Do medications differ in causing metabolic syndrome in first episode schizophrenia?Int J Neuropsypharm.Jan 2013


Patients with schizophrenia have higher mortality rate than the general population (2.5 fold).Metabolic syndrome contributes to this significantly.Prevalence of metablic syndrome (MetS) is around 10% in first episode cohorts.This rate is similar to that in general population studies. (Mitchell et a l2012).In chronic medicated patients the prevalence increase to 35%.Different antispychotics are considered to have differing potential to cause Met S.

Using data from The European first-episode schizophrenia trial (EUFEST), the largest longer-term study of first-episode schizophrenia patients, with little or no prior exposure to antipsychotic treatment available to date, Wolfgang Fleischhacke and colleagues examine the prevalence of MetS in first episode cases before and after treatment. Treatments compared were Haloperidol, Ziprasidone, Olanzapine, Quetiapine and Amisulpride.

Patient sample: 

Aged 18–40 yr , DSM4 schizophrenia /schizoaffective disorder. Less than 2 yr since the onset of positive symptoms and use of any antipsychotic drug for  less than 2 wk in the previous year or for less than 6 wk at any time. ( ie partially antipsychotic naive).Metabolic parameters were measured at baseline and at 26 and 52 wk.


Of the nearly 500 patients, MetS was present in 5.9% at baseline.Diabetes was present in 0.8%. Nearly half had at least one pre existing Met S risk factor. Prevalence of MetS was similar across antipsychotic naive and non- naive patients at baseline.  20% males and 14% females were obese (BMI >25)at baseline.

Treatment effects after 52 weeks: 

1.Body weight: Ziprasidone had least effect. Increase in weight from baseline:  Amisulpride 7 kg, Olanzapine 10 kg, Quetiapine 6.7kg, Haloperidol 5.4 kg were higher than ziprasidone’s 2.24 kg gain.

2.Abdominal obesity: Mean change at 52 weeks:  Ziprasidone 1 cm, Haloperidol 4.3 cm increase, Amisupride 6 cm, Quetiapine 7 cm ,Olanzapine 8 cm

3.Insulin resistance: Amisupride higher than Quetiapine or Ziprasidone.

4. Hyperglycaemia: ( more than 100mg/dl or more than 5.5 mmil/l).Treatment differences were not statistically different.

5. Hypertrigylceridemia: ( more than 150 mg/dl or more than 1.695mmol/l): Differences among medications were not statistically significant.

6.Hypercholesterolaemia: (more than 200mg/dl or 5.178mmol/l): No difference among treatments.

It is important to note that 58% of sample at baseline  had at least one pre-existing MetS risk factor.Medications differed in their ability to increase body weight and cause abdominal obesity.

The prevalence of MetS in general population is alarmingly high.  In USA, about half the adolescents aged 12–19 yr have at least one of the five components of metabolic disorders and about 45% of all adults aged >20 yr have hypercholesterolaemia, hypertension or diabetes, 13 % have two of the three conditions and 3 % have all three conditions .

In this study, four (0.8%) newly diagnosed cases of diabetes (two on olanzapine and two on amisulpride) occurred during the 52-wk treatment period. This overall rate is consistent with the 0.65% annual incidence rate of type 2 diabetes observed in the Danish follow-up study of antipsychotic-naive patients with schizophrenia (Nielsen et al., 2010) .

The  authors stress the importance of Waist Circumference change as a useful indicator for metabolic risks in schizophrenia. Monitoring change in WC and/or the waist:hip ratio is  a simpler and more reliable and significant predictor of metabolic disorders and conversion to type 2 diabetes mellitus than calculated BMI.

Summary of the article:

Metabolic risk factors in first-episode schizophrenia: baseline prevalence and course analysed from the European First-Episode Schizophrenia Trial Fleischhacker WWSiu COBodén RPappadopulos EKarayal ONKahn RSthe EUFEST study groupInt J Neuropsychopharmacol. Jan: 2013

3 thoughts on “Do medications differ in causing metabolic syndrome in first episode schizophrenia?Int J Neuropsypharm.Jan 2013

  1. Useful article review. I am not sure whether Risperidone, paliperidone and Aripiprazole lie in the middle territory like Olanzapine and Amisulpride!

    • In Eufest trial (Kahn et al 2008,Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial Lancet 2008; 371: 1085–97) : doses were as follows: haloperidol (1–4 mg per day; n=103), amisulpride (200–800 mg per day; n=104), olanzapine (5–20 mg per day; n=105), quetiapine (200–750 mg per day; n=104), or ziprasidone (40–160 mg per day; n=82). Mean doses were: haloperidol 3mg, Amisulpride 450,olanzapine 13 mg, Quetiapine 500mg, ziprasidone 108mg.

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