Prolaktinplasmaspiegel und Häufigkeit der endokrinologischen Begleitwirkungen unter Therapie mit den atypischen Neuroleptika

Zusammenfassung

Der Dopamin-Rezeptor-Blockade-bedingte Prolaktinanstieg unter Neuroleptika kann klinisch akut Gynäkomastie, Galaktorrhö, Amenorrhö, Libidominderung und Orgasmusstörungen sowie chronisch Osteoporose und kardiovaskuläre Erkrankungen bewirken. Ziel der vorliegenden Untersuchung war die Überprüfung des Zusammenhangs zwischen den Prolaktinplasmakonzentrationen und der Häufigkeit klinisch relevanter endokrinologischer Symptome unter Behandlung mit den atypischen Neuroleptika Amisulprid, Risperidon, Olanzapin und Quetiapin. Amisulprid und - in geringerem Ausmaß - Risperidon führten zu deutlicher, meist anhaltender Erhöhung der Prolaktinplasmaspiegel. Unter Quetiapin und Olanzapin wurden passagere Erhöhungen festgestellt. Keine Zusammenhänge konnten zwischen der Dosis der Medikation und den Prolaktinplasmaspiegeln gefunden werden. Insgesamt zeigten nur 22 % aller behandelten Patienten klinische Zeichen einer Hyperprolaktinämie. Bei den mit Amisulprid behandelten Frauen wurden diese signifikant häufiger festgestellt.

Abstract

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same - in minor degree - for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

Literatur

• 1 Jürgensen O. Hyperprolaktinämie - Prolaktinome: Physiologie - Klinik - Therapie. Berlin; Springer 1998
• 2 Peuskens J. Prolactin elevation and sexual dysfunction.  Clear Perspectives. 1998;  1 17-27
• 3 Petty R G. The impact of antipsychotic side effects over the course of treatment.  In: Raising the Standard of Patient Care in Schizophrenia. Brussels; CINP 2000
• 4 Callaghan J T, Bergstrom R F, Ptak L R, Beasley C M. Olanzapine pharmacokinetic and pharmacodynamic profile.  Clin Pharmacokinet. 1999;  37 177-193
• 5 Marder S R, Meibach R C. Risperidone in the treatment of schizophrenia.  Am J Psychiatry. 1994;  151 825-835
• 6 Arvanitis L A, Miller B G. and the Seroquel Trial 13 studys group . Multiple fixed doses of „Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo.  Biol Psychiatry. 1997;  42 233-246
• 7 Crawford A M, Beasley C M, Tollefson G D. The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations.  Schizophr Res. 1997;  26 41-54
• 8 Meltzer H Y, Goode D J, Schyve P M, Young M, Fang V S. Effect of clozapine on human serum prolactin levels.  Am J Psychiatry. 1979;  136 1550-1555
• 9 Santoni J PH, Saubadu S. Adverse events associated with neuroleptic drugs: focus on neuroendocrine reactions.  Acta Ther. 1995;  21 193-204
• 10 Coulouvrat C, Dondey-Nouvel L. Safety of amisulpride (Solian): a review of 11 clinical studies.  Int Clin Psychopharmacology. 1999;  14 209-218
• 11 Rein W, Coulouvrat C, Dondey-Nouvel L. Safety profile of amisulpride in short- and long-term use.  Acta Psychiatr Scand. 2000;  101 23-27
• 12 Ziegler B. Study of the efficacy of a substituted benzamide, amisulpride, versus haloperidol, in productive schizophrenia. In: Borenstein P, Boyer P, Braconnier A et al (eds) Amisulpride. Paris; Expansion Scientifique Francaise 1989: 73-82
• 13 Boyer P, Lecrubier Y, Puech A J, Dewailly J, Aubin F. Treatment of negative symptoms in schizophrenia with amisulpride.  Br J Psychiatry. 1995;  166 68-72
• 14 Bymaster F P, Calligaro D O, Falcone J F. et al . Radioreceptor binding profile of the atypical antipsychotic olanzapine.  Neuropsychopharmacology. 1996;  14 87-97
• 15 Fuller A, Snoddy H D. Neuroendocrine evidence for antagonism of serotonin and dopamine receptors by olanzapine (LY 170053) an antipsychotic drug candidate.  Res Commun Chem Pathol Pharmacol. 1992;  77 87-93
• 16 Berry S, Martinez R A, Myers J E, Mahmoud R. Serum prolactin in schizophrenia. Berlin; Germany Presented at the 7th World Congress of Biological Psychiatry July 1 - 6, 2001
• 17 David S R, Taylor C C, Kinon B J, Breier A. The Effects of olanzapine, risperidone, and haloperidol on Plasma Prolactin Levels in Patients with Schizophrenia.  Clin Therap. 2000;  9 1085-1096
• 18 Emsley R A, Raniwalla J, Bailey P J, Jones A M,. on behalf of the PRIZE Study Group . A comparison of the effects of quetiapine („Seroquel”) and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment.  Int Clin Psychopharmacology. 2000;  15 121-131
• 19 Peuskens J, Link C G. A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia.  Acta Psychiatr Scand. 1997;  96 265-273
• 20 Goldstein J M, Arvanitis L A. „Seroquel” (quetiapine), a promising new antipsychotic agent: Overview of safety and tolerability.  Schizophr Res. 1997;  24 12-16
• 21 Hirsch S R, Link C GG, Goldstein J M, Arvanitis L A. ICI 204,636: A New Atypical Antipsychotic Drug.  Br J Psychiatry. 1996;  168 45-46