Clinical and Neuroendocrine Effects of Zotepine - A New Neuroleptic Drug

Abstract

Zotepine, a new neuroleptic, was administered to 23 hospitalized patients with schizophrenia at doses of 75 to 600 mg/d for 21 to 42 days. Based upon analysis of conventional rating scales we observed a significant improvement (P less than 0.001) during week 1, which compound throughout the study period. After 21 days we identified 17 responders and 6 nonresponders, 2 of whom dropped out of the study because of a tonic-clonic seizure in one case and withdrawal of consent to further participation in the second case. During further treatment the improvement remaind stable in the responder group, while 1 nonresponder improved after 3 weeks of treatment. In 9 patients extrapyramidal symptoms were observed (6 parkinsonism, 2 early dyskinesia, 1 parkinsonism and early dyskinesia), which required sporadic (n = 3) or continuous (n = 2) treatment with biperiden in 5 cases. This low incidence of extrapyramidal symptoms necessitating coadministration of anticholinergic drugs suggests that the risk of inducing parkinsonism and dyskinesias during zotepine treatment is low. Comparison of cortisol, growth hormone and prolactin release in normal controls challenged with 25 mg zotepine showed that only prolactin secretion is increased, while secretion of cortisol and growth hormone remains unaffected. The clinical effects observed in the present study show that zotepine has potential value in the treatment of schizophrenia. The findings warrant further study in controlled trials.

The Effects of Antipsychotics on Prolactin Levels and Women’s Menstruation

“…Zotepine is an atypical agent, considered to cause prolactin elevation in humans after acute or long-term therapy [68, 69]. It is uncertain whether there are any published studies that systematically investigate the prevalence of menstrual disorders (Table 1).…”

Hyperprolactinemia associated with psychotropics—a review

“…Most of the medications, which increase prolactin, act by inhibiting the dopaminergic pathways. This includes dopamine receptor antagonists such as antipsychotics (Wieck and Haddad, 2002), metoclopramide (Tamagna et al ., 1979), domperidone (Fujino et al ., 1980) and labetalol (Barbieri et al ., 1982); drugs inhibiting dopamine synthesis such as opiates (Shin et al ., 1988), verapamil (Kelley et al ., 1996), oestrogen (Frantz, 1978) and decarboxylase inhibitors like carbidopa and beserazide; and those inhibiting dopamine release such as H 2 antagonists, opiates and storage depletor reserpine (Lee et al ., 1976).…”

“…Therapeutic effects on positive and negative psychotic symptoms occur via the dopamine D2 and D4 receptor modulation in the mesolimbic and mesocortical areas, respectively. Extrapyramidal side effects are mediated by D2 blockade in the nigrostriatal area while D2 blockade in the hypothalamic infundibular system causes hyperprolactinaemia (Wieck and Haddad, 2002).…”

“…The typical antipsychotics are frequently responsible for drug‐induced hyperprolactinaemia. These drugs block D2 receptors in the hypothalamic infundibular system (Wieck and Haddad, 2002). The receptor binding dynamics of atypical agents are more complex.…”

Thyroid Parameters during Therapy with Zotepine in Delusional Depression

“…In Germany, zotepine has been available as a moderately potent neuroleptic. One report postulated an antidepressant-anxiolytic effect besides the antipsychotic action [14]. We investigated this possible active principle for 2 years in a clinical observation study either as monotherapy with zotepine or as administration of zotepine in combination with paroxetine [15][16][17] in severely depressed patients on the Depression Ward.…”