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      N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

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      https://www.riss.kr/link?id=A101597093

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      다국어 초록 (Multilingual Abstract)

      Objective: Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area.
      Methods: PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders.
      Researchers with known involvement in NAC studies were contacted for any unpublished data.
      Results: Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400-3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation.
      Conclusion: Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research.
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      Objective: Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutama...

      Objective: Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area.
      Methods: PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders.
      Researchers with known involvement in NAC studies were contacted for any unpublished data.
      Results: Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400-3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation.
      Conclusion: Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research.

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      참고문헌 (Reference)

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      2 Piras F, "Widespread structural brain changes in OCD: A systematic review of voxel-based morphometry studies" 2013

      3 Stein DJ., "Trichotillomania(hair pulling disorder), skin picking disorder, and stereotypic movement disorder : toward DSM-V" 27 : 611-626, 2010

      4 Franklin ME., "Treatment of obsessive compulsive disorder" 7 : 229-243, 2011

      5 Smith QR., "Transport of glutamate and other amino acids at the blood-brain barrier" 130 (130): 1016S-1022S, 2000

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      7 Papakostas GI., "Tolerability of modern antidepressants" 69 (69): 8-13, 2008

      8 Wu K., "The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder" 100 : 726-735, 2012

      9 Berk M., "The promise of N-acetylcysteine in neuropsychiatry" 34 : 167-177, 2013

      10 Chamberlain SR., "The neuropsychology of obsessive compulsive disorder : the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers" 29 : 399-419, 2005

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      28 Berk M., "Nail-biting stuff? The effect of N-acetyl cysteine on nail-biting" 14 : 357-360, 2009

      29 Grant JE., "N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania : a double-blind, placebo-controlled study" 66 : 756-763, 2009

      30 Gray KM., "N-acetylcysteine(NAC)in young marijuana users : an open-label pilot study" 19 : 187-189, 2010

      31 Ghanizadeh A., "N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial" 12 : 223-228, 2013

      32 De Rosa SC., "N-acetylcysteine replenishes glutathione in HIV infection" 30 : 915-929, 2000

      33 Schmaal L., "N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients : a randomized crossover magnetic resonance spectroscopy study" 37 : 2143-2152, 2012

      34 Rodrigues-Barata AR., "N-acetylcysteine in the treatment of trichotillomania" 4 : 176-178, 2012

      35 Silva-Netto R., "N-acetylcysteine in the treatment of skin-picking disorder" 36 : 101-, 2014

      36 Van Ameringen M., "N-acetylcysteine augmentation in treatment resistant obsessive compulsive disorder : A case series" 2 : 48-52, 2013

      37 Lafleur DL., "N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder" 184 : 254-256, 2006

      38 Afshar H., "N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder : a randomized, double-blind, placebo-controlled trial" 32 : 797-803, 2012

      39 Egashira N., "N-acetyl-L-cysteine inhibits marble-burying behavior in mice" 119 : 97-101, 2012

      40 Baker DA., "N-acetyl cysteine-induced blockade of cocaineinduced reinstatement" 1003 : 349-351, 2003

      41 Grant JE., "N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling : a pilot study" 62 : 652-657, 2007

      42 Dean OM., "N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats : relevance to schizophrenia and bipolar disorder" 499 : 149-153, 2011

      43 Odlaug BL., "N-acetyl cysteine in the treatment of grooming disorders" 27 : 227-229, 2007

      44 Berk M., "N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial" 64 : 468-475, 2008

      45 Atkuri KR., "N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency" 7 : 355-359, 2007

      46 Bloch MH., "N-Acetylcysteine in the treatment of pediatric trichotillomania : a randomized, double-blind, placebo-controlled add-on trial" 52 : 231-240, 2013

      47 Chamberlain SR., "Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania" 163 : 1282-1284, 2006

      48 Das P., "Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo" 47 : 347-354, 2013

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      50 Bloch MH., "Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder" 15 : 850-855, 2010

      51 Chamberlain SR., "Lifting the veil on trichotillomania" 164 : 568-574, 2007

      52 Costa-Campos L., "Interactive effects of N-acetylcysteine and antidepressants" 44 : 125-130, 2013

      53 Menzies L., "Integrating evidence from neuroimaging and neuropsychological studies of obsessivecompulsive disorder : the orbitofronto-striatal model revisited" 32 : 525-549, 2008

