A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia

Figures & data

Figure 1 Study design.

Figure 2 Patient disposition.

Table 1 Demographic and clinical characteristics at baseline

Variable	Duloxetine 60/120 mg QD N = 162	Placebo N = 168	P value
Age (years), mean (SD)	50.75 (10.05)	50.23 (11.35)	0.723
Sex
Female, n (%)	149 (91.98)	159 (94.64)	0.382
Male, n (%)	13 (8.02)	9 (5.36)
Race (origin)
Caucasian, n (%)	150 (92.59)	150 (89.29)	0.555
African, n (%)	2 (1.23)	1 (0.60)
Hispanic, n (%)	10 (6.17)	15 (8.93)
Native American, n (%)	0	1 (0.60)
West Asian, n (%)	0	1 (0.60)
Weight (kg), mean (SD)	77.71 (16.79)	77.03 (19.24)	0.739
Diagnosis of MDD
No, n (%)	126 (77.78)	130 (77.38)	1.00
Yes, n (%)	36 (22.22)	38 (22.62)
Secondary diagnosis of anxiety
No, n (%)	152 (98.06)	165 (98.80)	0.675
Yes, n (%)	3 (1.94)	2 (1.20)
Previous antidepressant use
No, n (%)	91 (56.17)	96 (57.14)	0.912
Yes, n (%)	71 (43.83)	72 (42.86)
BPI average pain score, mean (SD)	6.58 (1.52)	6.43 (1.48)	0.380
FIQ total score, mean (SD)	49.55 (11.28)	50.62 (12.47)	0.380
Mean tender point threshold, mean (SD)	2.46 (0.92)	2.31 (0.74)	0.092
Count of low threshold, mean (SD)	16.38 (2.90)	16.81 (2.10)	0.128
CGI-S, mean (SD)	3.81 (1.20)	3.79 (1.26)	0.747
PGI-S, mean (SD)	3.97 (1.32)	3.84 (1.36)	0.388
HAMD17 total score, mean (SD)	9.32 (5.27)	9.31 (5.41)	0.865
Non-MDD patients, mean (SD)	7.98 (4.27)	7.81 (4.48)	0.621
MDD patients, mean (SD)	13.92 (5.85)	14.39 (5.24)	0.625

Notes: Some percentages do not add up to 100 due to rounding. For some variables, not all patients had data.

Abbreviations: QD, once daily; SD, standard deviation; MDD, major depressive disorder; BPI, Brief Pain Inventory; FIQ, Fibromyalgia Impact Questionnaire; CGI-S, Clinical Global Impressions of Severity; PGI-S, Patient’s Global Impressions of Severity; HAMD₁₇, 17-item Hamilton Depression Rating Scale.

Table 2 Least-squares (LS) mean change from baseline to endpoint or at endpoint: efficacy measures

	Duloxetine 60/120 mg QD		Placebo
	N	LS mean change (SE)	N	LS mean change (SE)	Duloxetine–placebo difference (95% CI)	PValue	Therapy-by-investigator interactionPValue
BPI average pain score	158	−1.62 (0.20)	167	−1.13 (0.19)	−0.49 (−0.99, 0.01)	0.053	0.015
BPI worst pain score	158	−1.75 (0.22)	167	−1.25 (0.21)	−0.49 (−1.04, 0.05)	0.077	0.019
BPI least pain score	158	−1.22 (0.19)	167	−0.73 (0.18)	−0.49 (−0.97, −0.01)	0.046	0.114
BPI pain right now score	158	−1.68 (0.21)	167	−1.16 (0.20)	−0.52 (−1.05, 0.01)	0.054	0.261
BPI average interference	158	−1.69 (0.20)	167	−1.03 (0.19)	−0.66 (−1.16, −0.17)	0.009	0.139
Mean tender point threshold	148	0.40 (0.09)	159	0.18 (0.08)	0.22 (−0.00, 0.44)	0.055	0.002
Count of low threshold	148	−1.50 (0.30)	159	−0.92 (0.28)	−0.58 (−1.32, 0.16)	0.121	<0.001
FIQ total score	153	−7.96 (1.35)	163	−5.81 (1.29)	−2.15 (−5.57, 1.28)	0.218	0.088
FIQ fatigue score	154	−0.94 (0.23)	163	−0.97 (0.22)	0.03 (−0.54, 0.60)	0.919	0.741
FIQ rested score	154	−1.09 (0.23)	163	−1.06 (0.22)	−0.03 (−0.61, 0.54)	0.916	0.779
FIQ physical impairment score	154	−0.02 (0.18)	163	−0.06 (0.17)	0.03 (−0.43, 0.49)	0.892	0.106
FIQ pain score	154	−1.69 (0.22)	163	−1.06 (0.22)	−0.63 (−1.20, −0.06)	0.030	0.054
CGI-S	156	−0.57 (0.09)	164	−0.28 (0.08)	−0.29 (−0.51, −0.07)	0.011	0.003
MFI general fatigue	152	−0.33 (0.30)	162	−0.37 (0.29)	0.03 (−0.73, 0.80)	0.930	0.090
MFI physical fatigue	152	−0.48 (0.30)	162	−0.29 (0.29)	−0.19 (−0.97, 0.58)	0.619	0.281
MFI mental fatigue	153	−0.99 (0.33)	161	−0.03 (0.31)	−0.96 (−1.79, −0.13)	0.023	0.417
MFI reduced motivation	152	−0.27 (0.32)	162	−0.07 (0.31)	−0.20 (−1.01, 0.61)	0.629	0.213
MFI reduced activity	151	−0.19 (0.34)	162	0.03 (0.33)	−0.21 (−1.09, 0.66)	0.632	0.158
HAMD17 total score	143	−2.04 (0.40)	158	−1.70 (0.37)	−0.34 (−1.35, 0.66)	0.503	0.639
BDI-II total score	154	−3.42 (0.63)	164	−1.45 (0.61)	−1.97 (−3.58, −0.36)	0.017	0.591
PGI-Ia	158	3.43 (0.13)	165	3.72 (0.12)	−0.30 (−0.62, 0.03)	0.073	0.004
AUC of pain relief b	162	270.07 (25.19)	168	185.25 (24.42)	84.82 (20.81, 148.8)	0.010	0.049

