WANG Yan-jun (王艳君)¹ HAN Yi-xu (韩一栩)² HU Yu-tong (胡雨桐)¹ ZHANG Li-hua (张丽华)^3*

1. Acupuncture-moxibustion Department, Hebei Province Traditional Chinese Medicine Hospital,Shijiazhuang 050011, Hebei Province, China; 2.Hospital of Traditional Chinese Medicine of Zhongshan, Zhongshan 528400, Guangdong Province, China; 3. Rehabilitation Department, Cangzhou Hospital of Integrated TCM-WM, Cangzhou 061000, Hebei Province, China (1.河北省中医院针灸科，石家庄 050011，中国；2.广东省中山市中医院,中山 528400，中国；  3.河北省沧州中西医结合医院康复科，沧州 061000，中国)

ARTICLE INFO

First author: WANG Yan-jun, chief physician, professor.

Research field: clinical study on acupuncture-moxibustion.

E-mail: wangyj8055@sina.com

^*Corresponding author: ZHANG Li-hua, female, chief  physician.

 Research field: clinical study on acupuncture-moxibustion and rehabilitation for stroke.

E-mail: doctorzhanglh@163.com.

* Supported by Project of Hebei Provincial Science and Technology Department: "Clinical study of the acupuncture manipulation of regulating governor vessel and unblocking brain for treatment of dominant diseases of acupuncture-moxibustion": 14277706D

Accepted on December 12,2017.

ABSTRACT

 Objective To observe the comprehensive curative effect of acupuncture manipulation of regulating governor vessel and unblocking brain for post stroke depression associated with anxiety. Methods  Sixty-four patients with post stroke depression associated with anxiety were randomly divided into 2 groups according to the random numbers generated by spss16.0 software, the group of acupuncture manipulation of regulating governor vessel and unblocking brain (group A) and medication group (group B), with 32 patients in each group. Acupuncture manipulation of regulating governor vessel and unblocking brain was performed in group A, Băihuì (百会GV 20), Shéntíng (神庭GV 24), Yămén (哑门GV 15) and Dànzhōng (膻中CV 17)， Gānshū (肝俞BL 18), Xīnshū (心俞BL 15), Shènshū (肾俞BL 23), Tàichōng (太冲LR 3), Tàixī (太溪KI 3), Shénmén (神门HT 7) and Nèiguān (内关PC 6) were selected. The treatment was conducted for once a day, and 5 times a week. Escitalopram oxalate tablets were given orally to the patients in group B for once a day. The treatment was conducted for 8 consecutive weeks in each group. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), Barthel index (BI) and Fugl-Meyer assessment (FMA) in the two groups before and after treatment were compared. Results  Comparison with the same group before treatment, HAMD score and HAMA sore in the two groups after treatment for 4 weeks and 8 weeks were all obviously lower than that in the same group before treatment (all P<0.01); after treatment for 8 weeks, BI score and FMA score in the two groups were all significantly higher than that in the same group before treatment (all P<0.01). Comparison between two groups after treatment, HAMD score and HAMA sore in group A after treatment for 4 weeks were significantly lower than that in group B (both P<0.05); only the HAMA sore in group A after treatment for 8 weeks was lower than that in group B (P<0.05), and there was no significant difference in HAMD score in the two groups (P>0.05); after treatment for 8 weeks, FMA score in group A was obviously higher than that in group B (P<0.05), and there was no significant difference in BI score in the two groups (P>0.05). Conclusion The curative effect of acupuncture manipulation of regulating governor vessel and unblocking brain on the anxiety state and motor function of the patients with post stroke depression is superior to that of escitalopram. With regard to the improvement of depression, this acupuncture manipulation was provided with the characteristic of rapid onset, and its long-term efficacy is equivalent to that of escitalopram. In terms of the improvement of activities of daily living, the curative effect of the two methods is equally well.

