Revision for Psychiatry & Clinical Neuroscience (PCN-0257-2019)-R3

An assessor-participant blinded, randomized controlled trial of dense cranial

electroacupuncture stimulation plus body acupuncture for neuropsychiatric
sequelae of stroke
(Running title: Acupuncture for poststroke)

Zhang-Jin Zhang, MD, PhD, a*§, Hong Zhao, MD b§, Gui-Xing Jin, MD c§, Sui-Cheung
Man, PhD a, Yi-Si Wang, MS b, Ying Wang, MD b, Hai-Rong Wang, MD b, Meng-Han Li,
MS b, Lo-Lo Yam, PhD a, Zong-Shi Qin, MS a, Kim-Kam Teresa Yu, MD d, Jing Wu, MD e,
Fung-Leung Bacon Ng, MS f, Tat-Chi Eric Ziea, PhD f, Pei-Jing Rong, PhD g

a
School of Chinese Medicine, the University of Hong Kong, Hong Kong, China
b
Department of Acupuncture and Moxibustion, First Teaching Hospital & National Clinical
Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin University of
Traditional Chinese Medicine, Tianjin 300193, China
c
Department of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang,
Hebei 050031, China
d
Department of Rehabilitation, Kowloon Hospital, Hong Kong, China
e
The Hong Kong Buddhist Association-the University of Hong Kong Clinical Centre for
Teaching and Research in Chinese Medicine, Kowloon, Hong Kong
f
Chinese Medicine Department, Hospital Authority, Hong Kong, China
g
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences,
Beijing 100700, China
* Corresponding Author:
Zhang-Jin Zhang, BMed, MMed, PhD
School of Chinese Medicine
The University of Hong Kong
10 Sassoon Road, Pokfulam
Hong Kong, China
Tel: (852)3917-6445
Fax: (852)2872-5476
E-mail: zhangzj@ hku.hk

§ These authors made equal contribution.

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/pcn.12959

This article is protected by copyright. All rights reserved.

Abstract

Aim: Acupuncture has benefits in the rehabilitation of neuropsychiatric sequelae of stroke.

This study was aimed to evaluate the effectiveness of dense cranial electroacupuncture
stimulation plus body acupuncture (DCEAS+BA) in treating poststroke depression (PSD),
functional disability, and cognitive deterioration.
Methods: In this assessor- and participant-blinded, randomized controlled trial, 91 stroke
patients who initially had PSD were randomly assigned to DCEAS+BA (n = 45) and
minimum acupuncture stimulation (MAS) as controls (n = 46) for 3 sessions per week over
8 consecutive weeks. The primary outcome was baseline-to-endpoint change in score of the
17-item Hamilton Depression Rating Scale (HAMD-17). Secondary outcomes included the
Montgomery-Asberg Depression Rating Scale (MADRS) for depressive symptoms, Barthel
Index (BI) for functional disability, and Montreal Cognitive Assessment (MoCA) for
cognitive function.
Results: DCEAS+BA-treated patients showed strikingly greater endpoint reduction than
MAS in scores of the three symptom domains. The clinical response rate, defined as an at
least 50% baseline-to-endpoint reduction in HAMD-17 score, was markedly higher in CAT-
treated group than that of controls (40.0% vs. 17.4%, P = 0.031). Incidence of adverse
events was not different in the two groups. Subgroup analysis revealed that DCEAS+BA
with electrical stimulation on forehead acupoints was more apparent than that without
electrical stimulation in reducing BI-measured disability.
Conclusions: DCEAS+BA particularly with electrical stimulation on forehead acupoints
reduces PSD, functional disability, and cognitive deterioration of stroke patients. It can serve
as an effective rehabilitation therapy for neuropsychiatric sequelae of stroke
[www.clinicaltrials.gov (NCT02644161)].

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Keywords: acupuncture; dense cranial electroacupuncture stimulation (DCEAS); cognitive
impairment; functional disability; post-stroke depression.

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Introduction

An apparent challenge in the management of stroke is neuropsychiatric sequelae which have

dramatically reduced stroke survivors’ quality of life.1 While a large proportion of stroke
survivors had physical disability 2 approximately 20%-30% of stroke patients experienced
post-stroke depression (PSD) and cognitive impairment.1,3 Although various rehabilitative
therapies have been introduced to the treatment of post-stroke neuropsychiatric sequelae, the
effectiveness is unsatisfactory and suboptimal.4 A search for alternative strategies is thus
greatly desired.