Notes:

a For PGI-I, endpoint was analyzed, and the baseline used as a covariate was the PGI-S;

b AUC of pain relief is a summary measure of change in the BPI average pain score over time, but is not a change from baseline to endpoint.

Abbreviations: QD, once daily; N, number of patients who had a baseline score (PGI-S for analysis of the PGI-I) and at least one nonmissing postbaseline score for that particular variable; SE, standard error; BPI, Brief Pain Inventory; FIQ, Fibromyalgia Impact Questionnaire; CGI-S, Clinical Global Impressions of Severity; MFI, Multidimensional Fatigue Inventory; HAMD₁₇, 17-item Hamilton Depression Rating Scale; BDI-II, Beck Depression Inventory-II; PGI-I, Patient’s Global Impressions of Improvement; AUC, area under the curve; SE, standard error; PGI-S, Patient’s Global Impressions of Severity.

Table 3 Least-squares (LS) mean change from baseline to endpoint: health outcome and quality-of-life measures

	Duloxetine 60/120 mg QD		Placebo
	N	LS mean change (SE)	N	LS mean change (SE)	Duloxetine–placebo difference (95% CI)	P Value	Therapy-by-investigator interaction P Value
SDS global functional impairment total score	143	−2.34 (0.59)	160	−2.35 (0.56)	0.01 (−1.48, 1.51)	0.986	0.012
SDS work/school score	128	−0.93 (0.23)	144	−0.77 (0.21)	−0.16 (−0.73, 0.41)	0.581	0.074
SDS social life/leisure activities score	147	−0.75 (0.21)	161	−0.72 (0.20)	−0.03 (−0.57, 0.50)	0.903	0.118
SDS family life/home responsibilities score	147	−0.82 (0.21)	161	−0.82 (0.20)	−0.00 (−0.54, 0.53)	0.997	0.007
SF-36 mental component summary	146	3.37 (0.91)	162	0.79 (0.85)	2.58 (0.30, 4.86)	0.026	0.175
SF-36 physical component summary	146	2.61 (0.67)	162	2.06 (0.63)	0.55 (−1.13, 2.24)	0.519	0.616
SF-36 bodily pain	148	10.35 (1.61)	162	6.82 (1.52)	3.53 (−0.51, 7.58)	0.086	0.193
SF-36 general health	147	5.16 (1.37)	162	2.49 (1.29)	2.67 (−0.77, 6.11)	0.128	0.570
SF-36 mental health	148	6.63 (1.52)	162	1.19 (1.43)	5.44 (1.63, 9.25)	0.005	0.224
SF-36 physical functioning	148	4.66 (1.50)	162	3.52 (1.41)	1.14 (−2.60, 4.89)	0.548	0.130
SF-36 role-emotional	146	10.45 (3.51)	162	4.27 (3.30)	6.18 (−2.63, 14.99)	0.168	0.085
SF-36 role-physical	147	10.45 (2.92)	162	5.60 (2.75)	4.85 (−2.47, 12.18)	0.193	0.013
SF-36 social functioning	148	5.99 (2.04)	162	4.55 (1.92)	1.44 (−3.67, 6.56)	0.579	0.579
SF-36 vitality	148	5.99 (1.64)	162	2.86 (1.55)	3.13 (−0.98, 7.25)	0.135	0.119
EQ-5D index score	146	0.10 (0.03)	160	0.05 (0.02)	0.05 (−0.01, 0.12)	0.109	0.436

Abbreviations: QD, once daily; N, number of patients who had a baseline score and at least one nonmissing postbaseline score for that particular variable; SE, standard error; SDS, Sheehan Disability Scale; SF-36, 36-item Short-Form Health Survey; EQ-5D, EuroQol Questionnaire-5 dimensions.

Table 4 Treatment-emergent adverse events that occurred in ≥5% of duloxetine patients and at least twice the rate in placebo patients

	Duloxetine N = 162, n (%)	Placebo N = 168, n (%)	PValue*
Nausea	44 (27.2)	16 (9.5)	<0.001
Headache	35 (21.6)	18 (10.7)	0.010
Dry mouth	32 (19.8)	9 (5.4)	<0.001
Diarrhoea	26 (16.0)	11 (6.5)	0.008
Constipation	26 (16.0)	9 (5.4)	0.002
Hyperhidrosis	17 (10.5)	4 (2.4)	0.003
Arthralgia	10 (6.2)	5 (3.0)	0.193
Somnolence	12 (7.4)	2 (1.2)	0.006
Dyspepsia	9 (5.6)	4 (2.4)	0.164
Sleep disorder	9 (5.6)	4 (2.4)	0.164

Note:

* Fisher’s exact P value.

Abbreviation: N, number of randomly assigned patients.