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Title: The endocrine side effects of antipsychotic medication: prevalence, impact and treatment.
Author: Howes, Dr Oliver
ISNI:       0000 0001 3582 792X
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2007
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Antipsychotic drugs have been known to have effects on the endocrine system since their introduction to clinical practice. However, until recently there has been little systematic investigation of the prevalence and end-organ effects of endocrine disturbance in people taking antipsychotic medications. This thesis presents a series of studies that investigate glucose-insulin homeostasis, hypothalamic-pituitary-gonadal (HPG) axis function, and the relationship between abnonnalities of the HPG axis and sexual function, bone mineral density (BMD), and glucose-insulin homeostasis in patients taking antipsychotic medication. Abnonnalities of glucose-insulin homeostasis were found in patients taking antipsychotic drugs, and switching antipsychotic treatment to clozapine was associated with the rapid development of glucoregulatory abnonnalities which were not related to changes in insulin, prolactin, insulin-like growth factor or growth honnone levels. The studies of the HPG axis found that, as expected, prolactin levels were commonly elevated in patients taking most antipsychotic drugs. Low testosterone, oestradiol and progesterone levels and high rates of sexual dysfunction were found in patients taking antipsychotic drugs, extending recent findings in a larger systematically acquired sample of subjects. However, no relationship was found between sex honnone or prolactin levels and sexual function. BMD was not found to be decreased to a clinically significant level in patients taking antipsychotic drugs, and was not related to prolactin levels. The findings presented in this thesis indicate that patients and clinicians need to be aware of the high likelihood of glucose-insulin and HPG axis disturbance, and sexual dysfunction associated with most antipsychotic treatments. Additionally these data indicate that the aetiology of sexual dysfunction and glucoregulatory abnonnalities is complex, and that the abnonnalities are not simply explained by the effects of prolactin elevation, reduced sex honnone levels, or disturbance of insulin homeostasis. A randomised controlled trial (RCT) was conducted to investigate the effects on sexual function, sex honnone levels, and bone mineral density of switching antipsychotic treatment to a relatively prolactinsparing medication compared with remaining on a relatively prolactin-raising drug. The RCT was discontinued early because inadequate recruitment and retention of subjects meant that there was insufficient power to detect differences between treatments. The factors contributing to the difficulties with the RCT are discussed and suggestions presented to guide the development of future studies to investigate treatment approaches to sexual dysfunction and hypogonadism in patients taking antipsychotic medications. 1 Supplied by The British Library - 'The world's knowledge' The thesis comprises introductory and concluding chapters, a description of the discontinued RCT and the following published papers: Howes OD, Rifkin L. Diabetic keto-acidotic (DKA) coma following olanzapine initiation in a previously euglycaemic woman and successful continued therapy with olanzapine. J Psychopharmacol (2004); 18(3): 435-7. Howes 0, Smith S. Alendronic acid for antipsychotic-related osteopenia. Am J Psychiatry (2004); 161(4): 756 Howes OD, Wheeler MJ, Pilowsky LS, Landau S, Murray RM, Smith S. Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder. J Clin Psychiatry 2007; 68(3): 361-7. Howes OD, Wheeler MJ, Meaney AM, O'Keane V, Fogelman I, Blake G, Murray RM, Smith S. Bone mineral density and its relationship to prolactin levels in patients taking antipsychotic treatment. J Clin Psychopharmacology. 2005; 25(3): 259-61. Howes OD, Smith S, Gaughran F, Murray RM, Pilowsky LS. The relationship between prolactin levels and glucose homeostasis in antipsychotic treated schizophrenic patients. J Clin Psychopharmacology 2006: 26(6); 629-31 Howes OD, Bhatnagar A, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS. A prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance. American Journal of Psychiatry. 2004: 161 (2); 361-363. Howes OD, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS. The Effect of Clozapine on Factors Controlling Glucose Homeostasis J Clin Psychiatry 2004; 65 (10): 1352- 1355
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available