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Clozapine in Psychology



Clozapine Using in Psychology

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Clozapine is one of the most dubious drugs that is used mainly for treating patients with psychological disorders and should be taken with extreme carefulness and attention. The drug has a wide range of side and negative effects. It was once forbidden but soon returned to the drug markets for its unarguable positive effects on patients with schizophrenia. The paper aims at analyzing the medication called clozapine and revealing its beneficial and harmful sides. It presents the history of the drug’s introduction to the market, information on the category, chemical name, and pharmacology of the medication. Moreover, it explains the mechanism of its action and points out the foremost benefits and side effects caused by the drug’s usage.

History of Clozapine

Clozapine was historically the first representative of the class of so-called "atypical antipsychotics", i.e. antipsychotics that differ from traditional ones by low probability of extrapyramidal side effects, better tolerability, and smaller influence on the secretion of prolactin (Beale and Block 10).

Clozapine was synthesized in the 1960s by Sandoz and released first in Austria and Switzerland under the name Leponex (Beale and Block 10). After in Finland in the 1970s 8 out of 16 patients died while taking clozapine (developed agranulocytosis), the drug was prohibited in the United States and many other countries (Beale and Block 11). However, some countries continued to use it. In 1990, the medication returned to the market in the United States after it was discovered that it is effective in treating schizophrenic psychoses resistant to therapy and less apt to cause general side effects typical for antipsychotics (Beale and Block 11).

Category and Chemical Name

By its chemical structure, clozapine is a tricyclic compound that has similarities with tricyclic antidepressants and partly with benzodiazepine tranquilizers (Beale and Block 4). It possesses a chemical name of tricyclic benzodiazepine with molecular formula C18H19ClN4 (8-chloro-11-(4 methyl piperazine-1 yl)-5H-dibenzo[b,e][1,4]diazepine) (Beale and Block 2). The first metabolite in the circuit of clozapine biotransformation in the liver is nor clozapine, which possesses the same pharmacological properties as the parent compound (Beale and Block 5). One of the metabolites of the nor clozapine in the body is called benzodiazepine, which partly conditions a strong anti-anxious activity of clozapine (Beale and Block 5).


Clozapine is "the most atypical" of all atypical anxiolytics because it causes fewer extrapyramidal disorders than any other antipsychotics (Beale and Block 16). Clozapine has potent antipsychotic, mild antimanic, and moderate tricyclic-like antidepressant activity coupled with a strong hypnotic, sedative, and anti-anxiety effect (Beale and Block 18). It blocks different subtypes of dopamine (D1, D2, D3, D4, D5), serotonin (5-HT1A, 5-HT2A, 5-HT1S), muscarinic (M1, M2, M3, M5), histamine (H1) and adrenergic (?1, ?2) receptors; possesses the features of agonism towards M4 receptors (Beale and Block 18).

Due to a very strong anxiolytic activity, clozapine expresses a particular selectivity for acute depersonalization syndrome, quickly, strongly, and selectively eliminating acute depersonalization emerged in depression patients (Devanand et al. 1501). The efficacy of clozapine regarding chronic depersonalization is much lower but still very significant (Devanand et al. 1501).

The clinical improvement in clozapine treatment in patients with schizophrenia is achieved more often than in the treatment using typical antipsychotics (Drake et al. 441). It is highly effective at treating productive symptoms, including those resistant to other antipsychotic drugs (Hayes et al. 646). Moreover, it is effective at the risk of suicide, persistent hostility, and aggressiveness (Hayes et al. 646). Concerning cognitive impairment, clinical trial results have produced conflicting outcomes (Hayes et al. 647). On the one hand, clozapine improves the condition, whereas under different circumstances it has no effect on cognitive impairment or even leads to deterioration (Hayes et al. 647).

Mechanism of Action

While clozapine is an antipsychotic medication, its main function is to change the way chemicals in brain activity. As a result, it is supposed to treat schizophrenia disorders, including suicidal thoughts and extreme aggressiveness. Clozapine binds to the receptors of dopamine and serotonin, therefore improving the general condition of the patient and reducing anxiety, schizophrenia disorders, and depression. The drug causes the production of D-serine and glutamate that significantly reduce astrocytic glutamate carriers. Furthermore, the drug averts the disabled NMDA receptor utterance induced by the antagonists of the NMDA receptor.

