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ORIGINAL RESEARCH ARTICLE

Brain glutamate level after treatment with N-acetylcysteine in obsessive-compulsive disorder patients: A randomized trial

Sadia Binte Anwar Sonia1 ,  Md Sayedur Rahman2 ,  Mahbuba Shirin3 ,  Muhammad Nurul Alam Siddiki4 ,  Sarmin Sultana5 ,  Iftekhar Hossain Chowdhury6* ,  Humayra Rumu7 ,  Nazla Shamsuddoha8
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1 Department of Pharmacology, Armed Forces Medical College, Dhaka, Bangladesh
2 Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
3 Department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
4 Department of Ophthalmology, Combined Military Hospital, Dhaka, Bangladesh
5 Department of Pharmacology, Army Medical College, Jashore, Bangladesh
6 Department of Pharmacology, Mugda Medical College and Hospital, Dhaka, Bangladesh
7 Department of Dental Pharmacology, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh
8 Department of Pharmacology, Medical College for Women and Hospital, Dhaka, Bangladesh
INNOSC Theranostics and Pharmacological Sciences, 4887 https://doi.org/10.36922/itps.4887
Submitted: 19 September 2024 | Revised: 5 December 2024 | Accepted: 18 December 2024 | Published: 17 January 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Selective serotonin reuptake inhibitors (SSRIs) are routinely used to treat patients with obsessive–compulsive disorder (OCD); however, 40 – 60% of patients with OCD do not respond to SSRIs. Glutamate dysfunction may play a key role in OCD pathogenesis. N-acetylcysteine (NAC), a glutamate-modulating drug, targets the glutamatergic system. This study aimed to assess whether the addition of NAC reduces the severity of OCD symptoms in patients with SSRI-treated moderate-to-severe OCD. A total of 60 patients with OCD were diagnosed according to the DSM-5 criteria, and severity of the symptoms was assessed using the Yale–Brown obsessive–compulsive scale (Y-BOCS). Patients were administered 2,400 mg/day of SSRIs plus placebo (placebo arm) or 2,400 mg/day (NAC arm) of SSRIs plus NAC for 10 weeks. Serum alanine aminotransferase, aspartate aminotransferase, creatinine, and electrocardiogram were monitored to evaluate the safety of NAC. The Y-BOCS score was not significantly different between the two arms at baseline; however, it was significantly different between the two arms after 4 (P = 0.03) and 10 (P = 0.00) weeks. The NAC arm had a reduction of 8.4 (25.51 – 17.15) points compared with 1.42 (25.07 – 23.65) points for the placebo arm from baseline to 10 weeks. NAC was well-tolerated and caused mild gastrointestinal adverse events. Thus, NAC is an effective glutamate-modulating drug as and can be used as an augmentation therapy with standard treatment in patients with moderate-to-severe OCD.

Keywords
Glutamate
N-acetylcysteine
Obsessive–compulsive disorder
Yale–Brown obsessive–compulsive scale
Funding
None.
Conflict of interest
The authors declared that they have no competing interests.
References
  1. American Psychiatric Association (APA). What is Obsessive- Compulsive Disorder? American Psychiatric Association; 2013. Available from: https://www.psychiatry.org/patients-families/ocd/what-is-obsessive-compulsivedisorder [Last accessed on 2023 Nov 20].

 

  1. Adam Y, Meinlschmidt G, Gloster AT, Lieb R. Obsessive-compulsive disorder in the community: 12-month prevalence, comorbidity and impairment. Soc Psychiatry Psychiatr Epidemiol. 2012;47(3):339-349. doi: 10.1007/s00127-010-0337-5

 

  1. Solish AJ. Parents’ Involvement in Behavioural Intervention for their Children with Autism. Vol. 73. Canada: York University; 2010. p. 632.

 

  1. Algin S, Sajib MW, Arafat SY. Demography and symptom severity of obsessive compulsive disorder in Bangladesh: A cross-sectional observation. Bangladesh J Psychiatry. 2016;30(2):23-26. doi: 10.3329/bjpsy.v30i2.45360

 

  1. World Health Organization (WHO). The Global Burden of Disease. World Health Organization; 2018. Available from: https://www.ocduk.org/ocd/world-health-organisation [Last accessed on 2023 Nov 26].

 

  1. Meier SM, Mattheisen M, Mors O, Schendel DE, Mortensen PB, Plessen KJ. Mortality among persons with obsessive-compulsive disorder in denmark. JAMA Psychiatry. 2016;73(3):268-274. doi: 10.1001/jamapsychiatry.2015.3105

 

  1. Norberg MM, Calamari JE, Cohen RJ, Riemann BC. Quality of life in obsessive-compulsive disorder: An evaluation of impairment and a preliminary analysis of the ameliorating effects of treatment. Depress Anxiety. 2008;25(3):248-259. doi: 10.1002/da.20298

 

  1. American Psychiatric Association: Washington, DC. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5th ed. Washington, DC: American Psychiatric Association; 2013. Available from: https://www.ocduk. org/ocd/clinical-classification-of/ocd/dsm-and/ocd [Last accessed on 2021 Nov 25].

