Antipsychotic Properties of Des-Enkephalin-γ-Endorphin in Treatment of Schizophrenic Patients

• Animal experiments have shown that the γ-endorphin fragment des-enkephalin-γ-endorphin (DEγE; β-lipotropin 66-77) is the shortest sequence with neuroleptic-like activity with potency comparable to des-tyrosine-γ-endorphin. We postulated that DEγE may be an endogenous peptide implicated in psychopathologic disease, particularly schizophrenia. To investigate the purported antipsychotic action of DEγE, 23 patients with different types of relapsing schizophrenia were treated with DEγE dissolved in saline or placebo. Neuroleptic medication was continued during the experimental period. In the first singleblind trial, two patients were treated with 1 mg of DEγE and two with 10 mg of DEγE intramuscularly (IM) daily for ten days. In the second double-blind placebo-controlled trial 13 patients were treated with 3 mg of DEγE IM daily for ten days and six received placebo. Of the 17 patients treated with DEγE, two did not respond, 11 had a slight to moderate effect, and four responded markedly. No side effects were observed. The response to DEγE appeared to be negatively correlated with the dosage of neuroleptic medication and the duration of the last psychotic episode. These results support the hypothesis that disturbances in γ-endorphin fragmentation might contribute to the pathogenesis of schizophrenic psychoses.