Acute dopamine receptor blockade by neuroleptics has long been known to induce a dose-dependent increase in prolactin as a consequence of the decreased activity of the inhibitory D2 receptors that govern the release of this hormone from the anterior pituitary. However, dose-response studies show that the dose of a neuroleptic required to raise the plasma prolactin concentration is lower than that necessary to have an optimal therapeutic effect. Furthermore, the time of onset of the rise in prolactin is short (hours), whereas the antipsychotic effect of a neuroleptic takes many days or even weeks. There is also evidence that raised serum prolactin levels persist throughout drug treatment, which suggests that tolerance of the tubero-infundibular dopaminergic system to the action of neuroleptics does not occur; it should be noted that not all investigators agree with such a view. There is little evidence to suggest that a relationship exists between the symptoms of schizophrenia, or the response to drug therapy, and changes in plasma prolactin concentrations.
The secretion of growth hormone is under the control of the dopaminergic, noradrenergic, serotonergic and possibly other neurotransmitter systems. The acute apomorphine growth hormone challenge test has been used to assess D2 receptor function in untreated schizophrenics and in patients during neuroleptic treatment. Apomorphine-stimulated growth hormone secretion is reported to be higher in untreated schizophrenics and to be
Table 11.10. Treatment decisions for schizophrenia
• First choice - atypical antipsychotic (e.g. risperidone, olanzepine, quetiapine, amisulpride, clozapine)
• Switching - alternative atypical antipsychotic to that previously used
• Augmentation - mood stabilizer, high potency first-generation neuroleptic (e.g. flupenthixol), possibly a benzodiazepine
• Other options - i.m. formulations blunted following both acute and chronic neuroleptic treatment, returning to control values within a few weeks of drug withdrawal.
Sexual dysfunction in schizophrenic patients on long-term neuroleptic therapy is well established and may result from hyperprolactinaemia. Menstrual cycle disruption is a common feature of neuroleptic treatment which may be complicated in hyperprolactinaemia. However, it seems unlikely that the changes in gonadotrophin secretion are a unique feature of schizophrenia, as patients with depression and anorexia nervosa also show such abnormalities. Furthermore, detailed studies of the luteinizing hormone and follicle-stimulating hormone levels in a group of male and female patients on very long-term neuroleptic therapy could not confirm an abnormality in sex hormone dysfunction due to drug treatment. Thus it must be concluded that unequivocal evidence showing that prolonged neuroleptic treatment results in sexual dysfunction due to a defect in gonadotrophin release is not yet available.
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