2 PAGE JOURNAL ANALYSIS Paper
Mohammed Adel
nihms684112.pdf
An Open Trial of Emotion Regulation Therapy For Generalized Anxiety Disorder and Co-Occurring Depression
Douglas S. Mennin, Hunter College, City University of New York
David M. Fresco, Kent State University
Michael Ritter, and G.V. (Sonny) Montgomery VA Medical Center
Richard G. Heimberg Temple University
Abstract
Background—Although CBT is efficacious for a wide variety of psychiatric conditions, relatively fewer GAD patients achieve high endstate functioning as compared to patients receiving
CBTs for other disorders. Moreover, GAD trials that utilized patient samples without prominent
depression have tended to report that effect sizes for depressive outcomes were small or
diminished to pre-treatment levels in the follow-up period. Emotion Regulation Therapy (ERT)
integrates principles from traditional and contemporary cognitive behavioral treatments with basic
and translational findings from affect science to offer a blueprint for improving intervention by
focusing on motivational, regulatory, and contextual learning mechanisms.
Method—The purpose of this investigation was to provide initial support for the efficacy of ERT in an open trial of patients with GAD and co-occurring depressive symptoms. Twenty-one patients
received a 20-session version of ERT delivered in weekly individual sessions. Standardized
clinician ratings and self-report measures were assessed at pre-, mid-, and post-treatment as well
as at three- and nine-month follow-ups. Intent-to-treat analyzes were utilized.
Results—GAD patients, half with comorbid major depression, evidenced statistically and clinically meaningful improvements in symptom severity, impairment, quality of life, and in
model-related outcomes including emotional/motivational intensity, mindful attending/acceptance,
decentering, and cognitive reappraisal. Patients maintained gains across the three and nine month
follow-up periods.
Conclusions—These findings, although preliminary, provide additional evidence for the role of emotion dysregulation in the onset, maintenance, and now treatment of conditions such as GAD
and co-occurring depressive symptoms.
Correspondence regarding this manuscript can be directed to Douglas S. Mennin, Ph.D., Department of Psychology, Hunter College, 695 Park Avenue, HN611, New York, NY 10065, USA. Tel: 212-772-5567, [email protected].
Statement of Conflict of Interest or Financial Disclosures No author has any conflicts of interest.
HHS Public Access Author manuscript Depress Anxiety. Author manuscript; available in PMC 2016 August 01.
Published in final edited form as: Depress Anxiety. 2015 August ; 32(8): 614–623. doi:10.1002/da.22377.
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Keywords
Generalized Anxiety Disorder; Depression; Mindfulness/Meditation; Treatment; Clinical Trials; Behavior Therapy; Anxiety/Anxiety Disorders; Emotion Regulation
Although often viewed as a mild problem of the “worried well”1 and, subsequently, under-
investigated2, generalized anxiety disorder (GAD) is a actually a chronic and debilitating
condition that is associated with diminished impairment equivalent to major depressive
disorder (MDD3), poorer life quality than MDD when only non-comorbid cases are
compared between the two disorders4, and independent associations with negative functional
outcomes when both disorders are comorbid5. Despite the considerable burden it can cause,
GAD, and conceptually related conditions (e.g., MDD with anxious apprehensive features)
lag behind in treatment efficacy compared to other anxiety and mood disorders6, makes
otherwise efficacious interventions for MDD refractory7, and are associated with notable
difficulties in maintaining durability of comorbid MDD gains over the long term8.
Much of our understanding of the phenomena underlying GAD (i.e., anticipatory anxiety,
worry) has stemmed from the work of Borkovec9, who demonstrated that worry serves an
avoidance function or, as more recently explicated, that worry becomes reinforced by
increasing predictability of negative emotional experience, often at the cost of experiencing
positive and rewarding states (i.e., diminishing emotional contrasts10). A functional
perspective of worry has been supported in studies utilizing neurobiological11,
psychophysiological12–14, behavioral15, and self-report16–17 measurement. Further,
investigators have built on Borkovec’s perspective by emphasizing the role of maladaptive
cognitive (i.e., intolerance of uncertainty18; meta-worry19), emotional (i.e., non-
acceptance17; dysregulation16, 20), and interpersonal21, 22 processes in increasing worry.
These findings have advanced our understanding of GAD but have also resulted in
conceptual heterogeneity. Affect science may provide a comprehensive yet empirically
sound framework for integrating these findings, particularly in relation to compensatory
functions of worry and other destructive forms of self-referential mentation23. Elsewhere,
we have developed an emotion regulation theory that posits that dysfunction in distress
disorders such as GAD can best be understood by 1) motivational mechanisms, reflecting
the functional and directional properties of an emotional response tendency; (2) regulatory
mechanisms, reflecting the alteration of emotional response trajectories utilizing less and
more elaborative systems; and (3) contextual learning consequences, reflecting, optimally,
the promotion of broad and flexible behavioral repertoires. Thus, dysfunction in GAD can
be understood by a failure in each of these normative systems of functioning24.
