Pharmacotherapy for social anxiety disorder

Dan J Stein; Jonathan C Ipser; Anton J van Balkom

doi:10.1002/14651858.CD001206.pub2

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Figure 1

CGI‐I funnel plot.

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Analysis 1.1

Comparison 1 Medication vs Placebo: Global and SP symptoms, Outcome 1 Global Impressions scale change item (CGI‐I) (or similar scale) non‐response.

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Analysis 1.2

Comparison 1 Medication vs Placebo: Global and SP symptoms, Outcome 2 Clinical Global Impressions scale severity item (CGI‐S).

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Analysis 1.3

Comparison 1 Medication vs Placebo: Global and SP symptoms, Outcome 3 Other SP Symptom Severity Scale.

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Analysis 1.4

Comparison 1 Medication vs Placebo: Global and SP symptoms, Outcome 4 Clinician‐rated: Liebowitz Social Anxiety Scale (LSAS): Fear.

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Analysis 1.5

Comparison 1 Medication vs Placebo: Global and SP symptoms, Outcome 5 Clinician‐rated: Liebowitz Social Anxiety Scale (LSAS): Avoidance.

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Analysis 1.6

Comparison 1 Medication vs Placebo: Global and SP symptoms, Outcome 6 Clinician‐rated: Liebowitz Social Anxiety Scale (LSAS): Total.

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Analysis 2.1

Comparison 2 Medication vs Placebo: Comorbid symptoms, Outcome 1 Depression Scale.

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Analysis 3.1

Comparison 3 Medication vs Placebo: Disability (Sheehan Disability Scale), Outcome 1 Work subscale.

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Analysis 3.2

Comparison 3 Medication vs Placebo: Disability (Sheehan Disability Scale), Outcome 2 Social subscale.

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Analysis 3.3

Comparison 3 Medication vs Placebo: Disability (Sheehan Disability Scale), Outcome 3 Family subscale.

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Analysis 4.1

Comparison 4 Medication vs Placebo: Drop‐out Rate, Outcome 1 Drop‐out Rate.

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Analysis 5.1

Comparison 5 Medication vs Placebo: Performance anxiety, Outcome 1 Performance anxiety scale.

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Analysis 6.1

Comparison 6 Medication vs Placebo: Maintenance studies, Outcome 1 Clinical Global Impressions scale change item (CGI‐I) non‐response.

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Analysis 6.3

Comparison 6 Medication vs Placebo: Maintenance studies, Outcome 3 Drop‐out Rate.

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Analysis 7.1

Comparison 7 Medication vs Placebo: Relapse Prevention, Outcome 1 Relapse rate.

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Analysis 8.2

Comparison 8 Subgroup analysis: Multi vs single centre, Outcome 2 Global Impressions scale change item (CGI‐I) (or similar scale) non‐response.

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Analysis 9.1

Comparison 9 Subgroup analysis: Generalized vs inclusive SP, Outcome 1 Clinical Global Impressions ‐ Improvement (CGI‐I or similar) scale.

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Comparison 1. Medication vs Placebo: Global and SP symptoms

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global Impressions scale change item (CGI‐I) (or similar scale) non‐response Show forest plot	26	3696	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.57, 0.73]

1.1 Moclobemide	5	1063	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.80, 0.98]
1.2 Brofaromine	2	177	Risk Ratio (M‐H, Random, 95% CI)	0.44 [0.20, 0.97]
1.3 SSRI	11	2031	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.59, 0.76]
1.4 MAOI	3	173	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.24, 0.76]
1.5 Other medication	5	252	Risk Ratio (M‐H, Random, 95% CI)	0.47 [0.26, 0.87]
2 Clinical Global Impressions scale severity item (CGI‐S) Show forest plot	11	1641	Mean Difference (IV, Random, 95% CI)	‐1.02 [‐1.52, ‐0.51]

2.1 SSRIs	2	582	Mean Difference (IV, Random, 95% CI)	‐0.43 [‐0.63, ‐0.23]
2.2 SSRIs ‐ difference scores	1	203	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐1.31, ‐0.31]
2.3 MAOIs	3	156	Mean Difference (IV, Random, 95% CI)	‐1.46 [‐2.53, ‐0.39]
2.4 RIMAs	3	565	Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.65, 0.02]
2.5 Other medication	2	135	Mean Difference (IV, Random, 95% CI)	‐2.19 [‐4.17, ‐0.21]
3 Other SP Symptom Severity Scale Show forest plot	12	1143	Std. Mean Difference (IV, Random, 95% CI)	‐0.80 [‐1.16, ‐0.43]

