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Abstract and Introduction
Abstract
Psychoses are major mental disorders marked by derangement of personality and loss of contact with reality, and are common in the elderly. Various hypotheses suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in psychotic patients, the most studied of which are the dopaminergic, serotonergic and glutamatergic systems. In particular, long-term treatment with antagonists at dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at glutamate receptors may improve symptoms. Treatment with antipsychotics is very common in the elderly and often indispensable. However, for successful treatment it is essential to have an adequate multidimensional assessment of the geriatric patient and of his or her polypathology and polypharmacy, together with knowledge of age-dependent pharmacokinetics and pharmacodynamic changes and drug-drug interactions.
Conventional antipsychotics such as haloperidol, chlorpromazine, promazine, tiapride and zuclopenthixol are D2-receptor antagonists and inhibit dopaminergic neurotransmission in a dose-related manner. They decrease the intensity of all psychotic symptoms, although not necessarily to the same extent and with the same time course. Negative symptoms may persist to a much more striking extent than delusions, hallucinations and thought disorders, and there is a dose-related incidence of extrapyramidal side effects (EPS). Newer antipsychotics, such as clozapine, olanzapine, risperidone, quetiapine and ziprasidone, have a different receptor-binding profile, interacting with both D and 5-HT receptors; they less frequently cause EPS and are better tolerated in the elderly. Their use is advantageous because they are effective both on positive and negative symptoms of schizophrenia and may also be used in the treatment of behavioural disturbances in elderly and/or demented individuals. The use of clozapine is limited by the onset of agranulocytosis, whereas olanzapine, risperidone, quetiapine and, more recently, ziprasidone are widely used, with good results in the above-mentioned diseases.
Introduction
Psychoses are common in the elderly, because they can be either the expression of a disease that had its onset at a young age or the complications of some organic diseases beginning in later life (e.g. dementia).
Psychoses are major mental disorders of organic or emotional origin marked by derangement of personality and loss of contact with reality. They are characterised by a deep division between common events and interior experiences, with delusions or prominent hallucinations occurring in the absence of insight; their prevalence varies from 6% to 10% in the elderly population. Various hypotheses suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in psychotic patients. The most studied are the dopaminergic, serotonergic and glutamatergic systems. In fact, long-term treatment with antagonists at dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at glutamate receptors may improve symptoms. Therefore, pathophysiological studies on dopaminergic, serotonergic and glutamatergic neurotransmission have been the basis of modern pharmacology for psychotic disorders. In particular, we have focused on neurobiological studies that have led to the development of modern antipsychotic drugs.
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