Sarcosine (N-methylglycine) has been investigated as an adjunctive treatment for schizophrenia, primarily due to its role as a glycine transporter-1 (GlyT1) inhibitor, which enhances glycine availability at the NMDA receptor. NMDA receptor hypofunction is implicated in the pathophysiology of schizophrenia, particularly in relation to negative and cognitive symptoms that are often resistant to standard antipsychotic therapy.

Several double-blind, placebo-controlled trials have explored the efficacy of sarcosine in patients with schizophrenia. Notably, studies published in Biological Psychiatry (2004, 2005) and subsequent meta-analyses have found that adjunctive sarcosine (typically 2 grams daily) can improve negative and cognitive symptoms when added to antipsychotic medications, especially those that are not clozapine. The effect size is generally moderate, and sarcosine appears to be well tolerated. However, results are mixed for patients taking clozapine, with some studies failing to show additional benefit.

Overall, while evidence supports a potential role for sarcosine as an adjunctive treatment, the quality and size of studies are moderate, and larger, more definitive trials are needed. Current clinical guidelines do not universally recommend sarcosine, but it is considered a promising investigational adjunct for certain symptom domains in schizophrenia.