Using this framework, GAD, especially when comorbid with MDD, can be seen as
characterized by subjective emotional intensity/distress20, reflecting greater temperamental
negative affect25–26 and activation of motivational systems that prize obtaining safety (from
perceived threat) over seeking reward27–29 [motivational mechanisms]. Subsequently, these
individuals may respond poorly to this motivational conflict, demonstrating deficits in
different systems of regulation30 encompassing attentional (e.g., attentional flexibility in
processing both interoceptive and exteroceptive emotional stimuli31–33, 11) and more
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cognitive elaborative strategies (e.g., meta-cognitive awareness, cognitive reappraisal34, 35).
Instead, individuals with GAD often resort to perseverative strategies (e.g., worry,
rumination, self-criticism) to compensate for an inability to manage distressing emotions
and motivations [regulatory mechanisms]. The net result of these regulatory failures is a
paradoxical maintenance of these negative states10 and reduced clarity in understanding and
optimally responding to them36. Indeed, worry results in increased threat conditionability,
greater stimulus generalization, and diminished ability to discriminate stimuli and learning
contingencies37–39 and GAD is associated with restrictions in valued actions and goals40.
Similarly, rumination is associated with decreases in the likelihood of new reward-based
learning, weakens instrumental action, and engagement of potentially rewarding social
networks41–43 [contextual learning consequences].
Emotion Regulation Therapy (ERT) was derived from this affect science perspective with
the goal of increasing motivational awareness, developing less and more elaborate
regulatory capacities, and engaging novel contexts to generate new learning repertoires.
ERT draws from traditional9, 44 and contemporary CBT45–48 as well as experiential
therapy49 to form an integrated, mechanism-targeted, CBT endeavoring to improve acute
and enduring treatment efficacy for GAD especially when comorbid with MDD. The present
study represents a preliminary examination of the efficacy of ERT utilizing an open trial
design. We hypothesized that ERT would diminish GAD and comorbid depressive
symptoms and produce durable gains in functioning/life quality as well as model-related
outcome measures including emotional intensity, mindful attention regulation (i.e.,
mindfulness, acceptance), and more elaborative meta-cognitive regulation (e.g., decentering,
reappraisal).
Method
Participants
Participants were 21 treatment-seeking individuals at two PhD training clinic sites in the
Northeastern United States (Site 1 was located in Philadelphia, PA, n = 11; Site 2 was
located in New Haven, CT, n = 10). Institutional Review Boards approved procedures for
the study at both sites and all patients offered informed consent. The Anxiety Disorders
Interview Schedule, Lifetime version for DSM-IV (ADIS50; site 1) and the Structured
Clinical Interview for DSM-IV (SCID51; site 2) are semi-structured diagnostic interviews
that were use to diagnosis GAD and other disorders. Interviewers at both sites were clinical
psychologists or doctoral students in clinical psychology trained according to the guidelines
of the ADIS or SCID. The intake clinician assessed for all Axis I disorders and provided a
rating of severity using the ADIS clinician severity rating (CSR). A score of 4 or greater
(range=0–8) is given for diagnoses that meet full DSM-IV criteria and are clinically
significant. GAD was expected to be primary or co-primary in all participants. In addition,
the GAD module was also administered prior to treatment by the independent assessor.
Diagnostic agreement (in diagnosis and CSR within 1 point; ADIS CSR was used at both
sites) was necessary for study inclusion.
Additional inclusion criteria consisted of being at least 18 years old; fluent in spoken and
written English; and willing and able to give informed written consent for the treatment
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protocol. Exclusion criteria consisted of a principal DSM-IV diagnosis other than or in
addition to GAD; prominent active suicidal ideation/intent; DSM-IV diagnosis of substance
abuse or dependence within the previous 6 months; a current DSM-IV diagnosis of organic
mental disorder; schizophrenia, psychotic disorder, bipolar I disorder, or dementia; an
unwillingness to terminate or suspend concurrent psychotherapy; and concurrent
psychotropic medication not stabilized for at least 3 months.
