Madeeha Mian

Introduction: Excoriation disorder (ED), the compulsive picking of skin, can cause individuals to suffer from physical, social, functional, and emotional consequences⁷. The etiology of ED is unknown, and standard antidepressant drug treatments for ED are largely ineffective⁶. ED is categorized as an obsessive-compulsive disorder (OCD) in the DSM-5¹. However, the behavior of ED patients shares features with addictions more so than OCD¹. N-Acetyl Cysteine (NAC) administration does not help treatment-resistant OCD², but facilitates abstinence in addiction; NAC’s mechanism of action is not fully understood², though literature emphasizes NAC’s role of modulating glutamate levels. Given the similarities between ED and addictions, we hypothesized that managing ED as an addiction and treating with NAC may improve patient treatment outcomes, and that NAC’s antioxidant properties are a possible mechanism of action in the periphery and CNS. Methods: Rats were given 1 (ShA) or 6-hour (LgA) cocaine self-administration, and then received saline or NAC (60 mg/kg) treatment; motivation for drug in rats was then tested³. ED patients were given NAC (1200-3000mg/d) or placebo for 12 weeks and their lesion severity was assessed using the Yale-Brown Obsessive-Compulsive-Scale (NE-YBOCS)⁶. Additionally, mice with ulcerative dermatitis (UD) were given glutathione (GSH) as a control, or NAC, followed by documentation of lesion severity⁵. Furthermore, mice pre-administered with NAC were treated with 3 lipopolysaccharide (LPS) injections (Salmonella typhimurium) and were studied 28 hours following the first injection⁴. Results: NAC promoted abstinence in LgA rats, and failed to recover pre-punishment cocaine intake levels³. Similarly, human ED participants receiving NAC had significantly lowered NE-YBOCS scores (18.9 to 11.5) compared to placebo (17.9 to 14.1)⁶. Moreover, all mice receiving NAC improved in lesion severity, whereas only 40% receiving GSH improved⁵. In the mice pre-administered with NAC and injected with LPS, NAC protected against LPS-induced Aβ-transport dysfunction in Alzheimer’s Disease (AD); this finding correlated with NAC exerting antioxidant effects in the periphery but not the brain, despite increased entry rate of NAC into the brain following LPS⁴. Conclusions: NAC appears to be a promising treatment for addictions³ and ED⁶. Additionally, findings support the role of oxidative stress in ED and mouse UD, and NAC’s antioxidant properties as a pre-cursor of glutathione as another important mechanism of action⁵. Results of LPS-injected mice also indicated that limiting oxidative stress in the periphery during inflammation protected the function of efflux proteins in the brain in AD, indicating a novel mechanism: NAC mediates its protective effects before entering the CNS⁴.

1.  Costa, Daniel LC, Juliana Belo Diniz, and Eurípedes Constantino Miguel. “How Similar Are the Disorders Included Under the Umbrella of Obsessive-Compulsive Disorder and Related Disorders?.” Jama psychiatry 73.8 (2016): 877-877.
2. Costa, Daniel LC, et al. “Serotonin Reuptake Inhibitor Augmentation with N-Acetylcysteine in Treatment Resistant Obsessive-Compulsive Disorder: A Double-blind Randomized Controlled Trial.” Biological Psychiatry. Vol. 77. No. 9. Elsevier Science Inc, 2015.
3. Ducret, Eric, et al. “N-acetylcysteine facilitates self-imposed abstinence after escalation of cocaine intake.” Biological psychiatry 80.3 (2016): 226-234.
4. Erickson, Michelle A., Kim Hansen, and William A. Banks. “Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood–brain barrier: protection by the antioxidant N-acetylcysteine.” Brain, behavior, and immunity7 (2012): 1085-1094
5. George, Nneka M., et al. “Antioxidant therapies for ulcerative dermatitis: a potential model for skin picking disorder.” PloS one 10.7 (2015): e0132092.
6. Grant, Jon E., et al. “N-Acetylcysteine in the treatment of excoriation disorder: a randomized clinical trial.” JAMA psychiatry 73.5 (2016): 490-496.
7. Jagger, Gina E., and William R. Sterner. “Excoriation: What Counselors Need to Know About Skin Picking Disorder.” Journal of Mental Health Counseling 38.4 (2016): 281-297.