Appendix 1. Search Strategy for Identifying HRQL Articles for Pharmaceutical Treatment in GAD

PUBMED

Search Query

#1 Search GAD[tiab] OR generalized anxiety[tiab]

#2 Search "Health Related Quality of Life"[TIAB] OR HRQL[TIAB] OR HRQOL[TIAB] OR "quality of life"[MESH] OR "quality of life"[TIAB] OR QOL[TIAB] OR well-being[tiab]

#3 Search "Controlled Clinical Trial "[Publication Type] OR "Randomized Controlled Trial "[Publication Type] OR "Clinical Trial "[Publication Type] OR "Clinical Trial, Phase IV "[Publication Type] OR "Clinical Trial, Phase III "[Publication Type] OR "Clinical Trial, Phase II "[Publication Type] OR "Clinical Trial, Phase I "[Publication Type] OR "Multicenter Study "[Publication Type] OR randomized[tiab] OR randomised[tiab] OR placebo[tiab] OR randomly[tiab] OR trial[tiab] OR groups[ti] OR "Clinical Trials as Topic"[Mesh] OR "Double-Blind Method"[Mesh] OR "Single-Blind Method"[Mesh] OR single-masked[tiab] OR double-masked[tiab]

#4 Search Animals[Mesh] NOT human[Mesh]

#5 Search #1 AND #2 AND #3 NOT #4 NOT (letter[pt] OR comment[pt] OR editorial[pt]) AND english[Language] Filters: Publication date from 2003/02/20 to 2014/04/07

EMBASE

No. Query

#1  gad:ab,ti OR 'generalized anxiety':ab,ti AND [embase]/lim

#2 'health related quality of life'/exp OR 'health related quality of life':ab,ti OR 'hrql'/exp OR 'hrql':ab,ti OR hrqol:ab,ti OR 'hr-qol':ab,ti OR 'quality of life'/exp OR 'quality of life':ab,ti OR qol:ab,ti OR 'life quality'/exp OR 'life quality':ab,ti OR 'well-being':ab,ti AND [embase]/lim

#3 

'randomized controlled trial'/exp OR 'controlled clinical trial'/exp OR 'clinical trial'/exp OR 'phase 1 clinical trial'/exp OR 'phase 2 clinical trial'/exp OR 'phase 3 clinical trial'/exp OR 'phase 4 clinical trial'/exp OR 'multicenter study'/exp OR randomized:ab,ti OR randomised:ab,ti OR placebo:ab,ti OR randomly:ab,ti OR trial:ab,ti OR groups:ti OR 'double blind':ab,ti OR 'single blind':ab,ti OR 'double blind procedure'/exp OR 'single blind procedure'/exp AND [embase]/lim

#4  'animal'/exp NOT 'human'/exp AND [embase]/lim

#5  #1 AND #2 AND #3 NOT #4 AND ([article]/lim OR [article in press]/lim OR [review]/lim) AND [english]/lim AND [embase]/lim AND [20-2-2003]/sd NOT [7-4-2014]/sd

Cochrane Reviews

ID Search

#1 "generalized anxiety disorder":ti,ab,kw from 2003 to 2014, in Cochrane Reviews (Reviews and Protocols) (Word variations have been searched)

#2 "quality of life" from 2003 to 2014, in Cochrane Reviews (Reviews and Protocols)

#3 #1 and #2

PsycInfoSearch ID#

Search Terms Search Options

S1 TI ( GAD OR "generalized anxiety" ) OR AB ( GAD OR "generalized anxiety" )

S2 TI ( "Health Related Quality of Life" OR HRQL OR HRQOL OR "quality of life" OR QOL OR well-being ) OR AB ( "Health Related Quality of Life" OR HRQL OR HRQOL OR "quality of life" OR QOL OR well-being )

S3 TI ( "Multicenter Study” OR randomized OR randomised OR placebo OR randomly OR trial OR single-masked OR double-masked OR single-blind OR double-blind ) OR AB ( "Multicenter Study” OR randomized OR randomised OR placebo OR randomly OR trial OR single-masked OR double-masked OR single-blind OR double-blind )

S4 S1 AND S2 AND S3 Limiters - Publication Year from: 2003-2014; Publication Type: All Journals; English; Document Type: Journal Article

Appendix 2, Table S1. Summary of GAD Trials: Population, Design and Methods

Citation Population Design and Methods PRO Measures HRQL FindingsAllgulander et al 2004 [1]