The sample was mostly women (n = 17), aged 35.25 (SD = 10.96), primarily Caucasian (n
=18) and well-educated (16 had at least a college education). Eleven patients were employed
full time with the remaining patients reporting working part-time (n = 2), being full-time
students (n = 5), or unemployed (n = 3). Median income for the sample was $40000 (Range
= $0 to $124000). Eleven patients had a concurrent MDD diagnosis. Sixteen patients had at
least one additional current diagnosis (Range: 1– 4) including obsessive compulsive disorder
(n = 2), panic disorder (n = 5), post-traumatic stress disorder (n = 2), social phobia (n = 6),
specific phobia (n = 2), dysthymic disorder (n = 1), eating disorder (n = 1), and an Axis II
diagnosis (n = 2). Four patients participated while receiving concurrent antidepressant
medication; four patients entered the trial receiving a benzodiazepine1. Twenty patients
completed the acute treatment phase of the trial and entered a no-treatment follow-up (three-
months & nine-months follow-up). The one patient who withdrew from the trial did so
following an emergent medical crisis unrelated to GAD or any other emotional difficulty.
Findings are based upon an intent-to-treat (ITT) analysis plan using data from all 21
patients. There were no demographic differences across the two sites, and no baseline
clinical and demographic differences associated with treatment response (analyses available
upon request). Thus, findings are aggregated across sites.
Treatment
ERT consisted of 20 weekly sessions of 60 minute duration except for Sessions 11–16
which lasted 90 minutes to accommodate exposure exercises. In the first half, sessions focus
on teaching emotion regulation strategies so that clients respond “counteractively” (instead
of “reactively”) via the utilization of mindful attending to somatic and emotional cues (i.e.,
attention regulation) and more verbally elaborate emotion regulation skills (i.e., meta-
cognitive regulation). In the second half of ERT, patients endeavor to become more
antecedent30 or “proactive” in their deployment of regulation skills by engaging contexts
that simultaneously invoke both elevated reward and threat motivations via in-session
exposure exercises and out-of-session exposure exercises conducted in the ensuing week. In
the final sessions, the focus shifts to consolidating gains and preparing for termination52, 53.
Measures
Patients completed both clinician-assessed and self-report measures of anxiety, depression,
worry, disability and quality of life as well as model-related outcome measures. The
assessment schedule of these measures was pre-treatment, mid-treatment, post-acute
1Outcome analyses reported below utilized the full sample. We reran analyses in either participants who did not have any medication usage (n=14) or who did not have anti-depressant medication usage (n=16). These analyses replicated the findings from the whole sample analyses. Thus, we report the whole sample analyses below.
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treatment, and three- and nine-month follow-up. Intake interviewers (pre-treatment) as well
as independent assessors (all time points) who were blind to particular details about the
patient (beyond receiving ERT) completed the clinician measures.
Clinician and Diagnostic Assessment
Independent assessors administered clinician and diagnostic assessments at all assessment
points including the ADIS CSR and a modified version of the Clinical Global Impression
Rating Scales (CGI54). Specifically, a version with anchor points developed specifically for
rating impairment and changes in symptoms associated with GAD was utilized. Clients
received a rating of 1 (very much improved) or 2 (much improved) were classified as
responders.
Self-report Symptom and Severity Measures
The Penn State Worry Questionnaire (PSWQ55) is a widely used 16-item measure of trait
worry. The Beck Depression Inventory-II (BDI–II56) is a 21-item self-report measure that
assesses the affective, cognitive, behavioral, and somatic symptoms of depression. The
Mood and Anxiety Symptom Questionnaire-Short Form (MASQ57) is a 62-item instrument
comprised of four subscales: General Distress Anxious Symptoms (GDA), General Distress
Depressive Symptoms (GDD), Anxious Arousal (AA), and Anhedonic Depression (AD).
The 7-item State-Trait Anxiety Inventory (STAI58, 59) is one of the most frequently used
measures of trait anxiety. The Sheehan Disability Scale (SDS60) is a commonly utilized
measure assessing impairment at work, in social relationships, and in responsibilities at
home and with family. The Quality of Life Inventory [QOLI61] assesses the degree to which
an individual is satisfied with 16 areas of his or her life (e.g., health, standard of living,
friendships, relationship with family, community, etc.)
Model-Related Outcome Measures
The 10-item Negative Intensity scale from the Affect Intensity Measure (AIM62) was used to
assess emotional intensity. The 11-item Decentering subscale of the Experiences
Questionnaire63 was used to assess the construct of decentering (i.e., the meta-cognitive
ability to observe items that arise in the mind with distance and perspective). The Difficulties
in Emotion Regulation Scale (DERS64) is a 36-item measure of the acceptance of emotions,
ability to engage in goal-directed behavior when distressed, impulse control, awareness of
emotions, access to strategies for regulation, and clarity of emotions. The Emotion
Regulation Questionnaire (ERQ65) is a 10-item rationally derived measure of two aspects of
emotion regulation: reappraisal and suppression. The Five Facet Mindfulness Questionnaire
(FFMQ66) is a 39-item self report measure assessing trait mindfulness.
