Efficacy and Safety of Electroacupuncture for Insomnia Disorder: A Multicenter, Randomized, Assessor-Blinded, Controlled Trial

Figures & data

Table 1 Demographic and Clinical Characteristics of the Participants

Characteristics^a	Electroacupuncture (n=49)	Sham (n=52)	Usual Care (n=49)	P value
Gender (Male/Female)^b	9 (18.37%)/40 (81.63%)	9 (17.31%)/43 (82.69%)	19 (38.78%)/30 (61.22%)	0.0253
Age (year)^c	51.78 (49.23, 54.32)	52.00 (49.52, 54.48)	52.00 (49.48, 54.52)	0.9894
Height (cm)^c	160.51 (158.09, 162.93)	159.59 (157.67, 161.51)	163.56 (160.48, 166.63)	0.0647
Weight (kg)^c	59.88 (56.98, 62.78)	59.65 (56.41, 62.90)	62.50 (58.95, 66.04)	0.3884
BMI (kg/m^2)^c	23.12 (22.42, 23.81)	23.35 (22.28, 24.42)	23.30 (22.18, 24.42)	0.9406
Smoke (Yes/No)^b	2 (4.08%)/47 (95.92%)	3 (5.77%)/49 (94.23%)	3 (6.12%)/46 (93.88%)	0.9999
Drink (Yes/No)^b	19 (38.78%)/30 (61.22%)	15 (28.85%)/37 (71.15%)	22 (44.90%)/27 (55.10%)	0.2304
Exercise (Yes/No)^b	12 (24.49%)/37 (75.51%)	16 (30.77%)/36 (69.23%)	11 (22.45%)/38 (77.55%)	0.6372
Treatment expectation^c,d	6.86 (6.43, 7.28)	6.56 (6.12, 6.99)	6.29 (5.91, 6.66)	0.1561
Duration of symptom (Month)^c	76.37 (53.54, 99.19)	72.35 (53.59, 91.10)	82.22 (55.85, 108.60)	0.8237

Notes: ^aData are presented as mean and 95% confidence interval or number (%). ^bFisher’s exact test. ^cAnalysis of variance test. ^dSelf-report questionnaires are used on a scale of 1 to 9, with higher scores indicating higher expectations.

Abbreviation: BMI, body mass index.

Figure 1 Study flowchart.

