How does memantine work for trichotillomania (hair-pulling disorder)?

Comment by InpharmD Researcher

The exact mechanism of memantine, a glutamate receptor antagonist, for trichotillomania (hair-pulling disorder) is not fully known. Trichotillomania is suspected to be caused by glutaminergic dysfunction. A 2023 randomized, controlled trial found memantine 10-20 mg/day resulted in significant reductions in hair pulling and skin-picking symptoms compared with placebo; however, these results need to be confirmed in other studies.

Background

A 2023 proof-of-concept placebo-controlled trial evaluated the use of memantine for disorders characterized by repetitive behaviors, trichotillomania (hair-pulling disorder) and skin-picking disorder (excoriation disorder), in 100 adults. Both disorders display similar neurobiology of significantly reduced fractional anisotropy in the anterior cingulate, the pre-supplementary motor area, and the temporal cortices. This suggests disorganization of white matter tracts in motor habit generation and suppression may contribute to their pathophysiology. This is also linked, neurochemically, to glutamenergic dysfunction. The proposed pathophysiology has been further testes in animal studies of knockout mice not containing glutamate receptor regulator proteins; the knockout mice exhibited compulsive grooming. Memantine is a glutamate receptor antagonist, working against excessive glutaminergic drive. Because the pathophysiology of trichotillomania is hypothesized to be due to glutaminergic dysfunction, the study aimed to assess if memantine 10-20 mg/day would be more effective than placebo in reducing the symptoms of hair pulling and skin picking over 8 weeks. The trial can be seen in Table 1. There is also limited evidence for N-acetylcysteine (NAC), which also has glutamate modulating properties, to be used for trichotillomania; however, larger controlled trials of glutamate modulators (e.g., riluzole, NAC, lamotrigine, memantine) have not been successful for other impulsive-compulsive repetitive behaviors. [1], [2]

References:


[1] Grant JE, Chesivoir E, Valle S, Ehsan D, Chamberlain SR. Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder. Am J Psychiatry. 2023;180(5):348-356. doi:10.1176/appi.ajp.20220737
[2] Greenberg EL, Geller DA. Cautious Optimism for a New Treatment Option for Body-Focused Repetitive Behavior Disorders. Am J Psychiatry. 2023;180(5):325-327. doi:10.1176/appi.ajp.20230226
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

How does memantine work for trichotillomania (hair-pulling disorder)?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Table 1 for your response.

 

Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder

Design

Randomized, single-center, double-blind, placebo-controlled trial

N= 100

Objective

To evaluate if memantine would be more effective than placebo in reducing the symptoms of hair pulling and skin picking and in improving overall psychosocial functioning after 8 weeks of treatment

Study Groups

Memantine (n= 55)

Placebo (n= 45)

Inclusion Criteria

 Adults aged 18-65; current DSM-V diagnosis of trichotillomania or skin-picking disorder; pulling or picking daily for at least 15 minutes

Exclusion Criteria

Unstable medical illness; history of seizures; lifetime bipolar disorder, dementia, or psychotic disorder; current (past 3 months) substance use disorder; current suicide risk; previous treatment with memantine; pregnancy or inadequate contraception in women of childbearing potential; initiation of pharmacotherapy or psychotherapy within 3 months prior to study entry

Methods

This was a single-center study of patients, recruited via advertisements or referrals, with either trichotillomania or skin-picking disorder in Chicago. Participants underwent a validated clinical interview with a psychiatrist before being randomized 1:1 to either memantine or placebo for 8 weeks.

The memantine group was started at 10 mg/day, with the dose increased to 20 mg/day after 2 weeks. Participants on a stable dose of a psychotropic medication for at least 3 months were allowed to continue the medication during this study. Of 100 patients recruited initially, only 79 completed the trial.

Duration

 8 weeks

Outcome Measures

Primary: National Institute of Mental Health (NIMH) Trichotillomania Symptom Severity Scale (range, 0-20)

Secondary: Massachusetts General Hospital Hairpulling Scale (MGH-HPS), modified to include skin picking; Sheehan Disability Scale (SDS); Clinical Global Impressions Improvement Scale (CGI-I); Hamilton Anxiety and Depression Rating Scales (HAM-A and HAM-D)

Baseline Characteristics

  

Memantine (n= 43)

Placebo (n= 36)

 p-value

Age, years

 30.2 ± 9.6 33.5 ± 12.2 0.183 

Female

 86.1% 72.2% 0.338

Diagnosis

Trichotillomania

Skin-picking disorder

Both

 

51.2%

46.5%

2.3%

 

52.8%

41.7%

5.6%

 0.728

Taking a therapeutic antidepressant

 44.2% 47.2% 0.966

Baseline assessments

NIMH scale

MGH scale

SDS

HAM-A

HAM-D

 

12.56 ± 3.23

19.36 ± 3.65

10.21 ± 7.18

7.47 ± 5.60

6.36 ± 4.18

 

12.36 ± 3.33

19.78 ± 3.33

9.50 ± 7.92

5.42 ± 6.06

4.50 ± 4.10

 

0.791

0.599

0.677

0.123

0.052

Data represented are for patients who completed the trial only. Dropout rates were similar between study groups.

Results

Endpoint

Memantine (n= 43)

Placebo (n= 36)

p-value

NIMH Scale

Week 2

Week 4

Week 6

Week 8

 

7.55 ± 0.54

7.11 ± .054

6.08 ± 0.54

5.62 ± 0.53

 

10.58 ± 0.56

10.76 ± 0.57

10.08 ± 0.59

11.10 ± 0.58

 <0.001

SDS week 8 score

 4.32 ± 0.97 7.88 ± 1.03 <0.001

HAM-A week 8 score

 3.35 ± 0.64 3.85 ± 0.69 <0.001

MGH week 8 score

 12.37 ± 0.72 16.41 ± 0.76 <0.001

No results were reported for the HAM-D scale. 

Results are reported as mean ± standard error.

Adverse Events

Fatigue/drowsiness (11.1% vs. 9.1%), gastrointestinal symptoms (8.9% vs. 5.5%), dizziness (6.7% vs. 7.3%)

No serious adverse events were observed in either group.

Of the patients who did not complete the trial, 2 in memantine and 3 in the placebo group discontinued because they were unable to tolerate the medication.

Study Author Conclusions

This study found that memantine treatment resulted in statistically significant reductions in hair-pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on the number needed to treat), and was well tolerated. The glutamate system may prove to be a beneficial target in the treatment of compulsive behaviors.

InpharmD Researcher Critique

Limitations of this study include the relatively short trial duration of 8 weeks for chronic disorders, modification of validated scales (trichotillomania scales were modified to include skin-picking), and inclusion of patients with mild-to-moderate disorder severity. Study visits were conducted virtually, making physical assessment of hair- and skin-damage not viable. This study only evaluated memantine versus placebo, without adjunctive cognitive-behavioral therapy. Additionally, the presented results and baseline scale scores suggest a degree of heterogeneity among the included patients.
References:

Grant JE, Chesivoir E, Valle S, Ehsan D, Chamberlain SR. Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder. Am J Psychiatry. 2023;180(5):348-356. doi:10.1176/appi.ajp.20220737