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Pharmacopsychiatry 2006; 39(2): 41-46
DOI: 10.1055/s-2006-931540
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Gender Aspects in the Clinical Treatment of Schizophrenic Inpatients With Amisulpride: A Therapeutic Drug Monitoring Study

M. J. Müller1 , 2 , B. Regenbogen1 , J. Sachse1 , F. X. Eich3 , S. Härtter1 , C. Hiemke1
  • 1Department of Psychiatry, University of Mainz, Mainz, Germany
  • 2Clinic for Psychiatry and Psychotherapy Marburg-Süd, Germany
  • 3Sanofi-Aventis GmbH, Berlin, Germany
This study was supported by an unrestricted grant from Sanofi-Aventis GmbH, Berlin, Germany. Dr. Eich is an employee of Sanofi-Aventis GmbH Berlin, Germany
Further Information

Publication History

Received: 27.6.2005 Revised: 21.10.2005

Accepted: 26.10.2005

Publication Date:
23 March 2006 (online)

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Introduction: It is assumed that female and male schizophrenic patients respond differentially to acute and chronic treatment with antipsychotics because of pharmacokinetic and pharmacodynamic factors linked to hormonal and constitutional gender differences. However, to date no empirical evidence exists in support of this notion. Methods: In a naturalistic clinical study, we investigated gender differences in a sample of schizophrenic inpatients with acute exacerbation treated with the atypical antipsychotic amisulpride, a selective dopamine D2/D3 receptor antagonist with proven antipsychotic efficacy. Prescribed amisulpride dose, plasma level, clinical response (CGI), and side effects (UKU) were assessed in 99 patients (62 % male, age 18-66 years) under antipsychotic monotherapy with amisulpride at daily doses ≥ 400 mg. Results: Female patients were significantly older (38.5 ± 11.8 years) than male patients (32.3 ± 10.9 years; P = 0.01). Prescribed amisulpride doses were comparable for men (673 ± 216 mg) and women (665 ± 229 mg). However, dose-corrected steady-state amisulpride plasma levels (men 0.41 ± 0.31 ng/mL/mg; women 0.60 ± 0.39 ng/mL/mg; P = 0.007) were significantly higher in female patients even after age adjustment. No significant differences between men and women emerged with respect to clinical response (77 % vs. 79 %, respectively) and the occurrence of any side effect (41 % vs. 37 %, respectively). Discussion: Except for higher dose-related plasma amisulpride levels in women, the explorative study unveiled no clinically relevant gender-specific aspects regarding prescribed dose, effectiveness, and side effects.