As an ancient therapeutic technique of traditional Chinese medicine (TCM), various

acupuncture therapies have been widely introduced into the management of poststroke

neurological deficits and PSD and suggested to be beneficial in poststroke rehabilitation,

including PSD, functional disability, and cognitive deterioration, although most related

clinical studies lacked the rigorousness of the design and details of methodologies.5-7

Recently, we have developed a novel acupuncture mode called dense cranial

electroacupuncture stimulation plus body acupuncture (DCEAS+BA) specifically used for

poststroke rehabilitation.8 Electrical stimulation on dense forehead acupoints is often used in

the treatment of various psychiatric symptoms and have been shown to have benefits in

treating major depression,9 postpartum depression,10 and obsessive-compulsive disorder

(OCD).11 Our pilot controlled trial has revealed the potential effects of DCEAS+BA in

reducing PSD and daily functional disability.12 These studies have led us to hypothesize that

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DCEAS+BA may be an effective therapy in the management of neuropsychiatric sequelae

of stroke.

To test this hypothesis, the present study was designed to determine whether DCEAS+BA

could produce better clinical outcomes in reducing PSD, functional disability, and cognitive

performance in comparison with minimum acupuncture stimulation (MAS) as controls

using assessor- and participant-blind, randomized controlled design.

Methods

Settings and subjects

This assessor- and participant-blind, randomized controlled trial was conducted in

Department of Rehabilitation of Kowloon Hospital at Hong Kong and Department of

Acupuncture and Moxibustion, the First Affiliated Hospital, Tianjin University of

Traditional Chinese Medicine at Tianjin of China between April 2016 and July 2018. The

study protocol was approved separately by Institutional Review Board (IRB) of the

University of Hong Kong, Hospital Authority Hong Kong West Cluster, and the First

Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, and registered in

www.clinicaltrials.gov (NCT02644161). All participants gave voluntary, written, informed

consent before entering the trial. We reported this trial according to CONSORT (see

supporting information) with CONSORT Figure (Fig. 1).

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Patients who meet the following criteria were eligible for the study: (1) men or women aged

35 to 80 years; (2) recently experienced an ischemic or haemorrhagic stroke, documented by

cerebral computed topographic scanning or magnetic resonance imaging before this study;

(3) had developed significant depressive episode, with the 17-item Hamilton Rating Scale

for Depression (HAMD-17) score of 16 or greater;13 and (4) had no difficulty to

communicate with investigators, give informed consent, and complete clinical assessments.

Patients who met one of the following criteria were excluded: (1) presence of severe

aphasia; (2) presence of epilepsy, Parkinson’s disease, severe cardiovascular, hepatic, and

renal condition; (3) suicide attempts or aggressive behavior; (4) investigational drug

treatment within the previous 6 months; (5) a history of alcohol or drug abuse within the

previous 12 months; (6) heart pacemaker or other electronic devices implanted in the body;

or (7) had bleeding tendency.

Randomization and blinding

Following conformance of patients’ eligibility, they were randomly assigned to

DCEAS+BA and MAS in a ratio of 1:1 based on central random codes which are were

simple, complete, non-sequential numbers and produced in advance using a computer-

generated random block at each site. The group allocation was done in a partially double-

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blind manner. Clinical assessors (S.C. M., Y.S.W., M.H.L.) were blinded to patients’

treatment. Patients were told that they would receive acupuncture treatment, but they were

not told about numbers of acupoints and stimulation modes.

Treatment procedures

Acupuncture intervention: Most participants who did not have psychotropic treatment at

entry started acupuncture treatment immediately. Five participants who were under

antidepressant treatment at entry were required to gradually withdraw their antidepressants

within one week and then started acupuncture procedure.

Acupuncture intervention was conducted for 3 sessions per week over 8 consecutive weeks.

The determination of 8 weeks of the treatment duration was based on the fact that the robust

effects of acupuncture in stroke survivors were generally observed within 8 weeks of

treatment.6 A brief introduction of acupuncture procedure was given by acupuncturists

during first visit. All sessions of acupuncture treatment for a patient were performed by the

same acupuncturist in order to eliminate deviations from different acupuncturists. Acupoints

used for DCEAS+BA and MAS are illustrated in Fig. 2.

