The cross-sectional study of 15 risperidone-treated patients with schizophrenia showed increased ghrelin levels compared with healthy controls.1 The study raises several questions. First, the interpretation is hampered by the contradicting results of studies in this field. Some studies showed decreased ghrelin during risperidone and olanzapine treatment,2 other studies showed increased ghrelin during clozapine, olanzapine, risperidone and quetiapine therapy.3 In two olanzapine studies, treatment resulted in increased4 or decreased ghrelin levels.5 In short: larger, preferably prospective studies are needed to decide whether risperidone (or any atypical) effects ghrelin levels and, if so, what the effect is: increase or decrease.

Second, the diabetogenic effect of risperidone – only three cases – is severely underestimated by the authors. A survey, published in 2003, reported 78 cases of new-onset diabetes mellitus.6 Together with two recently published case reports7,8 this adds up to a total of 80 cases.

Third, comparison of antipsychotic-treated schizophrenia patients with healthy controls bypasses the distinction between a drug-induced and a disease-inherent effect.9 The study design in the Murashita et al.1 study does not allow for this distinction, which means that further studies of both untreated, drug-naïve patients as well as antipsychotic-treated patients are needed to clarify this issue.


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  • 1
    Murashita M, Inoue T, Kusumi I et al. Glucose and lipid metabolism of long-term risperidone monotherapy in patients with schizophrenia. Psychiatry Clin. Neurosci. 2007; 61: 5458.
  • 2
    Togo T, Hasegawa K, Miura S et al. Serum ghrelin concentrations in patients receiving olanzapine or risperidone. Psychopharmacology 2004; 172: 230232.
  • 3
    Palik E, Birkas KD, Faludi G, Karadi I, Cseh K. Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics. Diabetes Res. Clin. Pract. 2005; 68 (Suppl. 1): S60S64.
  • 4
    Murashita M, Kusumi I, Inoue T et al. Olanzapine increases plasma ghrelin level in patients with schizophrenia. Psychoneuroendocrinology 2005; 30: 106110.
  • 5
    Hosojima H, Togo T, Odawara T et al. Early effects of olanzapine on serum levels of ghrelin, adiponectin and leptin in patients with schizophrenia. J. Psychopharmacol. 2006; 20: 7579.
  • 6
    Koller EA, Cross JT, Doraiswamy PM, Schneider BS. Risperidone-associated diabetes mellitus: A pharmacovigilance study. Pharmacotherapy 2003; 23: 735744.
  • 7
    Dibben CR, Kalavalapalli SS, Linnington HE et al. Diabetes associated with atypical antipsychotic treatment may be severe but reversible: Case report. Int. J. Psychiatry Med. 2005; 35: 307311.
  • 8
    Ananth J, Johnson KM, Levander EM, Harry LJ. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J. Clin. Psychiatry 2004; 65: 724.
  • 9
    Cohen D. Diabetes Mellitus in Schizophrenia or Schizoaffective Disorder: An Endogenic or Iatrogenic Problem? Thesis, Haarlem, 2007.