Recent Advances in The Treatment of Trichotillomania (Hair Pulling Disorder)

Gregory J. Everett, Mohammad Jafferany, Jonathon Skurya

Central Michigan University, Saginaw, MI 48603

Word Count: 3610

Conflicts of Interest: None

Funding sources: None

Contribution Statement: All authors contributed equally in the production of this manuscript.

Keywords: Trichotillomania, N-acetylcysteine, Glutamate, Psychodermatology, Psychocutaneous

Disorders

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through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/dth.13818

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 Abstract

Trichotillomania (TTM) is a condition in which affected individuals pull out their hair resulting

in hair loss. This disorder affects roughly 0.5% to 2.0% of the population and can have

significant psychological morbidity. Behavioral therapy has been used with success in the

treatment of TTM, but not all patients are willing or able to comply with this treatment strategy.

There is a need for effective pharmacological treatment options. Historically, pharmacotherapy

for trichotillomania has been inadequate in most cases, but recent advances have been made in

this regard. Fluoxetine, clomipramine, olanzapine, and naltrexone have all been used in the

treatment of TTM, but evidence of benefit has varied, and side effect profiles can limit practical

utility. Recent advances in the understanding of the pathophysiology of TTM, as well as

evidence of benefit seen with some glutamate modulating agents such as N-acetylcysteine and

dronabinol have provided newer potential pharmacotherapy options.

Keywords: Trichotillomania, N-acetylcysteine, Glutamate, Psychodermatology,

Psychocutaneous Disorders

Introduction

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Trichotillomania (TTM) is a condition in which those affected pull out their own hair to the point

of self-induced hair loss despite attempts to stop. It is classified under obsessive compulsive and

related disorders in the DSM V 1. This disorder can have devastating effects on the quality of life

of those affected including a reduced sense of self-confidence and comorbid psychiatric,

addictive and impulse control disorders 2,3. With an estimated prevalence between 0.5% and

2.0% of the general population, there is a need for effective treatment options 4. This disorder has

historically been thought to have a large female predominance, but recent data have challenged

this notion 5. Many of the pharmacologic treatments used for other psychiatric conditions have

historically been inadequate in the treatment of TTM and there are no FDA-approved

medications for this purpose. However, recent advances in treatment have been seen, especially

regarding the use of glutamatergic medications 6.

Prevalence and Epidemiology

In a large-scale survey recently conducted, TTM was shown to have a point prevalence of 1.7%

in adults ages 18-69 years 5. This falls within previous prevalence estimates of 0.5%-2.0%, but it

has been noted that prevalence may be underestimated due to underreporting 2,4. Interestingly, in

this study, no difference in prevalence was seen between male and female genders. This is in

contrast to some previous studies which have found a female predominance of TTM in adults,

but this is the first major large-scale survey conducted with a sample more representative of the

general population where sampling was done outside of a clinical setting 5,7. The authors

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acknowledge however that prevalence was determined from survey data without follow-up and

not from an in-person clinical evaluation 5.

Additionally, many smaller previous studies showing a female predominance of body focused

repetitive behaviors have relied on sample participants less applicable to the general population

such as college students or medical students 7,8. In this study, individuals who preferred not to be

categorized as either male or female gender, Asian individuals, Native Hawaiian or Other Pacific

Islanders, and those who reported lower income levels reported a higher prevalence of TTM, but

not significantly so 5.

