Has any new information about treatment of trichotillomania with N-Acetylcysteine emerged?

Fråga: Has any new information about treatment of trichotillomania with N-Acetylcysteine emerged since 2011, when this treatment option was discussed in a Drugline record?

Sammanfattning: Altogether, there is lack of evidence to establish N-Acetylcysteine as effective in treatment of trichotillomania. There is conflicting data which may reflect real differences in response between study populations (children and adults) or inability to capture consistent results with the methodology applied (eg non-validated outcome measures in children). Other compounds than N-Acetylcysteine also have to be considered. At present, optimum pharmacotherapy of trichotillomania cannot be established due to lack of comparable studies.

Svar: The drugline record (1) that is referred to by the questioner describes a randomized, placebo controlled study in 50 patients with trichotillomania, where a positive effect was seen after treatment with N-Acetylcysteine (NAC) for 12 weeks but long term data was lacking (2).

Meanwhile, more data on this topic has been published, including a randomized placebo-controlled study in 39 children with trichotillomania, 8-17 years of age, which showed lack of effect during a 12 week NAC treatment period (3), and a Drugline record discussing long-term safety of NAC (4). In addition, pharmacological treatment principles of trichotillomania have been discussed in a Cochrane-review (5) and a review article (6).

The previous positive study in adults (2) and the more recent negative pediatric study (3) showed different outcomes despite similar designs. In the report of the latter, the authors suggest that this could be due to differences between children and adults in pathophysiology and factors driving trichotillomania (eg response to sensory signal, regulator of mood and anxiety, or a means to create response from parents or the environment). As an alternative explanation, the authors discuss the lack of validation in a pediatric population of the primary variable (MGH-HPS), which is based on self-assessment.

The Chochrane-review (5) did not include the negative pediatric study (3), and the authors conclude that data supporting pharmacotherapy against trichotillomania is sparse and based on small studies. No drug can be established as effective but there is some data to support treatment with klomipramine, NAC or olanzapine. Differences in study design and endpoints hamper relevant comparison of efficacy between these compounds.

In a review-article (6) by a subset of the authors of the Cochrane-review, the negative pediatric study was included, but the conclusion remained virtually identical; there is not sufficient evidence to establish the optimum pharmacotherapy. The authors recommend larger studies with NAC, olanzapine and dronabinol (cannabinoid agonist).

A discussion of long term safety of NAC-treatment has been published on drugline (4). It concludes that even though study results are sparse, and at times conflicting, there is some support that NAC can be used longer than 3 months without serious adverse effects, but it is the responsibility of the prescribing physician to weigh potential risks of NAC-treatment against benefit. A reference in drugline was also made to pending data from a multi-center study in 1006 COPD patients on high-dose NAC (1200 mg/day) or placebo for one year (7). The report from that study has since been published and does not raise any serious safety concerns regarding NAC. Druglinesvar nr 24246, år 2011, www.drugline.se Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry 2009 Jul;66(7):756-63 Bloch MH, Panza KE, Grant JE, Pittenger C, Leckman JF. N-acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trial. J Am Acad Child Adolesc Psychiatry. 2013 Mar;52(3):231-40. Druglinesvar nr 24368, år 2013, www.drugline.se Rothbart R, Amos T, Siegfried N, Ipser JC, Fineberg N, Chamberlain SR, Stein DJ. Pharmacotherapy for trichotillomania. Cochrane Database Syst Rev. 2013 Nov 8;(11):CD007662. Rothbart R, Stein DJ. Pharmacotherapy of trichotillomania (hair pulling disorder): an updated systematic review. Expert Opin Pharmacother. 2014 Dec;15(18):2709-19. Zheng JP, Wen FQ, Bai CX, Wan HY, Kang J, Chen P, Yao WZ, Ma LJ, Li X, Raiteri L, Sardina M, Gao Y, Wang BS, Zhong NS; PANTHEON study group. Twice daily N-acetylcysteine 600 mg for exacerbation of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med 2014 Mar;2(3):187-94. Erratim in: Lancet Respir Med 2014 Apr;2(4):e4