JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY

Volume XX, Number XX, 2019

ª Mary Ann Liebert, Inc.
Pp. 1–10
DOI: 10.1089/cap.2019.0103

Measuring Treatment Response in Pediatric

Trichotillomania:
A Meta-Analysis of Clinical Trials

Luis C. Farhat,1 Emily Olfson, MD, PhD,2,3 Jessica L.S. Levine, BA,3 Fenghua Li, MS,3 Martin E. Franklin, PhD,4
Han-Joo Lee, PhD,5 Adam B. Lewin, PhD,6 Joseph F. McGuire, PhD,7 Omar Rahman, PhD,6
Eric A. Storch, PhD,8 David F. Tolin, PhD,9,10 Hana F. Zickgraf, PhD,4,11 and Michael H. Bloch, MD, MS2,3
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Abstract
Objectives: In clinical trials of pediatric trichotillomania (TTM), three instruments are typically employed to rate TTM
severity: (1) the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS), (2) the National Institute of Mental Health
Trichotillomania Severity Scale (NIMH-TSS), and (3) the Trichotillomania Scale for Children (TSC). These instruments lack
standardized definitions of treatment response, which lead researchers to determine their own definitions of response post hoc
and potentially inflate results. We performed a meta-analysis to provide empirically determined accuracy measures for
percentage reduction cut points in these three instruments.
Methods: MEDLINE was searched for TTM clinical trials. A total of 67 studies were initially identified, but only 5 were
clinical trials focused on TTM in pediatric populations and therefore were included in this meta-analysis (n = 180). A Clinical
Global Impressions Improvement score £2 was used to define clinical response. Receiver operating characteristic principles
were employed to determine accuracy measures for percentage reduction cut points on each one of the instruments. Meta-
DiSc software was employed to provide pooled accuracy measures for each cut point for each instrument. The Youden Index
and the distance to corner methods were used to determine the optimal cut point.
Results: The optimal cut points to determine treatment response were a 45% reduction on the MGH-HPS (Youden Index 0.40,
distance to corner 0.20), a 35% reduction on the NIMH-TSS (Youden Index 0.42, distance to corner 0.17), a 25% reduction on
the TSC child version (TSC-C; Youden Index 0.40, distance to corner 0.18), and a 45% (distance to corner 0.30) or 50%
reduction (Youden Index 0.33) on the TSC parent version (TSC-P). The TSC-C had less discriminative ability at determining
response in younger children in comparison to older children; no age-related differences were observed on the TSC-P.
Conclusions: This study provides empirically determined cut points of treatment response on three instruments that rate TTM
severity. These data-driven cut points will benefit future research on pediatric TTM.

Keywords: trichotillomania, children and adolescents, clinical trials, meta-analysis, Massachusetts General Hospital Hair
Pulling Scale (MGH-HPS), National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS), Tricho-
tillomania Scale for Children (TSC)

1
Departamento de Psiquiatria da Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil.
2
Department of Psychiatry, Yale University, New Haven, Connecticut.
3
Yale Child Study Center, New Haven, Connecticut.
4
Child and Adolescent OCD, Tic, Trich and Anxiety Group (COTTAGe), Department of Psychiatry, Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania.
5
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
6
Department of Pediatrics, University of South Florida, Tampa, Florida.
7
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
8
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.
9
Institute of Living, Hartford, Connecticut.
10
Yale University School of Medicine, New Haven, Connecticut.
11
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
Funding: No funding was received for this article.

