Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: A retrospective chart review

https://doi.org/10.1016/j.schres.2008.01.028Get rights and content

Abstract

The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available.

Methods

Data from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs). Rates of MetS were compared at baseline and after on average 3 years of treatment exposure.

Results

At first episode there was no difference in the prevalence of MetS between the historic and the current cohort. Rates of MetS increased over time in both groups, but patients started on SGAs had a three times higher incidence rate of MetS (Odds Ratio 3.6, CI 1.7–7.5). The average increase in weight and body mass index was twice as high in patients started on SGA. The difference between the FGA and SGA group was no longer significant when patients started on clozapine and olanzapine were excluded.

Conclusion

Rates of MetS at the first episode of schizophrenia today are not different from those of patients 15 to 20 years ago. This finding counters the notion that the high rates of metabolic abnormalities in patients with schizophrenia currently reported are mainly due to lifestyle changes over time in the general population. Some SGAs have a significantly more negative impact on the incidence of MetS compared to FGAs in first-episode patients.

Introduction

In the last decades prevalence rates of obesity have been rising globally (Kautiainen et al., 2002, Ogden et al., 2006, Wang and Beydoun, 2007). This has contributed to increased rates of the metabolic syndrome (MetS) which will impact on physical health in the general population (Byrne and Wild, 2005, Ford et al., 2002, Ford et al., 2004). The metabolic syndrome is a risk factor for diabetes and cardiovascular disease (Byrne and Wild, 2005, Hennekens et al., 2005, Grundy, 2005, Isomaa et al., 2001; Yusuf et al., 2004).

Several studies have shown high prevalence rates of MetS in patients with schizophrenia (Basu et al., 2004, Bobes et al., 2007, Cohn et al., 2004, Correll et al., 2006, De Hert et al., 2006a, Heiskanen et al., 2003, Holt et al., 2004, McEvoy et al., 2005, Meyer et al., 2005, Rejas et al., 2008, Sicras-Mainar et al., 2008, Srisurapanont et al., 2007, Thakore, 2005). Rates of MetS in people with schizophrenia are at least double compared to an age matched population sample (De Hert et al., 2006b). However, most studies were cross-sectional in nature. There are limited data on the evolution over time in patients with schizophrenia, in terms of cohort effects as well as within-person effects.

Metabolic abnormalities have consistently been identified as a part of schizophrenic illness, even before the era of antipsychotic medication (Allison et al., 1999, Homel et al., 2002, Meduna et al., 1942, Raphael, 1921). The interest in this topic has been renewed since the introduction of second-generation antipsychotics (SGAs) and their possible association with metabolic abnormalities (Allison and Casey, 2001, Henderson, 2005, Newcomer, 2005, Newcomer, 2007a, Scheen and De Hert, 2005, Scheen and De Hert, 2007, Tschoner et al., 2007). Next to the impact on physical health these metabolic abnormalities are of major clinical concern, because of their association with a lower functional outcome (Lyketsos et al., 2002), a worse perceived physical health (Dixon et al., 1999), poorer quality of life (Awad, 2004; De Hert et al., 2006c) and non-compliance (Weiden et al., 2004).

The reasons that underlie the high prevalence of these metabolic abnormalities are much debated, especially when considering the possible role of SGAs in the occurrence of these abnormalities. Many studies have suggested a role of (certain) SGAs in the occurrence of metabolic abnormalities (Newcomer, 2005). Some studies have provided evidence for an increased prevalence of central obesity and glucose abnormalities such as impaired fasting glucose and insulin resistance in drug-naïve first-episode patients, suggesting that metabolic disturbances may even be conceived as intermediary phenotypes associated with genetic risk for schizophrenia (de Leon and Diaz, 2007, Ryan et al., 2003, Spelman et al., 2007, Thakore et al., 2002, Thakore, 2005). Recently a few studies have explored the genetic variations associated with metabolic changes on antipsychotics (de Leon and Diaz, 2007, Ellingrod et al., 2008).Other authors have pointed to the increase in prevalence of metabolic abnormalities in the general population to explain the increase of metabolic abnormalities in schizophrenia (Holt et al., 2004, Holt and Pevelert, 2006).

The current study aimed to compare two different cohorts of patients with schizophrenia admitted for their first episode of psychosis: a historic cohort consisting of subjects who were admitted between 1984 and 1995 and who were treated with first-generation antipsychotics (FGAs), and a current cohort of subjects with similar age and sex distribution who were admitted between 2000 and 2005 and who were treated with SGAs only. To evaluate the potential impact of population changes over time rates of MetS were compared between both groups at baseline before treatment was started. The differential impact of treatment with FGAs compared to SGAs, on the incidence and prevalence of MetS, was evaluated in a subsample of both cohorts on which prospective data over the course of treatment was available. Given the possible impact of SGAs on prevalence rates of metabolic abnormalities in schizophrenia, we hypothesized that rates of MetS would be similar for both cohorts at first admission, and that rates of MetS would increase over time in both groups, but significantly more for the current cohort as a result of treatment with SGAs.

Section snippets

Methods

Two cohorts of first-episode patients with schizophrenia were compared. Routinely, all patients got a physical examination and a fasting blood assessment when they were admitted to our university psychiatric hospital.

