Luo_et_al-1998-psychiatry_and_clinical_neurosciences.pdf

Clinical research on the therapeutic effect of the electro-acupuncture treatment in patients . * with depression I

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

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 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 effectiveness 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 success.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 metabolic alternation of the N E system in rat brain after EA treatment. 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 antidepressants 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.

MATERIALS AND METHODS 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 Psychiatric 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) reconimended 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

s339

Electro-acupctlicturc in depression

Table 1.

Factor analysis of HRSD in deprcsscd patients with elcctro-acupinictim (€A) and miitriptylinc treatment Elcctro-acupuncture

Factor Anxiety somatization Wei~htchange Co-gitivc disturbance Diurnal variation

Ikfore 1.35 0.9s 1.02 1.02

f 0.05 f 0.07 ? 0.05

k 0.07

0.19

2.23 f 0.05

Hdplessncss

2.45 f 0.0s

1.12

0.17 f 0.03 0.0s f 0.03 0.14 2 0.03

Retardation Insomnia

f

O.OG

Aniitript).linc Before

Afrcr

1.74 rf: 0.06 0.95 f 0.09 1.09

f 0.04 0.57 f 0.07

1.06 2.23 1.09 2.43

0.21 rf: 0.04 2.43 2 0.09

f 0.0’3 f 0.0s f 0.06 f 0.06 f 0.09

After

0.32 f 0.05* 0.11 2 0.03 0.27 f 0.06* 0.19 f 0.04 0.74 t 0.0s 0.30 f 0.05

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 disorders 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 acupoints 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 connected 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 significantly 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 difference 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

Table 2.

H. Luo et or.

Rating score ofASI3ERG in t\vo groups

Electro-acupuncture Physical tiredness Headaches Dizziness Orthostatic syndrome Palpitation Tremor Perspiration Dryness ofmouth Constipation Micturition disturbance Drowsiness Sleep disturbance Intedercnce with sexval function

.Toul

26 14 14 2 16 5 9 16 8 0

0 18 10 138

Slight Amitriptyline 38 25 28 18 43 36

30 42 30 12 0 27 13 342

Electro-acupuncture

> 0.05

6

8

> 0.05 > 0.05 < 0.01 < 0.01 c 0.01 c 0.01 c 0.01 c 0.01 c 0.01

1

3

0 0

7

0

11

0

10 5 38 24

> 0.05 > 0.05 :

Severe Aniitriptyline

D

< 0.001

0 0 0

0 0 10 0 17

3

20

P > 0.05 > 0.05 < 0.05 0.05 < 0.01

'

< 0.01 > 0.05 < 0.001 < 0.001 < 0.001

0

2

> 0.05 > 0.03

142

< 0.001

7

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). Moreover, the EA treatment was more effective in the treatment of reactive depression than was the anlitriptyline.The score reduction 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 rnonoaniine 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 soniatization and correcting the disturbance of cognitive process. Moreover, 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 contrast, 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 neurotransmitters was jeopardized in patients suffering from depress 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 norepinephrine level changed greatly after EA treatn1ent.I' This suggested

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