psychopharmacological treatment of social phobia (sp)
DESCRIPTION
PSYCHOPHARMACOLOGICAL TREATMENT OF SOCIAL PHOBIA (SP). Professor Jiří Raboch, M.D. Psychiatric Department 1 st . Medical Faculty Charles University Prague. TREATMENT OPTIONS. CBT MONOAMINE OXIDASE INHIBITORS BENZODIAZEPINES BETA-BLOCKERS SSRIs DUAL REUPTAKE INHIBITORS - PowerPoint PPT PresentationTRANSCRIPT
PSYCHOPHARMACOLOGICAL TREATMENT OF SOCIAL PHOBIA (SP)
Professor Jiří Raboch, M.D.
Psychiatric Department
1st. Medical Faculty
Charles University Prague
TREATMENT OPTIONS
• CBT
• MONOAMINE OXIDASE INHIBITORS• BENZODIAZEPINES• BETA-BLOCKERS• SSRIs• DUAL REUPTAKE INHIBITORS• OTHER/NEWER AGENTS
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)
MONOAMINE OXIDASE INHIBITORS
PHENELZINE - controlled studiesStudy Duration
(weeks)
N Response rate (%)
Tyrer et al., 1973
8 40
Gelernter et al., 1991
12 65 63 +
Liebowitz et al., 1992
8 74 64 +
Versiani et al., 1992
16 78 96 +
Heimberg et al., 1998
12 133 65 +
+ stat. sign. better than placebo
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 12 ns
Schneier et al., 1998
77 12 ns
+ stat. sign. better than placebo
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 %
Placebo 20 % (+)
+ stat. sign. better than placebo
BUSPIRONE – controlled studies
Study N Duration
(weeks)
Response rate (%)
van Vliet et al., 1997
30 12 ns
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
SSRIs
FLUVOXAMINE – controlled studiesStudy N Duration
(weeks)
Response rate (%)
Van Vliet et al., 1994
30 12 46 +
Stein et al., 1999
86 12 43 +
Davidson et al., 2004 *
279 12 34 +++
Westenberg et al., 2004 *
300 12 48
+ p=0,05 +++ p=0,001* CR – controlled-release
PAROXETINE – controlled studies
Study N Duration
(weeks)
Response rate (%)
Stein et al., 1998
370 12 55 +
Allgulander et al., 1999
96 12 70 +
Baldwin et al., 1999
187 12 66 +
Lepola et al., 2004 *
370 12 57 +++
+ p=0,05 +++ p=0,001* CR – controlled-release
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=0,01 +++ p=0,001
FLUOXETINE – controlled studies
Study N Duration
(weeks)
Response rate (%)
Kobak et al., 2002
60 14 ns
Clark et al., 2003
60 16 ns
Davidson et al., 2004
295 14 51 +
+ p=0,05
s-CITALOPRAM – controlled studies
Study N Duration
(weeks)
Response rate (%)
Kasper et al., 2002
181 24 54 +++
Lader et al.,2004
167 5 mg
170 20 mg
24 79 +
88+++
Davidson et al., 2004
315 8 68++
Kasper et al., 2005
358 12 54++
+ p=0,05 ++p=0,01 +++ p=0,001
WHAT DOSAGE? Study N Duration
(weeks)
Response rate (%)
Liebowitz et al., 2002
384 20 mg 12 31.4+++
paroxetine 40 mg 12 24.5+
Drop on LSAS
60 mg 12 25.2+
Lader et al.,2004
504 5 mg 24 79 +
s-citalopram 10 mg 24 76
% CGI-I 1,2 20 mg 24 88 +++
+ p=0,05 +++ p=0,001
SNRI
VENLAFAXINE ER – controlled studies
Study Duration
(weeks)
N Response rate (%)
Rickels et al., 2004 12 272 50++
Allgulander et al., 2004
12 434 69+
Liebowitz et al., 2005 12 440 58,6+++
Liebowitz et al., 2005 12 271 44+
+ p=0,05 ++ p=0,01 +++ p=0,001
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., 2005 paroxetine
20-50 mg/d and venlafaxine ER 75-225 mg - similar effects
OTHER DRUGS
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
ATYPICAL ANTIPSYCHOTICS
Barnet et al., 2003
Study N Duration (weeks)
Response rate (%)
Barnett et al., 2002
olanzapine
12 8 Improvement (p=0,01)
COMPARISON OF DRUG CLASSES FOR TREATMENT OF SF
Class Efficacy Tolerability
Safety Speed of onset
Depression
MAOIs ++ - - - ++
RIMAs + ++ + - +
SSRIs ++ ++ + - ++
BZDN + + + + -
Beta-bl. - ++ + + -
SNRI ++ + + - ++
Adapted from Westenberg, 2004
SP – first choice TREATMENT
• SSRIs – s-citalopram, fluvoxamine (CR), paroxetine (CR), sertraline, (fluoxetine)
• SNRI – venlafaxine ER
• COMBINATION – CBT + ANTIDEPRESSANTS – few data (sequencing)
SP – second choice TREATMENT and future alternatives
• MAOIs (phenelzine)
• Moclobemide
• Clonazepam
• Performance anxiety – beta-blockers – propranolol, atenolol
• Anticonvulsants, atypical antipsychotics
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)
THANK YOU FOR YOUR ATTENTION!
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
TREATMENT PHASES acute 6 – 12 (or longer) weeks
continuation up to 1 yearmaintenance
CONTINUATION TREATMENT?
• Walker et al., 2000• 50 patients with generalized social phobia
much or very much improved after 20 weeks of treatments with sertraline (50-200 mg/day)
• Randomly assigned to sertraline or placebo for another 6 months
• Relapse rate: placebo group 36 %, sertraline group 4 % (p=0,01)
MAINTENANCE TREATMENT?
• Versiani et al., 1996
• 58 patients-responders with SF treated 2 years with moclobemide (600-750 mg/day)
• After 2 years moclobemide was withdrawn
• Relapse rate 88 %
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
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
TREATMENT RESISTENCE
• Switching – venlafaxine, phenelzine
• Augmentation – buspirone, pindolol, benzodiazepines (clonazepam), atypical antipsychotics (olanzapine, risperidone), tiababine
TREATMENT RESISTENCEcontrolled 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
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)
REMISSION CRITERIA
• No longer satisfying diagnostic criteria
• CGI-I very much improved
• LSAS > 70 % reduction, < 30
• SDS < 5
COMPARISON OF DRUG CLASSES FOR TREATMENT OF SF
Class Efficacy Tolerability
Safety Speed of onset
Depression
MAOIs ++ - - - ++
RIMAs + ++ + - +
SSRIs ++ ++ + - ++
BZDN + + + + -
Beta-bl. - ++ + + -
SNRI ++ + + - ++
Adapted from Westenberg, 2004