Improvement of schizophrenic patients treated with [des-Tyr1]-gamma-endorphin (DTgammaE).

It was postulated from animal experiments that gamma-endorphin and, in particular, the nonopiate-like peptide [des-Tyr1]-gamma-endorphin (DTgammaE, beta-lipotropin [beta-LPH]62-77) have neurolepic-like activity. To test this, 14 patients with long-lasting, relapsing schizophrenic or schizoaffective psychosis resistant to conventional neuroleptics were treated with DTgammaE. An open design was used first for six patients (study 1) and a double-blind, crossover design for the other eight (study 2). In study 1, all neuroleptic medication was discontinued and 1 mg of DTgammaE zinc phosphate was given daily intramuscularly for about seven days. In study 2, six patients were maintained with neuroleptic therapy and two patients were drug free; all eight received daily intramuscular injections of 1 mg of nonlasting DTgammaE in saline and solution for eight days. There was transient or semipermanent improvement in both studies in which the psychotic symptoms diminished or even disappeared. In study 2, there was a slight but significant improvement with the first treatment. Improvement continued and by day 4, the psychotic symptoms had almost disappeared. No toxic side effects were noted. These effects of DTgammaE may be a consequence of the normalization of beta-endorphin homeostasis in the brain.