3.1 SSRIs	4	655	Std. Mean Difference (IV, Random, 95% CI)	‐0.44 [‐0.79, ‐0.08]
3.3 MAOIs	2	96	Std. Mean Difference (IV, Random, 95% CI)	‐0.89 [‐2.20, 0.41]
3.4 RIMAs	2	179	Std. Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.92, 0.34]
3.5 Other medication	4	213	Std. Mean Difference (IV, Random, 95% CI)	‐1.51 [‐2.71, ‐0.32]
4 Clinician‐rated: Liebowitz Social Anxiety Scale (LSAS): Fear Show forest plot	14	1803	Mean Difference (IV, Random, 95% CI)	‐7.30 [‐9.58, ‐5.02]

4.1 Moclobemide	3	517	Mean Difference (IV, Random, 95% CI)	‐3.53 [‐8.75, 1.70]
4.2 Brofaromine	3	207	Mean Difference (IV, Random, 95% CI)	‐7.58 [‐12.66, ‐2.50]
4.3 SSRIs	5	884	Mean Difference (IV, Random, 95% CI)	‐9.07 [‐13.15, ‐4.98]
4.4 MAOIs	1	51	Mean Difference (IV, Random, 95% CI)	‐5.23 [‐13.97, 3.51]
4.5 Other medication	2	144	Mean Difference (IV, Random, 95% CI)	‐9.14 [‐13.55, ‐4.73]
5 Clinician‐rated: Liebowitz Social Anxiety Scale (LSAS): Avoidance Show forest plot	14	1804	Mean Difference (IV, Random, 95% CI)	‐6.60 [‐8.68, ‐4.51]

5.1 Moclobemide	3	517	Mean Difference (IV, Random, 95% CI)	‐4.03 [‐9.02, 0.95]
5.2 Brofaromine	2	178	Mean Difference (IV, Random, 95% CI)	‐6.38 [‐10.63, ‐2.12]
5.3 SSRIs	5	884	Mean Difference (IV, Random, 95% CI)	‐8.12 [‐12.09, ‐4.15]
5.4 MAOIs	1	51	Mean Difference (IV, Random, 95% CI)	‐5.42 [‐14.69, 3.85]
5.5 Other medication	3	174	Mean Difference (IV, Random, 95% CI)	‐6.59 [‐11.77, ‐1.41]
6 Clinician‐rated: Liebowitz Social Anxiety Scale (LSAS): Total Show forest plot	16	2086	Mean Difference (IV, Random, 95% CI)	‐18.00 [‐25.17, ‐10.83]

6.1 SSRIs	5	746	Mean Difference (IV, Random, 95% CI)	‐13.99 [‐24.07, ‐3.91]
6.2 SSRIs ‐ difference scores	2	367	Mean Difference (IV, Random, 95% CI)	‐13.97 [‐19.77, ‐8.17]
6.3 MAOIs	2	103	Mean Difference (IV, Random, 95% CI)	‐26.01 [‐56.92, 4.90]
6.4 RIMAs	3	657	Mean Difference (IV, Random, 95% CI)	‐7.24 [‐12.14, ‐2.35]
6.5 Other medication	4	213	Mean Difference (IV, Random, 95% CI)	‐31.82 [‐55.13, ‐8.51]

Comparison 1. Medication vs Placebo: Global and SP symptoms

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Comparison 2. Medication vs Placebo: Comorbid symptoms

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Depression Scale Show forest plot	18	1998	Std. Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.30, ‐0.11]

1.1 Moclobemide	3	506	Std. Mean Difference (IV, Random, 95% CI)	‐0.06 [‐0.24, 0.11]
1.2 SSRIs	6	960	Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.48, ‐0.03]
1.3 MAOIs	3	154	Std. Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.46, 0.18]
1.5 Other types of medication	3	171	Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐0.64, ‐0.04]
1.6 Brofaromine	3	207	Std. Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.57, ‐0.02]

Comparison 2. Medication vs Placebo: Comorbid symptoms

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Comparison 3. Medication vs Placebo: Disability (Sheehan Disability Scale)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Work subscale Show forest plot	13	1854	Mean Difference (IV, Random, 95% CI)	‐1.23 [‐1.94, ‐0.51]

