Clozapine is a neuroleptic drug. It is used to treat schizophrenia and psychosis when other medications are unsuitable for it.
What is clozapine?
The prescription antipsychotic clozapine is classified as a member of the neuroleptic group. The drug is used when other medications either do not have the hoped-for effect in treating psychosis or schizophrenia, or the patient cannot tolerate them. Before the neuroleptic is used, the patient’s blood count must be taken. Clozapine was developed in the late 1950s by the Swiss company Wander AG. This involved screening among approximately 2000 different substances to produce new antidepressants. In 1960, the compound was patented, although its antipsychotic effects initially remained undiscovered. In the mid-1960s, further trials took place on people suffering from chronic productive schizophrenia. During the studies, researchers eventually noticed clozapine’s antipsychotic effects. The drug entered the market in 1972 under the preparation name Leponex, which was often prescribed in Europe. In 1975, however, several patients in Finland suffered fatal cases of agranulocytosis, for which clozapine was responsible. For this reason, several countries such as Germany issued special regulations for the use of the drug. For example, physicians were required to notify the manufacturer of the prescription for clozapine, whereupon they received an information package about the drug. Only after the physician had given a written assurance that the data would be taken into account was he allowed to prescribe the antipsychotic. In 1990, the drug also entered the U.S. market under the trade name Clozaril. In the years that followed, several generic versions were released. To date, despite numerous research efforts, clozapine has remained the only drug of its kind that does not cause Parkinson’s symptoms at high doses. However, because other neuroleptics such as risperidone or quetiapine do not carry a higher risk of agranulocytosis, they are often given preference over clozapine.
Pharmacologic effects
Clozapine is one of the atypical neuroleptics. This means that it binds in the central nervous system to the receptors of the neurotransmitters serotonin and dopamine, where it blocks the docking sites. If there is an excess of dopamine, this becomes noticeable through an altered way of thinking and self-perception. Delusions are also possible. By blocking the dopamine receptors, clozapine can return brain functions to normal. Anxiety disorders as well as states of agitation are alleviated, and concentration and memory improve. Clozapine is absorbed into the blood almost entirely through the gastrointestinal tract. Most of the metabolism takes place within the liver. The active ingredient is excreted in the stool and urine. It takes 8 to 16 hours for clozapine to leave the body.
Medicinal use and application
Clozapine is used to treat severe schizophrenia. However, because the neuroleptic has severe side effects, it is used only when other medications fail to improve symptoms. The same applies to the treatment of severe psychoses in Parkinson’s disease. Here, too, treatment is given only after the usual therapy has failed. In most cases, clozapine is administered in tablet form. Sometimes an injection by syringe may also take place. The dose of the neuroleptic is determined by the treating physician on a case-by-case basis. As a rule, the patient initially receives a low dose, which is then gradually increased as the therapy progresses. If the treatment is nearing its end, it is advisable to slowly reduce the dosage again. Before therapy with clozapine can take place, the patient’s blood count must show a normal leukocyte count. This means that the leukocyte (white blood cell) count and differential blood count must be normal values.
Risks and side effects
Because treatment with clozapine may result in leukopenia (white blood cell deficiency) or agranulocytosis (granulocyte deficiency), it is necessary for patients to have regular blood count checks during treatment. The most common side effects of the neuroleptic include palpitations, constipation, drowsiness, and excessive salivation.Furthermore, visual disturbances, an increase in weight, a drop in blood pressure after standing up, tremors, headaches, tics, problems sitting still, seizures, loss of appetite, nausea, vomiting, high blood pressure, dry mouth, fever, problems with temperature regulation, and difficulties urinating are possible. In rare cases, there is a risk of hyperglycemia with metabolic derailment, severe myocarditis, circulatory collapse, acute pancreatitis or severe liver necrosis, in which the liver tissue dies. If the patient has hypersensitivity to clozapine, the neuroleptic must not be used. The same applies if the patient has experienced agranulocytosis during previous clozapine therapies, has blood count disorders or bone marrow damage. In addition, the patient must not receive any substances during treatment that could cause blood count disorders in him or her. Other contraindications include poisoning-induced psychosis, untreated epilepsy, clouding of consciousness, marked brain disorders, jaundice, liver disease, heart or kidney disease, and intestinal paralysis. Treatment of pregnant and breastfeeding women with clozapine is prohibited. There is a risk of harm to children from withdrawal symptoms or movement disorders. Interactions with other drugs may also occur. For example, the effect of clozapine is enhanced by taking erythromycin and cimetidine. In addition, nicotine and caffeine affect the effects of the neuroleptic, so patients should not suddenly change their consumption during treatment.