KEY WORDS regulate the governor vessel, acupuncture, post stroke depression, anxiety, escitalopram oxalate

Post stroke depression (PSD) refers to a kind of emotional disorder secondary to stroke with the main characteristics of black mood, interest decline, retardation of thinking and less words^[1]. An analysis of system review about PSD indicated that the incidence of PSD during the 2-5 months after stroke was up to 31%-46%^[2]. Compared with non-PSD patients, PSD patients suffer from poorer quality of life with higher risk of suicide^[3], and the mortality is 10 times of non-PSD patients^[4]. The incidence of post stroke anxiety in stroke patients is 20.4%^[5]. Post stroke anxiety and depression can exist concomitantly, but the treatment for anxiety associated with depression is more difficult. Thus, to select safe and effective therapies with good tolerance is very important. In recent years, the treatment of PSD with traditional Chinese medicine shows a better development tendency, mainly including body acupuncture, electroacupuncture, auricular acupuncture, Chinese herbal medicine and combination of acupuncture with drug^[6,7]. In this study, acupuncture manipulation of regulating governor vessel and unblocking brain, a particular acupuncture manipulation of Gao's manipulations in Hebei Province, was adopted to treat post stroke depression associated with anxiety by combining the advantages of different schools, and control study with escitalopram was carried out. The curative effect was satisfactory, and the details are reported as follows.

METERIALS AND METHODS

 General information

Sixty-four outpatients and inpatients with post stroke depression who visited Hebei Province Traditional Chinese Medicine Hospital and Cangzhou Hospital of Integrated TCM-WM from May 2015 to May 2017 were enrolled and numbered according to the registration sequence, then they were randomly divided into 2 groups according to the random numbers generated by spss16.0 software, the group of acupuncture manipulation of regulating governor vessel and unblocking brain (group A) and medication group (group B), with 32 patients in each group. The random grouping scheme was fully concealed in the sealed envelope. In group A, there were 20 males and 12 females with the age of 40—65 years old and an average age of (55.22±5.82) years old, the course of disease was 32—84 days with an average course of (54.97±13.41) days. In group B, there were 19 males and 13 females with the age of 42—70 years old and an average age of (57.28±7.01) years old, the course of disease was 36—79 days with an average course of (52.66±10.82) days. According to the comparison of general information on patients in the two groups, the differences in gender, age, course of desease were not statistically significant (all P>0.05), and the results were comparable. This study has been approved by the Ethics Committee of Hebei Province Traditional Chinese Medicine Hospital.

Diagnostic criteria

Stroke was diagnosed on the basis of Diagnostic Criteria of Cerebral Infarction and Cerebral Hemorrhage in Integrated Traditional Chinese and Western Medicine (trial) formulated by the Specialized Committee for Neurology Branch of China Society of Integrated Traditional Chinese and Western Medicine in 2006^[8], and all the cases were diagnosed with cerebral infarction through head CT or MRI. Depression was diagnosed on the basis of diagnostic criteria of depression in Classification and Diagnostic Criteria of Mental Disorders in China (3rd edition)^[9] (CCMD-3). The main manifestations of depression included loss of interest, mental decline, lower self-evaluation, thinking ability decline and recurrent suicidal intention, concomitantly with sleep disorder, appetite decrease and sexual hypoactivity. The course of disease lasted for more 2 weeks, and organic mental disorders were excluded.

 Inclusion criteria

① The patients who conformed to the above-mentioned diagnostic criteria, ②with the course of disease of stroke≥4weeks, ③ with the age of 38-70 years old, ④with anxiety symptom and the score of Hamilton anxiety scale (HAMA) ≤20 points, ⑤with the score of 17 items of Hamilton depression scale (HAMD) ≥18 points,⑥ with stable condition and dyskinesia, and the score of neurological deficit scale (NDS) <31 points, without disturbance of consciousness, and can cooperate with examination and treatment, ⑦signed the informed consent form.

