Clinical research on the therapeutic effect of the I

electro-acupuncture
. *
treatment in patients
with depression
HECHUN LUO, FANQIANG MENG, YUNKUI JIA AND XUEYING ZHAO
BeijirLq, PR Clrirro
Drprfrrrcrit oflidifiorrd Cliirrese .\fctlicirre, bistifirte 4fdfcrir.d Hrdrh, Brijirg .\fcdico/ Uiiii*ersif):

Abstract Electro-acupuncture (EA) stiniulation has been found to influence the brain (norepinephrine nietabolism in
experimental animals). Preliminary clinical research has shown that EA treatment is as effective as aniitriptyline for '
patients with depression. In this study, two consecutive clinical studies o n the treatment of depression with EA are
conducted.The first study was double blind placebo controlled, in which 29 depressed inpatients wvere recruited.
Patients were randomly divided into three groups: EA + placebo; aniitriptyline; and EA + amitriptyline. They
received EA and/or aniitriptyline treatment for 6 weeks.The Handton Rating Scale for Depression, Clinical Global
Impression and ASBERG scales for the side effect of antidepressants were used to evaluate the therapeutic efficacy
and side effects. Based on the results and research protocol of the first study, a multi-centered collaborative study
was conducted, in which 241 inpatients with depression were recruited. Patients \vere randonily divided into two
treatment groups: the EA + placebo and the aniitriptyline groups. The results from both studies showed that the
therapeutic efficacy ofEA w3s equal to that of aniitriptyline for depressive disorders ( P > 0.03).Electro-acupuncture
had a better therapeutic effect for anxiety somatization and cognitive process distnrbance of depressed patients than
aniitriptyline ( P < 0.05). Moreover, the side effects ofEA were much less than that ofaniitriptyline ( P < 0.001).The
article suggested that EA treatment was an effective therapeutic method for depressive disorders. Particularly, it was
a treatment of choice for depressed patients who were unable to comply with the classic tricyclic antidepressants
because of their anticholinergic side effects.The possible mechanisni of EA treatment is discussed.
Key words aniitriptyline depression, electro-acupuncture.

INTRODUCTION MATERIALS AND METHODS

Acupuncture has been used in China for more than 1000 years
in the treatment of both somatic diseases and mental disorders.
In the 1950s, electric stimnlation was applied to the acupuncture
needle to act o n the nerve cells around the acupoints, so called
electro-acupuncture (EA).The early trials during the 1960s and
1970s of EA treatment o n depression were not standardized
both in subject inclusion and treatment technique. T h e effec-
tiveness of the EA treatment o n depression could not be derived
from those trials. However, EA was adopted in many other
countries for the relief of localized pain with considerable suc-
cess.1*2Animal esperinients showed that brain norepinephrine
(NE) and its plain metabolite in the brain decreased significantly
after EA stimulation in rats: which indicated there was a meta-
bolic alternation of the N E system in rat brain after EA treat-
ment. O u r clinical pilot trial showed that the EA treatment was
as effective as amitriptyline for the patients with depression."
Moreover, it brought fewer side-effects than the traditional anti-
depressants did.To confirm our previous results, the present large
scale, double blind, and placebo-'controlled studies were
conducted.
Correspondence address: Luo Hechun, hl D , Department ofTraditiona1 Chinese
hledicinr. Institute of hlenwl Health, Ueijing hledical University. Beijing
100053, P I 1 China.
Subjects
All research subjects were inpatients. Patients recruited to our
study met the diagnostic criteria for depression that was revised
at the Huanghan symposium in 1981 by the Chinese Psychia-
tric A~sociation.~ Clinical data were collected with the present
state examination (PSE) and the schedule for a standardized
assessnient of patients with depressive disorders (SADD) reconi-
mended by the World Health Organization (WHO). Only the
patients whose total score o n the Hamilton Rating Scale for
Depression (24 was 20 or more were recruited into
our study.
The study consisted of two phases. The first phase was a
placebo-controlled, double blind study. All the research subjects
\vere hospitalized in the closed ward of Institute of Mental
Health, Beijing Medical University, Beijing, China. A total of
29 patients was recruited. T h e mean age was 36.9 k 2.3 years.
T h e mean course ofthe present depressive episode was 7.9 2 5.4
months. Nine patients were bipolar depressive and the rest were
single depressive episodes. T h e patients in the study were drug
free for at least 1 week prior to treatment. Then they were
randomly divided into the three treatment groups.
1. Electro-acupuncture treatment group ( 1 1 = 8). Apart from
receiving EA treatment that lasted for 6 weeks, a total of 36
Electro-acupctlicturc in depression s339

