Antipsychotics - The Future of Schizophrenia Treatment

George Beaumont


Curr Med Res Opin. 2000;16(1) 

In This Article

Side-effects of Typical Antipsychotics

Antipsychotic drugs are thought to act in schizophrenia by blocking dopaminergic receptors, thereby interfering with dopaminergic transmission. There is, however, growing evidence to suggest that typical antipsychotics also affect other neurotransmitter systems such as the cholinergic (muscarinic), alfa-adrenergic, histaminergic and serotonergic mechanisms. Typical antipsychotics are, therefore, essentially pharmacologically 'dirty' drugs and their use may consequently increase the risk of a wide variety of undesirable side-effects. For example, their anticholinergic side-effects include dry mouth, urinary hesitancy (and even retention), constipation and visual disturbance, while their effects on noradrenergic mechanisms lead to postural hypotension, disturbances of sexual functions and nasal congestion. As a consequence of their antihistaminic action, many of these compounds are sedative. Furthermore, their prolonged use may lead to weight gain. Interference with dopaminergic transmission can lead to both endocrinological side-effects such as hyperprolactinaemia, which may manifest itself as galactorrhoea, amenorrhoea and gynaecomastia, and extrapyramidal side-effects (EPS). Although the side-effects involving the extrapyramidal system are the most important for typical anti-psychotics, the combination of all those mentioned above is very likely to affect the patients' qualities of life adversely and their desire to continue with, and adhere to, therapy.

There is a variable relationship between the types of side-effect produced by typical antipsychotics. For example, the British National Formulary[9] divides the pheno-thiazines into three main groups:

  1. Group 1 includes chlorpromazine, methotrimeprazine and promazine. These compounds are very sedative, but have only moderate anti-muscarinic and extrapyramidal side-effects.

  2. Group 2 includes pericyazine, pipothiazine and thioridazine. Sedative effects are only moderate, antimuscarinic effects marked, but EPS occur less frequently than with drugs in Groups 1 and 3.

  3. Group 3 contains fluphenazine, perphenazine, prochlorperazine and trifluoperazine, and is characterised by less sedation, fewer antimuscarinic effects, but pronounced EPS.

Drugs belonging to other groups, such as the butyrophenones, diphenylbutyl piperidines, thioxanthenes and substituted benzamides, resemble the phenothiazines of Group 3.


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