 

  1. Zhang H, Wang B, Li K, et al. Altered functional connectivity between the cerebellum and the cortico-striato-thalamo-cortical circuit in obsessive-compulsive disorder. Front Psychiatry. 2019;10:522. doi: 10.3389/fpsyt.2019.00522

 

  1. Kariuki-Nyuthe C, Gomez-Mancilla B, Stein DJ. Obsessive compulsive disorder and the glutamatergic system. Curr Opin Psychiatry. 2014;27(1):32-37. doi: 10.1097/YCO.0000000000000017

 

  1. Berk M, Ng F, Dean O, Dodd S, Bush AI. Glutathione: A novel treatment target in psychiatry. Trends Pharmacol Sci. 2008;29(7):346-351. doi: 10.1016/j.tips.2008.05.001

 

  1. Fenske JN, Petersen K. Obsessive-compulsive disorder: Diagnosis and management. Am Fam Physician. 2015;92(10):896-903.

 

  1. Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14:S1. doi: 10.1186/1471-244X-14-S1-S1

 

  1. Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision. World J Biol Psychiatry. 2008;9(4):248-312. doi: 10.1080/15622970802465807

 

  1. Swierkosz-Lenart K, Dos Santos JFA, Elowe J, et al. Therapies for obsessive-compulsive disorder: Current state of the art and perspectives for approaching treatment-resistant patients. Front Psychiatry. 2023;14:1065812. doi: 10.3389/fpsyt.2023.1065812

 

  1. Janardhan Reddy YC, Sundar AS, Narayanaswamy JC, Math SB. Clinical practice guidelines for obsessive-compulsive disorder. Indian J Psychiatry. 2017;59(Suppl 1):S74-S90. doi: 10.4103/0019-5545.196976

 

  1. Pittenger C, Bloch MH. Pharmacological treatment of obsessive-compulsive disorder. Psychiatr Clin North Am. 2014;37(3):375-391. doi: 10.1016/j.psc.2014.05.006

 

  1. Pallanti S, Grassi G, Cantisani A. Emerging drugs to treat obsessive-compulsive disorder. Expert Opin Emerg Drugs. 2014;19(1):67-77. doi: 10.1517/14728214.2014.875157

 

  1. Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-compulsive disorder: Advances in diagnosis and treatment. JAMA. 2017;317(13):1358-1367. doi: 10.1001/jama.2017.2200

 

  1. Bloch MH, McGuire J, Landeros-Weisenberger A, Leckman JF, Pittenger C. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry. 2010;15(8):850-855. doi: 10.1038/mp.2009.50

 

  1. Bandelow B. The medical treatment of obsessive-compulsive disorder and anxiety. CNS Spectr. 2008;13(9 Suppl 14):37-46. doi: 10.1017/s1092852900026924

 

  1. Bakizadeh F, Mokhtari S, Saeed F, Mokhtari A, Akbari Koli P, Shalbafan M. Cognitive rehabilitation for adult patients with obsessive-compulsive disorder: A systematic review of randomized controlled trials. Basic Clin Neurosci. 2024;15(3):287-300. doi: 10.32598/bcn.2022.1604.3

 

  1. Eissazade N, Mosavari H, Eghdami S, Boroon M, Ashrafi F, Shalbafan M. Efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in augmentation with selective serotonin reuptake inhibitors (SSRIs) in the treatment of moderate to severe obsessive-compulsive disorder: A systematic review and meta-analysis of randomized clinical trials. Sci Rep. 2023;13(1):20837. doi: 10.1038/s41598-023-47931-x

 

  1. Askari S, Mokhtari S, Shariat SV, Shariati B, Yarahmadi M, Shalbafan M. Memantine augmentation of sertraline in the treatment of symptoms and executive function among patients with obsessive-compulsive disorder: A double-blind placebo-controlled, randomized clinical trial. BMC Psychiatry. 2022;22(1):34. doi: 10.1186/s12888-021-03642-z

 

  1. Shalbafan M, Malekpour F, Tadayon Najafabadi B, et al. Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: A placebo-controlled, randomized clinical trial. J Psychopharmacol. 2019;33(11):1407-1414. doi: 10.1177/0269881119878177

 

  1. Van Noppen BL, Pato MT, Marsland R, Rasmussen SA. A time-limited behavioral group for treatment of obsessive-compulsive disorder. J Psychother Pract Res. 1998;7(4):272-280.