Table 1. Factor analysis of HRSD in deprcsscd patients with elcctro-acupinictim (€A) and miitriptylinc treatment

Elcctro-acupuncture Aniitript).linc
Factor Ikfore Afrcr Before After

Anxiety somatization 1.35 f 0.05 0.17 f 0.03 1.74 rf: 0.06 0.32 f 0.05*
Wei~htchange 0.9s f 0.07 0.0s f 0.03 0.95 f 0.09 0.11 2 0.03
Co-gitivc disturbance 1.02 ? 0.05 0.14 2 0.03 1.09 f 0.0’3 0.27 f 0.06*
Diurnal variation 1.02 k 0.07 0.19 f 0.04 1.06 f 0.0s 0.19 f 0.04
Retardation 2.23 f 0.05 0.57 f 0.07 2.23 f 0.06 0.74 t 0.0s
Insomnia 1.12 f O.OG 0.21 rf: 0.04 1.09 f 0.06 0.30 f 0.05
Hdplessncss 2.45 f 0.0s 2.43 2 0.09 2.43 f 0.09 0.75 f 0.09
P < 0.05 compared with the corrcsponding value in EA group. EA, it = 133;anutriptylinc. II = 10s.

needlings, patients in this group also received placebo capsules
that were identical to amitriptyline in appearance.
2. Aniitriptyline treatment group ( I J = 1 l), patients with
depression received amitriptyline for 6 weeks. The dosage of
aniitriptyline was adjusted to an average of 175 mg per day.
3. Conibination treatment group (ti = 10). Patients in this
group were treated by EA with the same protocol as group 1
in addition to receiving amitriptyline, 150 mg per day for 6
weeks.
T h e second phase of the research was a collaborating study in
which 10 psychiatric hospitals participated and 241 depressed
inpatients were recruited (109 men and 132 wonien).The mean
age was 32 years with the present course of depression 5.4
months on average. Of the 241 patients, 193 were bipolar disor-
ders and 48 were reactive depression. After the inpatients had
remained drug free for at least 1 week they were randotidy
divided into two treatment groups. Group 1 consisted of 133
patients who were treated for 6 weeks with EA combining
placebo tablets that \vere identical to amitriptyline. Group 2
consisted of 108 patients who received aniitriptyline for 6 weeks
with an average dose of 161 mg per day.
Electro-acupuncture treatments
The acupoints applied were Baihui and Yingtang, which are
considered by traditional Chinese medicine to be effective acu-
points for relief of depression.The needle was inserted obliquely
in the frontal direction beneath the scalp for 2-3 cm at Baihui.
At theYingtang acupoint, the needle mas inserted obliquely and
upward, 2-3 cni beneath the skin. Then the needles were con-
nected to an EA stiniulator.Tlie applied current was 3-5 nlA.
The current wa! adjusted to the optimum when slight twitching
of the skin was visible around the needle and the patients
remained comfortable. The frequency of the stimuli was 2 Hz,
and 3.0-5.0 nlA was used. Each treatment session took 45 niin.
Patients received six treatment sessions per week. Each patient
received 36 treatments in total.
Assessment of effectiveness
Two trained psychiatrists who were blind to the treatments
esaniined the patients independently at the beginning of the
treatment and weekly aftenvards.The Hamilton Rating Scale for
Depression (HRSD), the Clinical Global Impression Chart
(CGI),’ and the Rating Scale for Side-effect (ASBERG)* were
used for eficacy evaluation. T h e grading system commonly
employed in China (GSC) for the assessnient of therapeutic
effects was used as wvell.Tlie GSC consisted of four categories:
cured, markedly improved, improved, and failed or deteriorated.
The agreements on the above rating scales between rates were
excellent (K > 0.80).
Equipment
The equipment used in our research were EA instruments,
models G6805.
Statistical m e t h o d
Student’s t-test was used for comparing the means between
different treatment groups, and X’ for side-effect comparison
between EA and aniitriptyline treatment groups.
RESULTS
The first phase of t h e research
The score of the H R S D in all the three groups reduced signi-
ficantly after the 6-week treatment period ( P < 0.01): EA +
placebo from 24.6 k 0.6 before treatment to 11.6 f 0.9 ( 1 2 = 8)
6 weeks 1ater;aniitriptyline from 28.9 k 0.7 to 9.9 f 0.7 (12 = 11);
and EA + amitriptyline from 30.1 2 0.6 to 13.0 f 0.8 (n = 10).
The HRSD score reductions were not different among three
groups ( P > 0.05).T h e changes of the CGI scores were almost
similar in each of the treatment groups after the 6-week
treatment.
The second phase of t h e research
T h e mean scores of H R S D in both the EA ( t i = 133) and the
amitriptyline group ( t i = 108) reduced significantly after the
6-week treatment ( P < O.Ol).The mean scores of the H R S D of
the EA group decreased from 36.5 2 0.8 before treatment to
8.9 2 1.0 ( 1 2 = 133) 6 weeks after treatment.The mean HRSD
score in the aniitriptyline-treated group decreased from 36.4 k
0.8 to 10.5 & 1.3 (12 = 108).The mean H R S D score reductions
were not different between the t\vo groups ( P > 0.03). No dif-
ference was observed o n the CGI rating between the two groups
after the 64veelr treatment ( P > 0.03).The GSC rating showed
that the rate for the cured together with the markedly improved
was 75.2% in the EA group and 66.7% in the aniitriptyline
S3-10 H. Luo et or.

