Long-Term Effects of the Substituted Benzamide Derivative Amisulpride on Baseline and Stimulated Prolactin Levels

Abstract

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.

Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients

“…After 4 months, PRL reached stable levels substantially lower than that at the onset of antipsychotic treatment. Schlosser et al (2002) have evaluated prolactin levels of amisulpride treated patients and found a similar pattern. Although the data presented here agree with the previously literature suggesting the development of tolerance with chronic antipsychotic treatment, it cannot be taken as a demonstration of tolerance to amisulprideinduced prolactin elevation.…”

“…PRL decreases with chronic antipsychotic treatment). Although some early studies indicated that PRL did not return to normal levels after long-term treatment with antipsychotics (Meltzer and Fang 1976;Gruen et al 1978), others did report a decrease over time (Rivera et al 1976;Laughren et al 1979;Naber et al 1979;Igarashi et al 1985;Meltzer 1985;Rao and Brown 1987;Schlosser et al 2002). Brown and Laughren (1981) followed schizophrenic on typical antipsychotic drugs and found that prolactinemia peaks in the first week of treatment and keep decreasing up 3-4 months.…”

Comparison of pramipexole and amisulpride on alertness, autonomic and endocrine functions in healthy volunteers

“…It is expected that amisulpride will have effects opposite to these. Indeed, it was reported that amisulpride has profound effects on prolactin levels, increasing prolactin release in healthy volunteers (Wetzel et al 1998;Coukell et al 1996) and patient populations (Schlosser et al 2002;Kopecek et al 2004).…”

Dosage finding and outcome in the treatment of schizophrenic inpatients with amisulpride. Results of a drug utilization observation study

“…Several authors stress that the safety profile of amisulpride is superior to standard reference compounds (Wetzel et al, 1998;Coulouvrat and Dondey-Nouvel, 1999;Peuskens et al, 1999;Carriere et al, 2000;Legangneux et al, 2000;Rosenzweig et al, 2002). On the other hand, amisulpride can, dose dependently, have a higher incidence of prolactin elevation (Mauri et al, 1996), which might decrease during treatment over 1 year (Schlösser et al, 2002).…”