Efficacy and Safety of Acetyl-L-Carnitine and Agmatine Sulfate Compared to Escitalopram in Major Depressive Disorder: A Double-Blind Study
DOI:
https://doi.org/10.37506/jfc9aw22Keywords:
MDD, Acetyl-L-carnitine, Agmatine Sulfate, Escitalopram, MADRSAbstract
Background: To evaluate the efficacy and safety of FDC containing Acetyl-L-carnitine and Agmatine Sulfate versus Escitalopram in treating Major Depressive Disorder (MDD).
Methods: Sixty participants, aged 18-65, diagnosed with MDD, were randomized to receive either FDC containing Acetyl-L-carnitine and Agmatine Sulfate or Escitalopram for 28 days. Depression severity was measured using the Hamilton Rating Scale for Depression (HAM-D17) and Montgomery-Asberg Depression Rating Scale (MADRS). Safety was assessed by monitoring adverse events and vital signs. FDC containing Acetyl-L-carnitine and Agmatine Sulfate significantly reduced HAM-D17 and MADRS scores more than Escitalopram (mean changes: -8.67 vs. -3.80 and -12.33 vs. -9.66, respectively). Adverse events were fewer in the FDC containing Acetyl-L-carnitine and Agmatine Sulfate group, with only one reported case compared to seven in the Escitalopram group.
Conclusion: FDC containing Acetyl-L-carnitine and Agmatine Sulfate demonstrated superior efficacy and a better safety profile compared to Escitalopram, suggesting it as a promising alternative treatment for MDD. Further research is needed to confirm long-term benefits and optimal dosing.
References
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1789-1858. doi: 10.1016/S0140-6736(18)32279-7. Epub 2018 Nov 8. Erratum in: Lancet. 2019 Jun 22;393(10190):e44. doi: 10.1016/S0140-6736(19)31047-5. PMID: 30496104; PMCID:
Nagy C, Maitra M, Tanti A, Suderman M, Théroux JF, Davoli MA, Perlman K, Yerko V, Wang YC, Tripathy SJ, Pavlidis P, Mechawar N, Ragoussis J, Turecki G. Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons. Nat Neurosci. 2020 Jun;23(6):771-781. doi: 10.1038/s41593-020-0621-y. Epub 2020 Apr 27. PMID: 32341540.
Fellinger M, Waldhör T, Serretti A, Hinterbuchinger B, Pruckner N, König D, Gmeiner A, Vyssoki S, Vyssoki B, Fugger G. Seasonality in Major Depressive Disorder: Effect of Sex and Age. J Affect Disord. 2022 Jan 1;296:111-116. doi: 10.1016/j.jad.2021.09.051. Epub 2021 Sep 22. PMID: 34600171.
Teufel F, Aggarwal A, Chwastiak L, Patel V, Ali MK. Depression Diagnosis, Treatment, and Remission Among Adults in India. JAMA Psychiatry. 2024 Dec 1;81(12):1265-1269. doi: 10.1001/jamapsychiatry.2024.3419. PMID: 39475926; PMCID: PMC11581718.
Yang, Jin-shuai& Zhang, Lu-yu& Yang, Cheng-hao & Li, Xin-yu& Li, Zhi-qiang. (2024). Global, Regional, and National Epidemiology of Depression in Working-Age Individuals, 1990–2019. Depression and Anxiety. 2024. 10.1155/2024/4747449.
Rice F, Riglin L, Lomax T, Souter E, Potter R, Smith DJ, Thapar AK, Thapar A. Adolescent and adult differences in major depression symptom profiles. J Affect Disord. 2019 Jan 15;243:175-181. doi: 10.1016/j.jad.2018.09.015. Epub 2018 Sep 11. PMID: 30243197.
Hasin DS, Sarvet AL, Meyers JL, Saha TD, Ruan WJ, Stohl M, Grant BF. Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States. JAMA Psychiatry. 2018 Apr 1;75(4):336-346. doi: 10.1001/jamapsychiatry.2017.4602. PMID: 29450462; PMCID: PMC5875313.
Kautzky A, James GM, Philippe C, Baldinger-Melich P, Kraus C, Kranz GS, Vanicek T, Gryglewski G, Wadsak W, Mitterhauser M, Rujescu D, Kasper S, Lanzenberger R. The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning. Transl Psychiatry. 2017 Jun 13;7(6):e1150. doi: 10.1038/tp.2017.108. PMID: 28608854; PMCID: PMC5537636.
McLachlan G. Treatment resistant depression: what are the options? BMJ. 2018 Dec 18;363:k5354. doi: 10.1136/bmj.k5354. PMID: 30563939.
Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 32119293.
Liu T, Deng K, Xue Y, Yang R, Yang R, Gong Z, Tang M. Carnitine and Depression. Front Nutr. 2022 Mar 14;9:853058. doi: 10.3389/fnut.2022.853058. PMID: 35369081; PMCID: PMC8964433.
Nasca C, Bigio B, Lee FS, Young SP, Kautz MM, Albright A, Beasley J, Millington DS, Mathé AA, Kocsis JH, Murrough JW, McEwen BS, Rasgon N. Acetyl-l-carnitine deficiency in patients with major depressive disorder. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8627-8632. doi: 10.1073/pnas.1801609115. Epub 2018 Jul 30. PMID: 30061399; PMCID: PMC6112703.
Valverde AP, Camargo A, Rodrigues ALS. Agmatine as a novel candidate for rapid-onset antidepressant response. World J Psychiatry. 2021 Nov 19;11(11):981-996. doi: 10.5498/wjp.v11.i11.981. PMID: 34888168; PMCID: PMC8613765.
Watts D, Pfaffenseller B, Wollenhaupt-Aguiar B, Paul Géa L, Cardoso TA, Kapczinski F. Agmatine as a potential therapeutic intervention in bipolar depression: the preclinical landscape. Expert Opin Ther Targets. 2019 Apr;23(4):327-339. doi: 10.1080/14728222.2019.1581764. Epub 2019 Feb 22. PMID: 30764678.
Bigio B, Azam S, Mathé AA, Nasca C. The neuropsychopharmacology of acetyl-L-carnitine (LAC): basic, translational and therapeutic implications. Discov Ment Health. 2024 Jan 2;4(1):2. doi: 10.1007/s44192-023-00056-z. PMID: 38169018; PMCID: PMC10761640.
Nie L-J, Liang J, Shan F, Wang B-S, Mu Y-Y, Zhou X-H and Xia Q-R (2021) L-Carnitine and Acetyl-L-Carnitine: Potential Novel Biomarkers for Major Depressive Disorder. Front. Psychiatry 12:671151. doi: 10.3389/fpsyt.2021.671151
Saelens J, Gramser A, Watzal V, et al. Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials. Neuropsychopharmacology :Official Publication of the American College of Neuropsychopharmacology. 2024 Dec. DOI: 10.1038/s41386-024-02044-5. PMID: 39739012.
Bigio B, Azam S, Mathé AA, Nasca C. The neuropsychopharmacology of acetyl-L-carnitine (LAC): basic, translational and therapeutic implications. Discov Ment Health. 2024 Jan 2;4(1):2. doi: 10.1007/s44192-023-00056-z. PMID: 38169018; PMCID: PMC10761640..
Harish, K. H., & Swamy, A. H. V. (2024). Agmatine as a Promising Neuroprotective Strategy for Treating Neurological Disorders. International Journal of Pharmaceutical Investigation, 14(3), 670–680. https://doi.org/10.5530/ijpi.s14.3.78
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