1
 2 FARHAT ET AL.
Introduction
T richotillomania (TTM) (or hair pulling disorder) is a psy-
chiatric condition characterized by pulling out of one’s own
hair, which results in noticeable hair loss (American Psychiatric
Association 2013). TTM typically develops during early adoles-
cence and then progresses into adulthood with a chronic course of
waxing-and-waning symptom severity throughout the lifetime
(Bloch 2009), so early diagnosis is critical. Studies of college
students suggest that between 1% and 3.5% of the general popu-
lation engage in hair pulling that leads to significant distress
(Christenson et al. 1991b; Odlaug and Grant 2010). Children with
TTM report that their hair pulling interferes moderately with their
social life and academic performance (Franklin et al. 2008), as peer
teasing is common and leads to avoidance of daily activities.
Children with TTM frequently present with comorbid anxiety and
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depressive disorders (Lewin et al. 2009) and there is some evidence
that these comorbidities develop after the onset of TTM, high-
lighting the importance of early intervention for TTM in childhood
(Woods et al. 2006; Franklin et al. 2008).
Currently, there is no sufficient evidence to support any inter-
vention as a first-line treatment of pediatric TTM as there are only
four randomized, controlled clinical trials (RCTs). Of these, two
evaluated behavioral therapy with habit reversal training (HRT)
procedures (Franklin et al. 2011; Rahman et al. 2017), one evaluated
behavioral therapy augmented with response inhibition training
(Lee et al. 2018), and one evaluated a pharmacological agent—
N-acetylcysteine (NAC), a glutamatergic modulator (Bloch et al.
2013). Findings indicated that HRT was more efficacious than
the control condition, whereas NAC did not separate from placebo.
These results are in line with those of RCTs for adult TTM, as meta-
analyses suggest behavioral therapy is the first-line intervention for
the management of TTM, while there is no clear first-line phar-
macological treatment (Bloch et al. 2007; McGuire et al. 2014).
Additional clinical trials are warranted to identify efficacious
therapeutic options for pediatric TTM. RCTs are considered the
optimal study design to evaluate the efficacy and safety of novel
interventions in medicine, including psychiatry (Emsley and
Hawkridge 2009; Fleischhacker and Goodwin 2009). Yet clinical
trials for pediatric TTM face several important issues, including
that rating scales of treatment efficacy often have not been spe-
cifically validated in children and lack standard definitions of
treatment response. The lack of standard definitions of response to
treatment is a significant issue for at least three reasons. First, it
unintentionally encourages researchers to develop their own defi-
nitions of treatment response through post hoc analysis, which can
inflate the results. Second, it creates challenges for comparing re-
sults across different trials. Third, it precludes assessment of clin-
ical benefit as statistically significant differences between active
and control groups do not necessarily correspond to individuals
actually experiencing clinical improvement with the proposed in-
tervention (Kraemer and Kupfer 2006).
We have recently addressed the lack of empirical definitions of
response to treatment on two instruments typically employed to
measure TTM symptom severity in RCTs of adults—the Massa-
chusetts General Hospital Hair Pulling Scale (MGH-HPS) and the
National Institute of Mental Health Trichotillomania Severity Scale
(NIMH-TSS) (Houghton et al. 2015; Farhat et al. 2019). The MGH-
HPS is a 7-item self-report, while the NIMH-TSS is a 6-item
clinician-rated instrument. Our study showed that a 35% or 7-point
reduction on the MGH-HPS or a 50% or 6-point reduction on the
NIMH-TSS were considered optimal cut points to classify an in-
dividual as a responder to the treatment in RCTs for TTM. Im-
portantly, our results also showed that both the MGH-HPS and the
NIMH-TSS had greater discriminative ability to determine re-
sponse when pediatric samples were excluded from the analyses.
Our study was limited considerably by the paucity of pediatric trials
and separate analyses of exclusively pediatric populations were not
carried out due to the small sample size available at the time. Yet,
the results suggest that both the MGH-HPS and the NIMH-TSS
might not be appropriate to measure response to treatment in RCTs
for pediatric TTM, and separate analyses, including exclusively
pediatric populations, are still warranted.
Although the MGH-HPS has been widely employed as a self-
report instrument to evaluate TTM severity in clinical trials for
pediatric TTM, significant issues should be considered. First, the
MGH-HPS has never been validated in pediatric TTM populations,
and some of its items feature language that is not appropriate for
children and adolescents. In addition, there is no parent-report
version of the MGH-HPS, so parents are not able to provide their
perspective on their children’s hair pulling behavior on this in-
strument. The self- and parent-report Trichotillomania Scale for
Children (TSC) was developed to address these limitations of the
MGH-HPS to rate symptom severity of pediatric TTM (Tolin et al.
2008). The TSC comprised 12 items divided into 2 subscales—
severity and distress/impairment; the TSC has shown strong psy-
chometric properties and, importantly, it can be completed by
children and/or their parents, using the child version (TSC-C) an-
d/or parent version (TSC-P). Indeed, the inclusion of parent- and
child-reported TTM severity is consistent with guidelines for an
evidence-based assessment in youth with TTM (McGuire et al.
2012).
In this meta-analysis, we present data that address these gaps in
the literature of pediatric TTM. The objective of this meta-analysis
is to determine the discriminative ability of the MGH-HPS, NIMH-
TSS, TSC-C, and TSC-P to determine response to treatment in
clinical trials for pediatric TTM. A Clinical Global Impressions
Improvement (CGI-I) (Busner and Targum 2007) score of either 2
(‘‘much improved’’) or 1 (‘‘very much improved’’) was determined
as the criterion measure to consider individuals as responders to
treatments. In addition, as younger children may struggle to rec-
ognize hair pulling behavior, we performed separate analyses for
younger and older children to examine sensitivity of these bench-
marks of treatment response.
Methods
Search strategy for identification of studies
and study selection
On February 2, 2019, MEDLINE was searched with the search
strategy Trichotillomania OR ‘‘hair pulling disorder.’’ The search
was limited to clinical trials. Language restrictions were not ap-
plied. Meta-analyses, systematic reviews, and review articles were
carefully read to look for other potentially eligible articles or un-
published research. No further efforts were made to look for un-
published research. Titles and abstracts of references obtained by
this search strategy were analyzed by two independent reviewers
(L.C.F. and M.H.B.) to determine if they met the inclusion criteria
required for our meta-analysis. To be included, studies had to (1)
include a patient population with a primary diagnosis of TTM, (2)
be a clinical trial, either an RCT or an open-label (OL) trial, and (3)
include exclusively a pediatric sample (age range 4–17 years of