 Exclusion criteria

① The patients with severe cognitive disorder, hearing impairment or aphasia, ②with serious suicidal intention or psychotic symptoms, and other antipsychotic drugs therapy or electric convulsive therapy were needed, ③concomitantly with severe primary diseases of heart, liver or kidney.

Drop-out criteria

① The patients who suffered from serious adverse events (life-threatening condition, hospitalization or death), ②the patients' treatment was terminated because of adverse effects, ③ the patients who didn't follow the agreement, ④ the patients who cannot finish the study due to a variety of reasons.

METHODS

Treatment methods

Basic treatment: since all patients included in this study were provided with stable condition and the course of cerebral infarction were more than 4 weeks, drug therapy for secondary prevention was routinely given to the patients. In addition, comprehensive rehabilitation technique focusing on Bobath therapy was applied. Bobath therapy^[11], which is also called neurodevelopment therapy, can be used to evaluate and treat motor dysfunction of patients with hemiplegia after cerebral palsy and stroke. This technology includes inhibition and facilitation techniques, which is implemented through controlling the key points. Hemiplegia was treated in three stages (slow stage, spasm stage and relative recovery stage) according to the conditions of motor function. In this study, individualized rehabilitation therapy schemes were formulated based on Bobath therapy. The rehabilitation training lasted for 45min per time, once a day, and 5 times a week. The treatment was conducted for 8 consecutive weeks.

Acupuncture manipulation of regulating governor vessel and unblocking brain was performed in group A in addition to basic therapy. Acupoint selection: Băihuì (百会GV 20), Shéntíng (神庭GV 24) and Yămén (哑门GV 15), Gānshū (肝俞BL 18) bilaterally, Xīnshū (心俞BL 15) bilaterally, Shènshū (肾俞BL 23) bilaterally, Tàichōng (太冲LR 3) bilaterally, Tàixī (太溪KI 3) bilaterally, Shénmén (神门HT 7) bilaterally, Nèiguān (内关PC 6) bilaterally and Dànzhōng (膻中CV 17). Manipulations: Huacheng brand 0.3mm×40mm sterile disposable acupuncture needles (Suzhou Dongbang Medical Co., Ltd.) were adopted. The patient was asked in sitting position and relax the neck. GV 15 was needled towards the lower jaw with a depth of 0.8 cun, and the needle was withdrawn after twirling for one minute. Then the patient was asked in prone position for acupuncture at BL 15, BL 18 and BL 23. Oblique insertion towards the spine with a depth of 0.8 cun was performed, and the needle was withdrawn after twirling for one minute in each acupoint. Finally, the patient was asked in supine position for acupuncture at GV 20, GV 24, CV 17, HT 7, PC 6, KI 3 and LR 3. Transverse insertion was conducted at GV 20 and GV 24 with a depth of 1 cun, and rapid twirling needle was performed for 150-200 times per minute, twirling was conducted for once every 15 min, and for 0.5 min at each acupoint. Perpendicular insertion was carried out at HT 7 with a depth of 0.5 cun, and at PC 6 with a depth of 0.8 cun. Transverse insertion was conducted upwards at CV 17 with a depth of 0.5 cun, and perpendicular insertion was performed at KI 3 and LR 3 with a depth of 0.8 cun. Twirling needle was conducted for once every 15min, and for 0.5min at each acupoint. In addition to scalp acupuncture which was conducted according to the twirling manipulation of scalp acupuncture, even reinforcing and reducing was adopted at other acupoints. For deficiency pattern, the acupuncture was conducted from bottom to top, and for excess pattern, the acupuncture was conducted from top to bottom. Needles were not retained at GV 15 and back-shu points, but were retained at other acupoints for 30 min. The treatment was performed for once a day, 5 times a week, and treatment for 8 consecutive weeks was needed.

