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

Wim M. A. Verhoeven, MD; Jan M. van Ree, MD; Ans Heezius-van Bentum, MD; David de Wied, MD; Herman M. van Praag, MD

Arch Gen Psychiatry. 1982;39(6):648-654.

Abstract
• Animal experiments have shown that the -endorphin fragment des-enkephalin--endorphin (DEE; β-lipotropin 66-77) is the shortest sequence with neuroleptic-like activity with potency comparable to des-tyrosine--endorphin. We postulated that DEE may be an endogenous peptide implicated in psychopathologic disease, particularly schizophrenia. To investigate the purported antipsychotic action of DEE, 23 patients with different types of relapsing schizophrenia were treated with DEE 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 DEE and two with 10 mg of DEE intramuscularly (IM) daily for ten days. In the second double-blind placebo-controlled trial 13 patients were treated with 3 mg of DEE IM daily for ten days and six received placebo. Of the 17 patients treated with DEE, two did not respond, 11 had a slight to moderate effect, and four responded markedly. No side effects were observed. The response to DEE 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 -endorphin fragmentation might contribute to the pathogenesis of schizophrenic psychoses.

Author Affiliations
From the Department of Psychiatry, State University, Utrecht (Drs Verhoeven and van Praag), Rudolf Magnus Institute for Pharmacology, Utrecht (Drs van Ree and de Wied), and Wolfheze Psychiatric Hospital (Dr Heezius-van Bentum), the Netherlands.

Footnotes
Accepted for publication Dec 11, 1981.

Reprint requests to Department of Psychiatry, State University, Nicolaas Beetsstraat 24, Utrecht, the Netherlands (Dr Verhoeven).

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