Hi, I have read conflicting things regarding sarcosine’s ability to help positive symptoms so I was wondering if you guys could please set the record straight… Does sarcosine help positive symptoms? Thanks.
Some limited information indicates that it can improve positive symptoms. But, as an antipsychotic, sarcosine is not recommended as a monotherapy or as a first-line agent for schizophrenia. Moreover, its effects on positive symptoms seem to be more speculative than well established.
I present you with a citation from the Journal of the American Medical Association:
According to meta analyses Sarcosine can indeed help with positive symptoms.
GE Tsai and PY Lin,
Current pharmaceutical design, 2010
Although hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission is proposed to play an important role in the pathophysiology of schizophrenia, results of the clinical trials of small molecules that enhance the NMDA function are inconsistent. A meta-analysis of all the double-blind, placebo-controlled studies in patients with schizophrenia was performed to examine their efficacy on different symptom domains, the dose-response, the effects of concomitant antipsychotics, and their side effects. About eight hundred subjects from 26 studies were included in current meta-analysis. Overall, the NMDA-enhancing molecules are effective in most schizophrenic symptom domains with the effect size (ES) of total psychopathology of 0.40 (p<1 x 10(-4)). The ES of clinical efficacy of the symptom domains were in the order of depressive (0.40, p=3 x 10(-4)), negative (0.38, p<1 x 10(-4)), cognitive (0.28, p=2 x 10(-3)), positive symptom (0.26, p=0.0006), and general psychopathology (0.26, p=0.006). Glycine, D-serine, and sarcosine treatments significantly improved multiple symptom domains, whereas D-cycloserine did not improve any symptom domain. Moderator analysis revealed that glycine, D-serine and sarcosine are better than D-cycloserine in improving the overall psychopathology. Patients receiving risperidone or olanzapine, but not clozapine, improved. No significant side effect or safety concern was noted. In addition to testing more lead compounds, long-term trials are required to determine their functional improvement capacity. Other drug targets that may enhance NMDA neurotransmission more than the molecules tested so far need to be explored.
SP Singh and V Singh,
CNS drugs, Oct 2011 01
Based on the glutamatergic NMDA receptor hypofunction theory of schizophrenia, NMDA receptor modulators (NMDARMs) may have therapeutic potential in the treatment of schizophrenia.This meta-analysis aimed to evaluate the potential of modulators of the NMDA receptor as adjunctive therapy for schizophrenia, using the results from published trials.A primary electronic search for controlled clinical trials using NMDARMs in schizophrenia was conducted on the PubMed, Cochrane Library, EMBASE, CINAHL® and PsycINFO databases. A secondary manual search of references from primary publications was also performed.Inclusion criteria were the application of an established method of diagnosis, randomized case assignment, comparison of NMDARM add-on therapy with placebo, and double-blind assessment of symptoms in chronic schizophrenia using standardized rating scales. Results were based on a total sample size of 1253 cases from 29 trials that fulfilled the specified criteria.Scores on rating scales or on their relevant subscales were obtained for all selected studies from published results for the minimum dataset to compute the difference between post- and pre-trial scores and their pooled standard deviation for NMDARM add-on therapy and placebo groups for negative, positive and total symptoms.A negative standardized mean difference (SMD) indicates therapeutic benefit in favour of NMDARM add-on therapy and all SMD results mentioned here are statistically significant. The overall effect size for NMDARMs as a group was small for negative (SMD -0.27) and medium for total (SMD -0.40) symptoms of chronic schizophrenia. Subgroup analysis revealed medium effect sizes for D-serine and N-acetyl-cysteine (NAC) for negative (SMD -0.53 and -0.45, respectively) and total (SMD -0.40 and -0.64, respectively) symptoms, and for glycine (SMD -0.66) and sarcosine (SMD -0.41) for total symptoms. As adjuvants to non-clozapine antipsychotics, additional therapeutic benefits were observed for NMDARM as a group (SMD -0.14) and glycine (SMD -0.54) for positive symptoms; D-serine (SMD -0.54), NAC (SMD -0.45) and sarcosine (SMD -0.39) for negative symptoms; and NMDARM as a group (SMD -0.38), D-serine (SMD -0.40), glycine (SMD -1.12), NAC (SMD -0.64) and sarcosine (SMD -0.53) for total symptoms. When added to clozapine, none of the drugs demonstrated therapeutic potential, while addition of glycine (SMD +0.56) worsened positive symptoms.Taking into consideration the number of trials and sample size in subgroup analyses, D-serine, NAC and sarcosine as adjuncts to non-clozapine antipsychotics have therapeutic benefit in the treatment of negative and total symptoms of chronic schizophrenia. While glycine improves positive and total symptoms as an adjuvant to non-clozapine antipsychotics, it worsens them when added to clozapine.
It is important to note that in those studies, Sarcosine was being tested as an add-on to antipsychotics.
Also, from the study:
In addition to testing more lead compounds, long-term trials are required to determine their functional improvement capacity.
So, it is possible Sarcosine can work alongside an antipsychotic to improve positive symptoms, but more research needs to be done. Interestingly, both of these studies said mixing sarcosine and clozapine can worsen symptoms. I hadn’t heard that before.
It helped me a lot it reversed an unknown brain manic brain damage (was 2 months on it), damage on my glutamate system or something caused by lamictal 25 mg, ( anti convulsant drug induced psychosis ), i had this for 7 years, it cured the damage also after quitting. a year off seroquel XR now
USA USA USA
JESUS JESUS JESUS
hey far_cry0 how are you doing?
Hey what is this? I’ve had quite a few manic episodes before should I be worried?
Describe to me what you feeling, and what caused it might be able to give you some advice to take serious and take it to doctor
In my experience yes, my positives have been a little bit less after taking sarcosine, my voices have been a little bit quieter. Also I have a horrible speech impediment but the sarcosine helps that too. it mostly helps negatives but it has a mild effect on positives.
I am good zeroenp …!!! i am waiting for next big breakthrough on sz research…!!!
There has been one study done with Sarcosine as a monotherapy that showed benefit.
HY Lane, YC Liu, CL Huang, YC Chang, CH Liau, CH Perng and GE Tsai,
Biological psychiatry, Jan 2008 01
Small molecules that enhance the N-methyl-D-aspartate (NMDA) neurotransmission have been shown to be beneficial as adjuvant therapy for schizophrenia. Among these compounds, sarcosine (a glycine transporter-I inhibitor), when added to an existing regimen of antipsychotic drugs, has shown its efficacy for both chronically stable and acutely ill patients. However, the efficacy of these agents as a primary antipsychotic agent has not yet been demonstrated.Twenty acutely symptomatic drug-free patients with schizophrenia were randomly assigned under double-blind conditions to receive a 6-week trial of 2 g or 1 g of sarcosine daily.Overall, patients in the 2-g group were more likely to respond as defined by a 20% or more reduction of the Positive and Negative Syndrome Scale total score, particularly among antipsychotic-naïve patients. However, there was no significant between-group difference in the sarcosine dose x time interaction analysis. Both doses were well tolerated with minimal side effects.Although patients receiving the 2-g daily dose were more likely to respond, it requires further clarification whether the effect is limited to the antipsychotic-naive population. Future placebo- or active-controlled, larger-sized studies are needed to fully assess sarcosine's effects.
That study is inconclusive at best, and it says so in the conclusion.