Patients with DSM-IV-defined GAD, HAM-A ≥18, and HAM-A item 1 “anxious mood” and item 2 “tension” ≥ moderate

Patients with MDD were excluded N=373 (N=340 in HRQL analysis) Mean age in years (SD):

o Placebo: 42 (12)o Sertraline: 40 (11)

Mean age at onset of GAD in years (SD): o Placebo: 26 (13)o Sertraline: 23 (12)

Mean HAM-A Total Scores at baseline (SD): o Placebo: 25 (5)o Sertraline: 25 (5)

Randomized, double-blind, multicenter, placebo-controlled, flexible dose study comparing the efficacy and tolerability of flexible doses of sertraline to placebo

Duration: 13 Weekso 1 week single-blind Placebo lead-

ino 12 week double-blind treatment

phase Treatment:

o Placebo o Sertraline: Initiated at 25 mg/day

for first week, followed by 3 weeks of treatment with a dose of 50 mg/day. From week 5 through 6, flexible dosing was permitted in range of 50 to 100 mg/day increasing from week 7 through week 12 to a range of 50–150 mg/day.

Q-LES-Q Endicott

Work Productivity Scale

Patients receiving Sertraline had significantly greater improvement in the Q-LES-Q total score compared to patients receiving placebo (p<0.0001).

Patients receiving Sertraline had significantly greater improvement in the Endicott Work Productivity scale score compared to patients receiving placebo (p<0.001).

Allgulander et al 2007 [2]

Patients with GAD, HAM-A ≥20 Patients with MDD were excluded Open Label N=491 RCT N=375 (195 in HRQL analysis) Mean age in years (SD):

o Placebo: 41 (12)o Escitalopram: 42 (11)

Mean age of onset of GAD in years (SD): o Placebo: 37 (12)o Escitalopram: 35 (13)

Mean HAM-A Total Scores at baseline (SD): o NR

Open-label trial of fixed dose Escitalopram, followed by Randomized, double-blind, placebo-controlled, flexible-dose, multicenter trial evaluating the efficacy of Escitalopram compared to placebo in patients that responded to treatment in the open-label phase

Duration:o 12 week open-label phaseo 24–76 weeks RCT (patient

discontinued if relapse or withdrawn)

Treatment:o Open label: All patients received

SF-36 Work

Limitations Questionnaire

Number of sick days

Patients receiving Escitalopram reported significantly higher quality of life (p<0.001) in the following dimensions of the SF-36: Social functioning, role emotional, mental health.

No significant differences between Escitalopram and placebo were found in the following dimensions of the SF-36: physical function, role limitations, bodily pain, general health perceptions, vitality.

During the open-label phase, patients reported significantly greater work limitations at baseline

Citation Population Design and Methods PRO Measures HRQL Findings20 mg/day of Escitalopram

o RCT: Placebo or 20 mg/day Escitalopram

(p<0.0001) than at the end of the open-label phase on the following WLQ scores: (index, VAS satisfaction, VAS efficacy). WLQ scores were not reported by treatment group during the RCT phase.

The reduction in sick leaves days was not significantly different between patients receiving Escitalopram or placebo.

Ball et al 2005 [3]

Primary diagnosis of DSM-IV-defined GAD, HAM-A total score ≥18.

Patients with other Axis I and anxiety depressive disorders were included

N=55 (53 in HRQL analysis)o Paroxetine (n=25)o Sertraline (n=28)

Mean age in years (SD): o Paroxetine: 35.6 (11.7)o Sertraline: 42.9 (14.7)

Mean age of onset of GAD in years (SD): NR

Mean HAM-A Total Scores at baseline (SD):o Paroxetine: 20.8 (2.3)o Sertraline: 21.4 (3.4)

Double-blind, randomized, parallel-group, flexible-dose study comparing the efficacy and tolerability of two SSRIs, paroxetine and sertraline, for the treatment of GAD.

Duration:o 8 weeks

Treatment:o 10–40 mg/day Paroxetineo 25–100 mg/day Sertraline

Q-LES-Q Q-LES-Q scores improved significantly from baseline for both groups (p<0.001); there were no significant differences in Q-LES-Q scores between the Paroxetine and Sertraline groups.