Table 2. Rating score ofASI3ERG in t\vo groups

Slight Severe
Electro-acupuncture Amitriptyline D Electro-acupuncture Aniitriptyline P
Physical tiredness 26 38 > 0.05 6 8 > 0.05 '

Headaches 14 25 > 0.05 1 3 > 0.05

Dizziness 14 28 > 0.05 0 7 < 0.05
Orthostatic syndrome 2 18 < 0.01 0 3 0.05
Palpitation 16 43 < 0.01 0 11 < 0.01
Tremor 5 36 c 0.01 0 10 < 0.01
Perspiration 9 30 c 0.01 0 5 > 0.05
Dryness ofmouth 16 42 c 0.01 0 38 < 0.001
Constipation 8 30 c 0.01 0 24 < 0.001
Micturition disturbance 0 12 c 0.01 0 20 < 0.001
Drowsiness 0 0 0 0
Sleep disturbance 18 27 > 0.05 10 7 > 0.05
Intedercnce with sexval function 10 13 > 0.05 0 2 > 0.03
.Toul 138 342 : < 0.001 17 142 < 0.001
EA, II = 133;an;itriptyline. II = 108.

group ( P > 0.05). Factor analysis o n HRSD showed that EA had
a better therapeutic effect for anxiety somatization and cognitive
process disturbance than anutriptyline (P < 0.05;Table 1). More-
over, the EA treatment was more effective in the treatment of
reactive depression than was the anlitriptyline.The score reduc-
tion of HRSD in the EA group (from 30.5 t 1.7 to 5.2 5- 1.4) is
greater than that in the amitriptyline group ( P < 0.03).
T h e results of the ASBERG rating scale are shown inTable 2.
T h e side effects were significantly fewer in the EA treatment
group than in the anutriptyline group.
DISCUSSION
For the past 30 decades, chemicals such as tricyclic and rnono-
aniine oxidase inhibitors have been considered the drugs of
choice for antidepression. Yet the use of these chemicals was
far from satisfactory. Since 1981 we have undertaken series of
studies with EA. O u r pilot study and our present results appear
to have strong positive results. Compared with amitriptyline, EA
was as effective if not better towvards the treatment of depressive
disorders. The HRSD factor analysis showed that EA appeared
to have better therapeutic efficacy in relieving anxiety soniatiza-
tion and correcting the disturbance of cognitive process. More-
over, EA was more effective in treating patients with reactive
depression.
Aniitriptyline and other classic antidepressants usually result
in various degrees of side effects during treatment?." In con-
trast, EA had virtually no side effects. Patients did complain of
some somatic symptoms during EA treatment, such as physical
tiredness, headaches, dizziness etc., but we believe that these
somatic complaints were caused by the depression rather than by
the EA treatment.
It was believed that the metabolism of monoanline neuro-
transmitters was jeopardized in patients suffering from depres-
s i o x ~ . ~ ~Electro-acupuncture
