Evaluation of Efficacy and Safety of add-on Sarcosine in Patients With Major Depressive Disorder

Summary

One-third of the patients with major depressive disorder do not respond to conventional antidepressants that act through the mono-aminergic system. The available treatment modalities, including SSRIs, are slow to act and have a lag time before showing improvement in symptoms of patients. To overcome these treatment hurdles, add-on therapy to standard antidepressant drugs may lead to better therapeutic outcomes. Sarcosine, which is a nutraceutical, modulates glutamate neurotransmission has an ameliorative effect on the disease symptoms of depression and negative symptoms of schizophrenia. The only clinical study done on depressive patients by Huang et al. cannot be generalized due to certain inherent limitations. To date, there is no randomized controlled trial with add-on sarcosine to current antidepressant therapy to the best of our knowledge. So, we considered sarcosine can be the candidate drug for add-on therapy due to its multiple mechanisms on the glutaminergic system. Adding sarcosine to ongoing antidepressant therapy may either increase their response rate or decrease adverse drug reactions by decreasing the dose requirement or may show a quicker therapeutic effect. Hence, the present randomized controlled trial has been planned to evaluate the efficacy and safety of sarcosine as add-on therapy in major depressive disorder.

Timeline

Start

2021-08-26

Primary completion

2023-04-30

Completion

2023-04-30

Publications

• Results Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095.
• Results Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005 Jun;62(6):593-602. doi: 10.1001/archpsyc.62.6.593.
• Results Hawton K, van Heeringen K. Suicide. Lancet. 2009 Apr 18;373(9672):1372-81. doi: 10.1016/S0140-6736(09)60372-X.
• Results Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry. 2010 Oct;9(3):155-61. doi: 10.1002/j.2051-5545.2010.tb00298.x.
• Results Ruhe HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry. 2007 Apr;12(4):331-59. doi: 10.1038/sj.mp.4001949. Epub 2007 Jan 16.
• Results Perez-Caballero L, Torres-Sanchez S, Romero-Lopez-Alberca C, Gonzalez-Saiz F, Mico JA, Berrocoso E. Monoaminergic system and depression. Cell Tissue Res. 2019 Jul;377(1):107-113. doi: 10.1007/s00441-018-2978-8. Epub 2019 Jan 10.
• Results Pochwat B, Nowak G, Szewczyk B. An update on NMDA antagonists in depression. Expert Rev Neurother. 2019 Nov;19(11):1055-1067. doi: 10.1080/14737175.2019.1643237. Epub 2019 Jul 22.
• Results Phillips C. Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection. Neural Plast. 2017;2017:7260130. doi: 10.1155/2017/7260130. Epub 2017 Aug 8.
• Results Lee MY, Lin YR, Tu YS, Tseng YJ, Chan MH, Chen HH. Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials. J Biomed Sci. 2017 Feb 28;24(1):18. doi: 10.1186/s12929-016-0314-8.
• Results Peyrovian B, Rosenblat JD, Pan Z, Iacobucci M, Brietzke E, McIntyre RS. The glycine site of NMDA receptors: A target for cognitive enhancement in psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:387-404. doi: 10.1016/j.pnpbp.2019.02.001. Epub 2019 Feb 6.
• Results Chen KT, Wu CH, Tsai MH, Wu YC, Jou MJ, Huang CC, Wei IH. Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress. Behav Brain Res. 2017 Jan 1;316:1-10. doi: 10.1016/j.bbr.2016.06.004. Epub 2016 Aug 21.
• Results Huang CC, Wei IH, Huang CL, Chen KT, Tsai MH, Tsai P, Tun R, Huang KH, Chang YC, Lane HY, Tsai GE. Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression. Biol Psychiatry. 2013 Nov 15;74(10):734-41. doi: 10.1016/j.biopsych.2013.02.020. Epub 2013 Apr 3.
• Results Commons KG, Linnros SE. Delayed Antidepressant Efficacy and the Desensitization Hypothesis. ACS Chem Neurosci. 2019 Jul 17;10(7):3048-3052. doi: 10.1021/acschemneuro.8b00698. Epub 2019 Mar 11.
• Results Chen KT, Tsai MH, Wu CH, Jou MJ, Wei IH, Huang CC. AMPA Receptor-mTOR Activation is Required for the Antidepressant-Like Effects of Sarcosine during the Forced Swim Test in Rats: Insertion of AMPA Receptor may Play a Role. Front Behav Neurosci. 2015 Jun 18;9:162. doi: 10.3389/fnbeh.2015.00162. eCollection 2015.
• Padhan M, Mohapatra D, Mishra BR, Maiti R, Jena M. Efficacy and safety of add-on sarcosine in patients with major depressive disorder: A randomized controlled trial. J Psychiatr Res. 2024 Oct;178:298-304. doi: 10.1016/j.jpsychires.2024.08.026. Epub 2024 Aug 22.

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