title: Glycine treatment of the risk syndrome for psychosis: report of two pilot studies.
abstract: Patients meeting criteria for the risk syndrome for psychosis have treatment needs including positive and negative symptoms and cognitive impairment. These features could potentially respond to NMDA glycine-site agonists. The present objective was to determine which symptoms or domains of cognition promise to show the greatest response to glycine in risk syndrome patients. We conducted two short-term pilot studies of glycine used without adjunctive antipsychotic medication. In the first trial, 10 risk syndrome subjects received open-label glycine at doses titrated to 0.8 g/kg/d for 8 weeks, followed by discontinuation and 16 weeks of evaluation for durability of effects. In the second, 8 subjects were randomized to double-blind glycine vs. placebo for 12 weeks, followed by open-label glycine for another 12 weeks. Patients were evaluated every 1-2 weeks with the Scale Of Psychosis-risk Symptoms (SOPS) and before and after treatment with a neurocognitive battery. Within-group and between-group effect sizes were calculated. Effect sizes were large for positive (open-label within-group -1.10, double-blind between-group -1.11) and total (-1.39 and -1.15) symptoms and medium-to-large (-0.74 and -0.79) for negative symptoms. Medium or large effect sizes were also observed for several neurocognitive measures in the open-label study, although data were sparse. No safety concerns were identified. We conclude that glycine was associated with reduced symptoms with promising effect sizes in two pilot studies and a possibility of improvement in cognitive function. Further studies of agents that facilitate NMDA receptor function in risk syndrome patients are supported by these preliminary findings.
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA. scott.woods@yale.edu
authors.forename: Scott W
authors.initials: SW
authors.lastname: Woods
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Walsh
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hawkins
authors.forename: Tandy J
authors.initials: TJ
authors.lastname: Miller
authors.forename: John R
authors.initials: JR
authors.lastname: Saksa
authors.forename: Deepak C
authors.initials: DC
authors.lastname: D'Souza
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Javitt
authors.forename: Thomas H
authors.initials: TH
authors.lastname: McGlashan
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior; D000328:Adult; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005998:Glycine / Q000009:adverse effects / Q000627:therapeutic use*; D018684:Glycine Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D064427:Nutritive Sweeteners / Q000009:adverse effects / Q000627:therapeutic use; D010865:Pilot Projects; D062706:Prodromal Symptoms; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D012306:Risk; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D018684:Glycine Agents; D064427:Nutritive Sweeteners; D005998:Glycine
keywords: Glycine; NMDA receptor; Prodrome; Psychosis; Risk syndrome; Schizophrenia