Duloxetine for Social Anxiety Disorder: Prediction of Long Term Outcome

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ClinicalTrials.gov Identifier: NCT00114127

Recruitment Status : Completed

First Posted : June 14, 2005

Results First Posted : June 7, 2012

Last Update Posted : June 10, 2014

Sponsor:

Information provided by (Responsible Party):

Naomi M. Simon, Massachusetts General Hospital

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
Condition	Anxiety Disorder
Interventions	Drug: Duloxetine Drug: Placebo
Enrollment	28

Participant Flow

Recruitment Details

Treatment seeking outpatients aged 18 years and older with a primary diagnosis of Generalized Social Anxiety Disorder (GSAD) were recruited by media advertisement.

Pre-assignment Details

Of the 39 participants who completed Phase I of this study, 28 moved on to Phase II.

1 subject was lost to follow up between baseline and week 1.


Arm/Group Title	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2)	Duloxetine 120mg/Day for 18 Weeks (Phase 2)
Arm/Group Description	Participants who did not achieve re...	Participants who did not achieve re...
Arm/Group Description	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 13 received 60mg duloxetine plus placebo for 18 additional weeks.	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 15 received 120mg duloxetine for 18 additional weeks.
Period Title: Overall Study
Started	13	15
Completed	9	11
Not Completed	4	4
Reason Not Completed
Adverse Event	2	1
Lost to Follow-up	1	0
Withdrawal by Subject	1	3