age). A few TTM trials with a predominantly adult population also
enrolled some adolescents—usually 15–17 years of age. In a
 TREATMENT RESPONSE IN PEDIATRIC TRICHOTILLOMANIA
separate recent analysis of adult TTM trials, we attempted to
contact these authors, but we were unable to attain these data
(described in Farhat et al. 2019), and therefore it was considered
unavailable. Any discrepancies between the two independent re-
viewers were resolved through discussing and reading the full text
of the article.
An e-mail was sent to either the corresponding or the senior
author of articles fulfilling the inclusion criteria for our meta-
analysis. In the e-mail, de-identified individual participant data
were requested; specifically, data requested included, for each
participant, (1) age, (2) gender, (3) CGI-I score posttreatment, and
(4) TTM severity scores pretreatment and posttreatment. We did
not adopt a hierarchy of preferred TTM severity outcomes; authors
could send pretreatment and posttreatment scores from any of the
following instruments: MGH-HPS, NIMH-TSS, TSC-C, and/or
TSC-P. To be definitively included in the meta-analysis, authors
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had to provide at least the CGI-I posttreatment score as well as
pretreatment and posttreatment scores on at least one instrument to
measure TTM severity for each individual included in their studies.
Meta-analytic and receiver operating
characteristic procedures
A similar analytic approach was employed as previously de-
scribed by our group (Farhat et al. 2019). Analyses were initially
carried out separately for each trial included in the meta-analysis.
Individuals were classified as responders to treatment if they pre-
sented a CGI-I score of either 2 (‘‘much improved’’) or 1 (‘‘very
much improved’’). Afterward, the percentage reduction in the score
of TTM severity from pretreatment to posttreatment was calculated
for each individual for each available instrument. Cut points for
percentage reduction were then established from 5% to 70% at
intervals of 5%. For each cut point, true positives, false positives,
true negatives, and false negatives were calculated; these values
were then employed to calculate sensitivity, specificity, positive
likelihood ratio (PLR), and negative likelihood ratio (NLR) for
each cut point, for each instrument.
Meta-DiSc software (Zamora et al. 2006) was employed to meta-
analyze sensitivity, specificity, PLR, and NLR across the studies for
each cut point. Meta-DiSc computes accuracy estimates from each
study and provides pooled measures with confidence intervals.
Heterogeneity was evaluated through a chi-square comparison. If
heterogeneity was significant ( p < 0.05), a random-effects model
was employed; otherwise, a fixed-effects model was employed.
Both the Youden Index and distance to the corner methods were
employed to determine the optimal cut point to dichotomize indi-
viduals into responders and nonresponders for each TTM severity
instrument. The Youden Index is an approach commonly employed
to maximize both sensitivity and specificity, and is calculated by
summing the sensitivity and the specificity, and then subtracting
one from the result. The distance to the corner is defined by the
Euclidean distance between the receiver operating characteristic
(ROC) curve and the (0,1) point (Unal 2017). Optimal cut points
should maximize the Youden index value and minimize the dis-
tance to the corner.
For sensitivity analyses, we performed the same analytical
procedures described above separately for younger and older
children. Given previous research indicates younger children are
more likely to experience automatic pulling in comparison to older
children, which are more likely to experience focused pulling
(Keuthen et al. 2008), we divided our entire sample in two age
groups: 8–13 and 14–17 years of age. Separate age-related analyses
3
for the MGH-HPS were not carried out as there were only two
studies that provided MGH-HPS data, and the resultant sample size
of each age group would be too small.
Results
Characteristics of trials
Supplementary Figure S1 illustrates the selection of studies for
inclusion in the meta-analysis. The search strategy initially yielded
67 articles as potentially eligible. We were able to include data
from all five clinical trials of pediatric TTM published to date
(Tolin et al. 2007; Franklin et al. 2011; Bloch et al. 2013; Rahman
et al. 2017; Lee et al. 2018). Of these five studies, four were RCTs
and one was OL. The interventions examined in these studies were
HRT (n = 3), computerized response inhibition training (n = 1), and
NAC (n = 1). Although we did not specifically look for additional
unpublished studies, we were also able to include unpublished data
from an RCT that compared HRT against supportive therapy for the
treatment of pediatric TTM (NCT00917098). Table 1 illustrates the
characteristics of all six trials included in this meta-analysis. In
total, data from 210 participants were included in the analyses and
the majority of participants were female (80.99%).
MGH-HPS and NIMH-TSS
Figure 1 depicts the ROC curves for the analyses of the MGH-
HPS (Fig. 1A) and NIMH-TSS (Fig. 1B) percentage reduction cut
points. The first panel of Figure 1 features the ROC curve depicting
the results from the overall analysis, including data from all chil-
dren. For the MGH-HPS, when data from all children (n = 75) were
included in the analysis, the area under the curve (AUC) for the
ROC curve was 0.68, indicating that the MGH-HPS had a fair
ability to determine treatment response as measured by a CGI-I £ 2.
The second panel of Figure 1 features three ROC curves; one of the
curves depicts the results from the overall analysis, including data
from all children, while the remaining two depict results from the
separate analyses for children 8–13 and 14–17 years of age. For the
NIMH-TSS, when data from all children (n = 126) were included in
the analysis, the AUC was 0.75, indicating that the NIMH-TSS had
a fair ability to determine treatment response as measured by a
CGI-I £ 2. When data from children 8–13 (n = 65) and 14–17
(n = 61) years of age were analyzed separately, the AUCs for the
ROC curves were 0.72 and 0.76, respectively, indicating that the
NIMH-TSS retained its fair discriminative ability to determine
treatment response among both age groups.
Tables 2 and 3 show pooled accuracy measures and parameters
to determine the optimal percentage reduction cut point for each cut
point on the MGH-HPS (Table 2) and NIMH-TSS (Table 3) when
data from all children were included in the analyses. For the MGH-
HPS, a 45% reduction on the scores from pretreatment to post-
treatment was considered the optimal cut point to determine
treatment response, as measured by a CGI-I £ 2, by both the
Youden Index (0.37) and the distance to corner (0.20) methods.
This 45% reduction cut point on the MGH-HPS had a sensitivity of
0.67 (95% CI [0.35–0.90]), a specificity of 0.70 (95% CI [0.57–
0.81]), a PLR of 2.31 (95% CI [0.39–13.70]), and an NLR of 0.57
(95% CI [0.11–3.09]). For the NIMH-TSS, a 35% reduction on
the scores from pretreatment to posttreatment was considered the
optimal cut point to determine treatment response, as measured
by a CGI-I £ 2, by both the Youden Index (0.42) and the distance
to corner (0.17) methods. This 35% reduction cut point on the
NIMH-TSS had a sensitivity of 0.65 (95% CI [050–0.78]), a
 4 FARHAT ET AL.

