When do you consider the use of N-acetylcysteine (NAC) in patients with trichotillomania?

Great question! NAC comes up frequently in clinical discussions of trichotillomania, and it's worth being clear-eyed about what we actually know.

NAC restores extrasynaptic glutamate homeostasis via the cystine-glutamate antiporter (system Xc⁻), which increases tonic activation of presynaptic mGluR2/3 autoreceptors and ultimately reduces pathological synaptic glutamate release in cortico-striatal circuits. There's also a plausible oxidative stress angle; roughly a third of TTM patients in one pi...

Generally speaking, there is no FDA-approved medication available to date for the treatment of trichotillomania. Various case reports have shown variable benefits with SSRIs, SNRIs, TCAs, and antipsychotics. However, Habit reversal therapy (HRT) is the gold standard for the treatment. N-Acetylcysteine (NAC) is the glutamatergic agent which have been used in the treatment of trichotillomania. It has shown 55% benefits in some trials versus placebo. My approach to treatment of trichotillomania is ...

Consider using memantine, which is well-tolerated and has evidence. I've used it successfully (Grant et al., PMID 36856701).

NAC is usually the go-to, but it doesn't always work, and apparently, it doesn't taste good. I've had memantine work as monotherapy for skin excoriation disorder or trichotillomania in a handful of patients.

Update:

I have not had much success with NAC, but each patient with memantine monotherapy I have had success with (granted, it is an n=3). It is worth it, and I have fou...

I completely agree with Dr. @Dr. First Last above. If patients have not benefited from targeted psychotherapy or have logistical hurdles to engaging in the therapy (cost, time, availability, motivation), then a trial of an SSRI or SNRI is worthwhile. I frequently will add N-acetylcysteine to the medication if there is not a response after 8 weeks or so. I use 1,800-2,400 mg daily NAC. The medical literature generally has studied doses of 2,000-2,400 mg in the studies; I have found 1,800 mg appea...

I’ve also had some meaningful success with cariprazine. Obviously, informed consent needs to be obtained, including that this is off-label and the risks with all SGA’s and akathisia, in particular here. I’ll also note I didn’t use this exclusively for the trichotillomania, so that the risk/benefit ratio became more favourable. Cariprazine was also providing support for the underlying mood disorder.