1.1 SSRIs	4	829	Mean Difference (IV, Random, 95% CI)	‐0.85 [‐1.22, ‐0.49]
1.2 SSRIs ‐ difference scores	1	187	Mean Difference (IV, Random, 95% CI)	‐1.22 [‐2.01, ‐0.43]
1.3 MAOIs	2	95	Mean Difference (IV, Random, 95% CI)	‐2.13 [‐3.53, ‐0.74]
1.4 RIMAs	4	608	Mean Difference (IV, Random, 95% CI)	‐0.13 [‐1.05, 0.80]
1.5 Other medication	2	135	Mean Difference (IV, Random, 95% CI)	‐3.58 [‐6.39, ‐0.78]
2 Social subscale Show forest plot	13	1853	Mean Difference (IV, Random, 95% CI)	‐1.10 [‐1.48, ‐0.72]

2.1 SSRIs	4	829	Mean Difference (IV, Random, 95% CI)	‐0.88 [‐1.28, ‐0.48]
2.2 SSRIs ‐ difference scores	1	187	Mean Difference (IV, Random, 95% CI)	‐1.38 [‐2.21, ‐0.55]
2.3 MAOIs	2	94	Mean Difference (IV, Random, 95% CI)	‐2.58 [‐6.40, 1.24]
2.4 RIMAs	4	608	Mean Difference (IV, Random, 95% CI)	‐0.64 [‐1.13, ‐0.15]
2.5 Other medication	2	135	Mean Difference (IV, Random, 95% CI)	‐2.31 [‐3.79, ‐0.83]
3 Family subscale Show forest plot	13	1854	Mean Difference (IV, Random, 95% CI)	‐0.56 [‐0.95, ‐0.17]

3.1 SSRIs	4	829	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐0.73, ‐0.11]
3.2 SSRIs ‐ difference scores	1	187	Mean Difference (IV, Random, 95% CI)	‐0.68 [‐1.35, ‐0.01]
3.3 MAIOs	2	95	Mean Difference (IV, Random, 95% CI)	‐1.48 [‐4.41, 1.44]
3.4 RIMAs	4	608	Mean Difference (IV, Random, 95% CI)	‐0.11 [‐0.75, 0.52]
3.5 Other medication	2	135	Mean Difference (IV, Random, 95% CI)	‐2.02 [‐4.26, 0.22]

Comparison 3. Medication vs Placebo: Disability (Sheehan Disability Scale)

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Comparison 4. Medication vs Placebo: Drop‐out Rate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Drop‐out Rate Show forest plot	28	3646	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.85, 1.09]

1.1 Moclobemide	3	637	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.57, 1.00]
1.2 Brofaromine	3	212	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.55, 1.61]
1.3 SSRIs	13	2367	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.88, 1.25]
1.4 MAOIs	2	121	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.46, 2.77]
1.5 Other medication	7	309	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.63, 1.42]

Comparison 4. Medication vs Placebo: Drop‐out Rate

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Comparison 5. Medication vs Placebo: Performance anxiety

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Performance anxiety scale Show forest plot	2	44	Mean Difference (IV, Random, 95% CI)	‐0.45 [‐0.90, 0.00]

Comparison 5. Medication vs Placebo: Performance anxiety

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Comparison 6. Medication vs Placebo: Maintenance studies

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Global Impressions scale change item (CGI‐I) non‐response Show forest plot	4	453	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.50, 0.77]

3 Drop‐out Rate Show forest plot	3	172	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.27, 1.36]

Comparison 6. Medication vs Placebo: Maintenance studies

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Comparison 7. Medication vs Placebo: Relapse Prevention

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Relapse rate Show forest plot	4	425	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.22, 0.49]

Comparison 7. Medication vs Placebo: Relapse Prevention

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Comparison 8. Subgroup analysis: Multi vs single centre

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2 Global Impressions scale change item (CGI‐I) (or similar scale) non‐response Show forest plot	25	3642	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.55, 0.72]

2.1 Single‐centre	13	1055	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.40, 0.70]
2.2 Multi‐centre	12	2587	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.60, 0.80]

Comparison 8. Subgroup analysis: Multi vs single centre

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Comparison 9. Subgroup analysis: Generalized vs inclusive SP

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Global Impressions ‐ Improvement (CGI‐I or similar) scale Show forest plot	25	3642	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.55, 0.72]

1.1 Generalized	9	1552	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.58, 0.76]
1.2 Inclusive	16	2090	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.50, 0.74]

Comparison 9. Subgroup analysis: Generalized vs inclusive SP

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