Table 1. Characteristics of Included Trials

Max dose Duration Sample Age, mean Females

ID Active (mg/day) Control (weeks) size (standard deviation) (%) TTM outcomes

Bloch et al. (2013) NAC 2400 PCB 12 35 PCB 13.1 (3.1) 85.71 MGH-HPS
TSC-C/TSC-P
NAC 14 (2.4) NIMH-TSS
Franklin et al. (2011) HRT — MAC 8 32 12.5 (2.7) 83.60 TSC-C/TSC-P
Lee et al. (2018) RIT — WL 4 20 RIT 12.91 (2.39) 75 TSC-C/TSC-P
WL 13.11 (2.52) NIMH-TSS
Rahman et al. (2017) HRT — TAU 8 40 11.85 (3.14) 83.33 MGH-HPS
Tolin et al. (2007) HRT — — 8 22 12.6 (3.0) 63.63 TSC-C/TSC-P
NIMH-TSS
NCT00917098 HRT — ST 61 13.49 (2.45) 83.6 TSC-C/TSC-P
NIMH-TSS

HRT, Behavioral Therapy with Habit Reversal Training Procedures; ID, identification; MAC, minimal attention control; MGH-HPS, Massachusetts
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General Hospital Hair Pulling Scale; NAC, N-acetylcysteine; NIMH-TSS, National Institute of Mental Health Trichotillomania Severity Scale; PCB,
placebo; RIT, Response Inhibition Training; ST, supportive therapy; TAU, treatment as usual; TTM, trichotillomania; TSC-C, Trichotillomania Scale for
Children Child Version; TSC-P, Trichotillomania Scale for Children Parent Version; WL, wait list.

specificity of 0.77 (95% CI [0.66–0.86]), a PLR of 2.18 (95% CI
[1.24–3.83]), and an NLR of 0.55 (95% CI [0.25–1.20]).
TSC child and parent versions
Figure 2 depicts the ROC curves for the analyses of the TSC-C
(Fig. 2A) and TSC-P (Fig. 2B) percentage reduction cut points.
Each panel of Figure 2 features three ROC curves; one of the curves
depicts the results from the overall analysis, including data from all
children, while the remaining two depict results from the separate
analyses for children 8–13 and 14–17 years of age. For the TSC-C,
when data from all children (n = 98) were included in the analysis,
the AUC for the ROC curve was 0.75, indicating that the TSC-C
had a fair ability to determine treatment response as measured by a
CGI-I £ 2. When data from children 8–13 (n = 52) and 14–17
(n = 46) years of age were analyzed separately, the AUCs for the
ROC curves were 0.71 and 0.80, respectively, indicating that the
TSC-C had a fair and good-to-great ability to determine response
among children 8–13 and 14–17 years of age, respectively. For the
TSC-P, when data from all children (n = 109) were included in the
analysis, the AUC was 0.63, indicating that the TSC-P had a fair
ability to determine treatment response as measured by a CGI-I £ 2.
When data from children 8–13 (n = 65) and 14–17 (n = 44) years of
age were analyzed separately, the AUCs for the ROC curves were
0.61 and 0.64, respectively, indicating that the TSC-P retained its
fair ability to determine response to treatment among both age
groups.
Tables 4 and 5 show pooled accuracy measures and parameters
to determine the optimal percentage reduction cut point for each cut
point on the TSC-C (Table 4) and TSC-P (Table 5) when data from
all children were included in the analyses. For the TSC-C, a 25%
reduction on the scores from pretreatment to posttreatment was
considered the optimal cut point to determine treatment response,
as measured by a CGI-I £ 2, by both the Youden Index (0.40) and
the distance to corner (0.18) methods. This 25% reduction cut point
on the TSC-C had a sensitivity of 0.74 (95% CI [0.56–0.87]), a
specificity of 0.66 (95% CI [0.53–0.77]), a PLR of 2.27 (95% CI
[1.46–3.54]), and an NLR of 0.52 (95% CI [0.18–1.48]). For
treatment response as measured by CGI-I £ 2, the optimal cut point
for reduction in TSC-P scores from pretreatment to posttreatment
was 45% by the distance to corner (0.30) method and 50% by the
Youden Index (0.33). The 45% reduction cut point on the TSC-P
had a sensitivity of 0.49 (95% CI [0.31–0.66]), a specificity of 0.81
(95% CI [0.70–0.89]), a PLR of 3.58 (95% CI [1.35–9.45]), and an
NLR of 0.66 (95% CI [0.44–1.0]); the 50% reduction cut point on
the TSC-P had a sensitivity of 0.46 (95% CI [0.29–0.63]), a spec-
ificity of 0.87 (95% CI [0.77–0.93]), a PLR of 4.39 (95% CI [1.19–
16.27]), and an NLR of 0.64 (95% CI [0.46–0.88]).
Discussion
This meta-analysis compares three commonly used instruments
to assess TTM severity in clinical trials of pediatric populations: the
MGH-HPS, NIMH-TSS, and TSC-C/P. Specifically, this study
provides accuracy measures of percentage reduction from pre-
treatment to posttreatment on these three instruments that corre-
spond to treatment response defined by a CGI-I score of 2 (‘‘much
improved’’) or 1 (‘‘very much improved’’). Furthermore, this study
also derives optimal percentage reduction cut points for each in-
strument to classify responders and nonresponders.
Our results indicate that a 45% reduction on the MGH-HPS
could be considered the optimal cut point to determine response to
treatment among children and adolescents with TTM according to
both the Youden Index (0.37) and distance to corner (0.20) meth-
ods. Our results also indicated that the MGH-HPS had a poorer
discriminative ability to determine treatment response in compar-
ison to the TSC-C (AUC = 0.68 vs. 0.75), the other self-report in-
strument employed to measure TTM severity. This could be
explained by the fact that the MGH-HPS features language that is
likely not appropriate for children; for instance, instead of inquiring
about hair pulling behavior itself, severity items of the MGH-HPS
query about urges (e.g., ‘‘On an average day, how often did you feel
the urge to pull your hair?’’), which might be somewhat difficult for
children to understand. Consistent with this hypothesis, the MGH-
HPS showed a good discriminative ability to determine response
among adults (AUC = 0.82) in our previous study (Farhat et al.
2019). Yet, it should be noted that for this study, only two trials had
data available on the MGH-HPS and we were unable to perform
separate analyses for different age groups as sensitivity analyses,
given the small sample sizes. In addition, although the AUC for the
MGH-HPS is smaller than the AUC for the TSC-C, we were not
able to compare both AUCs to evaluate if these numerical differ-
ences reach significance threshold. Future research should look
further into possible age-related differences in the ability of the
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FIG. 1. Receiver operating curves for the MGH-HPS and NIMH-TSS. (A, B) Depict the ROC curves of sensitivity versus one-
specificity for the MGH-HPS and NIMH-TSS percentage reduction cut points, respectively. For the MGH-HPS when all children were
included, the AUC for the ROC curve was 0.68, indicating that the MGH-HPS has a fair ability to determine response to treatment as
determined by a CGI-I £ 2. For the NIMH-TSS when all children were included, the AUC for the ROC curve was 0.75, also indicating
that the NIMH-TSS has a fair ability to determine response to treatment as determined by a CGI-I £ 2. AUC, area under the curve; CGI-
I, Clinical Global Impressions Improvement; MGH-HPS, Massachusetts General Hospital Hair Pulling Scale; NIMH-TSS, National
Institute of Mental Health Trichotillomania Severity Scale; ROC, receiver operating characteristic.

