Combined Pharmacotherapy and Psychotherapy for Anxiety Disorders: Is Efficacy Enhanced

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Combined Pharmacotherapy and Psychotherapy for
Anxiety Disorders  Is Efficacy Enhanced? An
Evidenced-Based Approach Heide Klumpp, Ph.D.
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Components of Evidence-Based Treatment
include Chambless and Hollon (1998)
Comparison with a no-treatment control group,
alternative treatment group, or placebo in a
randomized control trial or equivalent
time-samples design Study must have been
conducted with a) Treatment manual b)
Population, treated for specified problems c)
Reliable/valid outcome assessment measures d)
Appropriate data analysis
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Clinical scenario
18-year-old Caucasian woman is a full-time
freshman Born and raised in
a small Southern town
During interview, she describes herself as a shy
person but denies anxiety
ever interfered with her life until she
began college
Fears include speaking in class, going to
parties, talking to strangers
Symptoms include shaking, blushing, racing
heart, sweating She copes
with anxiety by avoiding situations
Family hx Father hx Panic Disorder
Older brother hx
Generalized Anxiety Disorder B/c of
family hx, she believes she has a chemical
imbalance in her brain
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Clinical questions
Does she meet DSM-IV criteria for Social
Phobia? Whats your Evidenced-Based Treatment
plan? 1) Pharmacotherapy (e.g., SSRI,
SNRI)? 2) Psychotherapy (e.g.,
cognitive-behavioral treatment)?
3) Combined therapy?
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Rationale for combined therapy
Medication may correct any underlying biological
abnormality CBT may correct maladaptive
cognitions or behavior Neither medication nor
CBT helps everyone so why not combine treatments
to maximize potential benefits?
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Sources for evidence regarding combined therapy
Literature search for databases (e.g., Medline,
PsycINFO) using keywords (e.g., anxiety and
disorder and social and phobia and
combined or pharmacotherapy or
psychotherapy) Results consisted of
Articles comparing treatment approaches
Provides details of research methods and
analysis - Difficult to
compare results across different studies
Meta-analytic studies
Synthesizes research by transforming results from
diff. studies into
a common metric (effect size)
- No gold standard exclusionary criteria my
bias conclusions
Literature reviews Allows
for gross comparison of different studies
- Exclusionary criteria may bias
conclusions
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Efficacy of combined pharmacotherapy and
psychotherapy for Social Phobia
Blomhoff, Haug, Hellström, Holme, Madsbu, et al.
(2001) Davidson, Foa, Huppert, Keefe,
Franklin, et al. (2004) Prasko, et al. (2006)
from Literature Review by Pull (2007) Rosser,
Erskine, and Crino (2004) Included in a
Literature Review by Black (2006) who excluded
studies that did not use rigorous criteria (p.
31) (e.g., random assignment, blind assessments,
adequate methods)
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Blomhoff, et al. (2001) Recruitment 61 of
patients recruited from physicians clinical
practices and the remainder from advertisements
387 patients with SP randomly assigned
to   Exposure therapy sertraline Exposure
therapy Sertraline (50mg-150mg) Placebo
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Blomhoff, et al. (2001) cont. Primary outcome
measure Clinician rated Clinic Global
Impression Inventory-Social Phobia Scale
(CGII-SPS) Patient rated
CGII-SPS Response defined as 1) Overall
severity score at final visit in the no mental
illness to mild severity range
2) Patient rated symptom reduction of at least
50 Week 16 44 did not respond and were
withdrawn from study 36 dropped out
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Blomhoff, et al. (2001) cont. Pharmacotherapy P
hysicians were blind to sertraline v. placebo
condition 1-wk single-blind placebo period to
identify fast placebo responders Pts received
either sertraline 50 mg or placebo daily If
CGII-SP overall improvement score not rated at
least min. improved after 4 weeks, dose increased
to 100 mg. Further escalations were allowed
after 8 and 12 weeks to max does of 150mg Dose
level achieved after 12 wks of treatment was
maintained for remainder of study
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Blomhoff, et al. (2001) Exposure therapy
Conducted by 47 Primary care physicians who
completed a 30-hr training program over
three weekends Instructions for ET provided in 8
sessions during the first 12 weeks of treatment
(duration about 15-20 min/wk) All patients
received homework (e.g., monitoring
exposure-based symptoms) Pts told to continue
exposures in the last 12 weeks of the
study Further encouragement and advice were
given at the Week 16 visit (p. 24)
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Blomhoff, et al. (2001) cont. Outcome after 24
weeks of treatment N Response
Partial Response Non-Response   Sertraline/expo
sure 88 40 (45.5) 21 (23.9)
27 (30.7) Sertraline 87 35 (40.2)
25 (28.7) 27 (31.0)
Exposure/placebo 91 30 (33.0) 22
(24.2) 39 (42.9) Placebo
88 21 (23.9) 18 (20.5)
49 (55.7) Pairwise comparisons Sertraline/expo
sure v. exposure p.06 Sertraline/exposure v.