Clinical Features of Trichotillomania

The DSM-5 (Diagnostic and Statistical Manual of Mental disorders 5th edition) Criteria for TTM

are as follows: “A. Recurrent pulling out of one’s hair, resulting in hair loss. B. Repeated

attempts to decrease or stop hair pulling. C. The hair pulling causes clinically significant distress

or impairment in social, occupational, or other important areas of functioning. D. The hair

pulling or hair loss is not attributable to another medical condition (e.g., a dermatological

condition). E. The hair pulling is not better explained by the symptoms of another mental

disorder (e.g., attempts to improve a perceived defect or flaw in appearance in body dysmorphic

disorder).” 1

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In a recent study, the mean age of onset for TTM was noted to be significantly different between

male and female genders. Overall mean age of onset was found to be 17.7 years with a mean of

14.8 years in females and 19.0 years for males 5. Many previous smaller studies have found the

mean age of onset to be closer to 10-13 years of age 9. Age of onset closer to puberty, in addition

to the female predominance noted by some studies may better support the hormonal aspects of

TTM discussed in some articles 6,7,10.

The most common sites where patients with TTM pull hair from are the scalp, eyebrows, and

pubic region, eyelashes, and beard 2,11.

Dermoscopic features of TTM include decreased hair density, broken hairs of different shaft

lengths, coiled or short vellus hairs, trichoptilosis (split hairs), occasional yellow dots and no

exclamation mark hairs as would be seen in alopecia areata 12.

Two distinct types of TTM, “automatic” and “focused”, have been described, but most

individuals with TTM engage in both at some point 9. People with automatic TTM often do not

realize they are pulling their hair out while doing so whereas those with the focused type often

describe the experience during the hair pulling process as an integral part of their condition 9.

Focused pulling often involves hairs with specific characteristics and feelings of enjoyment or

reduction in negative emotions are often reported as being experienced during pulling 2,9.

Variants of TTM

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Three main additional variants of psychodermatological trichoses which result in hair loss have

been described: trichoteiromania (scratching/rubbing hair), trichotemnomania (shaving/cutting

hair), and trichodaganomania (biting hair) 13,17,18.

Trichoteiromania:

Trichoteiromania is a term used to describe the hair loss resulting from recurrent rubbing or

scratching of the affected area 13. Lichen simplex chronicus is a condition in which dry, scaly and

thickened, oval plaques result from chronic rubbing/scratching of the skin due to pruritus of

different causes which are often psychological 14.

Dermoscopic findings of trichoteiromania include a tonsure hair pattern, fractured hair shafts

referred to as “broom fibers” resulting from mechanical stress, perifollicular scaling, and

erythema. Histopathological findings include bifid hairs with hyperkeratosis referred to as the

“hamburger sign” and acanthotic projections surrounding the affected root sheaths termed the

“gear wheel sign” 15.

Trichoteiromania is often treated with high potency glucocorticoid creams, success is variable 16.

A case report has shown good response to N-acetylcysteine treatment in a 47-year-old male who

had partial improvement at eight weeks and complete regrowth of hair at 16 weeks after

treatment with 1,200mg of NAC daily 16.

Trichotemnomania:

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Trichotemnomania is hair loss due to cutting or shaving 17. Patients with trichotemnomania show

signs of shaving or hair-cutting in the affected areas with an otherwise healthy appearing scalp

provided they do not have additional hair or skin pathologies. Hair loss is typically sudden in

congruence with the removal method.

Dermoscopic examination of trichotemnomania may show signs of cutting or shaving in the

affected areas and features include short, broken, non-vellus hairs, no decrease in follicle density,

no exclamation mark hairs, and no yellow or black dots 17.

Trichodaganomania:

Trichodaganomania was first described by Jafferany et al. in 2009 as the process of biting one’s

own hair on accessible sites resulting in hair loss in the affected areas 18. Trichodaganomania

shares some features with other variants of TTM including a compulsive need to remove hair

from the affected areas followed by feelings of gratification as well as a high level of psychiatric

comorbidity.

Due to the method of hair removal, the most common site of hair loss in other variants of TTM

(the scalp) is excluded from trichodaganomania and affected areas are generally accessible sites

such as the dorsal forearms 2,18. Microscopic features of examined hair may show a smooth

blunted shaft at the bite site and a lack of attached root sheaths or hair bulbs as would be seen in

trichotillomania 18.