For DCEAS+BA, the following 6 pairs of frontal acupoints with electrical stimulation were

used: Baihui (GV20, +) and Yintang (EX-HN3, -), left Sishencong (EX-HN1, -) and

Toulinqi (GB15, +), right Sishencong (EX-HN1, -) and Toulinqi (GB15, +), bilateral

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Shuaigu (GB8, L+, R-), bilateral Taiyang (EX-HN5, L+, R-), and bilateral Touwei (ST8,

L+, R-). Meanwhile, the following 15 body acupoints with only manual stimulation were

used: Shen-Men (HT7), He-Gu (LI4), Qu-Chi (LI11), Guan-Yuan (CV4), Zu-San-Li

(ST36), Feng-Long (ST40) and San-Yin-Jiao (SP6) (all in bilateral), and Shui-Gou (GV26).

Disposable acupuncture needles (0.30 mm in diameter and 25-40 mm in length) were

inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual

manipulation was then conducted to evoke needling sensation.

In Hong Kong site, electrical stimulation was additionally delivered on the 6 pairs of frontal

acupoints, with positive (+) and negative (-) electrode cord connection as shown above. The

output peak current and voltage of the machine (model: ITO ES-360) were 6 V and 48 mA,

respectively. Stimulation parameters were constant wave at frequency of 2 Hz and phase

duration of 100 µs for 30 min. The intensity of stimulation is adjusted to a level at which

patients feel most comfortable. The use of the low frequency rather high frequency is

because it could modulate biochemical adaptation of the brain in more favorable manner in

improving cognitive functions.14 The body acupoints were stimulated only manually at 15

min. In Tianjin site, due to procedure deviation, all frontal and body acupoints were

stimulated manually, i.e., after needling sensation was achieved, the needles were retained

for 30 min and manipulated at once again during retaining to maintain needling sensation.

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For MAS, the following 6 acupoints were used: bilateral Tong-Tian (GB17, L+, R-),

bilateral Shou-San-Li (LI10) and bilateral Fu-Yang (BL59). Electrical stimulation was only

performed on bilateral Tong-Tian (GB17) and the parameters are the same as above, but the

intensity are adjusted to a level at which patients just started feeling stimulation. The choice

of this control regimen was based on the following two criteria: (i) The acupoints chosen are

unrelated or less related to the treated syndromes according to TCM theory; and (ii) the

number of acupoints used and the intensity of electrical stimulation are kept to a minimum

level at which patients are still aware of receiving active acupuncture treatment.

Concomitant treatments: Considering the fact that a considerable portion of stroke patients

might have physical rehabilitation therapy and cardiovascular medications, participants

would be allowed for these concomitant treatments during the study. Antidepressant and

other psychotropic drugs were generally not allowed during the study. However, if clinically

significant insomnia occurred that could interfere with the continuation of experimental

treatment, benzodiazepines and non-benzodiazepines were allowed only for acute use.

Clinical assessment

The primary outcome was baseline-to-endpoint change in score of the 17-item Hamilton

Depression Rating Scale (HAMD-17). Secondary outcomes included the Montgomery-

Asberg Depression Rating Scale (MADRS)15 for depressive symptoms, Barthel Index (BI)

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for functional disability,16 and Montreal Cognitive Assessment (MoCA) for cognitive

function.17 The reason for the measurement of movement and cognitive function is that

acupuncture also has been confirmed to be beneficial in reducing physical disability and

cognitive deterioration.5,7 The clinical response, defined as <50% reduction at endpoint

from baseline on HAMD-17 score, and remission, defined as 7 points or less on HAMD-17

score were calculated. Adverse events are assessed using the Treatment Emergent Symptom

Scale (TESS).18

Data analysis

The sample size estimation was based on our previous pilot study12 revealing an
approximately 26% difference in the overall efficacy between the two groups with an

averaged standard deviation of 22%. A sample size of 45 each group would be sufficient to

yield a 90% power at a statistical level of 0.01.

Efficacy analyses were performed on the intention-to-treat population, defined as

participants who completed baseline and at least one evaluation after treatment. For the

missing data, the multiple imputation method was used under the missing at random

assumption. Sensitivity analysis with a tipping-point approach using pattern-mixture model

assessed the robustness of the missing data assumption at the end of treatment. Outcome

data were transformed as change from baseline in score of HAMD-17, MADRS, SDS, BI,

and MoCA at week 4 and 8. A generalized linear mixed-effect model was applied to

compare treatment outcomes over time between the two groups. The model was established

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using time and group for categorical fixed factors and random intercepts with scaled identity

covariance matrix. Study site and duration of the illness were treated as covariates.

