An Alzheimer’s drug outperforms placebo by a wide margin
STUDY: Grant JE et al, Am J Psychiatry 2023;180:348–356
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Independent
Background
There’s no FDA-approved medication for trichotillomania (compulsive hair pulling) or skin-picking disorder, and behavioral therapy — the first-line treatment — is hard to access. The glutamate system has been implicated in the compulsive, habit-driven behaviors that characterize both conditions, making memantine, an NMDA glutamate receptor antagonist approved for Alzheimer’s disease, a plausible candidate.
The Study
One hundred adults with trichotillomania, skin-picking disorder, or both were randomized to memantine (10–20 mg/day) or placebo for 8 weeks. The primary outcome was symptom severity on the NIMH Trichotillomania Symptom Severity Scale (NIMH scale), modified to include skin picking. Disability and anxiety were secondary outcomes.
By week 8, 60.5% of participants on memantine were rated much or very much improved on the Clinical Global Impressions scale, compared with 8.3% on placebo (a number needed to treat of 1.9). The effect size on the primary scale was large (Hedges’ g = 1.76), comparable to or exceeding behavioral therapy in prior meta-analyses. Disability (Sheehan Disability Scale) and anxiety (Anxiety scale (HAM-A)) also favored memantine. The drug was well tolerated; fatigue and dizziness were the most common side effects, and only two participants discontinued due to adverse effects.
The main limitations are the short duration — 8 weeks is unlikely enough for chronic conditions — and the single-center design. The sample was also mostly women and of mild-to-moderate severity, though a subgroup analysis in more severe cases found even higher response rates.
Practice Implications
- The effect size is striking, but large effects are common in small trials (this one is medium sized though).
- Consider memantine at 10–20 mg/day for trichotillomania.
- Another glutamatergic treatment, N-acetylcysteine, (NAC) may also work in trichotillomnia (it has one positive and one negative trial).
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