References

  • 1 Andreasen N. Vulnerability to mental illnesses: gender makes a difference, and so does providing good psychiatric care.  Am J Psychiatry. 2005;  162 211-213
    CrossrefPubMedSearch in Google Scholar
  • 2 Arnold L M, Strakowski S M, Schwiers M L, Amicone J, Fleck D E, Corey K B. et al . Sex, ethnicity, and antipsychotic medication use in patients with psychosis.  Schizophr Res. 2004;  66 169-175
    CrossrefPubMedSearch in Google Scholar
  • 3 Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Kuss H J. et al . The AGNP-TDM expert group consensus guidelines: Therapeutic drug monitoring in psychiatry.  Pharmacopsychiatry. 2004;  37 243-265
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Bergemann N, Kopitz J, Kress K R, Frick A. Plasma amisulpride levels in schizophrenia or schizoaffective disorder.  Eur Neuropsychopharmacol. 2004;  14 245-250
    CrossrefPubMedSearch in Google Scholar
  • 5 Croissant B, Hermann D, Olbrich R. Reduction of side effects by combining clozapine with amisulpride: case report and short review of clozapine-induced hypersalivation - a case report.  Pharmacopsychiatry. 2005;  38 38-39
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Davis J M, Chen N, Glick I D. A meta-analysis of the efficacy of second-generation antipsychotics.  Arch Gen Psychiatry. 2003;  60 553-564
    CrossrefPubMedSearch in Google Scholar
  • 7 de las Cuevas C, Sanz E, de la Fuente J A, Cabrera C, Mateos A. Prescribed daily doses and "risk factors" associated with the use of benzodiazepines in primary care.  Pharmacoepidemiol Drug Saf. 1999;  8 207-216
    CrossrefPubMedSearch in Google Scholar
  • 8 Drici M D, Clement N. Is gender a risk factor for adverse drug reactions? The example of drug induced long QT syndrome.  Drug Saf. 2001;  24 575-585
    CrossrefPubMedSearch in Google Scholar
  • 9 Fric M, Laux G. Prolactin levels and symptoms of hyperprolactinemia in patients treated with amisulpride, risperidone, olanzapine and quetiapine.  Psychiatr Prax. 2003;  30 Suppl 2 S97-101
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Goldstein J M, Cohen L S, Horton N J, Lee H, Andersen S, Tohen M. et al . Sex differences in clinical response to olanzapine compared with haloperidol.  Psychiatry Res. 2002;  110 27-37
    CrossrefPubMedSearch in Google Scholar
  • 11 Gründer G, Wetzel H, Schlösser R, Anghelescu I, Hillert A, Lange K. et al . Neuroendocrine response to antipsychotics: effects of drug type and gender.  Biol Psychiatry. 1999;  45 89-97
    CrossrefPubMedSearch in Google Scholar
  • 12 Guy D (Ed). ECDEU Assessment Manual for Psychopharmacology, revised. DHEU Publication NIMH: Rockville; 1976
    Search in Google Scholar
  • 13 Haddad P M, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management.  Drugs. 2004;  64 2291-2314
    CrossrefPubMedSearch in Google Scholar
  • 14 Häfner H. Gender differences in schizophrenia.  Psychoneuroendocrinology. 2003;  Supplement 2 17-54
    PubMedSearch in Google Scholar
  • 15 Hiemke C, Dragicevic A, Gründer G, Härtter S, Sachse J, Vernaleken I. et al . Therapeutic monitoring of new antipsychotic drugs.  Ther Drug Monit. 2004;  26 156-160
    CrossrefPubMedSearch in Google Scholar
  • 16 Kampmann J, Siersbaek-Nielsen K, Kristensen M, Hansen J M. Rapid evaluation of creatinine clearance.  Acta Med Scand. 1974;  196 517-520
    PubMedSearch in Google Scholar
  • 17 Kropp S, Ziegenbein M, Grohmann R, Engel R R, Degner D. Galactorrhea due to psychotropic drugs.  Pharmacopsychiatry. 2004;  37 Suppl 1 S84-88
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Kumari V, Aasen I, Sharma T. Sex differences in prepulse inhibition deficits in chronic schizophrenia.  Schizophr Res. 2004;  69 219-235
    CrossrefPubMedSearch in Google Scholar
  • 19 Labelle A, Light M, Dunbar F. Risperidone treatment of outpatients with schizophrenia: no evidence for sex differences in treatment response.  Can J Psychiatry. 2001;  46 534-541
    PubMedSearch in Google Scholar
  • 20 Lerner V, Bergman J, Borokhov A, Loewenthal U, Miodownik C. Augmentation with amisulpride for schizophrenic patients nonresponsive to antipsychotic monotherapy.  Clin Neuropharmacol. 2005;  28 66-71
    CrossrefPubMedSearch in Google Scholar
  • 21 Leucht S, Wagenpfeil S, Hamann J, Kissling W. Amisulpride is an ”atypical” antipsychotic associated with low weight gain.  Psychopharmacology. 2004;  173 112-115
    CrossrefPubMedSearch in Google Scholar