5
 6 FARHAT ET AL.

Table 2. Accuracy Measures, Youden Index, and Distance to Corner for Cut Points for the Massachusetts
General Hospital Hair Pulling Scale

Cut point, Positive likelihood Negative likelihood

% Sensitivity (95% CI) Specificity (95% CI) ratio (95% CI) ratio (95% CI) Youden Distance

5 0.83 (0.52–0.98) 0.41 (0.29–0.54) 1.54 (0.62–3.80) 0.49 (0.06–3.83) 0.24 0.38
10 0.75 (0.43–0.95) 0.43 (0.31–0.56) 1.24 (0.19–8.19) 0.69 (0.02–25.32) 0.18 0.39
15 0.75 (0.43–0.95) 0.49 (0.36–0.62) 1.40 (0.22–8.77) 0.59 (0.02–16.88) 0.24 0.32
20 0.75 (0.43–0.95) 0.52 (0.39–0.65) 1.48 (0.27–8.25) 0.56 (0.02–12.90) 0.27 0.29
25 0.75 (0.43–0.95) 0.56 (0.43–0.68) 1.61 (0.27–9.57) 0.52 (0.02–12.51) 0.31 0.26
30 0.67 (0.35–0.90) 0.62 (0.49–0.74) 1.78 (0.36–8.67) 0.64 (0.11–3.69) 0.29 0.25
35 0.67 (0.35–0.90) 0.62 (0.49–0.74) 1.78 (0.36–8.67) 0.64 (0.11–3.69) 0.29 0.25
40 0.67 (0.35–0.90) 0.65 (0.52–0.77) 1.97 (0.36–10.79) 0.61 (0.11–3.51) 0.32 0.23
45 0.67 (0.35–0.90) 0.70 (0.57–0.81) 2.31 (0.39–13.70) 0.57 (0.11–3.09) 0.37 0.20
50 0.58 (0.28–0.85) 0.71 (0.59–0.82) 1.75 (0.06–47.46) 0.63 (0.04–10.20) 0.29 0.26
55 0.50 (0.21–0.79) 0.79 (0.67–0.89) 2.84 (0.07–123.7) 0.69 (0.11–4.5) 0.29 0.29
60 0.50 (0.21–0.79) 0.81 (0.69–0.90) 2.97 (0.08–118.2) 0.68 (0.11–4.18) 0.31 0.29
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65 0.33 (0.1–0.65) 0.83 (0.71–0.91) 2.55 (0.10–62.6) 0.85 (0.37–1.99) 0.16 0.48
70 0.33 (0.1–0.65) 0.84 (0.73–0.92) 2.70 (0.12–59.36) 0.84 (0.38–1.89) 0.17 0.47

Bold indicates optimal cut point.

MGH-HPS to discriminate response among youth of different ages.
Given that younger children may have more difficulty with the
abstract language, it would be interesting to see if the MGH-HPS
has a higher discriminative ability among adolescents when com-
pared with young children. Nevertheless, considering that the
MGH-HPS has never been validated among children and adoles-
cents, data from this meta-analysis reinforce the notion that caution
is required about employing the MGH-HPS as a primary outcome
measure in trials for pediatric TTM.
This meta-analysis also showed that a 35% reduction on the
NIMH-TSS could be considered the optimal cut point to determine
response to treatment among children and adolescents with TTM
according to both the Youden Index (0.42) and distance to corner
(0.17) methods. Our results also indicated that the NIMH-TSS had
a fair ability to determine response to treatment in clinical trials for
pediatric TTM (AUC = 0.75). Although both the NIMH-TSS and
the CGI-I are clinician-rated instruments, the NIMH-TSS is a
semistructured interview that queries about specific subjects re-
garding hair pulling, whereas the CGI-I is a unitary score that as-
sesses the patient’s global well-being and functioning. It is possible
that some of the questions on the NIMH-TSS may be inappropriate
for young children because they require respondents to estimate
intervals of time (e.g., ‘‘How much time did you spend pulling hairs
yesterday?’’); this may explain why the NIMH-TSS had less dis-
criminative ability among pediatric populations in comparison to
adults (AUC = 0.92) (Farhat et al. 2019). At the present moment,
considering the NIMH-TSS has also never been validated among
pediatric populations, researchers should also be cautious about
employing the NIMH-TSS in their clinical trials as a primary
outcome to rate TTM severity.
Finally, our results suggest that for the TSC-C, a 25% reduction
on the TSC-C (Youden Index = 0.40, distance to corner = 0.18)
could be considered the optimal cut point to determine response to
treatment among children and adolescents with TTM. For the TSC-
P, a 45% reduction could be considered optimal according to the
distance to corner method (0.30); according to the Youden index
(0.33), a 50% reduction could be considered the optimal cut point.
Although both the 45% and 50% reduction cut points could be
considered optimal, it should be noted that the 45% cut point, in
comparison to the 50% cut point, had a slightly larger sensitivity

