Sarcosine as an add-on treatment to antipsychotic medication for people with schizophrenia: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT

Background: N-methyl-glycine (sarcosine) may improve symptoms of schizophrenia via NMDA-receptor modulation. We undertook a systematic review and meta-analysis to determine the short- and long-term effectiveness of sarcosine for schizophrenia.

Research design and methods: The databases Medline, Scopus, EMBASE, Cochrane Library, and PsycINFO were searched. We included six independent randomized controlled trials of sarcosine as add-on treatment to current antipsychotic medication, involving 234 adult participants with schizophrenia, and reporting data on symptom severity. Standardized mean differences (SMDs) were used to assess continuous outcomes.

Results: In all of the trials, sarcosine was administered orally at 2 g/day. Treatment with sarcosine did not show a significant effect size at any of the pre-established time points (2, 4, 6, or >6 weeks), due to marked quantitative heterogeneity. However, sarcosine was associated with significant reductions of symptom severity in the subgroups of people with chronic schizophrenia and no treatment resistance (namely, without added-on clozapine) in relation to the SMD after 6 weeks treatment at −0.36 and −0.31, respectively.

Conclusions: People with chronic and non-refractory schizophrenia may benefit from the use of sarcosine as an add-on treatment to antipsychotic medication. Due to the good tolerability of this compound, future trials with larger sample sizes appear worthwhile.

KEYWORDS:

• N-Methyl-D-Aspartate receptors
• sarcosine
• schizophrenia
• psychosis

Article highlights

• N-methyl-glycine (sarcosine) is a potent endogenous inhibitor of glycine transporter-1, with a growing interest in its possible use for the treatment of schizophrenia

• Six primary randomized controlled clinical trials have documented the outcome of treatment with sarcosine for schizophrenia, as an add-on agent

• Treatment with sarcosine (2 g/day) for 6 weeks added to ongoing antipsychotic treatment with FGA or SGA was not associated with a significant reduction in schizophrenia symptom severity in pooled analyses

• Subgroup analyses suggested that people with chronic and non-refractory schizophrenia may benefit from the use of sarcosine as an add-on treatment to antipsychotic medication

• Sarcosine generally has negligible side effects and was very well tolerated by people with schizophrenia

• Larger and longer studies are needed to better estimate the long-term effectiveness and safety of sarcosine as an augmentation to current antipsychotic treatment

Acknowledgments

The authors would like to thank International Edit for a thorough edit of the language.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

Data are available from the corresponding author upon reasonable request.

Author contributions

Conceptualization and planning: M.M., G.G., G.M.G.

Acquisition: M.M., G.G., F.M.M. (under the supervision of G.M.G.)

Analysis of the data: M.M.

Interpretation of the data: M.M., G.G., F.M.M., G.M., G.M.G.

Drafting: M.M., G.G., F.M.M.

Critical revision of the manuscript: G.M., G.M.G.

All authors approved the final submitted version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was not funded.