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

Marchi, Mattia; Galli, Giacomo; Magarini, Federica Maria; Mattei, Giorgio; Galeazzi, Gian Maria

doi:10.1080/17425255.2021.1885648

Cited by 17 publications

(11 citation statements)

References 66 publications

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“…Clinical trials with sarcosine revealed partly conflicting results. Two comprehensive meta-analyses confirmed positive effects of sarcosine combined with first-generation antipsychotics and second-generation antipsychotics (with the exception of clozapine) on clinical symptoms overall, but not on cognitive functions [ 91 , 92 ].…”

Section: The Glutamatergic Systemmentioning

confidence: 99%

Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia

Veselinović

Neuner

2022

CNS Drugs

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Cognitive impairments associated with schizophrenia (CIAS) represent a central element of the symptomatology of this severe mental disorder. CIAS substantially determine the disease prognosis and hardly, if at all, respond to treatment with currently available antipsychotics. Remarkably, all drugs presently approved for the treatment of schizophrenia are, to varying degrees, dopamine D 2 /D 3 receptor blockers. In turn, rapidly growing evidence suggests the immense significance of systems other than the dopaminergic system in the genesis of CIAS. Accordingly, current efforts addressing the unmet needs of patients with schizophrenia are primarily based on interventions in other non-dopaminergic systems. In this review article, we provide a brief overview of the available evidence on the importance of specific systems in the development of CIAS. In addition, we describe the promising targets for the development of new drugs that have been used so far. In doing so, we present the most important candidates that have been investigated in the field of the specific systems in recent years and present a summary of the results available at the time of drafting this review (May 2022), as well as the currently ongoing studies.

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Section: The Glutamatergic Systemmentioning

confidence: 99%

Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia

Veselinović

Neuner

2022

CNS Drugs

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“…Such NMDA receptor-enhancing agents in schizophrenia may be effective in improving common symptoms of disease, including cognitive impairment (Chang et al, 2019 ). Examples of such agents are N-methyl-glycine (sarcosine) and memantine—both substances by modulating NMDA receptor activity can improve the activity of NMDARs in schizophrenia and reduce schizophrenic symptoms (Andrade 2017 , Chang et al, 2019 , Marchi et al, 2021 ). Although the previous studies and meta-analyzes do not confirm the significant effectiveness of substances increasing the activity of NMDARs on cognitive disorders in schizophrenia (apart from N-acetyl cysteine), they indicate the direction of searching for new drugs to improve the effectiveness of schizophrenia pharmacotherapy (Marchi et al, 2021 , Andrad, 2017 , Chang et al, 2019 ).…”

Section: Pharmacomodulation Of Nmdars Function In Neuropsychiatrymentioning

confidence: 99%

Spider Neurotoxins as Modulators of NMDA Receptor Signaling

Pałasz

Krzystanek

2021

Neuromol Med

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Molecules that selectively act on N-methyl-D-aspartate (NMDA) receptors may have a multidirectional effect by modulating the activity of NMDARs, affecting their active sites as well as by changing the composition of their subunits. The results of the clinical trials conducted so far in mood disorders and schizophrenia indicate that such agents may become new effective drugs for the treatment of these diseases. Number of spider neurotoxins e.g. ctenitoxins extracted from Phoneutria sp. venom act as potent and selective NMDAR blockers that do not disturb cortical and hippocampal glutamate signaling, LTP generation and synaptic neurochemistry. Possibly this intriguing kind of promising neuroregulatory peptides and polyamines can be clinically applicable in a wide spectrum of neuropsychiatric disorders, including epilepsy, neurotrauma and ischemic injuries. These novel medications can potentially be helpful in the future treatment of stroke and several neurodegenerative diseases.

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“…The role of augmentation strategies with other psychotropic drugs is less clear. Beyond psychopharmacologic medications, some promising non-psychotropic repurposed medicines have also been investigated in meta-analyses 20–49. However, while meta-analyses aim to provide data for effectiveness and tolerance, they are often not designed to readily inform the clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs

Fond,

Mallet,

Urbach

et al. 2023

BMJ Ment Health

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QuestionThis umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.Study selection and analysisFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed.FindingsProvisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200–3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200–300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio.ConclusionsThe results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.

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

Cited by 17 publications

References 66 publications

Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia

Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia

Spider Neurotoxins as Modulators of NMDA Receptor Signaling

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs

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