Analysis Plan and Assessing Clinical Significance
For the purpose of statistical analysis, conceptually similar measures were grouped into
families of analyses: Diagnostic Outcomes, Self-Reported Anxiety Outcomes, Self-Reported
Depression Outcomes, Disability/Quality of Life Outcomes, and ERT Model-Related
Outcomes. A series of paired samples t-tests comparing Pre-Treatment to Mid-Treatment,
Post-Treatment, 3-Month Follow-up, and 9-Month Follow-up. Given multiple comparisons
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and to address the possibility of Type I errors, we utilized a Bonferroni correction for each
family of analysis, which resulted in only reporting significance if p-values were below .
0125 (.05/4) for Diagnostic Outcomes, .0125 (.05/4) for Self-Reported Anxiety outcomes, .
016 (.05/3) for Self-Reported Depression Outcomes, .025 (.05/2) for Disability/Quality of
Life outcomes, and .01 (.05/5) for Model-Related Outcomes. Further, Hedges’ g effect size
estimates of within-subject change are presented in Table 2. Like Cohen’s d67, Hedges’ g is
interpreted with conventions of Small = .20, Medium = .50, Large = .80.
Clinically significant improvement was also assessed in four ways (see Table 3). First,
simple clinical response was reflected in a CSR score less than 4, which reflects the
threshold for a full diagnosis (all current diagnoses including GAD and MDD) or a CGI-
Improvement (CGI-I) score less than 3 (only available for GAD). Two more stringent
indices of clinical significance were derived from procedures used by68 and69. Specifically,
patients were regarded as GAD responders by evidencing a clinically meaningful response
on at least 4 of the following 6 GAD indices: (GAD CSR < 4, CGI-I < 3, at least 30%
improvement on the PSWQ, STAI-7, MASQ-AA, & MASQ-GDA). Similarly, patients were
regarded as MDD responders if they evidenced a clinically meaningful response on at least 3
of 4 MDD indices (MDD CSR < 4,at least 30% improvement on the BDI-II, MASQ-AD, &
MASQ-GDD). Also, an index of high endstate functioning was derived by assessing
whether patients fell into the normative range (within one standard deviation of healthy
norms on published clinical measures69) on at least 4 of 6 GAD measures (GAD CSR, CGI-
I, PSWQ, STAI-7, MASQ-AA, & MASQ-GDA) and 3 of 4 MDD measures (MDD CSR,
BDI-II, MASQ-AD, & MASQ-GDD). These two measures of clinical significance yield
dichotomous scores (Responder = 1, Non-Responder = 0). Consistent with an ITT approach,
clinical significance during the acute treatment phase of the trial was assessed as a ratio of
the number of responders over the total number of patients enrolled in the acute phase (N =
21). In the follow-up phase, clinical significance was assessed based on the number of
completers at that time point as well as the total number of patients entering the no-treatment
follow-up phase (N = 20). Given that missing data were minimal in the follow-up period, a
last observation carried forward approach was employed by carrying forward post-acute
treatment data into the three month follow-up assessment point (n = 1) and carrying forward
three-month follow-up data into the nine-month follow-up assessment point (n = 3).
Results
Treatment Adherence
Treatment adherence ratings were completed by two independent raters who rated 25% of
the therapy recordings. Inter-rater agreement was derived by having raters concurrently code
40% of sessions being reviewed for adherence. Raters were instructed to code the frequency,
and degree of skillfulness evidenced by therapists. Raters also tallied the number of times
therapists broke protocol. High agreement was established for both frequency (90%) and
skillfulness (88%) ratings. In terms of treatment adherence, ERT therapists evidenced high
frequency (80% to 100%) and skillfulness (73% to 100%) of treatment component delivery.
Further, there were relatively few lapses into non-treatment components per session (0.1 to
1.6).
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Effects of treatment on diagnostic outcomes
See Tables 1 (means and standard deviations) and 2 (test statistics, significance levels, and
effect sizes). Findings demonstrated improvements from pre- to mid-treatment (g = 1.42) on
GAD CSR (other diagnoses were not assessed at mid-treatment). Diagnostic indices for all
anxiety and mood disorders significantly improved from pre-treatment to post-treatment and
the follow-up periods (g’s 0.52 to 3.90). For all measures, effect sizes approximate or
exceed conventions for a large effect size.
Effects of treatment on self-reported anxiety outcomes
See Tables 1 and 2. Findings reveal improvements by mid-treatment (g’s 0.71 to 0.98) with
additional gains by post-treatment (g’s 0.85 to 1.67). Relative to pre-treatment, gains in
anxiety outcomes were maintained at three-month follow-up (g’s 0.94 to 1.59) and nine-
month follow-up (g’s 1.04 to 1.77). For all measures, effect sizes approximate or exceed
conventions for a large effect size.