Table 3. Accuracy Measures, Youden Index, and Distance to Corner for Cut Points for the National Institute
of Mental Health Trichotillomania Severity Scale

Cut point, Positive likelihood Negative likelihood

% Sensitivity (95% CI) Specificity (95% CI) ratio (95% CI) ratio (95% CI) Youden Distance

5 0.81 (0.67–0.91) 0.41 (0.30–0.53) 1.35 (1.02–1.78) 0.46 (0.1–2.13) 0.22 0.38
10 0.81 (0.67–0.91) 0.47 (0.36–0.59) 1.46 (1.13–1.90) 0.4 (0.09–1.78) 0.28 0.32
15 0.77 (0.63–0.88) 0.54 (0.42–0.65) 1.51 (1.05–2.16) 0.48 (0.15–1.49) 0.31 0.27
20 0.77 (0.63–0.88) 0.58 (0.46–0.69) 1.6 (1.08–2.36) 0.45 (0.14–1.42) 0.35 0.23
25 0.77 (0.63–0.88) 0.6 (0.49–0.71) 1.64 (1.14–2.37) 0.44 (0.15–1.29) 0.37 0.21
30 0.71 (0.56–0.83) 0.65 (0.54–0.76) 1.7 (1.08–2.68) 0.56 (0.27–1.16) 0.36 0.21
35 0.65 (0.50–0.78) 0.77 (0.66–0.86) 2.18 (1.24–3.83) 0.55 (0.25–1.20) 0.42 0.17
40 0.6 (0.45–0.74) 0.8 (0.69–0.88) 2.3 (1.05–5.06) 0.57 (0.30–1.1) 0.4 0.20
45 0.56 (0.41–0.71) 0.85 (0.75–0.92) 2.63 (1.38–5.02) 0.58 (0.33–1.01) 0.41 0.22
50 0.52 (0.37–0.67) 0.87 (0.78–0.94) 2.91 (1.40–6.08) 0.651 (0.39–0.95) 0.39 0.25
55 0.46 (0.31–0.61) 0.94 (0.86–0.98) 4.44 (1.45–13.59) 0.64 (0.43–0.95) 0.4 0.30
60 0.42 (0.28–0.57) 0.94 (0.86–0.98) 4.12 (1.26–13.43) 0.7 (0.52–0.94) 0.36 0.34
65 0.33 (0.20–0.48) 0.94 (0.86–0.98) 3.09 (1.19–8.02) 0.78 (0.65–0.94) 0.27 0.45
70 0.31 (0.19–0.46) 0.96 (0.89–0.99) 4.17 (1.56–11.20) 0.77 (0.65–0.92) 0.27 0.48

Bold indicates optimal cut point.

Downloaded by COLUMBIA UNIVERSITY LIBRARY from www.liebertpub.com at 12/05/19. For personal use only.

FIG. 2. Receiver operating curves for the TSC-C and TSC-P Versions. (A, B) Depict the ROC curves of sensitivity versus one-
specificity for the TSC-C and TSC-P percentage reduction cut points, respectively. For the TSC-C, when data from all children were
included in the analysis, the AUC for the ROC curve was 0.75, indicating that the TSC-C has a fair ability to determine response to
treatment as determined by a CGI-I £ 2. For the TSC-P, when all children and adolescents were included in the analysis, the AUC for the
ROC curve was 0.63, also indicating that the TSC-P has a fair ability to determine response to treatment as determined by a CGI-I £ 2.
AUC, area under the curve; CGI-I, Clinical Global Impressions Improvement; ROC, receiver operating characteristic; TSC-C, Tri-
chotillomania Scale for Children Child Version; TSC-P, Trichotillomania Scale for Children Parent Version.

7
 8 FARHAT ET AL.

Table 4. Accuracy Measures, Youden Index, and Distance to Corner for Cut Points for the Trichotillomania
Scale for Children-Child Version

Cut point, Positive likelihood Negative likelihood

% Sensitivity (95% CI) Specificity (95% CI) ratio (95% CI) ratio (95% CI) Youden Distance

5 0.9 (0.73–0.98) 0.38 (0.26–0.52) 1.44 (1.12–1.86) 0.34 (0.13–0.92) 0.28 0.39
10 0.86 (0.68–0.96) 0.47 (0.33–0.60) 1.57 (1.16–2.13) 0.35 (0.15–0.82) 0.33 0.30
15 0.83 (0.64–0.94) 0.55 (0.42–0.68) 1.91 (1.31–2.79) 0.43 (0.18–1.04) 0.38 0.23
20 0.77 (0.59–0.89) 0.63 (0.50–0.74) 1.9 (1.03–3.50) 0.54 (0.18–1.69) 0.40 0.19
25 0.74 (0.56–0.87) 0.66 (0.53–0.77) 2.27 (1.46–3.54) 0.52 (0.18–1.48) 0.40 0.18
30 0.68 (0.50–0.83) 0.69 (0.56–0.80) 2.33 (1.43–3.82) 0.6 (0.25–1.40) 0.37 0.20
35 0.56 (0.38–0.73) 0.75 (0.63–0.85) 2.41 (1.32–4.40) 0.68 (0.40–1.15) 0.31 0.26
40 0.5 (0.32–0.68) 0.78 (0.66–0.88) 2.6 (1.34–5.01) 0.73 (0.46–1.15) 0.28 0.30
45 0.44 (0.27–0.62) 0.88 (0.77–0.94) 3.36 (1.47–7.68) 0.73 (0.54–0.98) 0.32 0.33
50 0.44 (0.27–0.62) 0.91 (0.81–0.97) 4.28 (1.67–10.97) 0.71 (0.53–0.96) 0.35 0.32
55 0.35 (0.20–0.54) 0.92 (0.83–0.97) 3.55 (1.30–9.74) 0.76 (0.60–0.96) 0.27 0.43
60 0.29 (0.15–0.48) 0.94 (0.85–0.98) 3.32 (1.07–10.33) 0.8 (0.65–0.99) 0.23 0.51
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65 0.27 (0.13–0.44) 0.94 (0.85–0.98) 3.09 (0.99–9.68) 0.82 (0.67–1.00) 0.21 0.54
70 0.24 (0.11–0.41) 0.94 (0.85–0.98) 2.81 (0.90–8.90) 0.85 (0.71–1.02) 0.18 0.58

Bold indicates optimal cut point.

