The antipsychotic drugs are those given to combat PSYCHOSIS, but in general it is taken as read that by antipsychotic one is referring to a drug given to treat the SIGNS AND SYMPTOMS of SCHIZOPHRENIA. The terms MAJOR TRANQUILLIZER and NEUROLEPTIC are to all intents and purposes synonymous with the term antipsychotic: antipsychotic is used for preference. The first antipsychotic to be given was CHLORPROMAZINE. In the 1940s Henri Laborit (1914–1995), a French surgeon, administered this to patients about to undergo surgery, in order to reduce STRESS. He hypothesized that the drug’s calming effect could have benefit in treating schizophrenic patients. It was tested for this property and found to be very successful. Other members of the class of drugs—the PHENOTHIAZINES—to which chlorpropmazine belongs were also found to have antipsychotic properties. From a class of drugs related to the phenothiazines, the THIOXANTHINES, were derived the BUTYROPHENONES. Included in this group are HALOPERIDOL and SPIROPERIDOL. The phenothiazines and butyrophenones are commonly used to treat schizophrenia. There are also the so-called ATYPICALANTIPSYCHOTIC drugs (or ATYPICAL NEUROLEPTICS) which are members of other classes: for example, SULPIRIDE (a benzamine), MOLINDONE (similar to SEROTONIN) and PIMOZIDE (a diphenylbutylpiperidine). CLOZAPINE has also been used as an antipsychotic. Antipsychotic drugs are generally characterized as being antagonists at DOPAMINE receptors (see ANTAGONIST). Studies have shown striking correlations between the ability of a drug to bind to dopamine receptors (particularly D2 dopamine receptors) and antipsychotic potency.
This relationship has been very influential in generating the DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA. However, clozapine is a marked exception to this general rule. Although it has an antagonistic effect at dopamine receptors, it also has a variety of other properties. Despite this lack of specificity it is a widely used antipsychotic, with more power to combat the negative symptoms of schizophrenia that the phenothiazines or butyrophenones. It does have other unwanted effects that limit its use.
Antipsychotic medication has had an enormous beneficial effect. Prior to their introduction there were no successful therapies with which to treat schizophrenia (see PSYCHOSURGERY). Some argued that antipsychotic drugs merely provided a ‘chemical straitjacket’, effectively imprisoning patients by sedation, rendering them incapable of independent action. But sedative drugs have no therapeutic benefit in schizophrenia, while the use of antipsychotic drugs has enabled countless numbers of patients to be treated as outpatients rather than as long-stay hospital patients. The increasing admission rates to psychiatric units that occurred in the 1940s and 50s, when mental illness was increasingly recognized as deserving medical attention, fell away dramatically following the introduction of antipsychotic drugs. They are not however without side-effects. Prolonged use of antipsychotic medication can lead to conditions resembling PARKINSON’S DISEASE and to TARDIVE DYSKINESIA. It is also clear that many patients will relapse into further episodes of schizophrenia despite using antipsychotic medication. However, the use of antipsychotic drugs offers the best relief available from schizophrenia.
Reference
Feldman R.S., Meyer J.S. & Quenzer L.F. (1997) Principles of Neuropsychopharmacology. Sinauer Associates: Sunderland MA.
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