Effects of treatment on self-reported depression outcome2
See Tables 1 and 2. Findings reveal some improvement by mid-treatment for depression
outcomes (g’s = 0.35 to 0.82) with sizable gains by post-treatment for all measures (g’s =
0.76 to 1.25). Relative to pre-treatment, gains in depression outcomes were maintained at
three-month follow-up (g’s = 0.65 to 1.17) and nine-month follow-up (g’s = 0.93 to 1.35).
MDD CSR and MASQ-AD effect sizes exceed conventions for a medium effect size (Pre-
Post; Pre-three-month) and approach conventions for a large effect size (Pre to nine-month).
For all other measures, effect sizes estimates approximate or exceed conventions for a large
effect size at all time points.
Effects of treatment on disability/quality of life
As seen in Tables 1 and 2, findings reveal improvement by mid-treatment for the SDS (g =
0.45), but not the QOLI (g = −0.30) but sizable gains by post-treatment for both measures
(g’s= −0.90 to 0.94). Relative to pre-treatment, gains in disability and quality of life are
maintained at three-month follow-up (g’s = −.77 to .79) and nine-month follow-up (g’s =
−1.05 to 1.11). Effect sizes estimates for pre to post-treatment and the follow-up periods
approximate or exceed conventions for a large effect size at all remaining time points.
Effects of treatment on ERT model-related outcomes
Findings reveal no improvements by mid-treatment for candidate mechanism measures (g’s
= −0.23 to −0.75). However, at post-treatment, all measures show sizable improvements (g’s
= −0.61 to −1.32). Relative to pre-treatment, gains in all but one model-related outcome
(i.e., AIM Negative Intensity) were maintained at three-month follow-up (g’s = 0.25 to
−1.30). At nine-month follow-up, all measures remain measurably improved (including AIM
Negative Intensity) relative to pre-treatment (g’s = 0.65 to −1.32). Across time points, effect
2All outcome analyses were also conducted within the subgroup of patients diagnosed with MDD (n=11). Baseline mean (SDs) for this group were: GAD CSR = 6.00 (0.71), MDD CSR = 4.67 (1.00), BDI = 23 (7.96), MASQ-AD = 74.8 (13.89), MASQ-GDA = 31.2 (5.63). Anxiety, Depression, Disability/Quality of Life, and Model-Related Outcomes had comparable effect sizes to analyses conducted on the whole sample (Hedge's g's ranged from 1.53 to 3.93).
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sizes for model related outcomes exceed conventions for medium effects and in some
instances exceed conventions for large effect sizes.
Clinical Significance Analyses for GAD and MDD Outcomes
Open-label ERT was associated with impressive rates of clinician-assessed improvement
(CSR < 4, 81.0% or CGI-I < 3, 95.2%) with gains maintained or increased at three months
and nine months post-treatment (Range = 85% to 95%). Using a more stringent index where
patients must evidence at least 30% improvement on at least 4 or 6 clinician or self-report
GAD measures, a considerable majority of patients receiving open-label ERT also
evidenced strong gains following treatment (81%) with the gains maintained at three months
(90%) and nine months (90%). Finally, patients were assessed against whether their
treatment gains resulted in normalization on at least 4 of 6 clinician and self-report measures
(i.e., high endstate functioning). Findings indicated that 66.7% of patients achieved high
endstate functioning following treatment and that the percent increased at three months
(75.0%) and nine months (85.0%).
With respect to MDD improvement, patients receiving ERT evidence considerable gains.
For instance, nine of 11 patients entering the trial with comorbid MDD achieved a CSR
score of less than four by the end of treatment. Moreover, all 11 of these patients remained
or achieved subclinical on the MDD CSR at three months and nine months following the
end of treatment. Using a more stringent index where patients must evidence at least 30%
improvement on at least 3 of 4 clinician or self-report MDD measures, a majority of patients
with comorbid MDD (54.5%) evidenced clinical improvement with the rate increasing at
three months (90.0%) but diminishing somewhat at nine months (60.0%). Finally, 45.5% of
patients with comorbid MDD achieved high endstate functioning following treatment, and
the percentage increased at three months (70%) and nine months (80.0%).
Discussion
Findings from this open trial offer initial support for the efficacy of ERT in the treatment of
GAD. In this trial, GAD patients, half meeting MDD diagnostic criteria, evidenced
statistically and clinically meaningful improvements in symptom severity, impairment,
quality of life, and in model-related outcomes including emotional/motivational intensity,
mindful attending/acceptance, decentering, and cognitive reappraisal. Patients were then
followed for nine months, and treatment gains were maintained. These findings, although
preliminary, provide additional evidence for the role of emotion dysregulation (see52, 53) in
the onset, maintenance, and now treatment of conditions such as GAD with and without
MDD.
