© 2006 The Royal College of Psychiatrists
Correspondence |
Metabolic syndrome and schizophrenia
Division of Psychiatry and Neuroscience, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK.
Correspondence: E-mail: g.reynolds{at}qub.ac.uk
In his recent editorial Dr Thakore (2005) rightly highlights the importance of the association of the metabolic syndrome and one of its consequences, type 2 diabetes, with schizophrenia. Despite acknowledging that antipsychotic drugs can induce substantial weight gain, he avoids ascribing the metabolic disturbances in schizophrenia to drug-induced obesity. His suggestion that untreated schizophrenia is itself associated with metabolic disturbance is based on a study of 19 people who had substantially greater deposits of intra-abdominal fat than a control group (Ryan et al, 2004). This contrasts with other studies showing that 40 antipsychotic-naïve patients with schizophrenia had no elevation in intra-abdominal fat compared with controls (Zhang et al, 2004) and that 50 did not differ from a control group in terms of body mass index, fasting plasma glucose or insulin (Arranz et al, 2004). In attempting to explain discrepancies in terms of methodological differences, Dr Thakore is wrong to state that the control group of Zhang et al consisted of ‘elderly men’; controls were well matched for age and gender with the patient group.
These larger studies also show that antipsychotic drug treatment is associated with increased intra-abdominal fat (Zhang et al, 2004) and insulin resistance (Arranz et al, 2004), despite negative findings from Ryan et al (2004). The risk of diabetes in schizophrenia is higher in patients receiving olanzapine rather than conventional antipsychotics (Koro et al, 2002); olanzapine is particularly liable to induce weight gain. These and other studies indicate that antipsychotic drug treatment can result in metabolic morbidity. It would thus be misleading, if not dangerous, to imply that obesity resulting from treatment with some antipsychotic drugs is not associated with the development of the metabolic syndrome and type 2 diabetes.
Dr Thakore listed criteria for the metabolic syndrome; these have now been superseded by a more clinically accessible and less stringent definition. The core criterion is central (abdominal) obesity, defined by waist circumference, plus two of four risk factors from elevated triglycerides, reduced high-density lipoprotein cholesterol, raised blood pressure and raised fasting plasma glucose (International Diabetes Federation, 2005).
Declaration of interest G.P.R. has received research support and honoraria from Bristol-Myers Squibb and Janssen-Cilag.
EDITED BY KIRIAKOS XENITIDIS and COLIN CAMPBELL
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- Arranz, B., Rosel, P., Ramirez, N., et al (2004) Insulin resistance and increased leptin concentrations in noncompliant schizophrenia patients but not in antipsychotic-naive first-episode schizophrenia patients. Journal of Clinical Psychiatry, 65, 1335 -1342.[Medline]
- International Diabetes Federation (2005) The IDF Consensus Worldwide Definition of the Metabolic Syndrome. http://www.idf.org/webdata/docs/Meta_syndrome_def.pdf
- Koro, C. E., Fedder, D. O., L'Italien, G. J., et al
(2002) Assessment of independent effect of olanzapine and
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[Abstract/Free Full Text] - Ryan, M. C. M., Flanagan, S., Kinsella, U., et al (2004) Atypical antipsychotics and visceral fat distribution in first episode, drug-naive patients with schizophrenia. Life Sciences, 74, 1999 -2008.[CrossRef][Medline]
- Thakore, J. H. (2005) Metabolic syndrome and
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[Free Full Text] - Zhang, Z.-J., Yao, Z.-J., Liu, W., et al
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[Abstract/Free Full Text]
Author's reply:
Neuroscience Centre, St Vincent's Hospital, Richmond Road, Dublin 3, Ireland.
Correspondence: E-mail: j.thakore{at}rcsi.ie
EDITED BY KIRIAKOS XENITIDIS and COLIN CAMPBELL
Critical methodological differences between the studies of Zhang et al (2004) and Ryan et al (2004) might explain why the two fail to agree. Zhang et al reported a standard deviation of 50 for the age of the controls, indicating that some were elderly; moreover the groups were not matched for gender. This is important as elderly males have higher amounts of intra-abdominal fat (IAF). Life-style parameters such as diet, exercise, smoking and alcohol intake were not measured or indeed compared between the two groups. Furthermore, we are not given any indication as to how an individual was selected for scanning, as not all of the controls and patients recruited had a magnetic resonance imaging (MRI) scan. The authors did not use the same scanning techniques as Seidell et al (1990), who were among the first to describe the single-slice technique for estimating IAF area. There were large differences in terms of inversion and repetition times. Moreover, the most critical aspect of using a single scan to estimate IAF is to ensure that the scan is taken at the level of L4/L5 vertebra, which is best located by a radiological lateral scout and not palpation as performed by Zhang et al. Furthermore, MRI is not a ‘precise and reliable means of determining the two fat measures with better resolution than computed tomography’, as it can erroneously estimate the amount of IAF by 20%.
From a statistical perspective, a one-way ANOVA should have been used to compare any differences between the three groups, as the use of multiple t-tests might have led to a type 1 error. A ‘non-fasting glucose’ level is not a standardised measure and is therefore meaningless. The actual values for fasting glucose decreased in both male and female patients, and fasting insulin levels decreased in females following treatment. Therefore, what Zhang et al show is that treatment with these two antipsychotics improves the metabolic profile of their patients despite an alleged increase in IAF.
Koro et al (2002) claim that olanzapine is associated with a higher risk of developing type 2 diabetes than risperidone, but this is difficult to interpret because Table 1 in their paper clearly indicates that the number of new cases of diabetes is greater in patients on risperidone (5.1%) than olanzapine (2.0%). There is little doubt that antipsychotics contribute to the development of type 2 diabetes in patients with schizophrenia. What is questionable is the magnitude of this effect. To date, the attributable risk for such an effect ranges between 2.03% for clozapine, 0.8% for quetiapine, 0.63% for olanzapine and 0.05% for risperidone (Leslie & Rosenheck, 2004).
Despite the evidence presented the debate still centres on the diabetogenic effects of certain atypical antipsychotics. The purpose of the editorial was to put these issues into perspective to ensure that patients with schizophrenia, irrespective of their prescribed medication, would be offered screening for both diabetes and the metabolic syndrome.
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- Leslie, D. L. & Rosenheck, R. A. (2004)
Incidence of newly diagnosed diabetes attributable to atypical antipsychotic
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[Abstract/Free Full Text] - Seidell, J. C., Bakker, C. J. & van der Kooy, K.
(1990) Imaging techniques for measuring adipose-tissue
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[Abstract/Free Full Text]
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