Original Article

Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial


Objective: Glutamate is considered a target for treating obsessive-compulsive disorder (OCD). The efficacy and safety of the nutritional supplement of N-Acetylcysteine (NAC) as an adjuvant to serotonin reuptake inhibitor (SSRI) for treating children and adolescents with OCD has never been examined.
Methods: This was a 10-week randomized double-blind placebo-controlled clinical trial with 34 OCD outpatients. The patients received citalopram plus NAC or placebo. Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Pediatric Quality of Life Inventory (PedsQL™) were used. Adverse effects were monitored.
Results: YBOCS score was not different between the two groups at baseline, but the score was different between the two groups at the end of this trial (P<0.02). The YBOCS score of NAC group significantly decreased from 21.0(8.2) to 11.3(5.7) during this study. However, no statistically significant decrease of YBOCS was found in the placebo group. The Cohen’s d effect size was 0.83.
The mean change of score of resistance/control to obsessions in the NAC and placebo groups was 1.8(2.3) and 0.8(2.1), respectively (P = 0.2). However, the mean score of change for resistance/control to compulsion in the NAC and placebo groups was 2.3(1.8) and 0.9(2.3), respectively. Cohen’s d effect size was 0.42.
The score of three domains of quality of life significantly decreased in N-Acetylcysteine group during this trial. However, no statistically significant decrease was detected in the placebo group. No serious adverse effect was found in the two groups.
Conclusion: This trial suggests that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents. In addition, it is well tolerated.

Stevanovic D, A Lakic,M Damnjanovic. Some psychometric properties of the Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales (PedsQL) in the general Serbian population. Qual Life Res 2011;20:945-949.

McElroy SL1, Arnold LM, Shapira NA, Keck PE Jr, Rosenthal NR, Karim MR, et al. Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry 2003;160:255-261.

Limbers CA, DA Newman, JW Varni. Factorial invariance of child self-report across socioeconomic status groups: a multigroup confirmatory factor analysis utilizing the PedsQL 4.0 Generic Core Scales. J Behav Med 2008; 31: 401-411.

Hollander E ,B Dell'Osso. Topiramate plus paroxetine in treatment-resistant obsessive-compulsive disorder. Int Clin Psychopharmacol 2006;21:189-191.

Varni JW ,CA Limbers. The PedsQL Multidimensional Fatigue Scale in young adults: feasibility, reliability and validity in a University student population. Qual Life Res 2008;17: 105-114.

Dannon PN1, Lowengrub K, Gonopolski Y, Musin E, Kotler M. Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clin Neuropharmacol 2005; 28: 6-10.

Dannon PN. Topiramate for the treatment of kleptomania: a case series and review of the literature. Clin Neuropharmacol 2003; 26:1-4.

Lemke NT ,JR Bustillo. Clozapine-induced obsessive-compulsive symptoms in bipolar disorder. Am J Psychiatry 2013;170: 930.

Kariuki-Nyuthe C, B Gomez-Mancilla,DJ Stein. Obsessive compulsive disorder and the glutamatergic system. Curr Opin Psychiatry 2014; 27: 32-37.

Doumy O ,B Aouizerate. [The OCD spectrum disorder revisited. Toward a bipolar impulsion-compulsion configuration.]. Presse Med 2014; 43:118-123

Wolf C, H Mohr, T Schneider-Axmann, et al. CACNA1C genotype explains interindividual differences in amygdala volume among patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 2014; 264:93-102.

Lardner AL. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutr Neurosci 2014; 17: 145-155.

Farzan F1, Barr MS, Hoppenbrouwers SS, Fitzgerald PB, Chen R, Pascual-Leone A, et al. The EEG correlates of the TMS-induced EMG silent period in humans. Neuroimage 2013; 83:120-134.

Ghanizadeh A ,E Moghimi-Sarani. A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders. BMC Psychiatry 2013;13:196.

Ghanizadeh A, N Derakhshan,M Berk. N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial. Antiinflamm Antiallergy Agents Med Chem 2013;12: 223-228.

Lakhan R. The coexistence of psychiatric disorders and intellectual disability in children aged 3-18 years in the barwani district, India. ISRN Psychiatry 2013: 875873.

Matsunami K. [The clinical meaning and academic significance of "endogenous depression" as an ideal type(persion)]. Seishin Shinkeigaku Zasshi 2013;115:267-276.

Catani M, Dell'acqua F, Thiebaut de Schotten M. A revised limbic system model for memory, emotion and behaviour. Neurosci Biobehav Rev 2013; 37: 1724-1737.

Lafleur DL, Pittenger C, Kelmendi B, Gardner T, Wasylink S, Malison RT, et al. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology (Berl) 2006;184: 254-256.

Bonavita S1, Tedeschi G, Gallo A.. Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis. Mult Scler Int 2013:102454.

Lin CY, Luh WM, Yang AL, Su CT, Wang JD, Ma HI. Psychometric properties and gender invariance of the Chinese version of the self-report Pediatric Quality of Life Inventory version 4.0: short form is acceptable. Qual Life Res 2012; 21: 177-182.

Kalra SK ,SE Swedo. Children with obsessive-compulsive disorder: are they just "little adults"? J Clin Invest 2009;119: 737-746.

Storch EA, Milsom VA, Merlo LJ, Larson M, Geffken GR, Jacob ML, et al. Insight in pediatric obsessive-compulsive disorder: associations with clinical presentation. Psychiatry Res 2008;160: 212-220.

Vivan Ade S, L Rodrigues, G Wendt, et al. Quality of life in adolescents with obsessive-compulsive disorder. Rev Bras Psiquiatr 2013; 35: 369-374.

Hollander E, Stein DJ, Fineberg NA, Marteau F, Legault M. Quality of life outcomes in patients with obsessive-compulsive disorder: relationship to treatment response and symptom relapse. J Clin Psychiatry 2010; 71: 784-792.

Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, et al. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry 1989; 46:1012-1016.

Feng L, Zhang Y, Chen R, Hao Y. The Chinese version of the Pediatric Quality of Life Inventory (PedsQL) 3.0 Asthma Module: reliability and validity. Health Qual Life Outcomes 2011; 9: 64.

Varni JW, M Seid,CA Rode. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care 1999; 37:126-139.

Jafari P, Ghanizadeh A, Akhondzadeh S, Mohammadi MR. Health-related quality of life of Iranian children with attention deficit/hyperactivity disorder. Qual Life Res 2011; 20: 31-36.

IssueVol 12 No 2 (2017) QRcode
SectionOriginal Article(s)
N-Acetylcysteine Adjuvant Obsessive Compulsive Disorder Treatment Clinical Trial Placebo

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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.