(0.49 vs. 0.46) and slightly smaller specificity (0.81 vs. 0.87). When
deciding on which one of these evidence-based cut points to adopt,
researchers and clinicians should consider these differences in the
accuracy measures of both cut points. Both the TSC-C (AUC =
0.75) and the TSC-P (AUC = 0.63) had a fair ability to determine
response to treatment, but the self-report measure had a higher
discriminative ability to determine treatment response than the
parent measure. Children often feel ashamed of their hair pulling
behavior and try to conceal or minimize their pulling in their ev-
eryday life; it is possible that this could interfere with parental
perceived change of hair pulling severity during the course of a
treatment trial.
Previous research on TTM (Keuthen et al. 2008) has shown that
parent-youth concordance for awareness of hair pulling and anxiety
scores among younger children (10–12 years old) is lower than
among older adolescents (15–17 years old). Phenotypical research
on TTM could help explain this discrepancy as two distinct hair
pulling styles have been described: automatic and focused (Chris-
tenson et al. 1991a; Flessner et al. 2007). While the automatic
pattern describes pulling that occurs out of one’s own awareness,
the focused pattern describes pulling with awareness. Cross-
sectional studies report findings that suggest that children may ex-
perience a transition from automatic to focused hair pulling, as
younger children are less aware of urges and less focused on their
pulling in comparison to older children (Diefenbach et al. 2002;
Panza et al. 2013). It is likely that the lower concordance of pulling
awareness observed in parent-child dyads could be explained by
the fact that young children may be more likely to pull their hair
without being consciously aware of doing so. In that sense, it is
possible that the TSC-C would be a less appropriate measure of
treatment response in RCTs with young children. This meta-
analysis provides some evidence to support this hypothesis, as the
TSC-C had a higher discriminative ability among older in com-
parison to younger children (AUC = 0.80 vs. 0.71). Yet, we were
unable to investigate whether these age-related differences are
mediated by differences in the hair pulling styles, given the small
sample sizes. Future research on this topic is warranted when more
data are available from trials for pediatric TTM.
At the moment, TTM remains a difficult-to-treat condition,
especially among children and adolescents. Pediatric TTM is

Table 5. Accuracy Measures, Youden Index, and Distance to Corner for Cut Points for the Trichotillomania
Scale for Children-Parent Version

Cut point, Positive likelihood Negative likelihood

% Sensitivity (95% CI) Specificity (95% CI) ratio (95% CI) ratio (95% CI) Youden Distance

5 0.74 (0.57–0.88) 0.32 (0.22–0.44) 1.15 (0.79–1.68) 1.17 (0.33–4.11) 0.06 0.53
10 0.71 (0.54–0.85) 0.35 (0.24–0.47) 1.15 (0.81–1.62) 1.14 (0.38–3.37) 0.06 0.51
15 0.69 (0.51–0.83) 0.41 (0.29–0.53) 1.23 (0.78–1.92) 1.06 (0.35–3.24) 0.1 0.44
20 0.66 (0.48–0.81) 0.49 (0.37–0.61) 1.38 (0.74–2.56) 0.93 (0.31–2.81) 0.15 0.38
25 0.63 (0.45–0.79) 0.57 (0.45–0.68) 1.58 (0.69–3.63) 0.9 (0.29–2.75) 0.2 0.32
30 0.54 (0.37–0.71) 0.68 (0.56–0.78) 2.23 (1.27–3.93) 0.74 (0.43–1.29) 0.22 0.31
35 0.49 (0.31–0.66) 0.73 (0.61–0.83) 2.36 (1.13–4.94) 0.73 (0.47–1.15) 0.22 0.33
40 0.49 (0.31–0.66) 0.77 (0.66–0.86) 3.11 (1.47–6.58) 0.68 (0.44–1.05) 0.26 0.31
45 0.49 (0.31–0.66) 0.81 (0.70–0.89) 3.58 (1.35–9.45) 0.66 (0.44–1.00) 0.3 0.30
50 0.46 (0.29–0.63) 0.87 (0.77–0.93) 4.39 (1.19–16.27) 0.64 (0.46–0.88) 0.33 0.31
55 0.37 (0.22–0.55) 0.87 (0.77–0.93) 3.66 (1.06–12.61) 0.7 (0.54–0.90) 0.24 0.41
60 0.34 (0.19–0.52) 0.88 (0.78–0.94) 3.52 (1.13–10.97) 0.7 (0.56–0.91) 0.22 0.45
65 0.29 (0.15–0.46) 0.89 (0.80–0.95) 3.15 (0.96–10.29) 0.76 (0.61–0.95) 0.18 0.52
70 0.2 (0.08–0.37) 0.93 (0.85–0.98) 2.45 (0.71–8.41) 0.87 (0.74–1.04) 0.13 0.65

Bold indicates optimal cut point.