The clinical differentials for TTM are summarized in table 1.

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The Genetics of TTM

Although psychiatric comorbidities seen in those with TTM have been shown to include

addictive disorders, impulse control disorders, obsessive compulsive disorder, major depressive

disorder and others, the possible genetic links between these concomitant conditions have not

been sufficiently studied 2. There are a few genes which have been associated with the condition

though, mostly through animal model research. These include Hoxb8, Sapap3, and Slitrk5 10.

Hoxb8 mutant mice have been shown to exhibit excessive grooming behavior similar to that seen

in humans with TTM. Furthermore, cortico-striatal synaptic and microglial defects have also

been demonstrated in Hoxb8 mutants showing a possible increase in synaptic activity 19.

Similar to Hoxb8 mutant mice, those with a deletion of the Sapap3 gene show behaviors

resembling TTM. Additionally, Sapap3 knockout mice have altered postsynaptic functioning of

their glutamatergic cortico-striatal synapses, which has also been proposed as a potential factor

in the pathogenesis of TTM 20,21. A study by Züchner et al. in 2009 also showed that rare

heterozygous variants of Sapap3 were present in 4.2% of humans diagnosed with TTM/OCD but

only in 1.1% of controls, supporting the possibility of Sapap3 involvement in TTM pathogenesis
22
.

Slitrk5 knockout mice have also displayed excessive grooming behavior. Additionally, Slitrk5

knockout mice show an increase in orbitofrontal cortical activity, and a reduction in striatal

volume with a decrease in striatal medium spiny neuron complexity 23.

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Treatment of Trichotillomania

Treatment of trichotillomania consists of both psychotherapeutic (non-pharmacological) and

pharmacological.

Age Specific Treatment Recommendations:

• Pre-school years: During this age group, TTM is considered as as habit disorder

analogous to thumb sucking and expected to disappear by its own. Parental support and

education about the benign course of disorder.

• School-age years: During school age years, behavioral approaches have been found more

efficacious than pharmacotherapy. Because of possibility of comorbid psychiatric

disorders, psychiatric referral is warranted in this age group.

• Adolescents and Adults: Inthis group, combination of pharmacotherapy, behavioral

therapy and treatment of comorbid psychiatric disorders, if any, offers most clinical

benefit.

A. Non-pharmacological treatments for TTM

Cognitive Behavioral Therapy (CBT)

Cognitive behavioral therapy has been used with success to treat TTM. Toledo et al. compared

group cognitive behavioral therapy to group support therapy in a 2015 study and found both

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therapies to be effective at significantly reducing hair pulling behavior but found CBT to be

significantly more effective than group support therapy 24.

Habit reversal training (HRT)

Habit reversal training, a type of CBT, is often used as a first-line non-pharmacologic treatment

for trichotillomania 2. This therapy involves helping the patient gain a greater awareness of their

hair-pulling behavior and its context, then replacing that behavior with another behavior (such as

making a fist) that can be sustained until the hair-pulling urge passes. A social support system to

aid them in this process is also usually established. HRT can also be coupled with stimulus

control training to treat TTM 25.

Stimulus Control Training

Stimulus control training involves modifying a person’s environment to make it less hospitable

to hair pulling behavior. This may include the removal of things which facilitate hair pulling or

the addition of things which impede such behavior. Examples include removal of mirrors or the

addition of an object to occupy the patient’s hands such as a stress ball or fidget spinner 25.

Acceptance and Commitment Therapy (ACT)

Acceptance and Commitment Therapy (ACT) can be used in combination with habit reversal

training and stimulus control techniques. ACT attempts to help the patients with TTM approach

hair pulling behavior from a perspective of interfering with the achievement of personal or life

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goals as opposed to viewing it as a means to avoid negative emotions or feelings (26 Snorrason

et al., 2015).

