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

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

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

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?

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?

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

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)

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

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

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

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)

Blomhoff, et al. (2001) cont. Outcome after 24 weeks of treatment N Response Partial Response Non-Response   Sertraline/exposure 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/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

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

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

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)

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

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

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.

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

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

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)

Rosser, et al. (2004) cont. CBT (n=84) CBT+AD (n=49) 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

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

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

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)?