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Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia

  • Anna Maria Meaney (a1), Shubulade Smith (a2), O. D. Howes (a3), Moira O'Brien (a4), Robin M. Murray (a5) and Veronica O'Keane (a5)...

Abstract

Background

High rates of osteoporosis in schizophrenia may result from the prolactin-raising effects of some antipsychotic medication.

Aims

To examine bone mineral density in relation to relevant endocrine variables in patients with schizophrenia taking prolactin-raising antipsychotics.

Method

Fifty-five patients who had been receiving prolactin-raising antipsychotic medication for > 10 years underwent dual-energy X-ray absorptiometry of their lumbar and hip bones. Among the endocrine variables assessed were plasma prolactin and sex hormones.

Results

Age-related reduced bone mineral density measures were found in 17 (57%) of the male and 8 (32%) of the female patients. Higher doses of medication were associated with increased rates of both hyperprolactinaemia and bone mineral density loss. Bone loss for the whole group was correlated with medication dose, and for men was inversely correlated with testosterone values.

Conclusions

These results suggestthat patients with schizophrenia on long-term prolactin-raising antipsychotic medication are at high risk of developing reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism.

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Copyright

Corresponding author

Veronica O'Keane, Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. Tel: +44 (0) 207 8480212; fax: +44 (0)207 8376982; e-mail: v.o'keane@iop.kcl.ac.uk

Footnotes

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Declaration of interest

Work supported by an unrestricted educational research grant from Eli-Lilly, Ireland.

Footnotes

References

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The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
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Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia

  • Anna Maria Meaney (a1), Shubulade Smith (a2), O. D. Howes (a3), Moira O'Brien (a4), Robin M. Murray (a5) and Veronica O'Keane (a5)...
Submit a response

eLetters

Osteoporosis and Typical Antipsychotics

Muzaffar Husain, SHO in General Adult Psychiatry
25 June 2004

Meaney at al’s paper(1) made an important contribution to the growingbody of evidence supporting the link between osteoporosis and long term treatment with typical antipsychotics. However, I would have some reservations in accepting this association unequivocally.

The study recruited 25 post-menopausal women and 30 men whose demographic and clinical details were clearly different at induction into the survey. Vital parameters like age, treatment duration, and smoking andexercise habits were very dissimilar between the two sexes. This was appropriately highlighted in the study. What could have been further clarified was that the chlorpromazine equivalence scores were statistically predictive of reduced bone mineral density in the lumbar region only when these two disparate groups were analyzed together as one group.

Of course the risk of osteoporosis in this patient group may be different for the two sexes. Most of the research in recent years has focused on this differential risk. For males, evidence for this association has been mixed. An earlier study by the same group(2) showed no association between typical antipsychotic use and reproductive hormones. In the absence of this, it has been difficult to describe a biologically plausible mechanism for osteoporosis in men taking typical antipsychotics(3). Clearly the results have to be consistent in a number of studies before any changes in treatment protocols can be made.

It is true that female patients have been extensively studied in the past regarding the risk of osteoporosis due to long term typical antipsychotic medication as an independent risk factor. However, by recruiting specifically post-menopausal women into this survey, it is feltthat this question is dealt with obliquely. A large number of other risk factors would already be operative in this group, and it would be difficult to establish any kind of direct association between typical antipsychotic usage per se and the onset of bone mineral density loss. This might have been evident if the female group had been analyzed separately.

The gravity of this issue cannot be questioned. NICE recommendations(4) ask for the clinician to continue typical antipsychotics in those patients who “achieve good control of their condition without unacceptable side effects”. The alternatives to typical antipsychotics are the newer atypical ones. As is mentioned in this study,these latter drugs have not been around for long. A few recent studies comparing exclusively female subjects exposed to typical and atypical medication for one to two years have not found any differences in bone mineral density in the two groups(5,6). This further signifies the risks inherent in making any premature decisions about typical antipsychotics, especially as they work well in many patients. We ought to weigh our options carefully, before restricting them.

References

1. Meaney, A.M., Smith, S., Howes,O.D. ,O’Brien,M., Murray,R.M., and O’Keane,V.(2004) Effects of long-term prolactin raising antipsychotic medication on bone mineral density in patients with schizophrenia. BritishJournal of Psychiatry, 184, 503-508.

2. Smith, S., Wheeler,M., Murray,R., et al (2002) The effects of antipsychotic induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis. Journal of Clinical Psychopharmacology, 22,109-114.

3. Lean, M. and De Smedt,G.(2004) Schizophrenia and osteoporosis.Int Clin Psychopharmacology, 19(1): 31-35.

4. National Institute of Clinical Excellence Recommendations : Guidance on the use of newer(atypical) antipsychotic drugs for the treatment of schizophrenia; November 2002.

5. Abraham, G., Paing, W.W., Kaminski, J., et al . (2003) Effects of elevated serum prolactin on bone mineral density and bone metabolism in female patients with schizophrenia: a prospective study. American Journal of Psychiatry, 160(9):1618-20.

6. Becker D et al.(2003) Risperidone, but not olanzapine, decrease bone mineral density in female premenopausal schizophrenic patients. Journal of Clinical Psychiatry, 64(7):761-66.
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