Table 2 Subjective Sleep Measures

Variables	Electroacupuncture (n=49)		Sham (n=52)		Usual Care (n=49)		P value (Electroacupuncture versus Sham)	P value (Electroacupuncture versus Usual Care)
	Mean (95% CI)	P value (Within Group)	Mean (95% CI)	P value (Within Group)	Mean (95% CI)	P value (Within Group)
ISI
Baseline	19.02 (17.80, 20.24)		19.59 (18.47, 20.72)		18.90 (17.52, 20.28)
Week 2	13.81 (12.58, 15.04)	<0.0001	14.38 (12.80, 15.96)	<0.0001	17.56 (16.07, 19.04)	0.0494	0.6404	<0.0001
Week 4	10.13 (8.84, 11.41)	<0.0001	11.91 (10.28, 13.54)	<0.0001	16.63 (15.29, 17.97)	0.0014	0.0866	<0.0001
Week 8	8.60 (7.19, 10.02)	<0.0001	11.28 (9.44, 13.11)	<0.0001	15.37 (14.03, 16.71)	<0.0001	0.0213	<0.0001
Week 12	8.02 (6.42, 9.62)	<0.0001	10.38 (8.65, 12.11)	<0.0001	14.62 (13.38, 15.86)	<0.0001	0.0446	<0.0001
PSQI
Baseline	11.18 (10.28, 12.09)		10.92 (9.73, 12.12)		11.63 (10.74, 12.52)
Week 2	9.02 (8.07, 9.97)	<0.0001	9.74 (8.71, 10.78)	<0.0001	10.82 (9.84, 11.80)	0.0374	0.4514	0.0048
Week 4	7.38 (6.48, 8.27)	<0.0001	7.94 (6.87, 9.00)	<0.0001	10.46 (9.49, 11.42)	0.0043	0.5178	<0.0001
Week 8	6.79 (5.79, 7.79)	<0.0001	7.70 (6.54, 8.86)	<0.0001	10.13 (9.12, 11.14)	0.0013	0.2488	<0.0001
Week 12	6.56 (5.53, 7.59)	<0.0001	7.21 (6.01, 8.41)	<0.0001	9.95 (8.87, 11.03)	0.0019	0.4848	<0.0001
Sleep diary (SOL, min)
Baseline	63.62 (51.42, 75.83)		54.28 (45.20, 63.35)		42.71 (35.26, 50.16)
Week 2	43.32 (33.77, 52.87)	0.0003	45.31 (36.39, 54.22)	0.0344	41.99 (33.72, 50.25)	0.7908	0.2690	0.0767
Week 4	39.31 (30.33, 48.30)	<0.0001	37.83 (29.85, 45.81)	0.0002	40.91 (33.18, 48.65)	0.5539	0.6164	0.0113
Week 8	37.44 (26.88, 48.00)	<0.0001	36.82 (28.87, 44.77)	0.0002	39.51 (32.79, 46.23)	0.2966	0.5705	0.0207
Week 12	33.95 (26.81, 41.09)	<0.0001	34.59 (27.67, 41.52)	<0.0001	37.40 (30.59, 44.22)	0.1363	0.4436	0.0234
Sleep diary (WASO, number)
Baseline	1.98 (1.69, 2.28)		2.27 (1.92, 2.61)		1.78 (1.45, 2.12)
Week 2	1.61 (1.38, 1.85)	0.0011	1.80 (1.51, 2.09)	0.0001	1.76 (1.44, 2.08)	0.8546	0.8811	0.0435
Week 4	1.51 (1.26, 1.76)	<0.0001	1.77 (1.48, 2.06)	<0.0001	1.65 (1.35, 1.94)	0.2294	0.5121	0.0667
Week 8	1.48 (1.21, 1.75)	<0.0001	1.82 (1.48, 2.17)	0.0067	1.64 (1.31, 1.96)	0.1669	0.3303	0.0588
Week 12	1.34 (1.10, 1.57)	<0.0001	1.78 (1.46, 2.09)	0.0004	1.68 (1.29, 2.07)	0.5923	0.0755	0.0392
Sleep diary (TST, min)
Baseline	327.3 (307.9, 346.8)		320.2 (298.6, 341.8)		325.6 (302.5, 348.9)
Week 2	357.0 (339.1, 374.9)	<0.0001	350.2 (329.9, 370.6)	0.0002	327.7 (306.7, 348.7)	0.7901	0.8489	0.0030
Week 4	365.0 (350.8, 379.3)	<0.0001	358.9 (337.0, 380.9)	<0.0001	332.3 (312.8, 351.8)	0.4640	0.8576	0.0010
Week 8	375.1 (359.9, 390.4)	<0.0001	363.9 (342.8, 385.1)	<0.0001	343.7 (321.7, 365.6)	0.0665	0.5071	0.0040
Week 12	375.3 (356.8, 393.8)	<0.0001	369.6 (348.6, 390.6)	<0.0001	349.2 (329.2, 369.2)	0.0195	0.8609	0.0310
Sleep diary (SE, %)
Baseline	79.6 (76.2, 83.1)		78.6 (74.4, 82.9)		83.1 (79.2, 87.1)
Week 2	84.4 (80.6, 88.3)	0.0115	81.8 (78.0, 85.6)	0.0628	83.5 (79.5, 87.4)	0.8185	0.3668	0.1510
Week 4	87.8 (84.9, 90.8)	<0.0001	82.9 (79.2, 86.8)	0.0313	83.1 (79.1, 87.1)	0.9755	0.0397	0.0002
Week 8	88.4 (85.1, 91.7)	<0.0001	84.7 (81.3, 88.1)	0.0005	83.3 (79.2, 87.3)	0.9189	0.1028	0.0001
Week 12	88.2 (85.2, 91.3)	<0.0001	84.6 (81.4, 87.9)	0.0042	85.9 (82.5, 89.3)	0.0834	0.1147	0.0307

Notes: Bold values mean statistical significance within-group or inter-group (P<0.05). Week 4 was the end of treatment.

Abbreviations: CI, confidence interval; ISI, insomnia severity index; PSQI, Pittsburgh Sleep Quality Index; SE, sleep efficiency; SOL, sleep onset latency; TST, total sleep time; WASO, waking after sleep onset.