Until now, two overarching themes characterized the extant literature on CBT treatments for
GAD. First, although CBT is clearly efficacious, relatively fewer GAD patients achieve high
endstate functioning as compared to patients receiving CBTs formulated for other mood and
anxiety disorders6. Second, many of these trials utilized samples of GAD patients without
prominent MDD or depression68–70 and, in some instances, found that effect sizes for
depression outcomes were small or diminished to pre-treatment levels in the follow-up
period8. Similarly, non-CBT treatments such as mindfulness-based interventions consisting
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solely of meditative practice71–73 or bias modification programs74, 75, which may be seen as
requiring less effort to deliver, have shown some promise in reducing GAD severity but
often did not enroll GAD patients with prominent levels of depression72), restore patients to
high endstate functioning75, 76, or significantly resolve depression when it was present at
pre-treatment74, 75.
One possible explanation for these relatively inferior efficacy findings is that these
treatments are often targeting different components of a heterogenous condition. For
instance, traditional CBTs largely utilize more cognitively elaborative, verbally mediated,
techniques that are focused on cognitively elaborate deficits such as distorted beliefs. In
contrast, mindfulness-based meditative interventions and bias modification programs focally
target less elaborative, attentional, deficits without relying heavily on verbal, linguistically
mediated, exchange. Although speculative, greater efficacy may be achieved for GAD
(particularly when comorbid diagnoses or symptoms are present) by treatments that target
both more and less elaborative deficits. Elsewhere, we have argued that core intervention
principles that address both lesser and greater elaborative processes (i.e., simultaneously
increasing attentional flexibility, improving meta-cognitive processing, and promoting the
engagement of both threat and reward contexts) may be the conceptual framework that
underlies successful CBT interventions77. Indeed, recent CBT interventions have integrated
both less and more elaborate training components by synthesizing mindfulness and attention
training with traditional CBT techniques78–80, resulting in high endstate functioning which
is achieved and maintained through follow-up periods, while also sampling patients
evidencing prominent depression features at baseline78–80. Although open trial designs have
several weaknesses (e.g., lack of a control comparison, ability to address expectancy
effects), ERT provided notably high response rates and endstate functioning levels, utilized
a sample with prominent baseline depression, and produced large reductions in MDD
symptoms and severity that were maintained into the follow-up period. Further, model-
related outcomes that span less and more elaborative regulatory capacities (e.g., mindful
attention/acceptance, decentering, and reappraisal) were improved and maintained. The
magnitude of these findings matches or exceeds findings from the trials noted above.
However, a well-powered, randomized control design is necessary to corroborate the
significance of these findings for the efficacy of ERT. Further, despite these strong effects,
this trial utilized a 20-session version of ERT. It is unclear if this length is necessary and
cost-effective. We are currently testing 16 and 8 session versions to determine the proper
level of dosing for clinically significant effects.
An important next step, and one that aligns well with NIMH priorities (i.e., Research
Domain Criteria [RDoC]24) is to refine interventions so that treatment components are
comprehensive in addressing the scope of dysfunction in GAD but still targeted to specific
candidate mechanisms which comprise this condition. Such an approach is consistent with
the model posited within ERT where GAD, especially when it co-presents with MDD, is
marked by motivational/emotional intensity and a reliance on maladaptive less elaborative
(i.e., attentional) and more elaborative (i.e., meta-cognitive) emotion regulation strategies,
which result in suboptimal threat- and reward-related contextual learning. Many of these
characteristics were assessed and shown to improve and maintain in the follow-up period,
suggesting their consideration as candidate mechanisms of change. However, we make this
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claim with appropriate caution, given the preliminary nature of this trial, the small sample
size, and the reliance on self-report indices.
It will also be important to contextualize our hypothesized mechanisms within other
frameworks for emotional phenomena (e.g.,81–83) as well as more actively test how our
treatment aligns and is distinguished from treatments utilizing similar components
(e.g.,47, 48), especially given meta-analytic findings demonstrating that common elements
such as mindfulness have been shown to contribute to efficacy in a number of intervention
approaches (see84, 85). Future studies using a randomized control design, with a larger
sample size, an assessment schedule that accounts for alternative mechanisms as well as
temporal precedence of these mechanisms before symptomatic change, ideally while
assessing objective biobehavioral indices, are necessary before stronger mechanism claims
can be made. We are currently utilizing cognitive, behavioral, psychophysiological, and
neural indices of our proposed mechanisms to examine their relationship to clinical
outcomes. Despite these caveats, findings from this trial do support the preliminary efficacy
of ERT for GAD and co-occurring depressive symptoms and suggest that affect science may
provide a useful framework for integrating efficacious approaches to anxiety and depression.
