Efficacy observation of Zhi Shen Tiao Sui acupuncture method for depression after ischemic stroke

Zhi Yong (智勇), Huo Xin-hui (霍新慧), Li Pan (李盼)

Xinjiang Medical University Institute of Traditional Chinese Medicine, Urumchi 830011, China

Abstract Objective: To observe the clinical efficacy of Zhi Shen Tiao Sui (regulating the mind and marrow) needling in treating depression after ischemic stroke.

Keywords: Acupuncture Therapy; Acupuncture Medication Combined; Complications; Ischemic Stroke; Depression; Activities of Daily Living; Randomized Controlled Trial

Depression is a common complication after ischemic stroke. It usually happens 2 months to 1 year after the onset of a stroke. While the incidence has been estimated to be 20%-60%, about 10% of the patients suffer from major depression and may have suicide attempt. Long-term mild-to-moderate depressive state will hinder neurological function and daily living abilities,which will in turn affect the mood, forming up a vicious cycle and making the depressive state worse[1].Therefore, it is of great significance to implement safe and effective measures amongst the patients suffering depression after ischemic stroke. Western medication is predominant in the current treatment for this medical condition. Together with psychological intervention, it usually can produce satisfactory efficacy. However,relapse will occur when medication is terminated in some cases and adverse reactions may happen in some patients who are intolerant of the medication[2].According to traditional Chinese medicine (TCM),depression after ischemic stroke is a combination of both stroke and depression syndrome. In these cases, stroke causes accumulation of turbid toxins such as phlegm and stasis in the clear orifice, disturbing qi activities and mind.TCM mainly uses Chinese medication and acupuncture to manage this condition[3]. Research reveals that acupuncture at certain acupoints can modulate the production and transmission of nerve impulses in the cerebral cortex, so as to treat some mental disorders[4].This study was to observe the effect of Zhi Shen Tiao Sui(regulating the mind and marrow) acupuncture method on neurological function in the patients with depression after ischemic stroke[5]. The report is as follows.

1 Clinical Materials

1.1 Diagnostic criteria

Conformed to the diagnostic criteria of both cerebral stroke[6-7]and depression[8-9].

1.2 Inclusion criteria

Conformed to the diagnostic criteria; ＞18 years old; no previous history of depression or other mental diseases before the onset of stroke; informed consent obtained from the patient and his or her families.

1.3 Exclusion criteria

Pregnant or breast-feeding women; disturbance of consciousness coupled with notable intelligence decline or aphasia; serious heart, liver or kidney dysfunctions;cognitive impairment or other mental diseases that prevented the patient from cooperating throughout the study.

1.4 Dropout criteria

Those who quitted the study halfway.

1.5 Statistical methods

SPSS 19.0 statistic software was chosen to process the data. The measurement data all conformed to normal distribution checked by Shapiro-Wilk test and were expressed as mean ± standard deviation (±s).Between-group comparisons were analyzed using independent samplest-test while intra-group comparisons were analyzed by paired samplest-test.Enumeration data were expressed as rate. Betweengroup comparisons were analyzed by Chi-square test,and Chi-square test with correction was applied when theoretical frequency was ＜5. Statistical significance was accepted whenP＜0.05.

1.6 General data

A total of 145 patients with depression after ischemic stroke who received treatment at the Acupuncturemoxibustion or Neurology Department of Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region were recruited between January 2016 and January 2018. They were allocated to two groups by random number table method, with 72 cases in the control group and 73 cases in the observation group. No cases dropped out during treatment from either of the two groups. This study had been approved by the Medical Ethics Committee of Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region (Approval No. 2016XE0106-8).There were no significant differences in the general data across the two groups (allP＞0.05), indicating the comparability. The details are presented in Table 1.

Table 1. Comparison of general data between the two groups

2 Treatment Methods

2.1 Control group

Conventional treatment for ischemic stroke and medication were offered to the control group.

Conventional treatment for ischemic stroke:Anticoagulation, thrombolysis, nutritional supply to brain cells, anti-inflammation, and reducing intracranial pressure, etc., along with symptomatic treatments targeting primary diseases such as diabetes, cardiac diseases and hypertension, as well as rehabilitation training.

Medication: Antidepressant sertraline hydrochloride tablets (State Food and Drug Administration Approval No.: H10980141, 50 mg/tablet, Pfizer, China), oral administration, 1-2 tablets each time, once a day.

2.2 Observation group

The observation group was given additional Zhi Shen Tiao Sui acupuncture treatment based on the treatment in the control group.

