1. An Evidenced-Based Approach
Combined Pharmacotherapy and Psychotherapy for Anxiety Disorders:  Is Efficacy Enhanced?
An Evidenced-Based Approach
Heide Klumpp, Ph.D.

2. 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

3. 18-year-old Caucasian woman is a full-time freshman
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

4. Clinical questions: Does she meet DSM-IV criteria for Social Phobia?
What’s your Evidenced-Based Treatment plan?
1) Pharmacotherapy (e.g., SSRI, SNRI)?
2) Psychotherapy (e.g., cognitive-behavioral treatment)?
3) Combined therapy?

5. 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?

6. 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

7. 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)

8. 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

9. 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

10. Blomhoff, et al. (2001) cont. Pharmacotherapy:
Physicians 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

11. 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 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)

12. Blomhoff, et al. (2001) cont. Outcome after 24 weeks of treatment
N Response Partial Response Non-Response
Sertraline/exposure (45.5%) (23.9%) (30.7%)
Sertraline (40.2%) (28.7%) (31.0%)
Exposure/placebo (33.0%) (24.2%) (42.9%)
Placebo (23.9%) (20.5%) (55.7%)
Pairwise comparisons:
Sertraline/exposure 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

13. 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

14. 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 (10mg–60mg)
Placebo

15. 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)

16. Davidson, et al. (2004) cont. Pharmacotherapy:
Double-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

17. Davidson, et al. (2004) cont. Cognitive-behavioral 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

18. 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.

19. 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

20. 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

21. 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)

22. Rosser, et al. (2004) cont. CBT (n=84) CBT+AD (n=49) Pre Post Pre Post
FNE (5.0) (6.6) (3.3) (6.8)
SPS (14.5) (10.7) (15.6) (16.5)
Conclusion:
Pre-existing antidepressants did not significantly enhance or detract
from CBT

23. 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

24. 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

25. 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 Pt’s preference contribute to your treatment plan)?
If combining therapy, do you discontinue pharmacotherapy after
psychotherapy is discontinued (if so, when)?