Student t-test was applied to detect between-group differences in continuous baseline

variables. Categorical variables, including categorical baseline variables and incidence of

adverse events were analysed using Chi-square (χ2) or Fisher Exact test. Two-way analysis

of variance (ANOVA) was used for endpoint subgroup analysis. Statistical significance was

defined as a two-tailed P < 0.05. The analyses were performed with SPSS version 16

software (Chicago, IL, USA).

Results

Baseline characteristics of participants

The enrolment information is summarized in CONSORT Figure (Fig. 1). Of 5830 patients

screened, 91 participants were randomly assigned to DCEAS+BA (n = 45) and MAS (n =

46) group and 82 (91.1%) completed the 8-week treatment. All 91 completed baseline and at

least one evaluation after treatment, and then were included in intent-to-treat (ITT) analysis.

Most baseline variables were not different between the two groups, but duration of the

illness of DCEAS+BA was significantly greater than that of MAS (P = 0.003) and then

served as a covariate in outcome analysis (Table 1). There were no differences in age (P =

0.177), genders (P = 0.157), and the illness duration (P = 0.228) among the four subgroups

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of DCEAS and MAS with electrical acupuncture (EA) and manual acupuncture (MA) (data

not shown). There were 5 participants who were under antidepressant treatment at entry.

Efficacy

Changes in score from baseline on HAMD-17, MADRS, BI, and MoCA over time are

illustrated in Table 2 and Fig. 3. Linear mixed-effects model revealed a significant

interaction between group and time on HAMD-17 (F2,258 = 5.35, P = 0.006), BI (F2,259 =

3.24, P = 0.041), and MoCA (F2,254 = 4.15, P = 0.017), but not MADRS (F2,258 = 2.60, P =

0.076). Significant time main effects were observed on all the 5 outcome measures.

Significant group main effects were present on HAMD-17 (F1,258 = 7.36, P = 0.008),

MADRS (F1,258 = 7.30, P = 0.007), and MoCA (F1,254 = 7.40, P = 0.007). Between-group

comparisons showed that DCEAS+BA-treated patients had a significantly greater reduction

at endpoint in all the 5 outcome measures than MAS (P < 0.001). Significant interactions on

HAMD-17, BI, and MoCA (P ≤ 0.034) and significant group main effects on HAMD-17,

MADRS, and MoCA (P ≤ 0.006) were also observed in the analysis with the exclusion of

the 6 subjects with haemorrhagic stroke.

The clinical response rate of the DCEAS+BA group was significantly higher than that of

MAS (40.0% vs. 17.4%, P = 0.031). The remission rate was not significantly different

between the two groups (20.0% vs. 8.7%, P = 0.215).

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Subgroup analysis revealed that electrical acupuncture (EA) had a strikingly greater

improvement on BI score compared to manual acupuncture (MA) on the DCEAS+BA

group (P < 0.001), but there was no significant difference between EA and MA on the MAS

group (P = 0.760) (Table 3).

Incidence of adverse events

No severe adverse events were reported. The incidence of adverse events is summarized in

Table 4. The incidence of overall and individual adverse events were not significantly

different between the two groups.

Discussions

This study revealed that the DCEAS+BA treatment produced strikingly greater endpoint

reduction of scores of the two depression measures (HAMD-17 and MADRS) than MAS.

The DCEAS+BA-treated group also had a markedly higher clinical response rate defined

with HAMD-17, although the remission rate was not significantly different. This clearly

indicate that DCEAS+BA was effective in alleviating the severity of depressive symptoms.

Furthermore, the DCEAS+BA-treated patients had considerably better outcomes in

improving functional disability associated with daily self-caring activity and cognitive

performance. However, the incidence of adverse events of both groups was not different.

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These results confirm findings obtained in previous studies,5-7 suggesting that DCEAS+BA

is not only effective in reducing PSD, but also beneficial in improving post-stroke functional

disability and cognitive impairment.

