The following appeared in "Psychiatry Drug Alerts", January '97 issue, page 5.

"Negative symptoms of schizophrenia and overall psychopathology improved with adjunctive glycine in patients with treatment-resistant schizophrenia."

  Background: Recent research has suggested that disturbances in glutamate neurotransmission may be the underlying cause of schizophrenia, in contrast to the traditional dopaminiergic hypothesis. Glycine acts as a co-agonist with glutamate at its receptor site. A few, small, mostly uncontrolled, studies have indicated that glycine may be beneficial in schizophrenia.
Methods: Study subjects were 12 inpatients with treat-resistant chronic schizophrenia. Early criteria for the study included: unsatisfactory response to at least 3 adequate trials with neuroleptics from 2 different classes; no period of good functioning in the past 5 years; and high test scores for both positive and negative symptoms. Subjects has been receiving stable doses of a conventional neuroleptic or clozapine for 3 months or more. They were randomly assigned to adjunctive treatment with either placebo or up to a daily maximum of 0.8 mg/kg glycine in 3 divided doses. After 6 weeks of treatment and a 2-week washout, patients were crossed over to the alternate study medication for 6 weeks.
Results: One placebo patient, who had an exacerbation of schizophrenia, did not complete the trial. The remaining 11 patients had statistically significant improvements in negative symptom scores on the Positive and Negative Symptom Scale after 6 weeks of glycine (a 7.3% improvement; p<0.0001). General psychopathology also improved with glycine treatment (a 10.5% improvement; p<0.0001). No significant improvement in positive symptoms occurred. Eight patients had reductions of 30% or more in negative symptom scores and 25% or more in total psychopathology scores. In the 7 patients who were randomly assigned to receive glycine in the first study period, improvement persisted for 8 weeks, up to the end of the subsequent placebo period. No clinical side effects were observed; nor did the glycine affect blood chemistry, hematology, or renal or heptic function. EPS and TD [my abbrv.] did not worsen in either group.
Discussion: Because of its small size, this trial should be viewed as a pilot study. The patients who responded best to glycine were those with lower serum glycine levels at baseline. Serum levels after treatment were not correlated with responses. These observations, along with the safety of glycine administration, suggest that this treatment may be useful in glycine-deficient patients with schizophrenia. Patients receiving this combination improved to the same degree as patients taking glycine with typical neuroleptics, despite the clinically different profiles of clozapine and traditional agents.

Heresco-Levy U, et al: Double-blind, placebo-controlled, crossover trial of glycine adjunctive therapy for treatment-resistant schizophrenia. British Journal of Psychiatry 1996;169(November):610-617. From Hadassah Medical School-Hebrew University, Jerusalem, Israel; and other institutions. Funded by the Hebrew University-MIlton Rosenbaum Endowment Fund for Research in Psychiatric Sciences, and the Israel National Institute of Psycholobiology-The Harry Stern/ENOSH Research Fund(UH-L)."

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