Metacognitive Therapy

Metacognitive therapy has also been used in TTM treatment. This therapy challenges a person’s

beliefs regarding thought processes to replace negative beliefs about their condition with beliefs

more suited to facilitate regulation of emotions and responses 27. A small study in 2018 found

that a combination of metacognitive therapy and habit reversal therapy was effective at reducing

hair pulling behavior in those with TTM with continued benefits at follow-up after 12 months 28.

Dialectical Behavioral Therapy

Dialectical behavioral therapy has been shown to significantly reduce hair pulling behavior and

improve emotional regulation as well as comorbid anxiety and depression in those with TTM 29.

This therapy seeks to increase a patient awareness and regulation of emotions 26.

Exposure and Ritual Prevention Therapy

Exposure and ritual prevention therapy have shown some success in TTM treatment in case

studies. This treatment involves examining the affected person’s hair pulling behavior including

context and triggers, ranking the intensity of pulling urges in different episodes, exposure to a

trigger or hair which would normally lead to pulling while encouraging the person to resist the

behavior, and confronting emotional dysregulation 30.

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B. Pharmacological treatment

Although no FDA-approved medications exist for TTM, first-line pharmacotherapy for TTM

usually consists of selective serotonin reuptake inhibitors (SSRIs) or the tricyclic antidepressant

(TCA) Clomipramine but this likely has more to do with psychiatric comorbidity than efficacy

for TTM 21. General pharmacotherapy for TTM are summarized in Table 2.

TCAs (Tricyclic Antidepressants)

Clomipramine is the TCA most often used in the treatment of TTM. This drug blocks the

reuptake of norepinephrine and serotonin and blocks muscarinic cholinergic, adrenergic, H1, and

5HT2 receptors 21. A placebo-controlled trial by Ninan et al. compared Clomipramine, CBT, and

placebo finding CBT significantly more effective than either clomipramine or placebo.

Clomipramine was found to decrease symptoms of TTM more than placebo, but not significantly

so 31. Sani et al. have pointed out that the average dosage used in the Ninan et al. trial (116.7

mg/day) was lower than that which is normally used to treat OCD, but there have been case

reports of successful clomipramine monotherapy at 125 mg/day and dual therapy at 50 mg/day

with behavioral therapy 21,32,33.

SSRIs (Selective Serotonin Reuptake Inhibitors)

SSRIs are widely used for the treatment of both adult and pediatric TTM, but evidence of benefit

is weak 21. In animal models, SSRIs have been shown to decrease excessive grooming behavior

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in mice who have genetic characteristics thought to be involved with the pathogenesis of TTM
19,20,23
. In human studies, meta-analysis by McGuire et al. found a moderate effect for SRIs for

the treatment of TTM 34. A previous meta-analysis however found a significant benefit of

clomipramine over placebo, but no such benefit for SSRIs 35.

A small 16-week, open study appeared to show benefit in reduction of hair pulling behavior in

those with TTM when treated with fluoxetine at doses of up to 80 mg/daily, but the study lacked

a control 36. Placebo-controlled, double-blind studies have failed to show significant benefit of

fluoxetine over placebo 21.

In a 12-week, randomized, waiting list-controlled trial where hair pulling and depressive

symptoms were measured after treatment with behavioral therapy, fluoxetine 60 mg/day, or

waitlist control, fluoxetine was found to be ineffective for short-term treatment of TTM.

Behavioral therapy however was effective 37.

As comorbid psychiatric conditions such as depression and anxiety are common in patients with

TTM, and SSRIs have shown efficacy in the treatment of these conditions, it is not unreasonable

to include this medication in an appropriate patient’s regimen 2,5,38.

Antipsychotics

Due to their efficacy in the treatment of tic disorders and the hypothesized similarities between

TTM and those disorders, antipsychotics have been studied as potential treatment options for

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TTM. Antipsychotics generally work through dopamine modulation among other mechanisms
21,25
.