The broad therapeutic effects observed may be related to acupuncture regimen used in this

study. Unlike previous studies in which most acupoints used for neuropsychiatric sequelae

of stroke are located on the body and generally stimulated only with manual manipulation,5-7

this study utilized a combination of dense forehead and body acupoints and electrical

stimulation was further conducted on the forehead acupoints. The forehead acupoints are

innervated by the trigeminal sensory pathway that has more intimate collateral connections

with the brainstem reticular formation, particularly the raphe nuclei containing serotonin (5-

HT)-producing neurons19,20 and the locus coeruleus containing noradrenaline (NA)-

producing neurons.21,22 A large body of evidence confirms that the brainstem 5-HT and NA

neuronal systems play a pivotal role in acupuncture modulation of multiple brain functions,

including the processing of locomotor, mood and cognition information.23,24 The addition of

electrical stimulation can enhance neuromodulatory effects of acupuncture.23,25 This notion

is confirmed by the subgroup analysis of this study that revealed much better outcomes of

electrical acupuncture (EA) than manual acupuncture (MA) in improving functional

disability of the DCEAS+BA-treated patients. Our previous studies have shown a rapid

antidepressant effect of EA on forehead acupoints9 and a long-lasting enhancement of the

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antidepressant effects of EA25 in the treatment of major depressive disorder. Moreover,

transcutaneous electrical stimulation on trigeminal branches-innervated forehead was

effective in reducing epilepsy, depression, and attention deficit hyperactivity disorder

(ADHD).26-29

It thus appears that a combination of DCEAS and body acupuncture particularly with

electrical stimulation on forehead acupoints could produce additive and even synergistic

effects by broadly modulating neurochemical pathways and brain regions. Indeed, it is well

documented that acupuncture with intense stimulation robustly modulate catecholaminergic

and endogenous opiate neuropeptides of the brain.30 It also affects brain regions associated

with neuropsychiatric sequelae of stroke.31

The superior efficacy achieved from DCEAS+BA may also be attributed to acupuncture

control mode and the number of acupoints used. Although there is a lack of standardized

control methods for acupuncture clinical trial research,32,33 it is generally accepted that MAS

is an appropriate design for controlling “placebo effect" of acupuncture.8 In this study, the

choice of MAS as control was based on neuroimaging findings that the more widespread

and intense effects of acupuncture in modulating brain regions are associated with more

efficient and effective acupuncture stimulation.8. This suggests that the optimal control for

brain effects of acupuncture should be kept at the minimum level in both quantity and

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quality of acupuncture stimulation. In addition, compared to other acupuncture control

procedures, MAS is more practicable and better maintenance of blinding.33 On the other

hand, there were a total of 25 acupoints used in this study, much more than most previous

similar studies.7 Inadequacy of acupuncture stimulation is thought to be an important factor

associated with negative results of acupuncture trials.8

Several limitations of this study should be considered. Firstly, although assessors and

participants were blind to treatment, acupuncturists were not blind to patients’ treatment.

Bias from acupuncturists could not be completely excluded.34 Furthermore, similar to most

previous studies,6 the determination of body acupoints used in this study was basically based

on empirical evidence. Empirical treatment regimens have resulted in a large variation in

acupuncture protocols and difficulties in comparing treatment outcomes among trials.

Secondly, the sample was mixed with ischemic and haemorrhagic strokes which

pathological profiles and symptom severity may vary. However, the results of outcome

analysis were similar in the inclusion and exclusion of subjects with haemorrhagic stroke.

One meta-analysis also has suggested the effectiveness of acupuncture in ischaemic and

haemorrhagic strokes.35 It is suggested that DCEAS+BA may have similar beneficial effects

in the two types of stroke. Thirdly, this study did not conduct follow-up and long-term

measurement. Whether DCEAS+BA could achieve similar long-term effects on

neuropsychiatric sequelae of stroke needs further clarification. Finally, no objective and

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biomedical approaches were included in the measurement of treatment outcomes. Our

neuroimaging study has suggested that acupuncture effects on stroke may be associated with

its activation of compensatory mechanism of residual neurons in affected brain regions.36

The further exploration of neuroimaging and molecular basis for acupuncture effects on

stroke would help gain some insights into neural mechanisms of acupuncture.

In summary, DCEAS+BA, particularly with electrical stimulation, is effective in improving

post-stroke depression, functional disability, and cognitive performance. It can serve as an

effective therapy for the treatment of neuropsychiatric sequelae of stroke.

