1. PSYCHOPHARMACOLOGICAL TREATMENT OF SOCIAL PHOBIA (SP)
Professor Jiří Raboch, M.D.
Psychiatric Department
1st. Medical Faculty
Charles University Prague

2. TREATMENT OPTIONS CBT MONOAMINE OXIDASE INHIBITORS BENZODIAZEPINES
BETA-BLOCKERS
SSRIs
DUAL REUPTAKE INHIBITORS
OTHER/NEWER AGENTS

3. RANDOMIZED CONTROLLED TRIALS
RESPONSE RATE
clinically significant reduction of symptoms
Clinical Global Impression Scale-Improvement (CGI-I) – „very much“ or „much improved“
50 % drop in the Liebowitz Social Anxiety Scale (LSAS)

4. MONOAMINE OXIDASE INHIBITORS

5. PHENELZINE - controlled studies
Study
Duration
(weeks) N
Response rate (%)
Tyrer et al., 1973 8 40
Gelernter et al., 1991 12 65
63 +
Liebowitz et al., 1992 74
64 +
Versiani et al., 1992 16 78
96 +
Heimberg et al., 1998
133
65 +
+ stat. sign. better than placebo

6. MOCLOBEMIDE – controlled studies
Study N
Duration (weeks)
Response rate (%)
Versiani et al., 1992 78 16
81 +
Int. Mult. St., 1997
578 12
47/41 +
Noyes et al., 1997
583 ns
Schneier et al., 1998 77
+ stat. sign. better than placebo

7. BENZODIAZEPINES – controlled studies
Study N
Duration
(weeks)
Results
Gelernter et al., 1991 65 20
Alprazolam 38 %
Placebo 20 % (+)
Davidson et al., 1993 75 10
Clonazepam 78,3 %
+ stat. sign. better than placebo

8. BUSPIRONE – controlled studies
Study N
Duration
(weeks)
Response rate (%)
van Vliet et al., 1997 30 12 ns

9. BETA-BLOCKERS – controlled studies
Study N
Duration
(weeks)
Response rate (%)
Performance anxiety
11 controlled studies
In 8 of them more than 50 % response
Liebowitz et al., 1992
atenolol 74 16 ns

10. SSRIs

11. FLUVOXAMINE – controlled studies
Study N
Duration
(weeks)
Response rate (%)
Van Vliet et al., 1994 30 12
46 +
Stein et al., 1999 86
43 +
Davidson et al., *
279
Westenberg et al., *
300 48
* CR – controlled-release
+ p=0, p=0,001

12. PAROXETINE – controlled studies
Study N
Duration
(weeks)
Response rate (%)
Stein et al., 1998
370 12
55 +
Allgulander et al., 1999 96
70 +
Baldwin et al., 1999
187
66 +
Lepola et al., *
* CR – controlled-release
+ p=0, p=0,001

13. SERTRALINE – controlled studies
Study N
Duration
(weeks)
Response rate (%)
Van Ameringen et al., 2001
203 20
53 ++
Blomhoff et al., 2001
387 24
40,2 +
Liebowitz et al., 2003
211 12
55,6 +++
++ p=0, p=0,001

14. FLUOXETINE – controlled studies
Study N
Duration
(weeks)
Response rate (%)
Kobak et al., 2002 60 14 ns
Clark et al., 2003 16
Davidson et al., 2004
295
51 +
+ p=0,05

15. s-CITALOPRAM – controlled studies
Study N
Duration
(weeks)
Response rate (%)
Kasper et al., 2002
181 24
54 +++
Lader et al.,2004 mg mg
79 +
88+++
Davidson et al., 2004
315 8
68++
Kasper et al., 2005
358 12
54++
+ p=0,05 ++p=0, p=0,001

16. WHAT DOSAGE? Study N Duration (weeks) Response rate (%)
Liebowitz et al., 2002 mg 12
paroxetine
40 mg
24.5+
Drop on LSAS
60 mg
25.2+
Lader et al.,2004 mg 24
79 +
s-citalopram
10 mg 76
% CGI-I 1,2
20 mg
88 +++
+ p=0, p=0,001

17. SNRI

18. VENLAFAXINE ER – controlled studies
Study
Duration
(weeks) N
Response rate (%)
Rickels et al., 2004 12
272
50++
Allgulander et al., 2004
434
69+
Liebowitz et al., 2005
440
58,6+++
271
44+
+ p=0,05 ++ p=0, p=0,001

19. WHICH IS BETTER? Few methodologically fair head to head comparisons
Lader et al., 2004
20 mg s-citalopram better (p=0,01) than 20 mg paroxetine
Liebowitz et al., paroxetine mg/d and venlafaxine ER mg - similar effects

