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PAPERS:
Anna Maria Meaney, Shubulade Smith, O. D. Howes, Moira O’brien, Robin M. Murray, and Veronica O’keane
Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia
The British Journal of Psychiatry 2004; 184: 503-508 [Abstract] [Full text] [PDF]
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[Read eLetter] Osteoporosis and Typical Antipsychotics
Muzaffar Husain   (25 June 2004)

Osteoporosis and Typical Antipsychotics 25 June 2004
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Muzaffar Husain,
SHO in General Adult Psychiatry
Leeds Mental Health NHS Trust, UK

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Re: Osteoporosis and Typical Antipsychotics

muzhusain{at}hotmail.com Muzaffar Husain

Meaney at al’s paper(1) made an important contribution to the growing body 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 and exercise 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 felt that 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. British Journal 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.