Review of: Grant JE et al, Am J Psychiatry 2023;180(5):348–356

Study Type: Randomized double-blind placebo-controlled trial

Pharmacologic options for trichotillomania (hair-pulling) and excoriation (skin-picking) disorder are extremely limited. Selective serotonin reuptake inhibitors, antipsychotics, N-acetylcysteine (NAC), naltrexone, and modafinil have all been tried but have not yielded consistent support from controlled trials. Glutamate plays a role in motor habits, and the glutamatergic modulator NAC improved trichotillomania in a small randomized controlled trial by Grant and colleagues. In the current study, Grant’s team tested memantine, a glutamate modulator and N-methyl-D-aspartate receptor antagonist that has been FDA approved only for the treatment of Alzheimer’s disease.

In this randomized, placebo-controlled, double-blind trial, 100 people with trichotillomania (53%), excoriation disorder (43%), or both (4%) received treatment over eight weeks. Most of the patients (86%) were women with an average age of 31.4 years. A total of 55 participants received memantine (10 mg/day for one week, then 20 mg/day for the remainder of the study) while the placebo group (n=45) received identical capsules for the same period. Some participants in both groups were in concurrent psychotherapy (including cognitive behavioral therapy) and/or receiving psychotropic medication. They were excluded only if there had been a change in treatment in the preceding three months. 

Treatment with memantine demonstrated superior outcomes at eight weeks compared to placebo, as indicated by significant improvement in scores on the National Institute of Mental Health’s Trichotillomania Symptom Severity Scale (60.5% experienced severity improvement in the memantine group vs 8.3% in the placebo group, Fisher’s exact test p<0.0001). The number needed to treat for improvement was 1.9. No serious adverse events were reported in either group. Two participants in the memantine group dropped out due to dizziness.

CARLAT TAKE

While the results are encouraging for memantine in trichotillomania and excoriation, we’ll add a note of caution as many treatments have failed after showing initial promise in these disorders.