Bidzan et al 2012 [4]

Patients with DSM-IV-TR-defined GAD, HAM-A ≥20 and HAM-A item 1 “anxious mood” and item 2 “tension” ≥ 2

Patients with a current diagnosis or history of major depression were excluded

N=301 (297 in HRQL analysis) Mean age in years (SD):

o Placebo: 45 (14)

Randomized, double-blind, placebo-controlled, multicenter, fixed-dose trial evaluating the efficacy of Vortioxetine compared to placebo

Duration:o 8 weeks

Treatment:o Placeboo 5 mg/day of Vortioxetine

SF-36 SDS

Patients who received Vortioxetine achieved significantly more improvement on the SF-36 social functioning scale compared to placebo (p<0.01). No other SF-36 scale score results were reported.

Patients who received Vortioxetine achieved significantly more improvement on the SDS compared to placebo (p<0.05).

Citation Population Design and Methods PRO Measures HRQL Findingso Vortioxetine: 45 (14)

Mean age of onset of GAD in years (SD):o NR

Mean HAM-A Total Scores at baseline (SD):o Placebo: 27 (4)o Vortioxetine: 26 (4)

Demyttenaere et al 2008 [5]a

Patients with DSM-IV-defined GAD, HAM-A ≥18

Patients with a primary DSM-IV Axis I diagnosis other than GAD (including MDD) were excluded

N=924 in HRQL analysiso Placebo (n=461)o Escitalopram (n=463)

Mean age in years (SD): o Pooled sample: NRo Study 1 [6]:

Placebo: 40 (13) Escitalopram: 40 (12)

o Study 2 [7]: Placebo: 41 (14) Escitalopram: 40 (13)

o Study 3 [7]: Placebo: 38 (12) Escitalopram: 37 (13)

o Study 4 [8]: Placebo:37 (12) Escitalopram: 38 (11)

Mean age of onset of GAD in years (SD): o NR

Mean HAM-A Total Scores at baseline (SD): o Pooled sample: NRo Study 1 [6]:

Placebo: 23 (4)

Pooled analysis of 3 nearly identical multicenter, randomized, double-blind, placebo-controlled, flexible dose trials evaluating the efficacy of Escitalopram compared to placebo

Duration:o All trials 8 weeks

Treatment:o Placeboo 10 to 20 mg/day Escitalopramo NOTE: 1 of the 4 trials [8] had a

third treatment arm of 75 to 225 mg/day of Venlafaxine. Results from this treatment arm are not reported in this manuscript.

Q-LES-Q-SF A significantly greater improvement was observed in patients receiving Escitalopram compared to those receiving placebo (p<0.001).

Citation Population Design and Methods PRO Measures HRQL Findings Escitalopram: 24 (5)

o Study 2 [7]: Placebo: 22 (4) Escitalopram: 23 (4)

o Study 3 [7]: Placebo: 23 (4) Escitalopram: 23 (3)

o Study 4 [8]: Placebo:24 (3) Escitalopram: 24 (4)

Endicott et al 2007 [9]b

Patients with DSM-IV-defined GAD, HADS anxiety subscale ≥10, CGI-S ≥4, Covi anxiety scale ≥9, and no item on Raskin depression scale >3.

Patients with a primary DSM-IV Axis I diagnosis other than GAD (including MDD) within the past 6 months were excluded

N=1,163 in HRQL analysis o Study 1 (N=513): Duloxetine 60

mg (N=168); Duloxetine 120 mg (N=170); Placebo (N=175)[10]

o Study 2 (n=327): Duloxetine 60–120 mg (N=168); Placebo (N=159)[11]

o Study 3 (N=323): Duloxetine 60–120 mg (N=162); 75-225 mg/day of venlafaxine (not reported); Placebo (N=161) [12]

Mean age in years (SD=NR): o Study 1[10]:

Duloxetine 60 mg: 43; Duloxetine 120 mg: 44; Placebo: 44

o Study 2 [11]: Duloxetine 60–120 mg: 42; Placebo: 41

Results are reported separately for three randomized, double-blind placebo-controlled multicenter trials evaluating the efficacy of Duloxetine compared to placebo.

Duration:o Studies 1 and 3: 12 weekso Study 2: 13 weeks

Treatment:o Placeboo Study 1: Fixed-dose 60 mg/day

or 120 mg/day Duloxetineo Studies 2–3: Flexible-dose 60 to

120 mg/dayo NOTE: Study 2 had a third

treatment arm of 75 to 225 mg/day of Venlafaxine. Results from this treatment arm are not reported in this manuscript.