 

  1. Figueroa Y, Rosenberg DR, Birmaher B, Keshavan MS. Combination treatment with clomipramine and selective serotonin reuptake inhibitors for obsessive-compulsive disorder in children and adolescents. J Child Adolesc Psychopharmacol. 1998;8(1):61-67. doi: 10.1089/cap.1998.8.61

 

  1. Treatment of obsessive-compulsive disorder. The expert consensus panel for obsessive-compulsive disorder. J Clin Psychiatry. 1997;58(Suppl 4):2-72.

 

  1. Decloedt EH, Stein DJ. Current trends in drug treatment of obsessive-compulsive disorder. Neuropsychiatr Dis Treat. 2010;6:233-242. doi: 10.2147/ndt.s3149

 

  1. Marinova Z, Chuang DM, Fineberg N. Glutamate-modulating drugs as a potential therapeutic strategy in obsessive-compulsive disorder. Curr Neuropharmacol. 2017;15(7):977-995. doi: 10.2174/1570159X15666170320104237

 

  1. Zhu Y, Fan Q, Han X, et al. Decreased thalamic glutamate level in unmedicated adult obsessive-compulsive disorder patients detected by proton magnetic resonance spectroscopy. J Affect Disord. 2015;178:193-200. doi: 10.1016/j.jad.2015.03.008

 

  1. Ting JT, Feng G. Neurobiology of obsessive-compulsive disorder: Insights into neural circuitry dysfunction through mouse genetics. Curr Opin Neurobiol. 2011;21(6):842-848. doi: 10.1016/j.conb.2011.04.010

 

  1. Hadi F, Kashefinejad S, Kamalzadeh L, Hoobehfekr S, Shalbafan M. Glutamatergic medications as adjunctive therapy for moderate to severe obsessive-compulsive disorder in adults: A systematic review and meta-analysis. BMC Pharmacol Toxicol. 2021;22(1):69. doi: 10.1186/s40360-021-00534-6

 

  1. Wu K, Hanna GL, Rosenberg DR, Arnold PD. The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem Behav. 2012;100(4):726-735. doi: 10.1016/j.pbb.2011.10.007

 

  1. Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive disorder: Neurobiology, pathophysiology, and treatment. Pharmacol Ther. 2011;132(3):314-332. doi: 10.1016/j.pharmthera.2011.09.006

 

  1. Ting JT, Feng G. Glutamatergic synaptic dysfunction and obsessive-compulsive disorder. Curr Chem Genomics. 2008;2:62-75. doi: 10.2174/1875397300802010062

 

  1. Chakrabarty K, Bhattacharyya S, Christopher R, Khanna S. Glutamatergic dysfunction in OCD. Neuropsychopharmacology. 2005;30(9):1735-1740. doi: 10.1038/sj.npp.1300733

 

  1. Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry. 2000;39(9):1096-1103. doi: 10.1097/00004583-200009000-00008

 

  1. Bhattacharyya S, Khanna S, Chakrabarty K, Mahadevan A, Christopher R, Shankar SK. Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder. Neuropsychopharmacology. 2009;34(12):2489-2496. doi: 10.1038/npp.2009.77

 

  1. Ozdemir E, Cetinkaya S, Ersan S, Kucukosman S, Ersan EE. Serum selenium and plasma malondialdehyde levels and antioxidant enzyme activities in patients with obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):62-65. doi: 10.1016/j.pnpbp.2008.10.004

 

  1. Ersan S, Bakir S, Erdal Ersan E, Dogan O. Examination of free radical metabolism and antioxidant defence system elements in patients with obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(6):1039-1042. doi: 10.1016/j.pnpbp.2006.03.034

 

  1. Tenório MCD, Graciliano NG, Moura FA, de Oliveira ACM, Goulart MOF. N-Acetylcysteine (NAC): Impacts on human health. Antioxidants (Basel). 2021;10(6):967. doi: 10.3390/antiox10060967

 

  1. Raghu G, Berk M, Campochiaro PA, et al. The multifaceted therapeutic role of N-acetylcysteine (NAC) in disorders characterized by oxidative stress. Curr Neuropharmacol. 2021;19(8):1202-1224. doi: 10.2174/1570159X19666201230144109

 

  1. Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: Current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011;36(2):78-86. doi: 10.1503/jpn.100057

 

  1. Baxter PS, Bell KF, Hasel P, et al. Synaptic NMDA receptor activity is coupled to the transcriptional control of the glutathione system. Nat Commun. 2015;6:6761. doi: 10.1038/ncomms7761

 

  1. Sarris J, Byrne G, Castle D, et al. N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2022;117:110550. doi: 10.1016/j.pnpbp.2022.110550

 

  1. Li F, Welling MC, Johnson JA, et al. N-acetylcysteine for pediatric obsessive-compulsive disorder: A small pilot study. J Child Adolesc Psychopharmacol. 2020;30(1):32-37. doi: 10.1089/cap.2019.0041

 

  1. Ghanizadeh A, Mohammadi MR, Bahraini S, Keshavarzi Z, Firoozabadi A, Alavi Shoshtari A. Efficacy of N-acetylcysteine augmentation on obsessive compulsive disorder: A multicenter randomized double blind placebo controlled clinical trial. Iran J Psychiatry. 2017;12(2):134-141.