Acknowledgement

We thank Dr. Jennifer Ma Wai-Wai Myint and Ms. Mei-Mei Mo for their support in patient

recruitment, Ms. Stella Chan for her assistance in data input. This study was supported by

fund from Chinese Medicine Department of Hospital Authority of Hong Kong, the National

Key R&D Program of China (2018YFC1705800, 2018YFC1705801), and “One Belt, One

Road” International Cooperation Project of Traditional Chinese Medicine of China

Academy of Chinese Medical Sciences (GH2017-07).

Disclosure of conflicts of interest

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The authors declare no financial or other conflicts of interest.

Author contributions

ZZJ, HZ, FLBN, and TCZ were involved in conception and design of the study and the

preparation of the manuscript. YSW, YW, HRW, LLY, KKTY, and JW screened, recruited,

and treated subjects. SCM and MHL conducted clinical assessment. ZZJ, GXJ, and ZSQ

conducted data analysis and re-analysis. GXJ and PJR critically read the revised manuscript.

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 Legends for figures

Fig. 1. CONSORT figure. DCEAS+BA, dense cranial electroacupuncture stimulation plus

body acupuncture; MAS minimum acupuncture stimulation.

Fig. 2. Acupoints used in dense cranial electroacupuncture stimulation plus body

acupuncture (DCEAS+BA) and minimum acupuncture stimulation (MAS) as controls.

Fig. 3. Treatment outcomes of stroke patients measured using the 17-item Hamilton Rating

Scale for Depression (HAMD-17) (A), Montgomery-Asberg Depression Rating Scale

(MADRS) (B), Barthel Index (BI) (C), and Montreal Cognitive Assessment (MoCA) (D).

Data were analyzed using covariance (ANCOVA), followed by Student–Newman–Keuls

test to detect between-group differences. * indicates P ≤ 0.005. DCEAS+BA, Dense Cranial

Electroacupuncture Stimulation plus Body Acupuncture; MAS, Minimum Acupuncture

Stimulation

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Table 1. Baseline characteristics
Variables DCEAS+BA (n = 45) MAS (n = 46) P value a,b
Male, n (%) a 30 (66.7) 26 56.5) 0.436
b
Age (y) 61.3 ± 8.9 63.9 ± 9.2 0.174
Having previous stroke, n (%) a 23 (51.1) 21 (45.7) 0.756
b
Post-stroke duration (month) 29.4 ± 60.0 8.9 ± 12.0 0.003
b
Duration of PSD onset (month) 2.1 ± 2.7 2.1 ± 2.2 0.756
a
Current antidepressant treatment, n (%) 3 (6.7) 2 (4.3) 0.677
Current physical therapy, n (%) a 18 (40.0) 21 (45.6) 0.739
a
Regular alcohol drinkers, n (%) 6 (13.3) 4 (8.7) 0.522
a
Regular smokers, n (%) 12 (26.7) 14 (30.4) 0.868
a
Comorbid cardiovascular diseases, n (%) 24 (53.3) 26 (56.5) 0.924
Comorbid diabetes, n (%) a 17 (37.8) 17 (37.0) 0.892
a
Previous acupuncture experience, n (%) 29 (64.4) 29 (63.0) 0.937
b
Stroke types, n (%) 1.000
Ischemic 42 (93.3) 43 (93.5)
Haemorrhagic 3 (6.7) 3 (6.5)
a
Brain regions lesioned, n (%) 0.897
c
Basal ganglia 9 (20.0) 12 (26.1)
Brainstem 4 (8.9) 5 (10.9)
Frontoparietal lobe 3 (6.7) 2 (4.3)
Multiple regions 27 (60.0) 26 (56.5)
Unknown 2 (4.4) 1 (2.2)
b
Baseline HAMD-17 23.8 ± 4.2 23.7 ± 4.0 0.943
Baseline MADRS b 23.4 ± 7.1 21.9 ± 6.9 0.287
b
Baseline BI 43.7 ± 6.9 42.5 ± 8.2 0.440
b
Baseline MoCA 23.8 ± 4.5 24.8 ± 5.0 0.311
a 2
Categorical data were examined using Chi-square (χ ) or Fisher Exact test.
b
Continuous data are expressed as mean ± SD and examined using Student t-test.
c
Including lesion of bilateral and unilateral basal ganglia.
d
Antidepressant agents included fluoxetine and sertraline.
DCEAS+BA, Dense Cranial Electroacupuncture Stimulation plus Body Acupuncture; MAS,
Minimum Acupuncture Stimulation; PSD, post-stroke depression; HAMD-17, 17-item Hamilton

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Rating Scale for Depression; MADRS, Montgomery-Asberg Depression Rating Scale; BI,
Barthel Index; MoCA, Montreal Cognitive Assessment.