SDS Q-LES-Q-SF EQ-5D

Patients who received Duloxetine achieved significantly more improvement on the SDS compared to placebo in all three studies:o Global functioning:

Study 1: p≤0.001 Study 2: p≤0.01 Study 3: p≤0.01

o Work/School domain: Study 1: p≤0.001 Study 2: p≤0.05 Study 3: p≤0.01

o Social Life: Study 1: p≤0.001 Study 2: p≤0.01 Study 3: p≤0.01

o Family/Home responsibility: Study 1: p≤0.001 Study 2: p≤0.05 Study 3: p≤0.05

Patients who received Duloxetine achieved significantly more improvement on the Q-LES-Q-SF compared to placebo in two of the three studies:

Study 1: p≤0.001 Study 3: p≤0.001

Patients who received Duloxetine

Citation Population Design and Methods PRO Measures HRQL Findingso Study 3 [12]:

Duloxetine 60–120 mg: 40; Placebo: 42

Mean age of onset of GAD in years (SD): o NR

Mean HAM-A Total Scores at baseline (SD=NR): o Study 1:

Duloxetine 60 mg: 25; Duloxetine 120 mg: 25; Placebo: 26

o Study 2: Duloxetine 60–120 mg:

22.6; Placebo: 24

o Study 3: Duloxetine 60–120 mg: 26; Placebo: 25

achieved significantly more improvement on the EQ-5D compared to placebo in Study 1:o Index Score:

Duloxetine 60 mg: p≤0.001;

Duloxetine 120 mg: p≤0.05;

o VAS health Score: Duloxetine 60 mg:

p≤0.001; Duloxetine 120 mg:

p≤0.01; Patients who received Duloxetine

did not achieve a significantly greater improvement on the EQ-5D index or VAS health score in Study 2 (p>0.05)

Endicott et al 2012 [13]c

Patients with DSM-IV-TR-defined GAD, HADS anxiety subscale score ≥10; CGI-S illness scale ≥4, Covi anxiety scale ≥9, and no item on Raskin depression scale >3.

Patients with any other DSM-IV-TR Axis I disorder within 6 months of enrollment were excluded

2,609 in HRQL analysiso N=2,171; Quetiapine Fumarate

50 mg/day (n=438), 150 mg/day (n=654), 300 mg/day (n=425), or placebo (n=654)

Mean age in years (SD): o Placebo: 39 (12)o Quetiapine Fumarate 50 mg/day:

40 (12)o Quetiapine Fumarate 150

mg/day: 40 (12)

Pooled analysis of 3 multicenter, double-blind, randomized, parallel-group, placebo-controlled Phase III studies of Quetiapine Fumarate monotherapy in patients with GAD [14-16]

Duration: All trials 8 weeks Treatment:

o Placeboo Fixed-dose 50, 150, 300 mg/day

Quetiapine Fumarateo NOTE: Only results from

Quetiapine Fumarate and Placebo groups are reported; results from comparator arms are not reported in this manuscript.

Q-LES-Q-SF Acute study participants who received 150 mg/day of Quetiapine Fumarate showed significantly greater improvements at week 8 on the Q-LES-Q-SF percent maximum total score relative to placebo (p≤0.001). The least square mean difference was not significant between patients receiving 50 mg/day or 300 mg/day relative to placebo.

Citation Population Design and Methods PRO Measures HRQL Findingso Quetiapine Fumarate 300

mg/day: 40 (12) Mean age of onset of GAD in years

(SD): NR

Time since first diagnosis of GAD in years (SD):o Placebo: 5 (7)o Quetiapine Fumarate 50 mg/day:

5 (6) o Quetiapine Fumarate 150

mg/day: 5 (6)o Quetiapine Fumarate 300

mg/day: 6 (7) Mean HAM-A Total Scores at

baseline (SD):o Placebo: 26 (4)o Quetiapine Fumarate 50 mg/day:

26 (4)o Quetiapine Fumarate 150

mg/day: 25 (4)o Quetiapine Fumarate 300

mg/day: 25 (4)Kasper et al 2014 [17]

Patients with DSM-IV-TR-defined GAD, HAM-A ≥18 and HAM-A item 1 “anxious mood” and item 2 “tension” ≥ 2; a subscore ≤21 points for psychic anxiety; Covi anxiety scale total score ≥9

Patients with any other DSM-IV-TR Axis I disorder (including major depression) within 6 months of enrollment were excluded

N=536 (523 in HRQL analysis) Mean age in years (SD)

o Placebo: 45 (12)o Silexan 160 mg/d: 47 (12)o Silexan 80 mg/d: 46 (12)

Randomized, double-blind, double-dummy, multicenter trial with four parallel groups

Duration: 10 weeks Treatment:

o Placeboo Silexan 160 mg/d o Silexan 80 mg/do Paroxetine 20 mg/d

NOTE: Silexan (lavender oil) was considered an alternative treatment. This trial was included based on the active comparator arm, Paroxetine. Only results for Paroxetine are summarized.

