Milk Thistle in Trichotillomania in Children and Adults

Pathological hair-pulling, trichotillomania, has been defined as repetitive, intentionally
performed pulling that causes noticeable hair loss and results in clinically significant
distress or functional impairment. Trichotillomania appears relatively common with an
estimated prevalence between 1-3%. Data on the pharmacological treatment of trichotillomania
is limited to case reports and conflicting double-blind studies of serotonin reuptake
inhibitors. One positive double-blind study of N-acetyl cysteine in adults was not successful
when examined for children and adolescents. Available data on the treatment of
trichotillomania in children are therefore limited.

Silymarin, a flavonoid and a member of the Asteraceae family, is extracted from the seeds of
milk thistle (Silybum marianum) and is known to have antioxidative and anti-apoptotic
properties. Furthermore, it has been demonstrated that its anti-oxidative activity is related
to the scavenging of free radicals and activation of anti-oxidative defenses: increases in
cellular glutathione content and superoxide dismutase activity. Milk thistle has been used
for a range of psychiatric disorders including methamphetamine abuse and obsessive compulsive
disorder. The flavonoid complex silymarin in preclinical studies has been found to increase
serotonin and dopamine levels in the cortex. In the frontal cortex one of the functions of
dopamine is to increase the signal to noise ratio, increased dopamine correlating with
increased frontal performance. Studies have shown that the higher cortical dopamine levels
are associated with improved frontal cortical cognitive performance. Cortical inhibition is
felt to be the basis for top-down control of motivated behaviors. A recent randomized
controlled study with milk thistle was conducted in Iran Thirty five participants with
moderate OCD were randomly assigned to 200 mg of milk thistle leaf extract or 10 mg of
fluoxetine three times daily for eight weeks. Results revealed no significant difference in
treatment effects between milk thistle and fluoxetine from baseline to endpoint as both
interventions provided a highly significant reduction in symptoms. Silymarin or Milk Thistle
may therefore offer promise for the treatment of individuals with trichotillomania.

The current pilot study examines the tolerability and efficacy of milk thistle in the
treatment of trichotillomania in children and adults. The investigators hypothesize that milk
thistle will reduce the severity of symptoms related to trichotillomania and improve
patients' overall functioning.

Inclusion Criteria:

1. Males and females ages 10-65.

2. Diagnosis of current trichotillomania (TTM) based on DSM-5 criteria and confirmed
using the clinician-administered Structured Clinical Interview for DSM-5 (SCID);

3. Hair-pulling behavior within 2 weeks prior to enrollment;

4. Child able and willing to provide active assent for participation;

5. Legal guardian available to provide consent for participation.

Exclusion Criteria:

1. Infrequent hair-pulling (i.e. less than one time per week) that does not meet DSM-5
criteria for trichotillomania;

2. Unstable medical illness as determined by the investigator;

3. History of seizures;

4. Current use of stimulants coinciding with onset or exacerbation of trichotillomania
symptoms or other current medications coinciding with exacerbation or onset or
trichotillomania symptoms;

5. Clinically significant suicidality (defined by the Columbia Suicide Severity Rating
Scale);

6. Baseline score of ≥17 on the Hamilton Depression Rating Scale (17-item HDRS);

7. Lifetime history of bipolar disorder type I or II, schizophrenia, autism, any
psychotic disorder, or any substance use disorder;

8. Initiation of psychotherapy or behavior therapy within 3 months prior to study
baseline;

9. Previous treatment with milk thistle;

10. Any history of psychiatric hospitalization in the past year.