Acknowledgments
This study was supported, in part, by NIMH Grant MH070682 (Heimberg, PI).
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D E
R S
= D
if fi
cu lt
ie s
in E
m ot
io n
R eg
ul at
io n
S ca
le ;
F F
M Q
= F
iv e
F ac
et M
in df
ul ne
ss Q
ue st
io nn
ai re
; E
R Q
= E
m ot
io n
R eg
ul at
io n
Q ue
st io
nn ai
re ;
E Q
= E
xp er
ie nc
es Q
ue st
io nn
ai re
; A
IM =
A ff
ec ti
ve I
nt en
si ty
S ca
le ;
* C
li ni
ci an
a ss
es sm
en t
no t
co nd
uc te
d at
M id
-T re
at m
en t;
P at
ie nt
s w
it ho
ut M
D D
c od
ed C
S R
= 0
Depress Anxiety. Author manuscript; available in PMC 2016 August 01.
A u th
o r M
a n u scrip
t A
u th
o r M
a n u scrip
t A
u th
o r M
a n u scrip
t A
u th
o r M
a n u scrip
t
Mennin et al. Page 16
T a b
le 2
t- st
at is
ti cs
a nd
H ed
ge ’s
g e
ff ec
t si
ze e
st im
at es
s ho
w in
g cl
in ic
al c
ha ng
e ov
er t
im e
P re
t o
M id
P re
t o
P os
t P
re t
o 3-
m o.
F ol
lo w
-u p
P re
t o
9- m
o. F
ol lo
w -u
p
t g
t g
t g
t g
D ia
g n o st
ic O
u tc
o m
es
G A
D C
S R
4. 39
* * *
1. 42
12 .0
6* * *
3. 90
9. 41
* * *
3. 39
10 .6
4* * *
3. 41
M D
D C
S R
* --
-- 2.
28 * *
0. 52
2. 80
* *
0. 63
3. 08
* *
0. 72
# A
nx ie
ty D
ia gn
os es
* --
-- 3.
16 * *
0. 84
3. 08
* *
0. 78
2. 91
* *
0. 91
# M
oo d
D ia
gn os
es *
-- --
3. 93
* *
1. 12
4. 36
* * *
1. 36
4. 32
* * *
1. 36
S el
f- R
ep o rt
ed A
n xi
et y
O u tc
o m
es
P S
W Q
5. 24
* * *
0. 83
7. 02
* * *
1. 40
6. 46
* * *
1. 50
5. 90
* * *
1. 77
S T
A I-
7 6.
47 * * *
1. 09
9. 19
* * *
1. 67
5. 45
* * *
1. 56
6. 56
* * *
1. 58
M A
S Q
-A A
2. 45
0. 71
3. 26
* *
0. 85
3. 00
* *
0. 94
2. 34
1. 04
M A
S Q
-G D
A 3.
30 * *
0. 98
7. 28
* * *
1. 79
5. 96
* * *
1. 59
3. 88
* * *
1. 49
S el
f- R
ep o rt
ed D
ep re
ss io
n O
u tc
o m
es
B D
I- II
5. 28
* * *
0. 82
6. 04
* * *
1. 25
4. 83
* * *
1. 17
5. 21
* * *
1. 35
M A
S Q
-A D
1. 69
0. 35
3. 53
* *
0. 76
3. 07
* *
0. 65
3. 19
* *
0. 93
M A
S Q
-G D
D 2.
60 0.
52 5.
85 * * *
1. 07
4. 36
* * *
0. 77
3. 00
* *
1. 10
D is
a b il
it y/
Q u a li
ty o
f L
if e
O u tc
o m
es
S he
eh an
D is
ab il
it y
S ca
le 2.
43 *
0. 45
4. 09
* * *
0. 94
4. 18
* * *
0. 79
3. 22
* *
1. 11
Q O
L I
− 1.
70 −
0. 30
6. 03
* * *
− 0.
90 3.
22 * *
− 0.
77 4.
03 * * *
− 1.
05
M o d el
R el
a te
d O
u tc
o m
es
D E
R S
T ot
al 1.
55 0.
37 3.
45 * *
1. 00
3. 05
* *
0. 72
3. 98
* * *
1. 00
F F
M Q
T ot
al −
1. 16
− 0.
23 −
3. 13
* *
− 0.
61 −
2. 23
− 0.
32 3.
12 * *
− 0.