Clozapine is not recommended for use for children and adolescents up to 16 years or in the period of pregnancy and breastfeeding (Devanand et al. 1506). As a rule, it is indicated to be used as monotherapy. There exists a long list of drugs that should not be combined with clozapine: other neuroleptics (e.g. phenothiazines and depot antipsychotics), antidepressants, analgesics, anti-rheumatic and anti-inflammatory drugs, antiepileptics, thyreostatic, antidiabetic, antiarrhythmic, cytotoxic, immunosuppressive, antimicrobial, antifungals, antihistamines and antimalarials (Devanand et al. 1505).

Indications and Beneficial Uses

The medication should by no means be used as first-line due to the frequent (1-2%) development of formidable and often deadly complications - granulocytopenia, up to agranulocytosis, and aplastic anemia (Beale and Block 856).

Clozapine is applied in case of the patient’s resistance to other neuroleptic (in the case at least two conventional neuroleptics taken in usual dosage over a long period do not improve clinical or subjective state) and in case severe adverse effects, mainly extrapyramidal, appear (Devanand et al. 1505). The medication requires a guarantee for the implementation of the relevant medical and control measures that determine the need for the material and technical basis for the control of blood and special training of medical staff (Devanand et al. 1506).

The antipsychotic dose (300-600 mg/ day) is used in the hallucinatory-delusional, catatonia gebrephen, catatonia-hallucinatory states, and states of psychomotor agitation in case of schizophrenia, a manic syndrome in bipolar affective disorder (Hayes et al. 649). In some cases, the drug is effective in terms of treatment resistance to other antipsychotics (neuroleptic) (Beale and Block 857).

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In small doses (12,5-25-50 mg/day), the drug is often used as a hypnotic, sedative, and anxiolytic remedy for insomnia and sleep disorders of various origins (Hayes et al. 653). Moreover, it is prescribed for patients suffering from anxiety, nervousness, agitated depression, and depression with depersonalization (Hayes et al. 647). It is also used in the case of psychopathy of excited patients, aggression, dysphoria, mood fluctuations, and disorders (Hayes et al. 647).

Frequent use of clozapine as sedation and the hypnotic drug is exposed to criticism as inconsistent with its basic profile indications for use in therapy (Hayes et al. 653). It is noted that in many cases, clozapine is prescribed without any good reason and consideration of the ratio between risk and benefit (Hayes et al. 653).

Among the beneficial uses of the drug, one should mention the reduction in alcohol use, which is the result of the drug’s influence on negative or positive psychotic symptoms (Drake et al. 445). Moreover, with the help of clozapine, the patients decrease the severity of alcohol abuse, abolish disorders caused by alcohol use and reduce the number of days of alcohol use (Drake et al. 446). Moreover, among the most significant benefits of using the drug, one should mention the reduction of recurrent suicidal actions, especially in patients suffering from schizophrenia.

Negative Possibilities

The patients treated by clozapine may experience drowsiness, confusion, headaches, dizziness, tremors, muscle rigidity, myoclonic jerks, dry mouth, orthostatic hypotension, tachycardia, constipation, nausea, vomiting, muscle weakness, increase in body weight (Covel, Weissman, and Essock 229), dysfunction of the sweat glands, hypersalivation, intestinal obstruction, paralytic ileus, violation of accommodation, priapism, excessive sedation, urinary incontinence, urinary retention, fatigue, fever, benign hyperthermia, dysregulation of sweating and body temperature, rarely - the development of vascular collapse leading to heart failure and/ or difficult breathing (dyspnoea) (Beale and Block 847).

It may also cause arrhythmia, pericarditis, thromboembolism, hypertension, myocarditis, and fatal cardiomyopathy (Covel, Weissman, and Essock 235). In rare cases, the medication can cause the development of side effects such as delirium and neuroleptic malignant syndrome (Beale and Block 847). Moreover, it can cause such diseases as jaundice, hepatitis B, acute pancreatitis, interstitial nephritis, renal dysfunction, and renal failure (Beale and Block 847).

In my opinion, the drug has such an enormous number of side effects and contraindications that it can hardly win patients’ trust and respect. On the other hand, positive effects, especially those saving human lives somehow overshadow its side effects. All in all, the medication should never be taken without the supervision of a professional and should never be overused. Moreover, the patient and doctor have to think twice and double-check whether it is of great importance to take the medication and whether the positive effects prevail on possible negative effects.

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reviewed on December 14, 2017, via SiteJabberClick to see the original review on an external website.


Clozapine appears to be of extreme interest while it is one of the most controversial and dubious medications of all time. On the one hand, it has a strict spectrum of activity and helps treat particular types of diseases and disorders. On the other hand, clozapine appears to have more negative possible effects than positive. Moreover, it should be prescribed and taken with extreme care and attention to all possible contraindications. All in all, the drug is a powerful and helpful element of successful treatment if it is utilized carefully and intelligently.

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