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Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes

Response to consensus statement

Endocrinology and Metabolism Unit, Development Origins of Health and Disease Division, School of Medicine, University of Southampton, Southampton, U.K

Address correspondence to Dr. R.I.G. Holt, Level F, Centre Block, MP 113, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K. E-mail: righ{at}soton.ac.uk

I commend the authors of the consensus statement in Diabetes Care for focusing our attention on the physical health of people with schizophrenia and serious mental illnesses and on the need for glucose monitoring (1). There is little consensus about the risk of diabetes in people with schizophrenia and the role of atypical antipsychotic drugs (2–4). Recently I was a member of a group of international psychiatrists and diabetologists who reviewed the evidence surrounding this issue (proceedings have been published in a supplement to the April 2004 issue of the British Journal of Psychiatry). I was, therefore, interested to see that the conclusions published in Diabetes Care differed in some respects from our deliberations and those of the U.S. Food and Drug Administration (FDA). In September 2003, the FDA wrote to the manufacturers of all atypical antipsychotic drugs to ask that their respective labels be changed to recommend regular glucose testing for all schizophrenia patients at risk of diabetes. The FDA went on to explain that "[p]recise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available."

The Diabetes Care consensus statement suggests that the risk of hyperglycemia for some "atypicals," such as clozapine and olanzapine, is greater than for others (1). It is unclear how this opinion was reached, because although a bibliography was given, the work was unreferenced. One may speculate that the weight given to the 35 retrospective studies was greater than that for the prospective trials (4); the placebo-controlled studies (5–7) and the longest prospective study (8), which assessed glucose over 1 year and compared clozapine and chlorpromazine, are not mentioned in the bibliography.

None of the retrospective studies can state how many patients given each drug received blood tests. This is a crucial confounder, as patients receiving typical antipsychotics have less blood monitoring than those receiving "atypicals" (9). Any study that introduces glucose screening will undoubtedly find new previously undiagnosed diabetes because of the high prevalence of undiagnosed type 2 diabetes.

I am unaware of any prospective trial showing any difference among "atypicals" in terms of emergent glucose abnormalities. The best trial data comparing aripiprazole with olanzapine over 6 months found that emergent glucose abnormalities were identical (4.7 vs. 4.5%) (5,7). The use of placebo cohorts is critical to understanding what part of the risk of glucose abnormalities is attributable to drugs. There are two such datasets, and the incidence of diabetes in the placebo cohorts does not differ from that in the active-drug group (5,6).

Interestingly, during the randomized control trials, weight gain was not associated with the development of diabetes and the incidence of diabetes did not differ among the various "atypicals," despite differing propensity for weight gain. Linking short-term weight gain to the risk of diabetes ignores the many other genetic and environmental reasons why people with schizophrenia develop diabetes (10,11).

Antipsychotic medication is essential for people with schizophrenia, and effectiveness should be the most important consideration when selecting treatment. The FDA was nearer to the mark in its judgement, and choosing an antipsychotic drug on the basis of its potential to worsen glycemia is failing to understand the available data.

Footnotes

R.I.G.H. has been a member of an advisory panel for, has received honoraria from, and has received grant support from Eli Lilly.

References

1. American Diabetes Association: Consensus development conference on antipsychotic drugs and obesity (Consensus Statement). Diabetes Care 27:596–601, 2004[Free Full Text]
   
2. Dinan TG, Kohen D: Atypical antipsychotics and diabetic propensity: more questions than answers. Hum Psychopharmacol Clin Exp 18:591–593, 2003
   
3. Buse JB: A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United States. J Clin Epidemiol 56:164–170, 2003[Medline]
   
4. Cerri K, Bushe CJ, Haddad P: How valid are retrospective epidemiological studies in evaluating differential rates of diabetes mellitus attributed to antipsychotics? Schizophr Res 67:S367, 2004
   
5. Food and Drug Administration: Ablify (aripiprazole) tablets [article online], 2003. Available from http://www.fda.gov/cder/foi/nda/2002/21-436_Abilify.htm. Accessed 1 June 2004
   
6. Cavazzoni P, Mukhopadhyay N, Carlson C, Brier A, Buse J: Retrospective analysis of risk factors in patients with treatment emergent diabetes during clinical trials of antipsychotic medications. Br J Psychiatry Suppl 47:S94–S101, 2004
   
7. Bushe CJ, Leonard B: Association between atypical antipsychotic agents and type 2 diabetes: review of prospective clinical data. Br J Psychiatry Suppl 47:S87–S93, 2004
   
8. Lieberman JA, Phillips M, Gu H, Stroup S, Zhang P, Kong L, Ji Z, Koch G, Hamer RM: Atypical and conventional antipsychotic drugs in treatment-naïve first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine. Neuropsychopharmacology 28:995–1003, 2003[Medline]
   
9. Citrome L: Antipsychotic medication treatment and new prescriptions for insulin and oral hypoglycaemics. Eur Neuropsychopharmacol 13 (Suppl. 4):S306, 2003
   
10. Ryan MC, Collins P, Thakore JH: Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry 160:284–289, 2003[Abstract/Free Full Text]
    
11. Bushe CJ, Holt R: Prevalence of diabetes and impaired glucose tolerance in patients with schizophrenia. Br J Psychiatry Suppl 47:S67–S71, 2004
    

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				R. I. G. Holt, C. Bushe, and L. Citrome Diabetes and schizophrenia 2005: are we any closer to understanding the link? J Psychopharmacol, November 1, 2005; 19(6_suppl): 56 - 65. [Abstract] [PDF]

				E. J. Barrett Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes: Response to Holt, Citrome and Volevka, Isaac and Isaac, and Boehm et al. Diabetes Care, August 1, 2004; 27(8): 2089 - 2090. [Full Text] [PDF]

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holt, R. I.G. Search for Related Content PubMed PubMed Citation Articles by Holt, R. I.G. Social Bookmarking                What's this?