures), or to have trouble with thinking or controlling body movements, which may lead to falls, fractures or other injuries.
Despite its superior efficacy and potential to reduce substantially the morbidity of schizophrenia and improve the outcomes, of patients, clozapine has not been used on a widespread basis or as a first-line treatment due to its potential for agranulocytosis.
Clozapine has unique and powerful side effects and risks, which often make it a drug of last resort.
Clozapine is associated with several significant adverse effects, including agranulocytosis, neutropenia, constipation (which can be severe), myocarditis and adverse metabolic effects. These adverse effects are not necessarily dose-related and may occur at any time during treatment.
Clozapine may cause myocarditis (swelling of the heart muscle that may be dangerous) or cardiomyopathy (enlarged or thickened heart muscle that stops the heart from pumping blood normally).
There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems.
Loxapine can be an excellent alternative to clozapine.
Abrupt withdrawal of clozapine has been associated with symptoms of “cholinergic rebound,” including nausea, vomiting, hypersalivation, diarrhea, diaphoresis, insomnia, and agitation, as well as rapid onset of psychosis.
Rapid discontinuation of clozapine has been reported to cause rebound psychosis and worsening of symptoms within 24 to 48 hours of drug cessation.
Clozapine differs from conventional antipsychotics for its greater efficacy in controlling positive symptoms in people with treatment-resistant illness and by inducing few extra-pyramidal effects (Kane 1988, Wahlbeck 1999).
A cohort study analysis shows clozapine is effective in treating schizophrenia, despite adverse effects. A new review of existing studies shows that clozapine is the best medication for treatment-resistant schizophrenia (TRS).
Clozapine's relatively rapid dissociation from D2 receptors [13] and its antagonistic activity at the 5-HT2A receptors [11] have been put forward as mechanisms responsible for its effectiveness as an antipsychotic, and its actions at multiple receptors account for many of its adverse effects [14].
However, research has shown that long-term use (7–11 years) of any antipsychotic treatment by people with schizophrenia is associated with lower mortality than no drug use and clozapine is associated with lower mortality than other commonly used first- and second-generation antipsychotic agents.
Results. Altogether, 24 studies reported on 1327 deaths from any causes during 217691 patient years in patients treated with clozapine. The unadjusted mortality rate in 22 unique samples during a follow-up of 1.1–12.5 (median = 5.4) years was 6.7 (95% confidence interval [CI] = 5.4–7.9) per 1000 patient years.
Clozapine, which has the strongest antipsychotic effect, can cause neutropenia. A problem in the treatment of schizophrenia is poor patient compliance leading to the recurrence of psychotic symptoms.
Of the atypical antipsychotics, risperidone is the weakest in terms of atypicality criteria.
FDA states the following Black Box warnings: Neutropenia (due to the risk of agranulocytosis) Orthostatic hypotension. Seizures.
A very common side effect of clozapine is sedation or drowsiness. This occurs in most patients when they are new to clozapine as they titrate the dosage up. Sedation is not always a problem, since early in treatment with clozapine, people are often agitated or psychotic, and sedation can be calming.
Many cases of sudden death may be attributable to cardiac complications of clozapine, but other unidentified causes of sudden death may be due to its metabolic side-effects.
Clozapine is an antipsychotic medicine that helps to adjust the levels of dopamine and other chemicals available in your brain. Clozapine reduces dopamine activity where it is too high, helping with symptoms like hallucinations.
Clozapine has an average rating of 7.6 out of 10 from a total of 67 ratings on Drugs.com. 71% of reviewers reported a positive effect, while 19% reported a negative effect. Risperidone has an average rating of 5.4 out of 10 from a total of 687 ratings on Drugs.com.
Clozaril (clozapine) and Seroquel (quetiapine) are antipsychotic medications used to treat schizophrenia. Clozaril is also used to help reduce the risk of suicidal behavior in people with schizophrenia or similar disorders. Seroquel is also used to treat major depression and bipolar disorder.
Clozapine is the most effective antipsychotic for the 25% to 33% of people with schizophrenia who are treatment resistant, but not all people achieve response.
Patients taking clozapine had more blood dyscrasias, hypersalivation, seizures, and sedation than those taking olanzapine, risperidone, or quetiapine.