SDS SF-36

Participants taking Paroxetine showed significantly greater improvements in SDS Total Score relative to placebo (p<0.05).

Participants taking Paroxetin showed significantly greater improvement in SF-36 MCS relative to placebo (p<0.01)

Participants taking Paroxetin showed did not show significantly greater improvements in SF-36 PCS relative to placebo (p=0.095).

Citation Population Design and Methods PRO Measures HRQL Findingso Paroxetine: 46 (12)

Mean age of onset of GAD in years (SD): NR

Time since first diagnosis of GAD in years (SD):o Placebo: 3(5)o Silexan 160 mg/d: 3 (5)o Silexan 80 mg/d: 2 (5)o Paroxetine: 2 (4)

Mean HAM-A Total Scores at baseline (SD):o Placebo: 25(5)o Silexan 160 mg/d: 26 (5)o Silexan 80 mg/d: 26 (5)o Paroxetine: 26 (5)

Katzman et al 2011 [18]

Patients with DSM-IV-TR-defined GAD.

Patients with any other DSM-IV Axis I disorder within 6 months of enrollment were excluded

N=432; 50–300 mg/day (n=216), or placebo (n=216)

Mean age in years (SD): o Placebo: 42 (12)o Quetiapine Fumarate 50–300

mg/day: 45 (11) Mean age of onset of GAD in years

(SD): NR Time since first diagnosis of GAD in

years (SD):o Placebo: 13 (14)o Quetiapine Fumarate 50–300

mg/day: 14 (14) Mean HAM-A Total Scores at

baseline (SD):o Placebo: 6 (3)o Quetiapine Fumarate 50–300

mg/day: 6 (3)

Multicenter, randomized-withdrawal, parallel-group, double-blind, placebo-controlled maintenance study to evaluate the efficacy and safety of Quetiapine Fumarate.

Duration: 52 weeks Treatment:

o Flexible dose 50–300 mg/day Quetiapine Fumarate

Q-LES-Q-SF SDS

A significant difference was observed in Q-LES-Q-SF total score from randomization to study end for Quetiapine Fumarate group relative to placebo (p≤0.05).

A significant difference was observed in the SDS global functional impairment score from randomization to study end for Quetiapine Fumarate group relative to placebo (p≤0.05).

Citation Population Design and Methods PRO Measures HRQL FindingsMahableshwarkar et al 2014 [19]

Patients with DSM-IV-TR-defined GAD, HAM-A ≥20 and HAM-A item 1 “anxious mood” and item 2 “tension” ≥ 2, MADRS total score <16

Patients with any concurrent psychiatric disorder other than GAD or prior history of psychiatric disorders were excluded

N=457 (438 in HRQL analysis) Mean age in years (SD):

o Placebo: 40 (14)o Vortioxetine 2.5 mg/day: 41 (14)o Vortioxetine 10 mg/day: 43 (15)

Mean age of onset of GAD in years (SD):NR Mean duration of current GAD in

months (SD): o Placebo: 41 (98)o Vortioxetine 2.5 mg/day: 37 (89)o Vortioxetine 10 mg/day: 57 (108)

Mean HAM-A Total Scores at baseline (SD): o Placebo: 25 (4)o Vortioxetine 2.5 mg/day: 25 (4)o Vortioxetine 10 mg/day: 25 (4)

Randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase 3 trial evaluating the efficacy of Vortioxetine compared to placebo

Duration: 8 weeks Treatment:

o Placeboo 2.5 mg/day of Vortioxetineo 10 mg/day of Vortioxetine

SF-36 social functioning scale

SDS

Patients receiving Vortioxetine 2.5 mg/day and 10 mg/day did not experience a significantly greater change in SF-36 social functioning compared to patients receiving placebo (p >0.05 for both treatment groups).