      54 Erickson MA., "Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood-brain barrier : protection by the antioxidant N-acetylcysteine" 26 : 1085-1094, 2012

      55 Flessner CA., "Hair pulling disorder(trichotillomania) : genes, neurobiology, and a model for understanding impulsivity and compulsivity" 199 : 151-158, 2012

      56 Lavoie S., "Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients" 33 : 2187-2199, 2008

      57 Lushchak VI., "Glutathione homeostasis and functions : potential targets for medical interventions" 2012 : 736837-, 2012

      58 Chakrabarty K., "Glutamatergic dysfunction in OCD" 30 : 1735-1740, 2005

      59 Arnold PD., "Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder" 63 : 769-776, 2006

      60 Grados MA., "Glutamate drugs and pharmacogenetics of OCD : a pathway-based exploratory approach" 8 : 1515-1527, 2013

      61 Pittenger C., "Glutamate abnormalities in obsessive compulsive disorder : neurobiology, pathophysiology, and treatment" 132 : 314-332, 2011

      62 Ersan S., "Examination of free radical metabolism and antioxidant defence system elements in patients with obsessive-compulsive disorder" 30 : 1039-1042, 2006

      63 Pallanti S., "Emerging drugs to treat obsessive-compulsive disorder" 19 : 67-77, 2014

      64 Burdo J., "Distribution of the cystine/glutamate antiporter system xc-in the brain, kidney, and duodenum" 54 : 549-557, 2006

      65 Arfsten DP., "Distribution of radio-labeled N-Acetyl-L-Cysteine in Sprague-Dawley rats and its effect on glutathione metabolism following single and repeat dosing by oral gavage" 26 : 113-134, 2007

      66 Baker DA., "Cystine/glutamate exchange serves as the source for extracellular glutamate : modifications by repeated cocaine administration" 23 : 161-162, 2002

      67 Moran MM., "Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking" 25 : 6389-6393, 2005

      68 Bauer J., "Craving in alcohol-dependent patients after detoxification is related to glutamatergic dysfunction in the nucleus accumbens and the anterior cingulate cortex" 38 : 1401-1408, 2013

      69 Chakraborty S., "Correlation between lipid peroxidation-induced TBARS level and disease severity in obsessive-compulsive disorder" 33 : 363-366, 2009

      70 Sarris J., "Complementary medicine, self-help, and lifestyle interventions for obsessive compulsive disorder(OCD)and the OCD spectrum : a systematic review" 138 : 213-221, 2012

      71 Harrison BJ., "Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder" 73 : 321-328, 2013

      72 Kau KS., "Blunted cystine-glutamate antiporter function in the nucleus accumbens promotes cocaine-induced drug seeking" 155 : 530-537, 2008

      73 Bulut M., "Beneficial effects of N-acetylcysteine in treatment resistant schizophrenia" 10 : 626-628, 2009

      74 Dickel DE., "Association testing of the positional and functional candidate gene SLC1A1/ EAAC1 in early-onset obsessive-compulsive disorder" 63 : 778-785, 2006

      75 Bhattacharyya S., "Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder" 34 : 2489-2496, 2009

      76 Yücel M., "Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessivecompulsive disorder" 42 : 467-477, 2008

      77 Miller JL., "An open-label pilot study of N-acetylcysteine for skin-picking in Prader-Willi syndrome" 164A : 421-424, 2014

      78 Panza KE., "Age and gender correlates of pulling in pediatric trichotillomania" 52 : 241-249, 2013

      79 Hardan AY., "A randomized controlled pilot trial of oral N-acetylcysteine in children with autism" 71 : 956-961, 2012

      80 Morgan JR., "A preliminary analysis of the phenomenology of skin-picking in Prader-Willi syndrome" 41 : 448-463, 2010

      81 Chamberlain SR., "A neuropsychological comparison of obsessive-compulsive disorder and trichotillomania" 45 : 654-662, 2007

      82 Brennan BP., "A critical review of magnetic resonance spectroscopy studies of obsessivecompulsive disorder" 73 : 24-31, 2013

      83 Slade T., "2007 National Survey of Mental Health and Wellbeing : methods and key findings" 43 : 594-605, 2009

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