High dose diazepam treatment and its effect on prolactin secretion in adolescent schizophrenic patients

Thirteen acute schizophrenic patients aged 14-18 years were treated with gradually increasing doses of diazepam to a maximum of 100-400 mg/day/p.o. with a total duration of treatment of 4 weeks. The clinical antipsychotic effect was evaluated by the Brief Psychiatric Rating Scale (BPRS), while the impact on the hypothalamic hypophyseal pathway was evaluated by monitoring the serum prolactin levels (SPL) determined by a highly sensitive homologous radioimmunoassay (RIA). High diazepam doses (100-400 mg/day) caused sedation but no clinical antipsychotic effect was observed. Diazepam treatment with doses up to 250 mg/day caused no significant rise in SPL, while the treatment with doses of higher than 250 mg/day resulted in a mild but still significant increase in SPL. The clinical and laboratory data suggest that diazepam has no direct antidopaminergic activity. The mild hyperprolactinemia achieved with the extremely high doses of diazepam (greater than 250 mg/day) is possibly due to activation of the GABA system which stimulates prolactin release directly or by inhibiting the dopaminergic neurons or alternatively to activation of the endorphinergic system.