RT Journal
A1 Lane H, Chang Y, Liu Y, Chiu C, Tsai GE
T1 Sarcosine or d-serine add-on treatment for acute exacerbation of schizophrenia: A randomized, double-blind, placebo-controlled study
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2005
FD November 1
VO 62
IS 11
SP 1196
OP 1204
DO 10.1001/archpsyc.62.11.1196
UL http://dx.doi.org/10.1001/archpsyc.62.11.1196
AB Context 
    Agents that enhance N-methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia.Objective 
    To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor−enhancing agents have beneficial effects for acute exacerbation of schizophrenia.Design 
    Randomized, double-blind, placebo-controlled trial.Setting 
    Inpatient units of 2 major medical centers in Taiwan.Patients 
    Sixty-five schizophrenic inpatients with acute exacerbation.Interventions 
    Six weeks of treatment with sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy.Main Outcome Measures 
    Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores.Results 
    The sarcosine group revealed more reductions in PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups. Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS−blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients (P≤.02 for all). Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores (P≤.04 for all). D-Serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains.Conclusions 
    This first short-term treatment study on NMDA receptor−enhancing agents suggests that sarcosine, superior to D-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed.