A Double-Blind Randomized Controlled Trial of Augmentation and Switch Strategies for Refractory Social Anxiety Disorder
Abstract
Objective
Method
Results
Conclusions
Method
Participants
Characteristic | Sertraline Plus Clonazepam (N=63) | Sertraline Plus Placebo (N=59) | Venlafaxine (N=59) | |||
---|---|---|---|---|---|---|
Mean | SD | Mean | SD | Mean | SD | |
Age (years) | 34.8 | 12.3 | 35.3 | 14.3 | 33.7 | 12 |
N | % | N | % | N | % | |
Site | ||||||
Massachusetts General Hospital | 21 | 33 | 19 | 32 | 19 | 32 |
University of California, San Diego | 16 | 25 | 15 | 25 | 15 | 25 |
McMaster University | 26 | 41 | 25 | 42 | 25 | 42 |
Male | 38 | 60 | 39 | 66 | 38 | 64 |
Female | 25 | 40 | 20 | 34 | 21 | 36 |
Race | ||||||
Asian | 8 | 13 | 10 | 17 | 3 | 5 |
Black/African American | 4 | 6 | 1 | 2 | 3 | 5 |
White | 50 | 79 | 44 | 75 | 48 | 81 |
Other | 1 | 2 | 4 | 7 | 5 | 8 |
Ethnicity | ||||||
Hispanic | 3 | 5 | 5 | 8 | 3 | 5 |
Non-Hispanic | 60 | 95 | 54 | 92 | 56 | 95 |
Week 10 social anxiety disorder severity (Liebowitz Social Anxiety Scale) | ||||||
Total score ≤70 | 28 | 40 | 27 | 46 | 26 | 44 |
Total score >70 | 35 | 56 | 32 | 54 | 33 | 56 |
Phase 1 instructions received | ||||||
Exposure | 38 | 60 | 26 | 44 | 29 | 49 |
Neutral | 25 | 40 | 33 | 56 | 30 | 51 |
Study completion status | ||||||
Discontinued early | 6 | 10 | 9 | 15 | 12 | 20 |
Completed | 57 | 90 | 50 | 85 | 47 | 80 |
History of psychotropic use | 28 | 44 | 31 | 53 | 25 | 42 |
Comorbidity | ||||||
Major depressive disorder | ||||||
Current (past 2 weeks) | 11 | 17 | 15 | 25 | 12 | 42 |
Lifetime | 33 | 52 | 28 | 47 | 30 | 51 |
Other anxiety disorder | ||||||
Current | 26 | 41 | 24 | 41 | 19 | 32 |
Lifetime | 28 | 44 | 25 | 42 | 19 | 32 |
Panic disorder | ||||||
Current | 7 | 11 | 3 | 5 | 7 | 12 |
Lifetime | 9 | 14 | 5 | 8 | 7 | 12 |
Generalized anxiety disorder | ||||||
Current (past 6 months) | 23 | 37 | 21 | 36 | 16 | 27 |
Lifetime | 23 | 37 | 21 | 36 | 16 | 37 |
OCD | ||||||
Current (past 6 months) | 6 | 10 | 7 | 12 | 4 | 7 |
Lifetime | 7 | 11 | 7 | 12 | 4 | 7 |
PTSD | ||||||
Current | 1 | 2 | 4 | 7 | 0 | 0 |
Lifetime | 2 | 3 | 4 | 7 | 1 | 2 |
Adult ADHD | ||||||
Current (past 6 months) | 2 | 3 | 5 | 8 | 3 | 5 |
Lifetime | 2 | 3 | 5 | 8 | 3 | 5 |
Any lifetime eating disordera | 0 | 0 | 1 | 2 | 1 | 2 |
Lifetime alcohol abuse or dependencea | 3 | 5 | 7 | 12 | 10 | 17 |
Lifetime drug abuse or dependencea | 5 | 8 | 3 | 5 | 6 | 10 |
Study Design and Procedures
Measures
Clinician-rated instruments.
Self-report questionnaires.