73
E Q
-D ec
en te
ri ng
− 1.
97 −
0. 42
− 5.
26 * * *
− 1.
30 −
4. 48
* * *
− 1.
00 5.
18 * * *
− 1.
32
E R
Q -R
ea pp
ra is
al −
2. 02
− 0.
75 −
4. 26
* *
− 1.
32 −
2. 85
* *
− 1.
30 2.
93 * *
− 1.
04
A IM
-N eg
at iv
e In
te ns
it y
0. 47
− 0.
07 3.
29 * *
0. 66
1. 42
0. 25
3. 48
* *
0. 63
N ot
e. G
A D
= ge
ne ra
li ze
d an
xi et
y di
so rd
er , C
S R
= C
li ni
ci an
’s S
ev er
it y
R at
in g
fr om
t he
A nx
ie ty
D is
or de
rs I
nt er
vi ew
S ch
ed ul
e fo
r D
S M
-I V
, L if
et im
e V
er si
on ;
C G
I= C
li ni
ca l
G lo
ba l
Im pr
es si
on ;
P S
W Q
= P
en n
S ta
te W
or ry
Q ue
st io
nn ai
re ;
S T
A I=
S ta
te T
ra it
A nx
ie ty
I nv
en to
ry ;
M A
S Q
= M
oo d
an d
A nx
ie ty
S ym
pt om
Q ue
st io
nn ai
re ;
A A
= A
nx io
us A
ro us
al ;
G D
A =
G en
er al
D is
tr es
s A
nx io
us ne
ss ;
M D
D =
M aj
or
Depress Anxiety. Author manuscript; available in PMC 2016 August 01.
A u th
o r M
a n u scrip
t A
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o r M
a n u scrip
t A
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o r M
a n u scrip
t A
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o r M
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t
Mennin et al. Page 17 D
ep re
ss iv
e D
is or
de r;
B D
I- II
= B
ec k
D ep
re ss
io n
In ve
nt or
y- II
; Q
O L
I= Q
ua li
ty o
f L
if e
In ve
nt or
y; A
D =
A nh
ed on
ic D
ep re
ss io
n; G
D D
= G
en er
al D
is tr
es s
D ep
re ss
io n;
Q O
L I=
Q ua
li ty
o f
L if
e In
ve nt
or y;
D
E R
S =
D if
fi cu
lt ie
s in
E m
ot io
n R
eg ul
at io
n S
ca le
; F
F M
Q =
F iv
e F
ac et
M in
df ul
ne ss
Q ue
st io
nn ai
re ;
E R
Q =
E m
ot io
n R
eg ul
at io
n Q
ue st
io nn
ai re
; E
Q =
E xp
er ie
nc es
Q ue
st io
nn ai
re ;
A IM
= A
ff ec
ti ve
I nt
en si
ty S
ca le
;
* p <
.0 5;
* * p <
.0 1;
* * * p <
.0 01
;
A ll
H ed
ge ’s
g ’s
c om
pu te
d as
I T
T /I
T F
( n =
2 1)
Depress Anxiety. Author manuscript; available in PMC 2016 August 01.
A u th
o r M
a n u scrip
t A
u th
o r M
a n u scrip
t A
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o r M
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t A
u th
o r M
a n u scrip
t
Mennin et al. Page 18
Table 3
Number of treatment responders (and % ITT sample size) using conventional indices of clinical significance
Post-Acute Treatment # Responders
(% ITT)
3-Month Follow-up # Responders
(% ITF)
9-Month Follow-up # Responders
(% ITF)
GAD Clinical Response
ADIS GAD CSR < 4 17/21 (81.0%) 17/20 (85.0%) 18/20 (90.0%)
CGI-Improvement < 3 20/21 (95.2%) 19/20 (95.0%) 19/20 (95.0%)
30% Improvement (4+ of 6 Criteria Met) 17/21 (81.0%) 18/20 (90.0%) 18/20 (90.0%)
High Endstate Functioning (4+ of 6 Criteria Met) 14/21 (66.7%) 15/20 (75.0%) 17/20 (85.0%)
MDD Clinical Response
ADIS MDD CSR < 4 9/11 (82.0%) 10/10 (100%) 10/10 (100%)
30% Improvement (3+ of 4 Criteria Met) 6/11 (54.5%) 9/10 (90.0%) 6/10 (60.0%)
High Endstate Functioning (3+ of 4 Criteria Met) 5/11 (45.5%) 7/10 (70.0%) 8/10 (80.0%)
Note. All findings based upon ITT analyses at post-acute (N = 21) and ITF in the no-treatment follow-up periods (N = 20)
Depress Anxiety. Author manuscript; available in PMC 2016 August 01.