Olanzapine is the most studied antipsychotic for the treatment of TTM, but others including

risperidone and haloperidol have shown some promise 25. A 2010 randomized, double-blind,

placebo-controlled trial of olanzapine showed significant benefit over placebo (85% responders

vs 17% in placebo). However, the primary outcome measure was the Clinical Global

Impressions-Improvement scale. Adverse events were tolerable as none of the 25 participants

withdrew from the study early, but 21 of the 25 reported at least one adverse event 39. Olanzapine

and other antipsychotic medications have many side effects including metabolic dysfunction and

extrapyramidal symptoms and these should be weighed against potential benefit in TTM 25.

Opioid Antagonists

The mechanism of action by which opioid antagonists may help in treatment of trichotillomania

is thought to be through reduction of the chemical reward experienced when hair pulling 21.

Naltrexone is the opioid antagonist most studied for the treatment of TTM. Similar to how

naltrexone is thought to treat the addictive aspect of alcohol dependence, it would result in lower

dopamine levels in the nucleus accumbens which is thought to be involved in the brain’s reward

pathway 40. Unfortunately, in a double-blind randomized controlled trial by Grant et al.,

naltrexone showed no significant difference in reduction of hair pulling compared to placebo for

the treatment of trichotillomania, although it significantly improved cognitive flexibility 41.

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Newer Pharmacotherapy for TTM

Newer pharmacotherapies for TTM are summarized in Table 3.

N-acetylcysteine (NAC)

N-acetylcysteine is a derivative of the naturally occurring amino acid L-cysteine which has been

shown to have both direct and indirect antioxidant activity and glutamate metabolism altering

effects. NAC has been used for decades in the treatment of acetaminophen toxicity due to its

glutathione replenishing effects 42.

For neurologic and psychiatric disorders, the mechanism of action of NAC is not fully

understood but may help protect against a number of pathologic processes such as oxidative

stress, neural inflammation, glutamine and dopamine dysregulation 21,43. For impulse-control

disorders including TTM, NAC is thought to mainly act via regulation of synaptic glutamate

levels in the brain, decreasing cytotoxicity 21. Changes in glutamatergic synaptic function have

also been shown in mice with genetic makeups thought to be related to the pathogenesis of TTM
20
.

Evidence of efficacy for NAC in the treatment of trichotillomania specifically has varied. In non-

placebo-controlled studies, the evidence has been promising. In the two main placebo-controlled

studies done, one has shown significant benefit over placebo while a second trial has not 44,45,46.

In a 2009 double-blind placebo-controlled trial studying NAC use in 50 adults with TTM, NAC

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1,200 mg twice daily was found to show significant benefit over placebo 45. A 2013 study failed

to reproduce this benefit in 39 pediatric patients aged 8-17 with TTM using the same dose of

NAC 1,200 mg twice daily 46. The authors hypothesized that this may be due to differing disease

processes in adult and pediatric TTM, possibly relating to an actual urge to pull being more

common in adults 44,46. A related study found that focused pulling increases with age in pediatric

patients, which may support this hypothesis 47. Both trials focused on reduction of hair-pulling

behavior and lasted 12 weeks 44,45,46.

More recent case studies have also shown potential benefit for treatment of TTM with NAC,

including possible benefit in an adolescent patient. Two patients with TTM were successfully

treated with NAC, a 30-year-old and a 14-year-old, both female. The adult and adolescent

patients had their hair pulling subside at by two months and two weeks respectively and

experienced complete hair regrowth after four and six months respectively. Neither patient

reported any adverse side effects of NAC treatment 48. Barroso et al. also reported a case of

significant improvement in the treatment of an 11-year-old male with TTM at a dose of 1,200

mg/day for three months with almost complete hair regrowth after increasing the dose to 1,800

mg/day 49.

Due to its relative safety and tolerability compared to other treatments for TTM such as

antidepressants or antipsychotics and its low cost, NAC has the potential to be an important

treatment option for those struggling with this disorder. Further studies are warranted however

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including larger, long-term randomized, placebo-controlled studies with more standardized

outcome measures 50.