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Table 2. Treatment outcomes of acupuncture a,d
DCEAS+BA P value
Variables P value b MAS (n = 46) b Difference P value c
(n = 45)
HAMD-17
Week 4 -6.3 (-8.1, -4.6) <0.001 -3.9 (-5.7, 2.2) <0.001 -2.4 (-4.8, 0.0) 0.051
Week 8 -10.3 (-12.1, -8.6) <0.001 -5.5 (-7.2, 3.7) <0.001 -4.9 (-7.2, -2.5) <0.001
MADRS
Week 4 -6.3 (-8.0, -4.6) <0.001 -4.7 (-6.5, -3.0) <0.001 -1.6 (-3.9, 0.8) 0.186
Week 8 -11.5 (-13.2, -9.8) <0.001 -7.6 (-9.4, -5.7) <0.001 -4.0 (-6.4, -1.6) 0.001

BI
Week 4 2.3 (0.5, 4.1) 0.014 2.8 (1.0, 4.7) 0.003 -0.6 (-3.1, 2.0) 0.869
Week 8 2.6 (0.8, 4.5) 0.006 -1.1 (-3.0, 0.8) 0.266 3.7 (1.1, 6.3) 0.005
MoCA
Week 4 1.3 (0.5, 2.1) 0.003 0.6 (-0.2, 1.5) 0.152 0.7 (-0.5, 1.8) 0.271
Week 8 2.2 (1.4, 3.1) <0.001 -0.1 (-1.0, 0.8) 0.889 2.3 (1.1, 3.5) <0.001
a.
Data denotes change from baseline and are expressed as mean with 95% CI. The values were
adjusted with study site and duration of the illness. Linear mixed-effects model was used to
examine overall effects and between-group differences.
b.
Compared to baseline value within group.
c.
Compared between the two groups at the same measurement point.
d.
DCEAS+BA, Dense Cranial Electroacupuncture Stimulation plus Body Acupuncture; MAS,
Minimum Acupuncture Stimulation; PSD, post-stroke depression; HAMD-17, 17-item Hamilton
Rating Scale for Depression; MADRS, Montgomery-Asberg Depression Rating Scale; BI,
Barthel Index; MoCA, Montreal Cognitive Assessment

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Table 3. Subgroup analysis on electrical and manual acupuncture effects on BI a,b
Variables DCEAS+BA (n = 45) MAS (n = 46)
EA 6.1 ± 4.8 (11) 1.9 ± 2.5 (10)
MA 0.6 ± 2.6 (34) 2.3 ± 4.4 (36)
P value <0.001 0.760
a.
Data are expressed as mean ± standard deviation. Subject numbers are indicated in
parenthesis. P values represent a comparison between EA and MA.
b.
DCEAS+BA, Dense Cranial Electroacupuncture Stimulation plus Body Acupuncture;
MAS, Minimum Acupuncture Stimulation; BI, Barthel Index; EA, electroacupuncture;
MA, manual acupuncture.

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 Table 4. Adverse events a
Event CAT (n = 45) MAS (n = 46) P value
Any 7 (15.6) 8(17.4) 0.963
Dizziness 1 (2.2) 1 (2.2) 1.000
Nausea 0 1 (2.2) 1.000
Vomiting 0 1 (2.2) 1.000
Tiredness 3 (6.7) 6 (13.0) 0.485
Depression exacerbated 0 1 (2.2) 1.000
Movement disorder 2 (4.4) 1 (2.2) 0.617
Needling-induced discomfort 5 (11.1) 4 (8.7) 0.739
Sweating 0 2 (4.4) 0.495
Palpitation 1 (2.2) 1 (2.2) 1.000
Headache 3 (6.7) 2 (4.4) 0.980
Insomnia 2 (4.4) 3 (6.5) 1.000
Drowsiness 1 (2.2) 3 (6.5) 0.617
a
Data were examined using Chi-square (χ2) or Fisher Exact test. DCEAS+BA, Dense Cranial
Electroacupuncture Stimulation plus Body Acupuncture; MAS, Minimum Acupuncture
Stimulation

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Accepted Article

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.