As shown by both meta-analyses, D-serine has shown promise at a dose of 30 mg/kg (~2 g per day). However, formal dose finding studies for D-serine were not performed prior to selection of this dose. Moreover, animal models suggest that higher doses of D-serine may be ideal. A 2010 study reported the first evaluation of D-serine at doses more than 30 mg/kg per day: a 4-week, open-label trial of adjunctive D-serine (30, 60 or 120 mg/kg per day) [29▪]. Significant improvement was noted across doses, including total symptoms and individual PANSS subscales (positive, negative, and general). Moreover, a significant dose-by-time effect was found for a measure of general cognitive functioning (Fig. 2). Whereas only nonsignificant improvement was noted at 30 mg/kg, a highly significant, large effect size improvement was seen for overall cognition for doses at least 60 mg/kg, leading to a significant dose-by-time interaction (P <0.01). No significant safety issues were noted in any patient taking less than 120 mg/kg. Pharmacokinetic analyses found significant dose-dependent increases in plasma D-serine levels. Furthermore, consistently with prior biomarker studies, lower baseline D-serine