Milk thistle

Milk thistle has been shown to have antioxidant properties and anecdotal evidence of benefit in

TTM. In a recent double-blind, placebo-controlled, crossover study, milk thistle was found to

have no significant benefit over placebo in decreasing TTM severity judged according to the

National Institute of Mental Health TTM severity scale. It was however found to have significant

benefits with regards to the Clinical Global Impression scale severity and in decreasing time

spent pulling hair each week. The study involved 20 individuals aged 12-65 years, 19 of whom

were female 51.

Probiotics

The brain-gut axis and probiotic use have been shown, mostly in animal models or anecdotal

evidence, to affect various mental health conditions such as depression, anxiety, and OCD 52,53.

Evidence of benefit in TTM however is lacking.

The gut microbiota are thought to affect behavior through several ways. These include effects on

vagus nerve signaling (possibly through serotonin synthesis of enterochromaffin cells), mineral

metabolism, modulation of circulating cytokine levels, and changes in neurotransmitter turnover.

Additionally, alteration of neurotrophic factor gene expression, short-chain fatty acid-mediated

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modulation of G-protein coupled receptors, and changes in the hypothalamic-pituitary axis are

thought to play a role 54,55.

Animal studies have shown that gut microbiota may also affect mammalian brain development,

including development of the striatum, which has (among other areas of the brain) been shown to

have structural abnormalities in patients with TTM 10,56,57. A possible relationship however

would require further investigation prior to any in-depth discussion. It would be interesting to see

whether microbial colonization could have any effect on hair pulling, but this has not been

studied adequately to recommend probiotic use for TTM specifically.

Dronabinol

Dronabinol, a cannabinoid agonist, has been proposed to have potential benefit in the treatment

of TTM through the reduction of glutamate cytotoxicity in the striatum 58.

In a small, open-label study, dronabinol showed significant benefit in the reduction in hair

pulling behavior in nine of 12 subjects 58.

A double-blind, placebo-controlled study of dronabinol for the treatment of TTM and other body

focused repetitive behaviors, NCT03530800, out of the University of Chicago is currently

underway and the results will be interesting to see 59.

Inositol

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Inositol is an isomer of glucose which plays a role in the phosphatidylinositol second messenger

system and has shown efficacy as an add-on therapy in other psychiatric conditions including

OCD and depression. The same level of promise in the treatment of TTM however has not been

seen 21,60.

A proposed potential mechanism of action for inositol’s effects on mental health conditions is

attenuation of serotonin-2 receptor desensitization as the phosphatidylinositol second messenger

system is used by these receptors 60. Early anecdotal evidence suggested possible benefit as

either primary or add-on treatment of the condition, but more recent studies have not shown

significant benefit 21,60,61.

In a double-blind, placebo-controlled study Leppink et al. found inositol to have no significant

benefit over placebo 61. The study lasted for 10 weeks and had 38, predominantly female,

participants. 19 received placebo and 19 received inositol. Reduction in hair pulling was

measured using the Massachusetts General Hospital Hair Pulling Scale, NIMH Trichotillomania

Severity Scale, Clinical Global Impression Scale. In this study however, subjects were allowed to

continue their pre-study medications which included psychiatric medications, and this was not

rigorously accounted for in analysis 21,61.

Conclusion

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Trichotillomania is a complex psychodermatologic disorder with much yet to be researched

regarding its pathogenesis and pharmacological treatment. Studies on its comorbidity and

genetics of have shown the potential for future investigation and novel strategies for patient-

specific treatment 19,20,22. Additionally, some newer pharmacotherapy options including potential

monotherapies or add-on treatments have shown promise. Notably, N-acetylcysteine appears to

be a well-tolerated and safe potential treatment of adult TTM 21,44,45,46,47,50. Other new potential

add-on treatments include probiotics and the cannabinoid agonist dronabinol, but further

investigation is needed 52,53,56.

