Safety, tolerability and pharmacokinetics of open label sarcosine added on to anti-psychotic treatment in schizophrenia – preliminary study. (2015)

A study expanding on previous research [see: Glycinergic, NMDA and AMPA augmentation – a review ] on the use of sarcosine in schizophrenia has recently been published:

Safety, tolerability and pharmacokinetics of open label sarcosine added on to anti-psychotic treatment in schizophrenia – preliminary study.

BACKGROUND: Hypofunction of NMDA receptor-mediated neurotransmission might play a critical role in schizophrenia. Sarcosine, N-methylglycine an inhibitor of the glycine transporter-1 (Gly-T1), has been suggested as a novel treatment for schizophrenia.

METHODS: Open label sarcosine was added to 22 stabilized patients: 5 patients received 2 gm/d, and 17 received 4gm/d. Pharmacokinetics samples, clinical and cognitive parameters using PANSS, CGI and MCCB were collected for all patients.

RESULTS: Significant improvement was observed after one week of treatment on PANSS sub-scale of ‘positive symptoms’ (Z= -2.68; P=0.007) and ‘general psychopathology’ (Z= -3.02; P=0.003), an improvement in PANSS total score and CGI-S showed a trend (Z= -2.72; P=0.06; Z=-2.69; P=0.08). Speed of processing (MCCB subscale) improved significantly (Z=-2.13; P=0.03). Sarcosine exhibited linear kinetics, with a Tmax and t½ of ~1½- 2½ hr and ~1hr, respectively.

LIMITATIONS: This was a short period, open label pilot study with small sample size per dosage group.

CONCLUSIONS: Sarcosine is a safe compound and might be efficacious in the treatment of schizophrenia.


“When looking at studies using sarcosine, 2,000mg sarcosine daily for six weeks in addition to antipsychotics noted improvements in symptoms in the range of 14-16% (BPRS and PANSS rating scales) reaching up to around 20% symptom reduction relative to control.

One study in persons on clozapine failed to find a benefit with sarcosine therapy at 2,000mg which is similar to null results seen with D-serine. Since clozapine is thought to be antipsychotic via D-serine signalling this signalling pathway may already be saturated in persons on clozapine.

This magnitude of response seen with sarcosine is somewhat comparable to D-Serine at a similar dose, Glycine at a higher dose (800mg/kg), and D-cycloserine. In direct comparative studies, however, sarcosine has been twice noted to outperform D-serine which may be due to the unreliability seen with D-serine supplementation.

It should be noted that some studies by the author Guochuan Tsai have potential conflicts of interest due to the aforementioned being the creator of sarcosine (US patent 6228875) alongside Joseph Coyle. These studies include the following, although publication bias does not seem likely as the authors have published negative results previously.”

Sarcosine at 2,000mg appears to be just as effective as D-serine for treating symptoms of schizophrenia when looking at the magnitude of benefit, but sarcosine seems to be more reliable and is thus currently seen as being a better therapeutic alternative

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