CLOZAPINE- A REVOLUTIONARY DRUG FOR SCHIZOPHRENIC PATIENTS
Clozapine
Clozapine is a psychotropic drug that belongs to the chemical class of benzisoxazole derivatives. It is a selective monoaminergic antagonist that binds to serotonin, dopamine, adrenergic, and histaminergic receptors.
Clozapine is used to treat schizophrenia, a disorder in which a person suffers from severe brain disorder characterized by impaired daily functioning, severely disordered thinking, and sometimes disabling.
Mechanism of action
Clozapine induces its antipsychotic effects by binding at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex and reduces positive symptoms of schizophrenia. Conversely, it reduces negative symptoms by antagonizing the 5HT2A receptors.
Therapeutic Use
In individuals suffering from acute schizophrenia, symptomatic improvement is seen by using clozapine. Usually, it produces anxiolytic effects when its use begins, followed by antipsychotic effects after 1 to 2 weeks. Subsequently, the behavioral disturbance is alleviated, which leads to social skills restoration. For its sustained therapeutic effects, maintenance therapy is given for less than equal to 6 years in patients with chronic schizophrenia.
Facts and figures of clozapine
- Clozapine was the first breakthrough after the discovery of chlorpromazine for treating schizophrenia. It is effective in treatment-resistant individuals and also lowers the rate of suicide among schizophrenia individuals.
- Clozapine was banished from psychotic pharmacopeia because of its severe lethal effect on agranulocytosis, but it was rescued because of its therapeutic effects compared with other drugs, such as chlorpromazine.
- Clozapine is the only antipsychotic medication with an anti-craving effect for the abuse or misuse of drugs.
- Different studies have shown that clozapine affects different dimensions of schizophrenia syndrome.
- Exceptionally, clozapine is the only antipsychotic drug with no motor side effects. It alleviates psychotic symptoms without any side effects on the movement of an individual. (4)
- With so many benefits to consider for clozapine, some side effects or adverse effects raise questions about its use; for instance, it leads to weight gain and impaired lipid and glucose metabolism.
- Although clozapine is a standard gold drug in treating refractory schizophrenia, adverse effects are associated with its use, such as agranulocytosis or weight gain, which necessities scientists to find some new drug that is equivalent in therapeutic effects to clozapine but does not have its side effects.
- As clozapine is associated with the severe or fatal side effects of agranulocytosis, its use is restricted to refractory schizophrenia, and constant monitoring is done regularly during therapy.
- Occasionally, clozapine may result in hepatotoxicity, characterized by abdominal discomfort, nausea, and weakness. If hepatotoxicity occurs, clozapine therapy should be discontinued immediately.
- Clozapine may also induce agranulocytosis, which is characterized by a reduction in neutrophils and white blood cells and increase the risk of infection among patients. Therefore, strict monitoring is required during clozapine therapy to detect agranulocytosis, which usually begins 3-6 months after initiating therapy.
- Patients who enter the RED ZONE with WBC <2*109/L should not be rechallenged with clozapine therapy.
REFERENCES
- PubChem. (n.d.). Clozapine. Pubchem.ncbi.nlm.nih.gov. Retrieved August 28, 2022, from https://pubchem.ncbi.nlm.nih.gov/compound/Clozapine#section=Pharmacology-and-Biochemistry
- Mayo Clinic. (2020, January 7). Schizophrenia - Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443#:~:text=Schizophrenia%20is%20a%20serious%20mental
- Fitton, A., & Heel, R. C. (1990). Clozapine. Drugs, 40(5), 722–747. https://doi.org/10.2165/00003495-199040050-00007
- Joober, R., & Boksa, P. (2010). Clozapine: a distinct, poorly understood, and under-used molecule. Journal of Psychiatry & Neuroscience: JPN, 35(3), 147–149. https://doi.org/10.1503/jpn.100055
- Aringhieri, S., Carli, M., Kolachalam, S., Verdesca, V., Cini, E., Rossi, M., McCormick, P. J., Corsini, G. U., Maggio, R., & Scarselli, M. (2018). Molecular targets of atypical antipsychotics: From the mechanism of action to clinical differences. Pharmacology & Therapeutics, 192, 20–41. https://doi.org/10.1016/j.pharmthera.2018.06.012
