In a child with persistent skin‑picking (excoriation) disorder refractory to behavioral therapy, can N‑acetylcysteine (NAC) be used and what is the appropriate dosing schedule?

N-Acetylcysteine for Pediatric Skin Picking Disorder

N-acetylcysteine (NAC) can be used as a treatment option for children with excoriation (skin-picking) disorder refractory to behavioral therapy, with dosing of 1200-3000 mg/day divided into 2-3 doses, though efficacy is modest and response rates vary considerably. 1

Evidence Base and Efficacy

The strongest evidence comes from a randomized, double-blind, placebo-controlled trial in adults with excoriation disorder, where NAC (1200-3000 mg/day) demonstrated statistically significant improvements compared to placebo, with 47% of NAC-treated participants showing much or very much improvement versus 19% on placebo. 1 This represents the highest quality evidence available for NAC in skin-picking disorders.

For pediatric populations specifically:

• In Prader-Willi syndrome (PWS), an open-label pilot study of 35 individuals (ages 5-39 years) using NAC 450-1200 mg/day showed improvement in all participants after 12 weeks, though 29% had incomplete resolution. 2

• However, a more recent retrospective case series in PWS found much more limited efficacy, with only 6 of 14 patients showing improvement, and notably, two male patients with solitary rectal picking developed new-onset skin picking during NAC treatment. 3 This study reported higher adverse effects than previously documented and suggested reduced efficacy when NAC was co-administered with neuroleptics. 3

Mechanism of Action

NAC appears to work through glutamatergic modulation—either via NMDA glutamate receptor modulation or by increasing glutathione levels—which helps restore extracellular glutamate concentration in the nucleus accumbens. 1 The glutamate system represents a promising therapeutic target for obsessive-compulsive and related disorders, including excoriation disorder. 4, 1

Dosing Algorithm for Children

Starting dose: 450-600 mg/day, divided into 1-2 doses 2

Titration schedule:

• Increase by 450-600 mg every 1-2 weeks as tolerated
• Target therapeutic range: 1200-2400 mg/day divided into 2-3 doses 3, 2, 1
• Maximum dose: 3000 mg/day (based on adult data) 1

Duration of trial: Minimum 12 weeks to assess response 2, 1

Clinical Monitoring

Assess treatment response using:

• Clinical Global Impression-Improvement (CGI-I) scale to quantify symptom change 3
• Direct counting and measurement of active skin lesions at baseline and follow-up visits 2
• Monitor for adverse effects at each visit, particularly gastrointestinal symptoms 3, 5

Safety Profile

NAC is generally well-tolerated with minimal adverse effects. 1, 5 The most common side effects are:

• Gastrointestinal symptoms (nausea, abdominal discomfort)—mild and self-limited 5
• One case report documented severe aggression in a child, though this is rare 5
• No significant differences in adverse effects between NAC and placebo groups in the largest controlled trial 1

Critical Caveats and Pitfalls

Avoid in patients with solitary rectal picking: Two cases demonstrated paradoxical development of skin picking when NAC was used for isolated rectal picking in PWS patients. 3 This suggests NAC may shift rather than eliminate compulsive behaviors in some individuals.

Reduced efficacy with concurrent neuroleptics: The 2022 PWS case series found diminished NAC effectiveness when co-administered with antipsychotic medications. 3 Consider this interaction when planning treatment.

Distinguish from body dysmorphic disorder (BDD): Before initiating NAC, confirm that skin picking represents true compulsive behavior rather than appearance-driven picking characteristic of BDD, as treatment approaches differ fundamentally. 6 In excoriation disorder, picking provides temporary relief or occurs during boredom/anxiety states, not to improve perceived appearance defects. 6

Gender considerations: The 2022 PWS study showed all responders were female, while males showed poorer outcomes or paradoxical effects. 3 This may suggest sex-based differences in NAC response, though more research is needed.

Context Within Broader OCD-Related Disorders

NAC has demonstrated efficacy as an augmentation strategy in treatment-resistant OCD, with three of five randomized controlled trials showing superiority to placebo. 4 This broader evidence base supports NAC's role in glutamatergic modulation of compulsive behaviors, though effect sizes remain modest. 4

Alternative Considerations

For severe, refractory cases in adolescents, the Prader-Willi syndrome guideline mentions topiramate as a medication option for the most severe skin-picking cases, though this is reserved for extreme situations. 4 Behavioral management remains the primary intervention, with pharmacotherapy as adjunctive treatment. 4