*'~ has been shown to release
monoaniine~in the central nervous systeni." Biochemical study
of our depressed patients showed that their plasma norepineph-
rine level changed greatly after EA treatn1ent.I' This suggested
that the therapeutic efficacy o f EA treatment possibly exhibits
by acting on the metabolic niechanism of N E in the central
nervous system.
REFERENCES
1. Kaiser RS, Khatami MJ, Gatchel RJ, Huang XY, Bhatia K, Alrsshuler
KZ. Acupuncture relieve of chronic pain syndrome correlates with
increased plasma met-enkephalin concentration. Lancer 1983; 2:
1391-1396.
2. SzczudIikA, K\nsucki J. Beta endorphin-like immunorcactivity in the
blood ofpatients with chronic pain treated by pinpoint receptor stim-
ulation. A'eiirol. A'eiiroc/iir.pol. 1984; 18: 415-420.
3. Zhang\.V, ShenY. Changes in levels of monoamine neurotransmitters
and their main metabolites of rat brain after electro-acupuncture treat-
ment. 1iif.j. A'eriroxierice 1981; 15: 147-149.
4. Luo HC, Jia YK. Zhan L. Electroacupuncture versus amitridtyline in
the treatment of depressive states.J. E d . Chi. ,\fed. 1985; 5: 3-8 (in
Chinese).
5. Clinical Diagnosis Criterion for Depressive disorders. C/iiti.j.A'erirol.
Psyrliiarry 1985; 18:317 (in Chinese).
6. Kaplan HI er ol. Coritprchsirr Texfbook o/ Psychiafry V. Williams S-
Wilkins Press.Baltimore, 1989.
7. Luo HC, Jia YK. Efecfroanprtrrritre ?iearrrmit 4DeprPssiorr arid Related
A'CWTrrliiiiqiies or1 Corriliii~rioirojrrtstrrri arid Cliiiiese dfedicirie. Ueijing
Medical University Press, Beijing, 1992 (in Chinese).
8. Luo HC, JiaYK.Wu XH, Dai WM. Electroacupuncture in the treat-
ment of depressive psychosis. 1rif.J. Cliri.Aorpririctirre1990; 1: 7-13.
9. Richelson E, Nelson A. Anugonism by antidepressantsof neurotrans-
mitter receptor of normal human brain iit vitro.J. P/iariiracol.€ ~ p 77ier. .
1984;230:9+102.
10. Beasley CM. Fluoxtine: relationship among dose, response, adverse
events, and plasma concentration in the treatment of depression.
Psyclioyltarriracol. 1990; 87:253-259.
11. Morris JB. Beck AT.The efficacy of antidepressive drugs.A review of
research (1958-1972). Arch. Geri. Psychiatry 197-1;30: 179-182.
12. Zhou DF. Dexamethasone suppression test and urinary MHPG. SO4
excretion in depressive patients. Biol. PsycbLtry 1987; 22: 883.
13. Riederer I? Manipulation of neurotransmitters by acupuncture (a pre-
liminary communication).J. h'ciirJI. ?hiistii. 1975;37: 81-84.
14. Meng E LUO H, ShenY, Shu L, Lui J. Plasma NE concentration and 24
hour urinary MHPG. so4 escrerion changes after electro-acupuncture
treatment in endogenous depression. llbrld J. Acrrp. dfox. 1994; 4:
45-52.