Main acupoints: Zusanli (ST 36) and Baihui (GV 20).

Adjunctive acupoints: Taixi (KI 3) and Sanyinjiao (SP 6)were added for those with feverish sensation in the five centers; Shenmen (HT 7) and Neiguan (PC 6) for insomnia and dreaminess; Geshu (BL 17) and Xuehai(SP 10) for purple tongue body and unsmooth pulse.

Method: The patient took a supine position and exposed the acupoints thoroughly for routine sterilization. Filiform needles of 0.30 mm in diameter and 40 mm in length (Suzhou Acupuncture Goods Co., Ltd.,China) were adopted. Bahui (GV 20) was treated first with the needle inserted forward for 1.0-1.5 cm. Then Zusanli (ST 36) was inserted perpendicularly for 2.5-3.5 cm. Twirling reducing manipulation was performed when needling qi was obtained and the needles were retained for 30 min, during which twirling reducing manipulation was applied every 10 min. The acupuncture treatment was given twice a day. Both the control and observation groups were treated for 4 consecutive weeks.

3 Therapeutic Efficacy Observation

3.1 Observation measures

3.1.1 Neurological function pertinent scores

Hamilton depression scale (HAMD)[10]: Consisted of 17 items which were scored 0-4 points each according to the severity, the higher the score, the more serious the condition. The sum of the 17 component scores reflected the level of depression.

Clinical neurological deficit scale (CNDS)[11]: Eight items were covered, including consciousness, gazing forward, facial paralysis, language, upper-limb muscle strength, hand muscle strength, lower-limb muscle strength and walking ability, scored 1-5 points each, The higher the score, the more serious the disease. The sum of the 8 component scores reflected the severity of neurological deficit.

Activities of daily living (ADL)[12]: Ten items were measured, including defecation, urination, grooming,eating, toileting, translocation, mobility, getting dressed,climbing stairs and bathing. The maximum score was 100 points. The score ＞95 points meant the patient was able to live independently; 75-95 points meant mild disability in daily living; 50-74 points suggested moderate disability;21-49 points suggested severe disability; 0-20 points meant extremely severe disability in daily living.

Fugl-Meyer assessment scale (FMA): Both upper-limb and lower-limb functions were involved, including 33 items for the upper-limb (66 points) and 17 items for the lower-limb (34 points), making a full score of 100 points.A higher score indicated a better motor function.

Barthel index (BI): This scale covered feeding, bathing,toilet use, grooming, bowels and bladder, etc., to evaluate the daily living independence, the higher the score, the better the independence.

3.1.2 Cortisol (CORT) and adrenocorticotropic hormone (ACTH)

Each patient contributed 5 mL fasting venous blood to test the levels of serum CORT and plasma ACTH by enzyme-linked immunosorbent assay after the blood samples were treated with heparin and centrifuged. The operation strictly followed the instruction from the kits(CORT, batch No. BFNE80316; ACTH, batch No.BFNE81680. R&D Systems, USA).

3.2 Therapeutic efficacy criteria[13]

The efficacy was estimated based on the posttreatment reduction rate of HAMD score. HAMD reduction rate = (Pre-treatment HAMD score - Posttreatment HAMD score) ÷ Pre-treatment HAMD score ×100%.

Recovered: HAMD reduction rate ≥75%.

Markedly effective: HAMD reduction rate ≥50% but＜75%.

Effective: HAMD reduction rate ≥25% but ＜50%.

Invalid: HAMD reduction rate ＜25%.

3.3 Results

3.3.1 Comparison of clinical efficacy

The clinical total effective rate was 82.2% in the observation group, significantly higher than 66.7% in the control group (P＜0.05). The details are shown in Table 2.

3.3.2 Comparison of neurological and motor function scores

There were no significant differences in the HAMD,CNDS, ADL, FMA and BI scores between the two groups prior to treatment (allP＞0.05). After treatment, HAMD and CNDS scores dropped markedly in both groups (allP＜0.05), and the ADL, FMA and BI scores rose significantly (allP＜0.05); the HAMD and CNDS scores were markedly lower in the observation group than in the control group (bothP＜0.05), and the ADL, FMA and BI scores were significantly higher in the observation group than in the control group (allP＜0.05). The details are exhibited in Table 3.

3.3.3 Comparison of the serum CORT and plasma ACTH levels

Before treatment, there were no significant betweengroup differences in the serum CORT and plasma ACTH levels (bothP＞0.05). After treatment, the levels of CORT and ACTH declined significantly in both groups (allP＜0.05), and the levels of CORT and ACTH were markedly lower in the observation group than in the control group(bothP＜0.05). See Table 4 for details.