Baseline Characteristics

Arm/Group Title		Duloxetine 60mg/Day + Placebo for 18 Weeks(Phase 2)	Duloxetine 120mg/Day for 18 Weeks (Phase 2)	Total
Arm/Group Description		Participants who did not achieve re...	Participants who did not achieve re...	Total of all reporting groups
Arm/Group Description		Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 13 received 60mg duloxetine plus placebo for 18 additional weeks.	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 15 received 120mg duloxetine for 18 additional weeks.	Total of all reporting groups
Overall Number of Baseline Participants		13	15	28
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Customized Mean (Standard Deviation) Unit of measure: Years
Age Baseline	Number Analyzed	13 participants	15 participants	28 participants
Age Baseline		36.6 (14.2)	35.5 (11.6)	36 (12.6)
Sex/Gender, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Female		7	4	11
Male		6	11	17
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Caucasian		9	13	22
Asian		1	1	2
Black		1	1	2
Alaskan Native		1	0	1
Native Hawaiian or Pacific Islander		1	0	1
Educational status, college graduate Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
College Graduate		10	7	17
Not College Graduate		3	8	11
Duration of illness, mean years (SD) Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	13 participants	15 participants	28 participants
		27.6 (17.0)	20.1 (12.3)	23.7 (14.9)
Age of onset, mean age Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	13 participants	15 participants	28 participants
		9.9 (3.3)	13.9 (8.1)	12.0 (6.46)
Current comorbidity, Major depressive disorder (MDD) Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Comorbid MDD		5	0	5
No Comorbid MDD		8	15	23
Current comorbidity, Dysthymia Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Comorbid Dysthymia		2	0	2
No Comorbid Dysthymia		11	15	26
Current comorbidity, Panic Disorder (PD) Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Comorbid PD		1	0	1
No Comorbid PD		12	15	27
Current comorbidity, Generalized anxiety disorder (GAD) Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Comorbid GAD		2	0	2
No Comorbid GAD		11	15	26
At least one concurrent mood or anxiety disorder Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Concurrent mood or anxiety disorder		7	1	8
No concurrent mood or anxiety disorders		6	14	20
Lifetime depression Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Lifetime depression		6	4	10
No Lifetime depression		7	11	18
Lifetime alcohol or substance abuse or dependence Measure Type: Number Unit of measure: Participants	Number Analyzed	13 participants	15 participants	28 participants
Lifetime Alcohol/substance abuse/dependence		3	3	6
No Lifetime Alcohol/substance abuse/dependence		10	12	22
Liebowitz Social Anxiety Scale (LSAS) ^[1] Mean (Standard Deviation) Unit of measure: LSAS Score
	Number Analyzed	13 participants	15 participants	28 participants
		75.2 (6.90)	74.1 (6.20)	74.6 (4.52)
		[1] Measure Description: The Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987) is a 24-item scale that provides separate scores for fear and avoidance in social and performance situations with higher scores representing increased social anxiety (55-65 Moderate social phobia, 65-80 Marked social phobia, 80-95 Severe social phobia, Greater than 95 - Very severe social phobia). It is widely used in treatment studies of SAD. The instrument shows very good psychometric properties (Heimberg et al., 1999; Safren et al., 1999). Baseline collected for Phase 1 at week 0 and for Phase 2 at week 6.
Clinical Global Impression-Severity (CGI-S) ^[1] Mean (Standard Deviation) Unit of measure: CGI-S Score
	Number Analyzed	13 participants	15 participants	28 participants
		5.10 (0.43)	4.93 (0.36)	5.00 (0.27)
		[1] Measure Description: The Clinician Global Impression-Severity Scale (CGI-S) is a clinician-rated instrument used to assess global severity of symptoms (Guy, 1976). The CGI ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Baseline collected for Phase 1 at week 0 and for Phase 2 at week 6.
Clinical Global Impression-Improvement (CGI-I) ^[1] Mean (Standard Deviation) Unit of measure: CGI-I Score
	Number Analyzed	13 participants	15 participants	28 participants
		3.25 (0.97)	3.36 (1.22)	3.31 (1.09)
		[1] Measure Description: The Clinician Global Impression-Improvement Scale (CGI-I) is a clinician-rated instrument used to assess global improvement of symptoms (Guy, 1976). The CGI ranges from 1 (very much improved) to 7 (very much worse). Baseline CGI-I was not collected in Phase 1 as it is a measure of improvement. Baseline CGI-I was collected in Phase 2 because patients were transitioning from week 6 to 7.
Montgomery Asberg Depression Rating Scale (MADRS) ^[1] Mean (Standard Deviation) Unit of measure: MADRS Score
	Number Analyzed	13 participants	15 participants	28 participants
		8.08 (5.00)	10.3 (7.79)	9.17 (6.60)
		[1] Measure Description: MADRS; Montgomery & Asberg, 1979. The MADRS is designed to measure the overall severity of depressive symptoms and has demonstrated good reliability and sensitivity to change with treatment. It includes 10 items and uses a 0-6 severity scale with higher scores indicating increasing depressive symptoms. Ratings can be added to form an overall score (range 0 to 60); no weights are used. Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression. Baseline MADRS only collected in Phase 2 at week 6.
Sheehan Disability Scale (SDS) ^[1] Mean (Standard Deviation) Unit of measure: SDS Score
	Number Analyzed	13 participants	15 participants	28 participants
		11.2 (6.06)	14.1 (5.52)	12.9 (5.71)
		[1] Measure Description: The SDS is a brief self-report questionnaire that was developed to assess functional impairment in three inter-related domains; work/school, social and family life. The patient rates the extent to which work/school, social and family responsibilities are impaired by his/her symptoms on a 10 point visual analog scale. The three items are summed into a single dimension measure of global function impairment that ranges from 0 (unimpaired) to 30 (highly impaired). Baseline SDS only collected in Phase 2 at week 6.
Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) ^[1] Mean (Standard Deviation) Unit of measure: Q-LES-Q Score
	Number Analyzed	13 participants	15 participants	28 participants
		49.1 (8.83)	46.2 (9.47)	47.5 (9.12)
		[1] Measure Description: Q-LES-Q; Endicott et al., 1993. This questionnaire rates 16 aspects of quality of life, including physical health, mood, activities of daily living, and overall life satisfaction. The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score. The last two items are not included in the total score but are standalone items. The raw total score ranges from 14 to 70, with higher scores indicating higher satisfaction with quality of life. Baseline QLESQ only collected in Phase 2 at week 6.
Liebowitz Self-Rated Disability Scale (LSDSR) ^[1] Mean (Standard Deviation) Unit of measure: LSDSR Score
	Number Analyzed	13 participants	15 participants	28 participants
		7.58 (6.43)	10.0 (5.41)	8.79 (5.83)
		[1] Measure Description: The Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987) is a 24-item scale that provides separate scores for fear and avoidance in social and performance situations with higher scores representing increased social anxiety. The LSAS contains three total scores: 1) total fear score (0-72), 2) total avoidance score(0-72), 3) and total overall score (0-144). Suggested interpretations: 55-65 Moderate social phobia, 65-80 Marked social phobia, 80-95 Severe social phobia, Greater than 95 - Very severe social phobia. Baseline was only collected for Phase 2 at week 6

