Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels.
In the present study, we investigated the long-term effects of treatment with amisulpride, a substituted benzamide derivative, as compared with the effects of treatment with flupenthixol, a thioxanthene, on the prolactin levels in schizophrenic patients. After completing 6 weeks of medication with either amisulpride or flupenthixol, the patients entered a long-term maintenance treatment with amisulpride 200-600 mg/day or flupenthixol 5-15 mg/day for a maximum of 12 months with a subsequent drug-free follow-up until month 15. Eighteen initially included patients were still participating in the study at month 6. In the flupenthixol group, only 1 patient treated reached month 12, and none of the patients reached month 15. For the amisulpride treatment group, months 12 and 15 were completed by 9 and 6 patients, respectively. After 1, 3, 6, and 12 months of treatment, and finally 3 months after cessation of treatment, the basal and thyrotropin-releasing hormone-stimulated secretions of prolactin were investigated. The prolactin plasma levels were elevated in both treatment groups during the course of maintenance treatment with a maximum effect at month 1. Flupenthixol treatment initially raised the prolactin levels about two- or threefold, and a subsequent decline during months 3 and 6 occurred. However, only the changes for month 1 reached the level of a statistical trend. The prolactin secretion was initially increased over tenfold by amisulpride. The prolactin levels at months 1, 3, 6, and 12 were significantly elevated as compared with the baseline values. A continuous decline of prolactin levels in both treatment groups occurred over the course of the next months. The prolactin response after the thyrotropin-releasing hormone challenge was not significantly changed over the long-term course. Notably, in the amisulpride group, 3 months after cessation of treatment at month 12, the elevated levels of prolactin returned to baseline at month 15. In summary, amisulpride demonstrated more pronounced effects than flupenthixol on the prolactin levels. However, the findings indicate also that treatment with amisulpride at clinically effective doses can be achieved at significantly lower prolactin levels during the long-term maintenance phase than during the prior acute phase.
Schlösser
R
R
Department of Psychiatry, University of Mainz, Germany. Ralf.Schloesser@uni-jena.de
Gründer
G
G
Anghelescu
I
I
Hillert
A
A
Ewald-Gründer
S
S
Hiemke
C
C
Benkert
O
O
D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005260:Female; D005475:Flupenthixol / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood* / Q000187:drug effects*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D013469:Sulpiride / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000097:blood; D013997:Time Factors
D014150:Antipsychotic Agents; D013973:Thyrotropin-Releasing Hormone; D013469:Sulpiride; D000077582:Amisulpride; D011388:Prolactin; D005475:Flupenthixol