N-acetylcysteine (NAC) is a synthetic N-acetyl derivative and prodrug of L-cysteine, an endogenous amino acid.1 NAC is widely considered to be a well-tolerated and safe medication with little bothersome side effects and its use is increasing. It is important for the practicing dermatologist to be familiar with the history of NAC as well as its uses and potential adverse events. It is commonly used to reverse the toxicity of high doses of acetaminophen. NAC achieved FDA approval for the oral acetaminophen overdose 72-h protocol in 1985.2 Additionally, NAC has been shown to be effective as a mucolytic in chronic obstructive pulmonary disease (COPD), a renal protectant in nephropathy, an adjunct therapy in HIV-infection, and a preventative agent for atrial fibrillation.1
There has been a recent and growing interest in NAC as a potential treatment for a variety of psychiatric disorders such as anxiety, neurodevelopmental disorders, schizophrenia spectrum disorders, bipolar-related disorders, and obsessive compulsive-related disorders. These conditions are thought to be treated through NAC’s anti-inflammatory, antioxidant, and glutamate modulatory effects. While there is a multitude of preclinical evidence that supports this conjecture, clinical trials have yielded a diverse set result.3 Current research has shown that NAC is effective in treatment of obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders (OCRDs), specifically body focused repetitive behaviors (BFRBs).4
Body Focused Repetitive Behaviors
Examples of BFRBs in dermatology include trichotillomania (hair pulling) and excoriation disorder (skin picking), both falling under the umbrella of pyschodermatological disorder. Trichotillomania is characterized by a sense of tension before pulling hair which is relieved by the act of hair pulling. Excoriation disorder can be defined similarly with skin picking being the driving tension and relief behaviors.5 It is thought that BFRBs are closely linked with OCD and OCRDs, but distinct in that BFRBs are not triggered by obsessions but rather boredom or anxiety.
Neuroimaging of patients with these conditions has consistently shown hyperactivity in the striatum and orbitofrontal cortex.6 This hyperactivity is thought to be due to reduced GABAergic inhibition or increased glutaminergic excitation. NAC’s ability to modulate glutamate activity is likely what has given way to anecdotal clinical successes in treatment. An excellent summary of these successes and results can be found at the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180086/.
Clinical Usage
The advantages of N-acetylcysteine lie in its rare-to-limited side effects, relatively low cost, and easy accessibility. It is being promoted on social media and patients may be taking NAC when they present to the dermatologist. Many dermatologists are also prescribing NAC. NAC can be found at an average of $10 US for one hundred 600 mg capsules (the typical starting dose for treatment) on Amazon and other over-the-counter vendors. It is commonly prescribed orally with a dosage range of 600 to 2400mg/day for one to eight months but can also be used topically in gel or solution form.4
Side effects are largely dose dependent and can include muscle pains, abdominal discomfort, insomnia, dizziness, nasal congestion, runny nose, nausea, weight loss, restlessness, and headache. There are minor drug interactions that can occur with charcoal and ifosfamide and moderate interactions with rapid acting insulin inhalation. Very high doses of oral NAC have the potential to affect the results of cholesterol blood tests and IV administration of NAC has been known to produce false-positive results for urine ketones, but dosages required to produce these results would have to occur at levels outside ordinary clinical range.7 In addition to this, anaphylaxis has occurred at these high dosage levels when delivered intravenously. Anaphylaxis in these cases has presented most commonly with mild-to-moderate severity, with major reactions like bronchospasm and hypotension occurring in 1% of patients. In cases when NAC IV use is indicated patients must be monitored for manifestations of anaphylactoid reactions such as these.8
When dealing with BFRBs such as trichotillomania and excoriation disorder there is a great variation and nuance to treatment. The low risk and high reward quality of NAC suggests great promise in a supplementary role for NAC in treatment of such disorders.
The authors have no relevant financial disclosures.
1. Slattery JD, Kumar N, Delhey L, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neurosci Biobehav Rev. 2015;55:294-321.
2. Yarema MC, Sivilotti, ML, Gilbert, EH. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med. 2009;54(4):606-14.
3. Adil M, Amin SS, Mohtashim M. N-acetylcysteine in dermatology. Indian J Dermatol Venereol Leprol. 2018;84(6):652-659.
4. Bradlow RCJ, Berk M, Kalivas PW, Back SE, Kanaan RA. The potential of N-Acetyl-L-Cysteine (NAC) in the treatment of psychiatric disorders. CNS Drugs. 2022;36(5):451-482.
5. Lee DK, Lipner SR. The potential of N-Acetylcysteine for treatment of trichotillomania, excoriation disorder, onychophagia, and onychotillomania: An updated literature review. Int J Environ Res Public Health. 2022;19(11):6370.
6. Jung WH, Yücel M, Yun JY, et al. Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder. Hum Brain Mapp. Epub 2016;38(1):109-119.
7. El-Serafi I, Remberger M, El-Serafi A. The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation. Sci Rep. 2018;8(1):8293.
8. Ershad M, Naji A, Vearrier D. N-Acetylcysteine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. URL: https:// www.ncbi.nlm.nih.gov/books/NBK537183/
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Meena Singh, MD
