Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies

• Published in: European neuropsychopharmacology Vol. 23; no. 8; pp. 931 - 940
• Main Authors: Woods, Scott W, Walsh, Barbara C, Hawkins, Keith A, Miller, Tandy J, Saksa, John R, D'Souza, Deepak C, Pearlson, Godfrey D, Javitt, Daniel C, McGlashan, Thomas H, Krystal, John H
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2013
• Subjects: Adolescent; Adolescent Behavior; Adult; Clinical trials; Cognition Disorders - etiology; Cognition Disorders - prevention & control; Dietary Supplements - adverse effects; Double-Blind Method; Female; Follow-Up Studies; Glycine; Glycine - adverse effects; Glycine - therapeutic use; Glycine Agents - adverse effects; Glycine Agents - therapeutic use; Humans; Internal Medicine; Male; NMDA receptor; Nutritive Sweeteners - adverse effects; Nutritive Sweeteners - therapeutic use; Pilot Projects; Prodromal Symptoms; Prodrome; Psychiatric Status Rating Scales; Psychiatry; Psychosis; Psychotic Disorders - epidemiology; Psychotic Disorders - physiopathology; Psychotic Disorders - prevention & control; Risk; Risk syndrome; Schizophrenia; United States - epidemiology; Young Adult; United States; Psychosis; Schizophrenia; Prodrome; Risk syndrome; Glycine; NMDA receptor
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2012.09.008

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.