Figure 2 Mean Insomnia Severity Index scores of three groups during the study period *Significant difference between electroacupuncture and usual care, P<0.0001; ^#Significant difference between electroacupuncture and sham, P<0.05; ⁺The end of treatment.

Table 3 Other Clinical Outcome Measures

Variables	Electroacupuncture (n=49)		Sham (n=52)		Usual Care (n=49)		P value (Electroacupuncture versus Sham)	P value (Electroacupuncture versus Usual Care)
	Mean (95% CI)	P value (Within Group)	Mean (95% CI)	P value (Within Group)	Mean (95% CI)	P value (Within Group)
HADS (anxiety)
Baseline	4.59 (3.59, 5.60)		4.85 (3.75, 5.94)		6.24 (5.15, 7.34)
Week 2	3.71 (2.78, 4.64)	0.0142	4.11 (3.15, 5.06)	0.0059	6.18 (5.04, 7.31)	0.2617	0.9797	0.0010
Week 4	3.23 (2.35, 4.11)	<0.0001	3.40 (2.47, 4.34)	<0.0001	6.13 (5.03, 7.23)	0.5874	0.7394	<0.0001
Week 8	2.90 (1.97, 3.82)	<0.0001	3.49 (2.47, 4.51)	0.0002	6.09 (4.94, 7.23)	0.7099	0.5891	<0.0001
Week 12	2.63 (1.83, 3.42)	<0.0001	3.28 (2.29, 4.26)	<0.0001	5.80 (4.64, 6.96)	0.9999	0.4060	<0.0001
HADS (depression)
Baseline	5.22 (4.91, 5.54)		4.87 (4.57, 5.16)		6.22 (5.93, 6.52)
Week 2	4.47 (4.20, 4.74)	0.0257	4.52 (4.26, 4.78)	0.0856	6.44 (6.11, 6.77)	0.3488	0.4332	0.0062
Week 4	3.79 (3.48, 4.10)	<0.0001	3.71 (3.47, 3.96)	0.0021	6.04 (5.74, 6.34)	0.7241	0.7104	0.0011
Week 8	3.62 (3.31, 3.94)	0.0004	3.63 (3.37, 3.90)	0.0013	6.09 (5.76, 6.41)	0.7978	0.6628	0.0011
Week 12	3.20 (2.94, 3.47)	<0.0001	3.15 (2.90, 3.40)	<0.0001	6.04 (5.70, 6.38)	0.8079	0.7382	<0.0001
HADS (total)
Baseline	9.82 (7.90, 11.74)		9.71 (7.78, 11.64)		12.47 (10.53, 14.40)
Week 2	8.17 (6.48, 9.86)	0.0105	8.77 (7.08, 10.45)	0.0084	12.38 (10.23, 14.53)	0.2613	0.5984	0.0007
Week 4	7.00 (5.21, 8.79)	<0.0001	7.23 (5.65, 8.82)	<0.0001	12.00 (10.03, 13.97)	0.9204	0.9710	<0.0001
Week 8	6.50 (4.62, 8.38)	<0.0001	7.21 (5.50, 8.93)	<0.0001	12.00 (9.91, 14.09)	0.9238	0.5667	<0.0001
Week 12	5.81 (4.26, 7.36)	<0.0001	6.49 (4.82, 8.16)	<0.0001	11.64 (9.47, 13.82)	0.8917	0.4514	<0.0001
EQ-5D
Baseline	0.910 (0.893, 0.927)		0.895 (0.869, 0.920)		0.880 (0.859, 0.901)
Week 2	0.912 (0.889, 0.934)	0.9421	0.910 (0.894, 0.926)	0.1914	0.889 (0.868, 0.911)	0.3278	0.7050	0.9548
Week 4	0.927 (0.916, 0.938)	0.0597	0.919 (0.904, 0.935)	0.0607	0.882 (0.853, 0.911)	0.8392	0.5679	0.0384
Week 8	0.915 (0.893, 0.936)	0.7142	0.921 (0.902, 0.940)	0.0785	0.895 (0.865, 0.925)	0.0801	0.5022	0.6480
Week 12	0.928 (0.912, 0.944)	0.0589	0.923 (0.906, 0.941)	0.0763	0.902 (0.883, 0.921)	0.0186	0.7368	0.2018
EQ-VAS
Baseline	73.14 (68.65, 77.63)		73.29 (69.74, 76.83)		63.84 (59.08, 68.60)