20. OTHER DRUGS

21. ANTIEPILEPTIC DRUGS -controlled studies
Study N
Duration
(weeks)
Response rate (%)
Pande et al., 1999
Gabapentin 69 14
32 +
Pande et al., 2004
Pregabalin
600 mg
135 10
Better than placebo
p=0,024
+ stat. sign. better than placebo

22. ATYPICAL ANTIPSYCHOTICS
Study N
Duration (weeks)
Response rate (%)
Barnett et al., 2002
olanzapine 12 8
Improvement (p=0,01)
Barnet et al., 2003

23. COMPARISON OF DRUG CLASSES FOR TREATMENT OF SF
Efficacy
Tolerability
Safety
Speed of onset
Depression
MAOIs ++ -
RIMAs +
SSRIs
BZDN
Beta-bl.
SNRI
Adapted from Westenberg, 2004

24. SP – first choice TREATMENT
SSRIs – s-citalopram, fluvoxamine (CR), paroxetine (CR), sertraline, (fluoxetine)
SNRI – venlafaxine ER
COMBINATION – CBT + ANTIDEPRESSANTS – few data (sequencing)

25. SP – second choice TREATMENT and future alternatives
MAOIs (phenelzine)
Moclobemide
Clonazepam
Performance anxiety – beta-blockers – propranolol, atenolol
Anticonvulsants, atypical antipsychotics

26. CONCLUSION
THERE ARE NUMBER OF EMPIRICALLY VALIDATED ACUTE TREATMENTS FOR SOCIAL PHOBIA
THE GOAL OF TREATMENT NEEDS TO BE REFOCUSED FROM ACHIEVING RESPONSE TO ACHIEVING REMISSION IN A LONGER PERSPECTIVE (CONTINUATION AND MAINTENANCE PHASES IN THE TREATMENT)

27. THANK YOU FOR YOUR ATTENTION!

28. HOW LONG?
Stein et al., 2003
112 patients with SAD, improved after 12 weeks treatment with sertraline CR (100 – 300 mg/day)
24 weeks extension phase
Subjects continued to improve compared to placebo treated, although changes were smaller

29. TREATMENT PHASES. acute 6 – 12 (or longer) weeks
TREATMENT PHASES acute 6 – 12 (or longer) weeks continuation up to 1 year maintenance

30. CONTINUATION TREATMENT?
Walker et al., 2000
50 patients with generalized social phobia much or very much improved after 20 weeks of treatments with sertraline ( mg/day)
Randomly assigned to sertraline or placebo for another 6 months
Relapse rate: placebo group 36 %, sertraline group 4 % (p=0,01)

31. MAINTENANCE TREATMENT?
Versiani et al., 1996
58 patients-responders with SF treated 2 years with moclobemide ( mg/day)
After 2 years moclobemide was withdrawn
Relapse rate 88 %

32. Pharmacological treatment of SF: a meta-analysis
Drug
Effect size
95 % CI
Phenelzine
1.02
0.52 – 1.52
Clonazepam
0.97
0.49 – 1.45
Gabapentin
0.78
0.29 – 1.27
Brofaromine
0.66
0.38 – 0,94
SSRIs
0.65
0.50 – 0.81
CI – confidence interval
Blanco et al., 2003

33. PREDICTORS OF TREATMENT RESPONSE
Alcohol abuse
Comorbid personality disorder
Earlier age of onset
Higher heart rate and blood pressure
Elevated baseline measures of anxiety and depression

34. TREATMENT RESISTENCE Switching – venlafaxine, phenelzine
Augmentation – buspirone, pindolol, benzodiazepines (clonazepam), atypical antipsychotics (olanzapine, risperidone), tiababine

35. TREATMENT RESISTENCE controlled studies
Study N
Duration
Results
Clonazepam + paroxetine
Seedat and Stein, 2004 28
10 weeks
79 % resp. 43 %, p=0,06
Pindolol + paroxetine
Stein et al., 2001 14
4 weeks NS

36. CONTINUATION TREATMENT?
Stein et al., 2002
… patients with SAD improved after 12 weeks treatment with paroxetine (20-50 mg/day)
Randomly assigned to paroxetine or placebo for another 6 months
Relapse rate: placebo group 40 %, sertraline group 14 % (p=0,0001)

37. REMISSION CRITERIA No longer satisfying diagnostic criteria
CGI-I very much improved
LSAS > 70 % reduction, < 30
SDS < 5

38. COMPARISON OF DRUG CLASSES FOR TREATMENT OF SF
Efficacy
Tolerability
Safety
Speed of onset
Depression
MAOIs ++ -
RIMAs +
SSRIs
BZDN
Beta-bl.
SNRI
Adapted from Westenberg, 2004