Statistical Methods
Results
Overview
Remission
Change in LSAS Score
Comparison Outcomea | Sertraline Plus Clonazepam (N=63) | Sertraline Plus Placebo (N=59) | Venlafaxine (N=59) | Analysis | ||||||
---|---|---|---|---|---|---|---|---|---|---|
N | % | N | % | N | % | β Estimate | SE | χ2 (df=1) | p | |
Remission (LSAS≤30) | 17 | 27 | 10 | 17 | 11 | 19 | ||||
Sertraline+clonazepam and sertraline+placebo | 0.62 | 0.47 | 1.74 | 0.19 | ||||||
Venlafaxine and sertraline+placebo | 0.32 | 0.51 | 0.41 | 0.52 | ||||||
Sertraline+clonazepam and venlafaxine | 0.30 | 0.47 | 0.40 | 0.53 | ||||||
Response (LSAS≤50) | 35 | 56 | 21 | 36 | 27 | 46 | ||||
Sertraline+clonazepam and sertraline+placebo | 0.93 | 0.42 | 4.91 | 0.029b | ||||||
Venlafaxine and sertraline+placebo | 0.70 | 0.43 | 2.67 | 0.10 | ||||||
Sertraline+clonazepam and venlafaxine | 0.23 | 0.41 | 0.30 | 0.58 | ||||||
Mean | SD | Mean | SD | Mean | SD | β Estimate | SE | t (df=1) | p | |
Change in LSAS Score | –26.5 | 24.4 | –16.5 | 23.0 | 17.6 | 19.1 | ||||
From week 10 to last visit (intention to treat) | ||||||||||
Sertraline+clonazepam and sertraline+placebo | –8.78 | 3.75 | –2.34 | 0.020b | ||||||
Venlafaxine and sertraline+placebo | –2.14 | 3.81 | –0.56 | 0.57 | ||||||
Sertraline+clonazepam and venlafaxine | –6.64 | 3.77 | –1.76 | 0.080 | ||||||
From week 10 to week 22 (completers) | –28.5 | 24.2 | –19.6 | 22.4 | –21.7 | 19.0 | ||||
Sertraline+clonazepam and sertraline+placebo | –9.16 | 4.16 | –2.20 | 0.029b | ||||||
Venlafaxine and sertraline+placebo | –2.34 | 4.38 | –0.53 | 0.59 | ||||||
Sertraline+clonazepam and venlafaxine | –6.82 | 4.24 | –1.61 | 0.11 |
Response
Dosing and Treatment Tolerability
Secondary Outcomes
Measure and Comparisona | Sertraline Plus Clonazepam (N=63) | Sertraline Plus Placebo (N=59) | Venlafaxine (N=59) | Analysis | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Mean | SD | Mean | SD | Mean | SD | β Estimate | SE | t (df=1) | p | |
CGI-I Score (R2=0.19) | ||||||||||
Last visit | 2.2 | 1.1 | 2.5 | 1.2 | 2.3 | 1.2 | ||||
Sertraline+clonazepam and sertraline+placebo | –0.24 | 0.19 | –1.22 | 0.23 | ||||||
Venlafaxine and sertraline+placebo | –0.25 | 0.20 | 1.26 | 0.21 | ||||||
Sertraline+clonazepam and venlafaxine | 0.013 | 0.07 | 0.07 | 0.95 | ||||||
MADRS total score (R2=0.066) | ||||||||||
Week 10 | 8.7 | 6.6 | 7.0 | 6.0 | 8.3 | 7.5 | ||||
Last visit | 6.7 | 5.7 | 6.3 | 7.0 | 6.7 | 6.7 | ||||
Change | –2.1 | 5.9 | –0.8 | 5.1 | –1.6 | 4.5 | ||||
Sertraline+clonazepam and sertraline+placebo | –1.27 | 0.93 | –1.37 | 0.17 | ||||||
Venlafaxine and sertraline+placebo | –0.88 | 0.95 | –0.91 | 0.37 | ||||||
Sertraline+clonazepam and venlafaxine | –0.42 | 0.93 | –0.44 | 0.66 | ||||||
SDS total score (R2=0.18) | ||||||||||
Week 10 | 14.2 | 5.7 | 11.5 | 5.8 | 14.0 | 6.1 | ||||
Last visit | 10.0 | 6.1 | 10.1 | 6.8 | 11.1 | 6.8 | ||||
Change | –4.3 | 5.5 | –1.4 | 5.2 | –2.9 | 4.4 | ||||
Sertraline+clonazepam and sertraline+placebo | –2.62 | 0.86 | –3.03 | 0.0028b | ||||||
Venlafaxine and sertraline+placebo | –1.69 | 0.88 | –1.91 | 0.058 | ||||||
Sertraline+clonazepam and venlafaxine | –0.93 | 0.88 | –1.07 | 0.29 | ||||||
HAM-A total (R2=0.051) | ||||||||||
Week 10 | 10.2 | 5.4 | 10.3 | 6.9 | 9.8 | 6.6 | ||||
Last visit | 7.9 | 5.5 | 9.0 | 6.7 | 8.3 | 5.1 | ||||
Change | –2.3 | 5.3 | –1.3 | 5.8 | –1.5 | 5.0 | ||||
Sertraline+clonazepam and sertraline+placebo | –0.88 | 0.97 | –0.91 | 0.36 | ||||||
Venlafaxine and sertraline+placebo | –0.19 | 0.98 | –0.19 | 0.85 | ||||||
Sertraline+clonazepam and venlafaxine | –0.70 | 0.97 | –0.72 | 0.48 | ||||||
Q-LES-Q total (R2=0.11) | ||||||||||
Week 10 | 47.1 | 8.0 | 47.9 | 8.0 | 45.9 | 8.5 | ||||
Last visit | 49.9 | 8.2 | 50.1 | 8.9 | 48.1 | 8.4 | ||||
Change | 2.8 | 6.5 | 2.2 | 5.4 | 2.2 | 5.2 | ||||
Sertraline+clonazepam and sertraline+placebo | 0.40 | 1.01 | 0.40 | 0.69 | ||||||
Venlafaxine and sertraline+placebo | 0.16 | 1.02 | 0.15 | 0.88 | ||||||
Sertraline+clonazepam and venlafaxine | 0.24 | 1.01 | 0.24 | 0.81 |
Discussion
Acknowledgments
Footnote
Supplementary Material
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