3.3.4 Comparison of adverse reactions

During treatment, 3 cases (4.2%) from the control group showed nausea and vomiting, and 2 cases (2.7%)from the observation group had hematoma at the treated acupoints. These reactions were substantially improved after symptomatic treatment, and there was no significant difference in the adverse reaction rate between the two groups (correctedχ2=0.002,P=0.987).See Table 5 for details.

Table 2. Comparison of clinical efficacy (case)

Table 3. Comparisons of HAMD, CNDS, ADL, FMA and BI scores (±s, point)

Table 3. Comparisons of HAMD, CNDS, ADL, FMA and BI scores (±s, point)

Scale Group n Pre-treatment Post-treatment t-value P-value Observation 73 25.51±6.32 11.88±3.71 15.863 0.000 HAMD Control 72 25.78±6.07 17.05±4.03 10.216 0.000 t-value 0.262 8.039 P-value 0.794 0.000 Observation 73 18.53±6.74 10.82±3.97 8.407 0.000 CNDS Control 72 18.12±7.08 14.76±4.39 3.440 0.001 t-value 0.357 5.670 P-value 0.722 0.000 Observation 73 61.54±9.03 73.66±7.25 8.918 0.000 ADL Control 72 60.11±9.26 65.19±8.06 3.525 0.001 t-value 0.941 6.655 P-value 0.348 0.000 Observation 73 29.01±11.03 37.58±11.35 2.559 0.012 FMA Control 72 29.16±10.58 33.58±10.47 4.619 0.000 t-value 0.084 2.206 P-value 0.934 0.029 Observation 73 36.14±14.02 47.56±12.02 3.088 0.002 BI Control 72 36.02±13.88 42.63±11.14 5.354 0.000 t-value 0.052 2.561 P-value 0.959 0.011

Table 4. Comparison of CORT and ACTH levels (±s)

Table 4. Comparison of CORT and ACTH levels (±s)

Item Group n Pre-treatment Post-treatment t-value P-value Observation 73 27.14±4.92 13.84±3.71 18.395 0.000 CORT(μg/dL)Control 72 27.62±5.03 16.25±4.63 14.165 0.000 t-value 0.581 3.461 P-value 0.562 0.001 Observation 73 48.52±7.38 25.39±6.21 20.489 0.000 ACTH(pmol/L)Control 72 49.23±8.11 32.07±7.34 13.312 0.000 t-value 0.551 5.919 P-value 0.582 0.000

Table 5. Comparison of adverse reactions (case)

4 Discussion

Depression after ischemic stroke has a rather complicated pathogenesis, about which, the point of view hasn’t been unified yet in modern medicine.Currently, the mainstream theories include endogenous and exogenous mechanisms. The endogenous mechanism holds that this type of depression should be related to brain damage caused by stroke, bringing on changes in the secretion of pertinent neurotransmitters.The exogenous mechanism believes that after a stroke,the patient’s family status, social abilities and occupation status will change, which will break the mental balance but cause negative emotions, finally leading to depression[14]. For this condition, though Western medicine treatment can achieve satisfactory efficacy in the short term, it could be disappointing in the long run,let alone relapse in some cases after termination of the treatment. Therefore, it is necessary to find a safer effective treatment.

There is no such term of depression after ischemic stroke in ancient classics on TCM. But according to its typical clinical manifestations, it can be classified as a combination of stroke and depression syndrome, caused by stagnation of qi and blood, unbalanced emotions, and poor nourishment to the brain. In recent years, studies have shown that acupuncture at certain acupoints on the head can produce significant efficacy for brain-derived diseases[15-16]. Therefore, this study targeted at the effect of Zhi Shen Tiao Sui acupuncture method on the neurological function of patients with post-ischemic stroke depression, aiming to provide reference for clinical research.