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 Table 1
Clinical Differentials for TTM 1,2,5,6,9,11,12
Condition Distinguishing features
TTM - Age of onset is generally between 10-13 years in clinical
settings but may be closer to 17.7 years in the general
population.
- Possible female predominance in adults but not in children.
- Individuals are often embarrassed by their condition and may try
Accepted Article

to hide it.
- Hair-pulling may be a way to regulate unwanted negative
emotions.
- Dermoscopic features include decreased hair density, broken
hairs of different shaft lengths, coiled or short vellus hairs,
trichoptilosis (split hairs), occasional yellow dots and no
exclamation mark hairs.
- Scalp may show asymmetric patches of alopecia, especially on
the vertex and frontal regions.
- Hair pull test is typically negative.
- The most common pulling sites are the scalp, eyebrows, and
pubic region, eyelashes, and beard.
OCD - Ritualistic activities are typically not enjoyed or pleasurable.
- Unwanted, intrusive and repetitive thoughts do not commonly
precede hair pulling in TTM as they do in OCD.
- Those with OCD often have other rituals where individuals with
TTM may only exhibit hair-pulling.
BDD - Individuals tend to only pull hair in order to correct a self-
perceived physical defect where those with TTM do not
typically share this motivation.
- Individuals hold the belief that removing hair will lead to a more
attractive physical appearance where those with TTM are often
embarrassed by their hair loss.
Neurodevelopmental - Age of onset is often earlier than in TTM, first showing signs in
Disorders early childhood.
- Repetitive hair-pulling is often less purposeful and more
rhythmic than in TTM.
Cluster B Traits - Although the hair-pulling seen in TTM may cause physical self-
mutilation, the sensation of pain often central to the process of
this cluster B-type behavior is not typically a motivator reported
by those with TTM.
Alopecia Areata (AA) - Hair-pulling behavior is absent, but hair loss pattern may grossly
resemble that of TTM, so dermoscopic evaluation is helpful.
- Dermoscopic features of AA compared to TTM:
o Pathognomonic finding on dermoscopy is exclamation
mark hairs.

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 o Patches of hair loss are more often round or oval and
mores symmetrical than those seen in TTM.
o Yellow dots are generally more numerous than would be
seen in TTM and coiled hairs with split ends are
typically absent in AA.

Table 2
Accepted Article

Traditional Pharmacotherapy for TTM 2,5,19,20,21,23,25,31,32,33,34,35,36,37,38,39,40,41

Evidence of

Drug Name Proposed Mechanism of Action in TTM Significant Benefit

in TTM

Tricyclic Antidepressants Blocks norepinephrine and serotonin Weak

(Clomipramine) reuptake, blocks muscarinic cholinergic,

adrenergic, H1, and 5HT2 receptors

TTM Specific MOA

Selective Serotonin Inhibit reuptake of serotonin in synapses Weak

Reuptake Inhibitors

(Fluoxetine)

Second Generation Modulation of Dopamine receptors Moderate

Antipsychotics (Olanzapine,

Aripiprazole)

Opioid Antagonists Reduction of chemical reward process Very Weak

(Naltrexone) experienced when pulling hair by

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 antagonizing opioid receptors
Accepted Article

Table 3

Newer Pharmacotherapy for TTM 10,20,21,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61

Evidence of

Drug Name Proposed Mechanism of action in TTM Significant Benefit in

TTM

N- Regulation of synaptic glutamate levels and reduction Moderate

acetylcysteine of glutamate toxicity

Milk Thistle Antioxidant Very weak

Probiotics Multiple proposed mechanisms via the brain-gut axis Very weak

Dronabinol Reduction of glutamate toxicity in the striatum Weak

Inositol Attenuation of serotonin-2 receptor desensitization Very Weak

via the phosphatidylinositol second messenger system

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