  • 22 Leung A, Chue P. Sex differences in schizophrenia, a review of the literature.  Acta Psychiatr Scand Suppl. 2000;  401 3-38
    PubMedSearch in Google Scholar
  • 23 Lin J, Knight E L, Hogan M L, Singh A K. A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease.  Am Soc Nephrol. 2003;  14 2573-2580
    CrossrefPubMedSearch in Google Scholar
  • 24 Linden M, Scheel T, Eich F X. Dosage finding and outcome in the treatment of schizophrenic inpatients with amisulpride. Results of a drug utilization observation study.  Hum Psychopharmacol. 2004;  19 111-119
    PubMedSearch in Google Scholar
  • 25 Lingjaerde O, Ahlfors U G, Bech P, Dencker S J, Elgen K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients.  Acta Psychiatr Scand. 1987;  334 -100
    PubMedSearch in Google Scholar
  • 26 McKeage K, Plosker G L. Amisulpride: a review of its use in the management of schizophrenia.  CNS Drugs. 2004;  18 933-956
    CrossrefPubMedSearch in Google Scholar
  • 27 Meaney A M, Smith S, Howes O D, O'Brien M, Murray R M, O'Keane V. Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia.  Br J Psychiatry. 2004;  184 503-508
    CrossrefPubMedSearch in Google Scholar
  • 28 Melkersson K I, Hulting A L, Rane A J. Dose requirement and prolactin elevation of antipsychotics in male and female patients with schizophrenia or related psychoses.  Br J Clin Pharmacol. 2001;  51 317-324
    CrossrefPubMedSearch in Google Scholar
  • 29 Mühlberg W, Platt D. Age-dependent changes of the kidneys: pharmacological implications.  Gerontology. 1999;  45 243-253
    CrossrefPubMedSearch in Google Scholar
  • 30 Müller M J, Benkert O. Der Stellenwert von Amisulprid in der Behandlung von Patienten mit schizophrenen Erkrankungen - Ergebnisse kontrollierter Studien. In Hippius H (ed.) Amisulprid. München; Urban und Vogel 2002: p. 33-57
    Search in Google Scholar
  • 31 Müller M J, Wetzel H, Benkert O. Differential effects of high-dose amisulpride versus flupentixol on latent dimensions of depressive and negative symptomatology in acute schizophrenia: an evaluation using confirmatory factor analysis.  Int Clin Psychopharmacol. 2002;  17 249-261
    PubMedSearch in Google Scholar
  • 32 Müller M J, Wetzel H, Eich F X, Rein W, Puech A, Benkert O. Dose-related effects of amisulpride on five dimensions of psychopathology in patients with acute exacerbation of schizophrenia.  J Clin Psychopharmacol. 2002;  22 554-560
    CrossrefPubMedSearch in Google Scholar
  • 33 Puech A, Fleurot O, Rein W. Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol.  Acta Psychiatr Scand. 1998;  98 65-72
    CrossrefPubMedSearch in Google Scholar
  • 34 Rademaker M. Do women have more adverse drug reactions?.  Am J Clin Dermatology. 2001;  2 349-351
    PubMedSearch in Google Scholar
  • 35 Sachse J, Härtter S, Weigmann H, Hiemke C. Automated determination of amisulpride by liquid chromatography with column switching and spectrophotometric detection.  J Chromatogr B. 2003;  784 405-410
    CrossrefPubMedSearch in Google Scholar
  • 36 Salokangas R K. Gender and the use of neuroleptics in schizophrenia.  Schizophr Res. 2004;  66 41-49
    CrossrefPubMedSearch in Google Scholar
  • 37 Schlösser R, Gründer G, Anghelescu I, Hillert A, Ewald-Gründer S, Hiemke C. et al . Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels.  Neuropsychobiology. 2002;  46 33-40
    PubMedSearch in Google Scholar
  • 38 Seeman M V. Gender differences in the prescribing of antipsychotic drugs.  Am J Psychiatry. 2004;  161 1324-1333
    CrossrefPubMedSearch in Google Scholar
  • 39 Smith S, Wheeler M J, Murray R, O'Keane V. The effects of antipsychotic-induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis.  J Clin Psychopharmacol. 2002;  22 109-114
    CrossrefPubMedSearch in Google Scholar
  • 40 Sota T L, Heinrichs R W. Sex differences in verbal memory in schizophrenia patients treated with ”typical” neuroleptics.  Schizophr Res. 2003;  62 175-182
    CrossrefPubMedSearch in Google Scholar
  • 41 Vernaleken I, Siessmeier T, Buchholz H G, Härtter S, Hiemke C, Stoeter P. et al . High striatal occupancy of D2-like dopamine receptors by amisulpride in brain of patients with schizophrenia.  Int J Neuropsychopharmacol. 2004;  7 421-430
    Search in Google Scholar

PD Dr. Matthias J. Müller

Clinic for Psychiatry and Psychotherapy Marburg-Süd

Cappeler Str. 98

D-35039 Marburg

Germany

Phone: +49-6421-404227

Fax: +49-6421-404533

Email: mjmueller@gmx.de