Week 2	73.35 (69.49, 77.22)	0.8151	76.85 (72.53, 81.17)	0.0306	65.42 (60.47, 70.38)	0.5091	0.1141	0.2809
Week 4	78.71 (74.52, 82.89)	0.0004	79.13 (75.11, 83.14)	0.0029	67.48 (62.77, 72.19)	0.0861	0.9727	0.0350
Week 8	77.79 (73.18, 82.40)	0.0035	80.65 (76.56, 84.74)	0.0003	69.22 (64.33, 74.10)	0.0253	0.3047	0.3966
Week 12	81.42 (76.55, 86.28)	<0.0001	80.26 (75.62, 84.89)	0.0027	72.07 (67.95, 76.19)	0.0011	0.5689	0.1365
PGIC (treatment success, %)
Week 2	14.58 (7.25, 27.17)		17.02 (8.89, 30.14)		2.22 (0.39, 11.57)		RR 0.86 (0.34, 2.17)	RR 6.56 (0.84, 51.26)
Week 4	50.00 (36.39, 63.61)		31.91 (20.40, 46.17)		6.52 (2.24, 17.50)		RR 1.57 (0.95, 2.59)	RR 7.67 (2.48, 23.73)
Week 8	58.33 (44.28, 71.15)		41.30 (28.29, 55.66)		6.52 (2.24, 17.50)		RR 1.41 (0.93, 2.15)	RR 8.94 (2.92, 27.41)
Week 12	62.50 (48.36, 74.78)		44.68 (31.41, 58.75)		11.11 (4.84, 23.50)		RR 1.40 (0.95, 2.06)	RR 5.63 (2.39, 13.23)
Saliva melatonin (10PM)
Baseline	5.03 (3.37, 6.68)		7.17 (4.63, 9.71)		7.25 (5.08, 9.43)
Week 4	5.44 (3.55, 7.34)	0.6640	6.45 (4.27, 8.62)	0.4208	7.00 (4.65, 9.35)	0.6855	0.9594	0.5316
Saliva melatonin (7AM)
Baseline	7.53 (5.39, 9.66)		8.06 (5.81, 10.31)		8.79 (6.38, 11.19)
Week 4	7.06 (4.98, 9.14)	0.5747	7.16 (4.92, 9.40)	0.5766	7.99 (5.61, 10.37)	0.8639	0.9211	0.5064
Saliva cortisol (10PM)
Baseline	0.053 (0.036, 0.070)		0.050 (0.031, 0.070)		0.081 (0.046, 0.115)
Week 4	0.049 (0.036, 0.062)	0.6249	0.050 (0.036, 0.064)	0.9619	0.067 (0.050, 0.084)	0.4944	0.7964	0.1109
Saliva cortisol (7AM)
Baseline	0.267 (0.226, 0.309)		0.253 (0.207, 0.298)		0.263 (0.208, 0.319)
Week 4	0.276 (0.234, 0.318)	0.6522	0.225 (0.179, 0.271)	0.2262	0.243 (0.189, 0.298)	0.6632	0.1374	0.3100

Notes: Bold values mean statistical significance within-group or inter-group (P<0.05). Week 4 was the end of treatment.

Abbreviations: CI, confidence interval; EQ-5D, EuroQol five dimension; EQ-VAS, EuroQol visual analogue scale; HADS, Hospital Anxiety and Depression Scale; PGIC, Patient Global Impression of Change; RR, relative risk.

Table 4 Number of Adverse Events

Adverse Event	Electroacupuncture (626 Visits)	Sham (616 Visits)	Usual Care (231 Visits)	Total
Overall	42	27	37	106
Serious adverse event	0	0	0	0
Upper respiratory infection	24 (57.14%)	13 (48.15%)	25 (67.57%)	62 (58.49%)
Dyspepsia	7 (16.67%)	4 (14.81%)	4 (10.81%)	15 (14.15%)
Headache	1 (2.38%)	4 (14.81%)	0	5 (4.72%)
Low back pain	1 (2.38%)	0	1 (2.70%)	2 (1.89%)
Pruritus	1 (2.38%)	1 (3.70%)	0	2 (1.89%)
Others	8 (19.05%)	5 (18.52%)	7 (18.92%)	20 (18.87%)