- 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.
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- 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.
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- 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.
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- 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.
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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)."