sertraline p.64 Conclusions Combined exposure
treatment sertraline was more effective than
placebo but not more effective that just
exposure therapy or sertraline
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Blomhoff, et al. (2001) cont. Points to
consider Almost half of patients were recruited
by advertisement (selective sample) Physicians
were not blind to exposure treatment did not
have extensive training for exposure
therapy Independent raters not used for outcome
measures Not certain if type of treatment
interacted with non-responders or those who
withdrew from study
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Davidson, et al. (2004) Recruitment two
outpatient programs at medical centers 295
patients with SP were randomly assigned to
  CBT fluoxetine CBT placebo
CBT Fluoxetine (10mg60mg) Placebo
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Davidson, et al. (2004) cont. Response primarily
via Clinical Global Impressions Improvement
(CGII) Score of 1 (very much improved)
or 2 (much improved) Other outcome measure
Brief Social Phobia Scale
Social Phobia and Anxiety Inventory Primary
outcome assessments by blinded independent
evaluator 211 completed treatment 68 dropped out
(no differences among treatment conditions)
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Davidson, et al. (2004) cont. Pharmacotherapy D
ouble-blind administration Fluoxetine started at
10 mg/d, increasing on Day 8 to 20 mg/d Day 15
to 30mg/d Day 29 to 40 mg/d Goal was for Pts to
reach 40 mg/d At Days 43 and 57, dose was raised
to 50 mg/d and 60 mg/d, respectively, if Pts
failed to achieve CGI Improvement score of 1 or
2
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Davidson, et al. (2004) cont. Cognitive-behavior
al treatment 14-wk group treatment that
combines in vivo exposure, cognitive
restructuring, and social skills
training Conducted by 2 therapists (1 male, 1
female) who received extensive training Each
group consisted of 5-6 patients
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Davidson, et al. (2004) cont.
At week 4, patients in the Fluoxetine group
showed enhanced response to treatment compared to
the other groups. However, this effect went away
by Week 8 and Week 14. By Week 14, patients in
any of the treatment groups had better response
compared to placebo group.
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Davidson, et al. (2004) cont. Points to
consider Group treatment may have excluded some
people from participating Investigators
question whether fluoxetine was most appropriate
drug Patients with major depression excluded
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Prasko, et al. (2006) from Literature Review by
Pull (2007) 66 patients with SP were randomly
assigned to   CBT moclobemide
CBT Moclobemide Placebo Treatment 24 weeks
After 3 mo., CBT moclobemide showed most
rapid response Moclobemide reduced
self-reported anxiety but not avoidant behavior
CBT reduced avoidant behavior but reduction
of self-reported general anxiety occurred
later Relapse rate during 24-mon follow-up was
lower in CBT group than moclobemide alone
group
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Rosser, et al. (2004) Recruitment 133
participants from Cognitive behavioral treatment
program at an Anxiety Disorders Clinic at a
hospital 49 reported taking antidepressants (by
PCP or psychiatrist) at the time of
treatment (CBT AD) group 84 denied taking
antidepressants (CBT) group Psychotherapy 40 h
of group-based treatment over 7-week
period Conducted by psychologist or psychiatrist
extensively trained in use of CBT Outcomes
measures included Fear of Negative
Evaluation Scale (FNE) Social Phobia Scale
(SPS)
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Rosser, et al. (2004) cont.
CBT (n84)
CBTAD (n49) Pre
Post Pre
Post FNE 22.9 (5.0) 19.0 (6.6)
24.4 (3.3) 19.6 (6.8) SPS
33.7 (14.5) 21.2 (10.7)
36.5 (15.6) 23.6 (16.5)

Conclusion Pre-existing antidepressants did not
significantly enhance or detract from CBT
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Rosser, et al. (2004) cont. Points to
consider No experimental design No uniformity
in medications and doses Use of antidepressants
was self-report Outcome measure were
self-report Group therapy may have excluded
some participants
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Summary
Relatively few studies have examined combined
pharmacotherapy psychotherapy to monotherapy in
social phobia Empirical support for combined
treatment is limited Conclusions are limited to
the type of medication and psychotherapy used in
studies
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Questions regarding clinical scenario
Should you combine pharmacotherapy and
psychotherapy? Are there potential deleterious
effects in combining treatments? What factors
will help you make a decision (e.g., to what
extent does Pts preference contribute to your
treatment plan)? If combining therapy, do you
discontinue pharmacotherapy after psychotherapy
is discontinued (if so, when)?