Outcome Measures

1.Primary Outcome


Title	Anxiety Symptoms as Assessed by Liebowitz Social Anxiety Scale
Description	The Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987) is a 24-ite...
Description	The Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987) is a 24-item scale that provides separate scores for fear and avoidance in social and performance situations with higher scores representing increased social anxiety. The LSAS contains three total scores: 1) total fear score (0-72), 2) total avoidance score(0-72), 3) and total overall score (0-144). Suggested interpretations: 55-65 Moderate social phobia, 65-80 Marked social phobia, 80-95 Severe social phobia, Greater than 95 - Very severe social phobia.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2)	Duloxetine 120mg/Day for 18 Weeks (Phase 2)
Arm/Group Description:	Participants who did not achieve re...	Participants who did not achieve re...
Arm/Group Description:	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 13 received 60mg duloxetine plus placebo for 18 additional weeks.	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 15 received 120mg duloxetine for 18 additional weeks.
Overall Number of Participants Analyzed	13	15
Mean (Standard Error) Unit of Measure: Scores on a scale
	67.9 (7.60)	53.7 (7.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2), Duloxetine 120mg/Day for 18 Weeks (Phase 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.132
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

2.Secondary Outcome


Title	CGI-S
Description	The Clinician Global Imp...
Description	The Clinician Global Impression-Severity Scale (CGI-S) is a clinician-rated instrument used to assess global severity of symptoms (Guy, 1976). The CGI ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Baseline collected for Phase 1 at week 0 and for Phase 2 at week 6.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2)	Duloxetine 120mg/Day for 18 Weeks (Phase 2)
Arm/Group Description:	Participants who did not achieve re...	Participants who did not achieve re...
Arm/Group Description:	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 13 received 60mg duloxetine plus placebo for 18 additional weeks.	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 15 received 120mg duloxetine for 18 additional weeks.
Overall Number of Participants Analyzed	13	15
Mean (Standard Error) Unit of Measure: Scores on a scale
	4.42 (0.48)	3.60 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2), Duloxetine 120mg/Day for 18 Weeks (Phase 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.292
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2)		Duloxetine 120mg/Day for 18 Weeks (Phase 2)
Arm/Group Description	Participants who did not achieve re...		Participants who did not achieve re...
Arm/Group Description	Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 13 received 60mg duloxetine plus placebo for 18 additional weeks.		Participants who did not achieve remission at the end of Phase 1 entered Phase 2 and were randomized. 15 received 120mg duloxetine for 18 additional weeks.
All-Cause Mortality
	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2)		Duloxetine 120mg/Day for 18 Weeks (Phase 2)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2)		Duloxetine 120mg/Day for 18 Weeks (Phase 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.38%)		0/15 (0.00%)
General disorders
Elevated Liver Function Tests ^[1]	1/13 (7.69%)	1	0/15 (0.00%)	0
Study medication overdose ^[2]	1/13 (7.69%)	1	0/15 (0.00%)	0
[1] The elevated LFTs were later diagnosed by primary care physician on evaluation as unrelated to study medication and a result of rhabdomyolysis from a week of intensive weight lifting and exercises. [2] The study medication overdose was in the context of alcohol use and suicidal ideation and had no medical consequences: this was deemed possibly related to duloxetine and the participant was transferred to clinical care.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Duloxetine 60mg/Day + Placebo for 18 Weeks (Phase 2)		Duloxetine 120mg/Day for 18 Weeks (Phase 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0.00%)		2/15 (13.33%)
General disorders
Sedation and other side effects	0/13 (0.00%)	0	1/15 (6.67%)	1
Increased drinking	0/13 (0.00%)	0	1/15 (6.67%)	1

Limitations and Caveats

Open-label in phase Phase 1; Limited power due to small sample size.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Dr. Naomi Simon
Organization:	Massachusetts General Hospital
Phone:	617-726-7913
EMail:	nsimon@partners.org

Layout table for additonal information

Responsible Party:	Naomi M. Simon, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00114127
Other Study ID Numbers:	2004-P-001384
First Submitted:	June 13, 2005
First Posted:	June 14, 2005
Results First Submitted:	January 27, 2012
Results First Posted:	June 7, 2012
Last Update Posted:	June 10, 2014

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