D-serine for Schizophrenia


by Erin Hawkes, MSc

D-serine is an amino acid that can be made in the body. It plays a role in metabolism, and acts as a “helper” molecule to open receptors (“gates” across cell walls) in the brain. Having the “gate” open makes a brain cell more likely to become active. It is thought that D-serine may therefore have a role in memory.

Likely Effectiveness:  Very promising, supported by many studies, particularly when paired with other antipsychotics. However, one study found no improvement over placebo.

Effective Dosage: Greater than 2 grams per day (less than 2 gram is no better than placebo). Good sources of D-serine include eggs, soy, and dairy; powder supplements are available commercially.

Research: High-quality, reputable meta-analysis and randomized double-blind, placebo-controlled studies; review; pre-clinical and clinical experiments.

Risks:  Kidney problems (rare).

Do Not Take With:  In our discussions with the researcher Heresco-Levy U, he stated that he D-serine and Sarcosine (N-Methyl Glycine) should not be taken at the same time due to the risk of over stimulating the neurons.

Selected References

1) Heresco-Levy U, Javitt DC, Ebstein R, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. 2005;57: 577-585.

This reliable study (double-blind, placebo-controlled, cross-over) evaluated 39 patients who were taking either risperidone or olanzapine for treatment-resistant schizophrenia, after adding a D-serine supplement or a placebo. Those taking D-serine showed improvement on a variety of standard tests of the symptoms of schizophrenia. Depression and motor side effects of the antipsychotics also improved with D-serine treatment. There were no reported side effects of the D-serine.

2) Kantrowitz JT, Malhotra AK, Cornblatt B, et al., High dose D-serine in the treatment of schizophrenia. Schizophr Res .2010;121: 125-130.

This study, in which both patient and doctor did not know who was receiving which treatment, examined the effects of different, high doses of D-serine on symptoms of schizophrenia. The 42 patients were stable (taking antipsychotics). The response was very dose-dependent: those taking higher levels of D-serine showed fewer symptoms while those taking lower levels were more impaired. Moreover, blood levels of D-serine were higher when symptoms had improved. The doses were considerably greater than those used in previous studies (60-120 mg/kg versus 30 mg/kg), but were well tolerated (one individual reported kidney-related side-effects). Standard tests were used to assess symptom levels.

3) de Bartolomeis A, Sarappa C, Magara S, and Iasevoli F. Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia. European J Pharmacol.2012;682: 1-11.

Most studies use 2 grams or 30 mg/kg of D-serine daily, and show little or no benefit over antipsychotics alone or placebos. More recent trials are now examining high (60-120 mg/kg) doses and are finding positive results; most notably reductions in negative and cognitive symptoms. However, the effect of D-serine as an add-on to another antipsychotic depends on the antipsychotic: no effect when paired with clozapine, but good effects when given with other another antipsychotic.

They reference a meta-analysis (evaluating results by pooling many studies and their many subjects), of D-serine, where they examined 26 studies, including approximately 800 subjects; no effects of D-serine were noted, although all studies used a low dose (30 mg/kg) for a short (6 week) trial. When D-serine is withdrawn, however, symptoms and involuntary movements can reappear.

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