Two patients dropped out during the single-blind placebo phase, and one patient dropped out on day 4 of glycine treatment. One patient receiving glycine stopped all medications during week 5 and required hospitalization; this subject’s final assessment at week 4 was carried forward for statistical analysis. Although an adverse effect of glycine cannot be ruled out in this patient, ratings of psychosis and general psychopathology were lower at week 4 than baseline. No patient met the placebo response criterion (20% improvement in total SANS) during the placebo lead-in phase. Clinical staff observed medication administration in 10 of the 14 subjects randomly assigned to receive glycine.
We analyzed results from 27 patients. Six were women, and 21 were men; their mean age was 39 years (SD=7), mean duration of illness was 16 years (SD=7), mean clozapine dose was 455 mg/day (SD=116), mean baseline Hamilton depression scale score was 13 (SD=7), and mean Simpson-Angus Rating Scale score was 3 (SD=2). Fourteen patients received glycine, and 13 received placebo. There was no significant difference between the glycine and placebo groups in age, clozapine dose, or duration of illness. Change scores on all clinical measures, analyzed by using Student’s t test, showed no significant treatment effect (t1). Ninety-five percent confidence intervals for the change from baseline to week 8 for the glycine group and for the difference between the glycine and placebo groups included zero for all clinical and cognitive scales. Repeated measures analysis of variance revealed no significant treatment effect on any measure of positive or negative symptoms from baseline through week 8: SANS total (F=1.5, df=4, 24, p=0.21); Positive and Negative Syndrome Scale total (F=1.1, df=4, 24, p=0.35), positive subscale (F=0.7, df=4, 24, p=0.58), and negative subscale (F=0.4, df=4, 24, p=0.81); and BPRS (F=1.1, df=4, 22, p=0.38).
Mean serum glycine at baseline was 239 μmol/liter (SD=41); mean serum glycine at week 8 was 1390 μmol/liter (SD=1033). One patient had less than a three-fold increase in serum glycine. With that patient excluded, the mean increase in glycine levels was sixfold. Mean serum serine at baseline was 87 μmol/liter (SD=17); mean serine at week 8 was 274 μmol/liter (SD=195).