 TREATMENT RESPONSE IN PEDIATRIC TRICHOTILLOMANIA 9

considerably understudied as currently there are only 5 published Clinical Significance

clinical trials evaluating treatments for pediatric TTM. Importantly,
Pediatric TTM is an often underrecognized and difficult-to-treat
these trials exhibit significant methodological limitations, such as
condition. Currently, there are no clear first-line pharmacological
small sample sizes and primary outcome measures that were not
agents for hair pulling and efficacious behavioral interventions are
validated among pediatric samples and lack standardized defini-
often difficult to access in community settings. Additional research is
tions of treatment response. These methodological limitations
warranted to identify novel, efficacious treatments for pediatric TTM.
hamper further advancements in the development of novel treat-
Future clinical trials evaluating interventions for TTM should define
ments for pediatric TTM. In this meta-analysis, we demonstrated
treatment response a priori to facilitate comparisons across studies as
the discriminative ability of different TTM severity instruments to
well as to avoid potential problems with post hoc definitions of re-
determine response to treatment in clinical trials for pediatric TTM;
sponse. This study provides evidence-based definitions of treatment
we also provided accuracy measures for percentage reduction cut
response of three most commonly used TTM severity instruments in
points, as well as parameters to determine the optimal cut point to
pediatric populations. In that way, this study might be helpful in
dichotomize children as responders and nonresponder for each
guiding researchers and clinicians in assessing treatment response.
instrument. This meta-analysis has several significant limitations.
For instance, although all pediatric TTM clinical trials were in-
cluded in this meta-analysis, the sample size (n = 210) was con- Disclosures
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siderably small and limited considerably the findings we reported

Mr. Farhat reports no disclosures. Dr. Olfson receives research
for the sensitivity analyses. Furthermore, we only employed as
support from the American Academy of Child & Adolescent Psy-
criterion measure the CGI-I posttreatment score. Although the
chiatry and the Alan B. Slifka Foundation through the Riva Ariella
CGI-I is typically employed to determine response to treatment in
Ritvo endowment. Ms. Levine reports no disclosures. Mr. Fenghua
clinical trials for pediatric TTM, it does not correspond to a clini-
reports no disclosures. Dr. Franklin reports no conflicts of interest.
cally meaningful response to treatment as defined by Jacobson and
Dr. Lee has received research grant from the Trichotillomania
Truax (1991). These authors developed a reliable change (RC)
Learning Center Research Foundation. Dr. Lewin has received
index that compares the individual’s change in scores from pre-
research grants from CDC, All Children’s Hospital, and Tourette
treatment to posttreatment with the distribution of the possible
Association of America. He also received an honorarium from
changes in scores from pretreatment to posttreatment if no change
Springer and has been awarded travel grants from the IOCDF
at all had occurred; an RC index higher than 1.96 is highly sug-
Scientific & Clinical Advisory Board. He is board of the board of
gestive ( p < 0.05) that the posttreatment score indeed represents a
directors from the American Board of Clinical Child & Adolescent
clinically significant change. Nevertheless, although the use of
Psychology. He is a consultant for Bracket LLC. Dr. McGuire has
CGI-I as a criterion measure does not consider this complex liter-
received research support from the Tourette Association of
ature on clinically meaningful response to treatment, we decided to
America, American Academy of Neurology, the Brain Research
employ it as the gold standard of response, given this is currently
Foundation, American Psychological Foundation, and the Hilda
the standard in clinical trials for TTM, including pediatric TTM.
and Preston Davis Foundation. He receives royalties from Elsevier,
Therefore, using the CGI-I as a criterion measure has important
and serves as a consultant for Bracket, Syneos, Health, and Lu-
practical considerations for previous, as well as future, clinical
minopia. Dr. Rahman reports receiving research support from
trials for pediatric TTM. Future research should investigate how
Neurocrine Biosciences, Roche, Otsuka, and Nuvelation, and
TTM severity instruments correspond to clinically meaningful
consulting fees from Bracket. Dr. Storch is a consultant for Levo
treatment response.
therapeutics. He receives research support from the National In-
stitute of Health, the Red Cross, ReBuild Texas, the Texas Higher
Conclusions Education Coordinating Board, and the Greater Houston Commu-
nity Foundation. He also reported receiving royalties from Elsevier
To conclude, our findings provide evidence-based optimal cut
Publications, John Wiley & Sons, Inc., American Psychological
points for the three most commonly used TTM severity instruments
Association, Springer, and Lawrence Erlbaum. Dr. Tolin reports no
to help guide clinicians and researchers for assessing treatment
disclosures. Dr. Zickgraf is funded by the T32MH082761-10
response in children and adolescents. We recommend that clinical
NIH/NIMH, Midwestern Regional Eating Disorders Training
trials for pediatric TTM determine response to treatment a priori as
Grant. Dr. Bloch is on the Scientific Advisory Board of Therapix
post hoc definitions of response are likely to inflate the results of the
Biosciences and receives research support from Biohaven Phar-
clinical trials, limiting the accuracy of their findings. Given our
maceuticals, Janssen Pharmaceuticals, Neurocrine Biosciences,
findings that these three instruments show similar, modest dis-
and Therapix Biosciences. Dr. Bloch also receives research support
criminative abilities to determine treatment response in pediatric
from the National Institute of Health, Tourette Association of
populations, an expert consensus is warranted to determine an
America, the Brain & Behavior Research Foundation (formerly
agreed-upon definition of response to treatment for pediatric TTM
NARSAD), and the Patterson Foundation.
clinical trials. Data from this meta-analysis, as well as from the
previous one performed by our group (Farhat et al. 2019) and others
(Houghton et al. 2015), should be considered in forming expert Supplementary Material
consensus recommendations. Further continued collaborative ef-
forts to validate rating scales for pediatric TTM particularly in Supplementary Figure S1
relation to symptom improvement are needed. Importantly, two of
the most commonly used hair pulling severity instruments, the References
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Address correspondence to:
Michael H. Bloch, MD, MS
Yale Child Study Center
PO Box 207900
New Haven, CT 06520
E-mail: michael.bloch@yale.edu