Routine laboratory tests have been performed at our hospital in the same laboratory since the seventies. Assessment of triglycerides became available in 1981 and assessment of HDL cholesterol in 1984.

The historic cohort is derived from a cohort of 1119 patients with schizophrenia

Patients and rate of MetS at baseline

Between 1984 and 1995, 301 first-episode patients were admitted to our hospital. A complete laboratory assessment including all the parameters of Mets was available in 148 patients (49.2%) before start of medication. There were no significant differences between patients with or without a complete assessment, neither on clinical variables nor on available laboratory results. All patients were started on high-potency FGAs (butyrophenones, diphenylbutylperidines or thioxanthenes).

The matched

Discussion

To our knowledge this is the first study evaluating baseline and prospective MetS data in first-episode patients comparing treatment with FGAs and SGAs.

There were no significant difference in rates of MetS at the first episode between patients admitted to hospital today and patients admitted 15 to 20 years ago in the sample under study, although there were significant differences in rates on individual MetS criteria. This suggests that possible population lifestyle changes do not play an

Role of funding source

None.

Contributors

Study design: M De Hert, R van Winkel.

Data collection: M De Hert, V Schreurs, K Sweers, S Šinko, D Van Eyck.

Statistics: M Wampers.

Writing manuscript: M De Hert wrote the first draft of the manuscript. V Schreurs, K Sweers, S Šinko, D Van Eyck, L Hanssens, M Wampers, R van Winkel, A Scheen and J Peuskens commented on this first draft and contributed to the subsequent revision.

Conflict of interest

None.

Acknowledgements

None.

References (68)

  • McEvoyJ.P. et al.

    Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III

    Schizophr. Res.

    (2005)
  • MeyerJ.M. et al.

    The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial: clinical comparison of subgroups with and without the metabolic syndrome

    Schizophr. Res.

    (2005)
  • OsbyU. et al.

    Mortality and causes of death in schizophrenia in Stockholm county, Sweden

    Schizophr. Res.

    (2000)
  • SaddichhaS. et al.

    Incidence of new onset metabolic syndrome with atypical antipsychotics in first episode schizophrenia: a six-week prospective study in Indian female patients

    Schizophr. Res.

    (2007)
  • ScheenA. et al.

    Abnormal glucose metabolism in patients treated with antipsychotics

    Diabetes Metab.

    (2007)
  • WeidenP.J. et al.

    Obesity as a risk factor for antipsychotic noncompliance

    Schizophr. Res.

    (2004)
  • YusufS. et al.

    Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study

    Lancet

    (2004)
  • AllisonD.B. et al.

    Antipsychotic-induced weight gain: a review of the literature

    J. Clin. Psychiatry

    (2001)
  • AllisonD.B. et al.

    The distribution of body mass index among individuals with and without schizophrenia

    J. Clin. Psychiatry

    (1999)
  • AttuxC. et al.

    Weight gain, dyslipidemia and altered parameters for metabolic syndrome on first episode psychotic patients after six-month follow-up

    Rev. Bras. Psiquiatr.

    (2007)
  • AwadG.A.

    Antipsychotic medications: compliance and attitudes towards treatment

    Curr. Opin. Psychiatry

    (2004)
  • BasuR. et al.

    The prevalence of the metabolic syndrome in patients with schizoaffective disorder-bipolar subtype

    Bipolar Disord.

    (2004)
  • BrownS. et al.

    Causes of the excess mortality of schizophrenia

    Br. J. Psychiatry

    (2000)
  • ByrneC.D. et al.

    The global burden of the metabolic syndrome and its consequences for diabetes and cardiovascular disease

  • CohnT.A. et al.

    Metabolic monitoring for patients treated with antipsychotic medications

    Can. J. Psychiatry

    (2006)
  • CohnT. et al.

    Characterizing coronary heart disease risk in chronic schizophrenia: high prevalence of the metabolic syndrome

    Can. J. Psychiatry

    (2004)
  • CorrellC.U. et al.

    Metabolic syndrome and the risk of coronary heart disease in 367 patients treated with second-generation antipsychotic drugs

    J. Clin. Psychiatry

    (2006)
  • De HertM. et al.

    Prevalence of diabetes, metabolic syndrome and metabolic abnormalities in schizophrenia over the course of the illness: a cross-sectional study

    Clin. Pract. Epidemiol. Ment. Health (2:14 online)

    (2006)
  • De HertM. et al.

    Metabolic abnormalities associated with second generation antipsychotics: fact or fiction? Development of guidelines for screening and monitoring

    Int. Clin. Psychopharmacol.

    (2006)
  • De NayerA. et al.

    Conference report: Belgian consensus on metabolic problems associated with second-generation antipsychotics

    Int. J. Psychiatry Clin. Pract.

    (2005)
  • DixonL. et al.

    The association of medical comorbidity in schizophrenia with poor physical and mental health

    J. Nerv. Ment. Dis.

    (1999)
  • Expert Panel on Detection and Evaluation of Treatment of High Blood Cholesterol in Adults

    Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III)

    JAMA

    (2001)
  • FordE.S. et al.

    Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey

    JAMA

    (2002)
  • FordE.S. et al.

    Increasing prevalence of the metabolic syndrome among US

    Adults Diabetes Care

    (2004)
  • Cited by (211)

    View all citing articles on Scopus
    View full text