 

  1. Costa DLC, Diniz JB, Requena G, et al. Randomized, double-blind, placebo-controlled trial of N-acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry. 2017;78(7):e766-e773. doi: 10.4088/JCP.16m11101

 

  1. Paydary K, Akamaloo A, Ahmadipour A, Pishgar F, Emamzadehfard S, Akhondzadeh S. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: Randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther. 2016;41(2):214-219. doi: 10.1111/jcpt.12370

 

  1. Sarris J, Oliver G, Camfield DA, et al. N-Acetyl Cysteine (NAC) in the treatment of obsessive-compulsive disorder: A 16-week, double-blind, randomised, placebo-controlled study. CNS Drugs. 2015;29(9):801-809. doi: 10.1007/s40263-015-0272-9

 

  1. Afshar H, Roohafza H, Mohammad-Beigi H, et al. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2012;32(6):797-803. doi: 10.1097/JCP.0b013e318272677d

 

  1. Yazici KU, Percinel I. N-acetylcysteine augmentation in children and adolescents diagnosed with treatment-resistant obsessive-compulsive disorder: Case series. J Clin Psychopharmacol. 2015;35(4):486-489. doi: 10.1097/JCP.0000000000000362

 

  1. Lafleur DL, Pittenger C, Kelmendi B, et al. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology (Berl). 2006;184(2):254-256. doi: 10.1007/s00213-005-0246-6

 

  1. Yolland CO, Hanratty D, Neill E, et al. Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia. Aust N Z J Psychiatry. 2020;54(5):453-466. doi: 10.1177/0004867419893439

 

  1. Bhaskara S. N-Acetylcysteine augmentation in refractory obsessive-compulsive disorder. J Psychiatry Neurosci. 2019;44(3):215-216. doi: 10.1503/jpn.180179

 

  1. Goodman WK, Price LH, Rasmussen SA, et al. The yale-brown obsessive compulsive scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989;46(11):1006-1011. doi: 10.1001/archpsyc.1989.01810110048007

 

  1. Saxena S, Bota RG, Brody AL. Brain-behavior relationships in obsessive-compulsive disorder. Semin Clin Neuropsychiatry. 2001;6(2):82-101. doi: 10.1053/scnp.2001.21833

 

  1. Moran MM, McFarland K, Melendez RI, Kalivas PW, Seamans JK. Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking. J Neurosci. 2005;25(27):6389-6393. doi: 10.1523/JNEUROSCI.1007-05.2005

 

  1. Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: Evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008;11(6):851-876. doi: 10.1017/S1461145707008401

 

  1. Farokhnia M, Azarkolah A, Adinehfar F, et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: A randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013;36(6):185-192. doi: 10.1097/WNF.0000000000000001

 

  1. Nikoo M, Radnia H, Farokhnia M, Mohammadi MR, Akhondzadeh S. N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: A randomized, double-blind, placebo-controlled clinical trial of efficacy and safety. Clin Neuropharmacol. 2015;38(1):11-17. doi: 10.1097/WNF.0000000000000063

 

  1. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007;7(4):355-359. doi: 10.1016/j.coph.2007.04.005

 

  1. Berk M, Malhi GS, Gray LJ, Dean OM. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci. 2013;34(3):167-177. doi: 10.1016/j.tips.2013.01.001

 

  1. Selek S, Herken H, Bulut M, et al. Oxidative imbalance in obsessive compulsive disorder patients: A total evaluation of oxidant-antioxidant status. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(2):487-491. doi: 10.1016/j.pnpbp.2007.10.002

 

  1. Nascimento MM, Suliman ME, Silva M, et al. Effect of oral N-acetylcysteine treatment on plasma inflammatory and oxidative stress markers in peritoneal dialysis patients: A placebo-controlled study. Perit Dial Int. 2010;30(3):336-342. doi: 10.3747/pdi.2009.00073

 

  1. Ooi SL, Green R, Pak SC. N-acetylcysteine for the treatment of psychiatric disorders: A review of current evidence. Biomed Res Int. 2018;2018:2469486. doi: 10.1155/2018/2469486

 

  1. Van Ameringen M, Patterson B, Simpson W, Turna J. N-acetylcysteine augmentation in treatment resistant obsessive compulsive disorder: A case series. J Obsessive Compuls Relat Disord. 2013;2(1):48-52. doi: 10.1016/j.jocrd.2012.10.003
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