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