This study will test the safety and effectiveness of the amino acid glycine in treating
psychotic disorders in children. The drug will be given as an adjunct (in addition) to the
patient's current antipsychotic medication.
Children age nine to 18 with schizophrenia or schizoaffective disorder whose symptoms began
before age 13 may be eligible for this 10-week study. Patients will be hospitalized during
the course of the trial. Weekend visits home may be permitted.
Children enrolled in the study will be evaluated during a two-week pre-treatment period with
written tests for IQ and academic functioning and with a magnetic resonance imaging (MRI)
scan of the brain. For the MRI, the child lies on a table that slides into a large
donut-shaped machine with a strong magnetic field. This procedure produces images of the
brain that may help identify brain abnormalities in schizophrenia that develop in childhood.
During the eight-week treatment phase, patients will receive glycine powder dissolved in
water once a day, in addition to their other antipsychotic medications. They will undergo
the following additional procedures during the course of treatment:
1. Comprehensive psychiatric examination
2. Blood pressure and pulse monitoring once a week
3. Blood tests every other week - About one ounce of blood is drawn per week to measure
4. Eye movement study at week eight - Using a technique called infrared oculography,
special detectors measure infrared light reflected off the child's eyes while he or she
watches a moving square on a video monitor.
5. Lumbar puncture (spinal tap) once during the study - About one-half ounce of
cerebrospinal fluid (the fluid surrounding the brain and spinal cord) is withdrawn
through a needle placed in the lower part of the spine for analysis of brain chemicals.
Patients who respond well may continue to receive glycine treatment through their referring
physician after the study is completed.
NIMH will follow patients by phone every six months and with visits at two-year intervals.
The ability of glycine to potentiate the NMDA receptor-complex, along with the fact that it
is well tolerated in short-and long-term administration, has raised the possibility that it
may provide an effective treatment of augmentation for neuroleptic-resistant negative
symptoms of schizophrenia. Up to ten children and adolescents, ages 9-18, meeting DSM-IV
criteria for schizophrenia, schizoaffective disorder and psychotic disorder not otherwise
specified with onset of psychosis by age 12 who have failed at least two prior
antipsychotics entering this protocol on their current antipsychotic medication(s) will
participate in an open 8-week trial of adjunctive glycine therapy. In addition to the
potential benefits, if glycine therapy ameliorates enduring negative symptoms of
schizophrenia, we anticipate that recruiting these rare patients will be facilitated by the
availability of this new treatment.
This study will provide pilot data regarding the beneficial effects and safety of adjunctive
glycine therapy for children and adolescents with treatment refractory psychotic disorders.
The availability of newer alternate treatments is also important for recruitment of patients
in the broader study of the neurobiology and genetics of very early onset schizophrenia.
Children and adolescents ages nine to eighteen will be allowed into the study. Subjects
entering the protocol as new patients will be characterized by clinical phenomenology, eye
tracking, MRI brain imaging, cerebrospinal fluid, plasma and urinary biochemistry, and
chromosomal analysis. Patients with prominent mood symptoms who have required the addition
of mood stabilizing agents such as lithium or valproic acid will be allowed to remain on
these medications for the duration of the treatment trial, if clinically indicated. Liver
chemistries will be checked at baseline and at the end of the study.
All first-degree relatives are interviewed in person and undergo eye tracking measurement
and contribute blood cell lines as part of a genetic study of the cohort (84-M-0050).
Patients with their psychosis in a moderate to severe range defined as a SANS score of 5
or above, a SAPS score of 5 or above and/or a BPRS score of 30 or above.
Males and females, age 9-18 meeting DSM-IV criteria for schizophrenia, schizoaffective
disorder or psychotic disorder not otherwise specified with onset of psychosis before
their 13th birthday.
Patients must have had their 9th birthday by the end of drug washout.
Patients with failure of two prior antipsychotic treatments, or discontinuation of
effective clozapine or olanzapine treatment due to intolerable side effects.
Patients with a premorbid IQ test less than 70.
No patients with any significant neurological/medical disorder; and/or active alcohol or
No patients judged to be at serious suicidal risk.
Females who are physically capable of pregnancy must agree to avoid pregnancy throughout
the study. Should pregnancy occur during the study, the patient will be unable to
MRI exam will not be given to patients with any metal prostheses, surgical clips, or other
metal implants, or cannot tolerate the procedure.