Escitalopram oxalate tablets (Lundbeck, trade name: Lexapro) were given orally to the patients in group B in addition to basic therapy. On 1st day and 2nd day,  1.25 mgwas given every day. On 3rd day and 4th day, 2.5 mg was given every day. From 4th day to 6th day, 3.75 mg was given every day. From the 7th day, 5 mg was gradually increased to 10 mg every day. The treatment was performed for once a day for 8 consecutive weeks.

Observational indices and methods

 (1) Hamilton depression scale (HAMD)

 The depression state was evaluated by adopting HAMD scale^[10]. Evaluation was conducted before treatment and after treatment for 4 weeks and 8 weeks. HMAD scale consisted of 17 items, including depressive mood, sleep condition, work and interest, intense, slow, gastrointestinal symptoms, psychic anxiety and constitutional symptoms, etc. The score range was 0-4 or 0-2 for each item, the lighter the symptoms, the lower the score, and vice versa. The highest total score was 52 points.

 (2) Hamilton anxiety scale (HAMA)

The anxiety state was evaluated by adopting HAMA scale. Evaluation was conducted before treatment and after treatment for 4 weeks and 8 weeks. HAMA scale consisted of 14 items, including anxious mood, tension, fear, insomnia, depressive mood, cognitive function, talk, somatesthesia, cardiovascular system and respiratory system, etc. The score range was 0-4 for each item, the higher the score, the severer the symptoms.

 (3) Fugl-Meyer assessment (FMA)

Motor function was evaluated by adopting FMA ^[11]. Evaluation was conducted for 2 times respectively before treatment and after treatment for 8 weeks. The total score of FMA was 100 points. The upper limb and lower limb were evaluated respectively. The total score of upper limb was 66 points, including 9 items such as reflex activity, synkinesia and separation movement, etc. The total score of lower limb was 34 points, including 6 items such as reflex activity, synkinesia and separation movement, etc. in different positions. The score range was 0-2 for each item, 0 point represented complete inactivity, 2 points represented full-scale activity, and 1 point represented the state between the former two.

 (4) Barthel index (BI)

Activities of daily living were evaluated by adopting BI^[11]. Evaluation was conducted for 2 times respectively before treatment and after treatment for 8 weeks . BI consisted of 10 items, including feed, bath, dressing and defcation, etc., totally 100 points. The higher the score, the more independent the patient.

The evaluators were the physicians in our department who were unaware of the patients’ grouping. After a unified training, the evaluators can perform evaluation.

Statistical analysis

All the data were analyzed by one person via SPSS16.0 statistical software. Measurement data were expressed as mean ± SD (SE), intra-group comparison before and after treatment was conducted by applying paired-samples t test, intergroup comparison was performed via independent-sample t test, and ranked data were analyzed through Wilcoxon rank-sum test. P<0.05 indicated that the difference was statistically significant.

RESULTS

 Comparison of HAMD score of the patients of post stroke depression associated with anxiety in the two groups before and after treatment

Table 1 showed that there was no significant difference in HAMD score in the two groups before treatment (P>0.05), after treatment for 4 weeks, the differences in the same group before and after treatment were statistically significant (both P<0.01). The HAMD score in group A was lower than that in group B after treatment for 4 weeks (P<0.05), but the differences were not statistically significant after treatment for 8 weeks although the HAMD score in group A was lower than that in group B (P>0.05).

Table 1 Comparison of HAMD score of  patients with post stroke depression associated with anxiety in the two groups before and after treatment  [mean ± SD (SE)]

Notes: compared with the same group before treatment, ^1）P<0.01; compared with group B, ^2）P<0.05

Comparison of HAMA score in the two groups before and after treatment

Table 2 showed that there was no significant difference in HAMA score in the two groups before treatment (P>0.05), after treatment for 4 weeks, the differences in the same group before and after treatment were statistically significant (both P<0.01). The HAMA score in group A was lower than that in group B after treatment for 4 weeks and 8 weeks (P<0.05).

Table 2 Comparison of Hamilton Anxiety Scale score in the two groups  of  patients with post stroke depression associated with anxiety before and after treatment

[mean ± SD (SE)]