The results of this study showed that the total clinical effective rate was significantly higher in the observation group than in the control group, suggesting that compared with Western medication alone, adding Zhi Shen Tiao Sui acupuncture method can significantly enhance the clinical efficacy in treating depression after ischemic stroke. Jiao DY,et al[17]pointed out in their research that acupuncture at Baihui (GV 20) combined with conventional Western medicine treatment can notably improve the depressive state and enhance the clinical efficacy in treating patients with post-ischemic stroke depression, which is consistent with this study.Post-ischemic stroke depression happens after a stroke,caused by reverse flow of qi and blood disturbing the upper clear orifice. The ancients believed that people’s spiritual wisdom should originate from the brain, and the dysfunction of heart shouldn’t be the only cause of mental and emotional diseases but also the brain diseases. The head is the joint of yang, where the meridian qi of the hand and foot yang meridians meet.Thus, acupuncture at Baihui (GV 20), a point located at the top of the head, can balance yin and yang of the internal organs, soothe the five Zang-organs, and calm the mind. Moreover, since Baihui (GV 20) is located at the crown of the head, closely connecting with the brain, this point has been recognized as a key point for regulating brain function. According to modern medicine, the bottom of the temporal lobe and the ascending reticular system are linked with emotions, and their body surface projections are gathered near the Governor Vessel.Baihui (GV 20) is a main point of the Governor Vessel, so acupuncture at this point can directly affect the related functions of the brain[18]. As the He-Sea point of the Stomach Meridian of Foot Yangming, Zusanli (ST 36) can produce significant health care effects. Acupuncture at Zusanli (ST 36) can regulate the spleen and stomach and supplement qi, so as to nourish the brain when there is sufficient qi and blood. Zhang HJ,et al[19]reported that acupuncture at Baihui (GV 20) and Zusanli (ST 36) can significantly improve the neurological function of a mouse model of post-stroke depression. Modern medicine holds that depression is related to the continuous hyper-activation of the hypothalamicpituitary-adrenal axis. After the onset of ischemic stroke,the brain remains in a long-term chronic stress state, the level of CORT is increased and the hypothalamuspituitary-adrenal axis is activated, prompting the hypothalamus to secrete corticotropin releasing hormone (CRH) and stimulating the pituitary gland to produce ACTH, subsequently triggering the adrenal cortex to produce glucocorticoids. Continuous secretion of glucocorticoids can lead to neuroendocrine disorders,which makes mental diseases such as depression more possibly to occur[20]. Baihui (GV 20) is located at the intersection of the Governor Vessel and the Bladder Meridian of Foot Taiyang, and it can connect with the kidney via Back-Shu points from the Bladder Meridian.Acupuncture at Baihui (GV 20) can regulate the function of kidney and reduce adrenal hyperfunction,consequently inhibiting the synthesis of glucocorticoids[21]. In addition, the kidney governs bones and marrow, and brain is the sea of marrow.Acupuncture at Baihui (GV 20) can regulate the function of kidney, improve brain cell dystrophy, reduce chronic stress stimulation, and then lower the levels of CORT and ACTH, and improve the neurological function of patients with depression after ischemic stroke[22]. One study showed that acupuncture at Baihui (GV 20) can downregulate the expression of CRH mRNA, resulting in a decrease in the levels of CORT and ACTH, thereby suppressing the continuous hyper-activation of the hypothalamic-pituitary-adrenal axis and improving depression symptoms[23]. Besides, in patients with ischemic stroke, brain cell damage due to insufficient blood supply to the brain interferes with the nerve conduction pathway that regulates the secretion of norepinephrine and serotonin (a sensitive indicator of depression) in the thalamus, frontal cortex and basal ganglia, causing a decrease in the two factors, which in turn leads to depression[24]. Acupuncture at Baihui(GV 20) can improve cerebral blood circulation in the patients and promote the recovery of nerve cell function,then up-regulate the levels of norepinephrine and serotonin, and consequently improve depression symptoms[25].

The results of this study showed that the HAMD and CNDS scores in the observation group were significantly lower than those in the control group after treatment(bothP＜0.05), the ADL, FMA and BI scores were significantly higher than those in the control group (allP＜0.05), and the CORT and ACTH levels were significantly lower than those in the control group (bothP＜0.05),suggesting that compared with Western medication alone, Zhi Shen Tiao Sui acupuncture plus Western medication can better promote the recovery of neurological function in patients with depression after ischemic stroke.

To sum up, compared with the treatment of Western medication alone, Zhi Shen Tiao Sui acupuncture plus Western medication can promote the recovery of neurological function in patients with depression after ischemic stroke and enhance the clinical efficacy.

Conflict of Interest

The authors declare that there is no potential conflict of interest in this article.

Acknowledgments

This work was supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region (新疆维吾尔自治区自然科学基金, No. 2018D01C163); National Natural Science Foundation of China (国家自然科学基金, No.82060894).

Statement of Informed Consent

This study had been approved by the Medical Ethics Committee of Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region (Approval No.2016XE0106-8). Informed consent was obtained from all individual participants.

Received: 30 March 2020/Accepted: 9 July 2020