Patients receiving Vortioxetine 2.5 mg/day and 10 mg/day did not experience a significantly greater change in SDS total score compared to patients receiving placebo (p >0.05 for both treatment groups).

Mezhebovksy et al 2013 [20]

Patients (≥66 years) with GAD based on DSM-IV diagnosis and confirmed by the Mini International Neuropsychiatric Interview, HAM-A total score of ≥20 with item 1 (anxious mood) and 2 (tension) scores of ≥2, CGI-S score of ≥4, and MADRS total score of ≤16.

Patients with any DSM-IV Axis I disorder other than GAD within 6 months of enrollment were excluded

N=450 (448 in HRQL analysis)o Placebo (n=226)

Randomized, parallel-group, double-blind, placebo-controlled flexible-dose study of evaluating the efficacy of Quetiapine Fumarate monotherapy compared to placebo in patients with GAD.

Duration: 11 weeks Treatment:

o Placeboo 50–300 mg/day Quetiapine

Fumarate

Q-LES-Q-SF Participants who received Quetiapine Fumarate showed significant improvements versus placebo at week 9 on the Q-LES-Q-SF percent maximum total score (p≤0.001)

Citation Population Design and Methods PRO Measures HRQL Findingso Quetiapine Fumarate 50–300 mg

(n=222) Mean age in years (SD):

o Placebo: 71 (4.4)o Quetiapine Fumarate 50–300 mg:

70 (4) Mean age of onset of GAD in years

(SD): NR Time since first diagnosis of anxiety

symptoms in years (SD):o Placebo: 9 (11)

o Quetiapine Fumarate 50–300 mg: 9 (12)

Mean HAM-A Total Scores at baseline (SD): o Placebo: 25 (4)o Quetiapine Fumarate 50–300 mg:

25 (4)Woelk et al 2010 [21]

Primary diagnosis of GAD based on DSM-IV, HAM-A total score ≥18, HAM-A item 1 “anxious mood” and item 2 “tension” ≥ 2

Patients without a DSM-IV-defined diagnosis of GAD or HAM-A total score ≥18, HAM-A item 1 “anxious mood” and item 2 “tension” ≥ 2 were excluded

N=77 (77 in HRQL analysis)o Silexan (n=40)o Lorazepam (n=37)

Age range in years: 21–65 Mean years since first diagnosis of

GAD (SD): o Silexan 5(5)o Lorazepam 4 (4)

Mean HAM-A Total Score (SD):o Silexan: 25 (4)

Multi-center, double blind, randomized study comparing Silexan (Lavender oil preparation) to Lorazepam for the treatment of GAD.

Duration: 6 weeks Treatment:

o Silexan: 80 mg/day plus placeboo Lorazepam: 0.5 mg/day plus

placebo

SF-36 SF-36 mental health scores improved by 21.2±18.6 points in the Silexan group and 24.3±18.7 points in the Lorazepam group.

SF-36 physical health scores improved by 12.5±17.4 points in the Silexan group and 16.9±18.9 points in the Lorazepam group.

Note: no significance ratings were reported.

Citation Population Design and Methods PRO Measures HRQL Findingso Lorazepam: 25 (4)

a Trial results based on pooled data from four 8-week clinical trials evaluating the efficacy of Escitalopram [6-8]. b Trial results based on pooled data from three 12- to 13-week clinical trials evaluating the efficacy of Duloxetine [10-12].c Trial results based on pooled data from three 8-week clinical trials evaluating efficacy of Quetiapine Fumarate. Results from Katzman et al were also reported in this study, separate from the pooled analysis of the

three acute trials. Given Katzman et al was a maintenance study, and results were not pooled, they are reported separately under the primary reference [18].Abbreviations: DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision; GAD, generalized anxiety disorder; HAM-A,

Hamilton Anxiety Rating Scale; HRQL, health-related quality of life; MADRS, Montgomery-Åsberg Depression Rating Scale; MCS, Mental Component Summary; mg, milligram; MDD, Major Depressive Disorder; Q-LES-Q, Quality of Life and Enjoyment Scale; Q-LES-Q-SF, Quality of Life and Enjoyment Scale Short Form, RCT, randomized controlled trial; SD, standard deviation; SE, Standard Error; SF-36, Short Form 36 Health Survey; VAS, visual analog scale; WPAI-SHP, work productivity and activity impairment questionnaire-specific health measure.

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