ARTICLE INFO

First author: LU Hui-peng, attending physician. Research field: TCM encephalopathic science (mentality and sleep). E-mail: 314333060@qq.com

*Supported by Medical Science Foundation in Zhongshan City: 2017A02056.

Accepted on November 9, 2017.

ABSTRACT  Objective To observe the clinical efficacy difference between electroacupuncture at Băihuì (百会GV 20) and Yìntáng (印堂EX-HN3) and oral administration of sertraline hydrochloride for treatment of post-schizophrenic depression. Methods Sixty patients with post-schizophrenic depression were randomly divided into electroacupuncture group and western medicine group in the proportion of 1:1, with 30 patients in each group. The patients in the two groups were all given antipsychotics as the basic treatment. Electroacupuncture at GV 20 and EX-HN3 was performed additionally in electroacupuncture group with 30 min/time and once every other day. The treatment was given for 3 times a week, lasting for 6 weeks. Oral administration of sertraline hydrochloride was given in western medicine group additionally for once a day, lasting for 6 weeks. The comprehensive conditions of patients in the two groups were evaluated before and after treatment by adopting Global Assessment Scale (GAS). The degree of depression of patients in the two groups was assessed before treatment, after treatment for 1 week, 2 weeks and 4 weeks, after treatment as well as during follow-up visit by adopting Hamilton Depression Scale-17 (HAMD-17). Results GAS: GAS scores of the patients in the two groups after treatment were higher than those before treatment (both P<0.05), but the difference of GAS scores of the patients in the two groups after treatment was not statistically significant. HAMD-17: The HAMD-17 scores of patients in electroacupuncture group reduced gradually in the six time points of before treatment, after treatment for 1 week, 2 weeks and 4 weeks, after treatment as well as during follow-up visit, and the differences of scores between the two adjacent time points were statistically significant (all P<0.05). The HAMD-17 scores of patients in western medicine group reduced gradually in the 6 time points, and the differences of scores between the two adjacent time points among after treatment for 2 weeks and 4 weeks, and after treatment were statistically significant (all P<0.05). The HAMD-17 scores of patients in electroacupuncture group were lower than that in western medicine group after treatment for 1 week, 2 weeks and 4 weeks, and the differences were statistically significant (all P<0.05). Conclusion According to the comparison of the clinical efficacies of electroacupuncture at GV 20 and EX-HN3 and oral administration of sertraline hydrochloride for treatment of post-schizophrenic depression, the overall conditions were improved effectively and the difference was not statistically significant. Electroacupuncture takes effect more rapidly in treatment of depression, and its effect can last for a longer time.

KEY WORDS: schizophrenia; depression; electroacupuncture; Băihuì (百会GV 20), Yìntáng (印堂EX-HN3)；sertraline hydrochloride

Post-schizophrenic depression can attack during the aftermath of schizophrenia, and it may persist for a long time, while some symptoms of schizophrenia may still exist ^[1]. Post-schizophrenic depression is not a simple depression attack but a group of symptoms that is secondary to schizophrenia and manifests as depressive symptoms and schizophrenic symptoms combined together. The complexity lies in its unclear nature. The understanding of post-schizophrenic depression is generally considered as the following three viewpoints. (1) It is the adverse effect of antipsychotics. (2)  It is a part of the course of disease of schizophrenia. (3) It is the disappoint response to the future along with the recovery of the mind. Anyway, depressive symptom is an important factor for the poor effectiveness of schizophrenia. The incidence of post-schizophrenic depression in the patients with schizophrenia is 7%—75%, and the mode is 25% ^[2-3]. Conventional treatment of post-schizophrenic depression has certain limitations, for example, strengthening of the combination use of antipsychotics and antidepressants may increase the incidences of the adverse effects; the repeatability and consistency of psychotherapy are very difficult to control. Therefore, to explore better treatment methods for post-schizophrenic depression is an important issue in this field.

Electroacupuncture is a kind of modern treatment method which combines acupuncture-moxibustion with electrical stimulation. In recent years, a number of clinical trials ^[4-8] have proved that electroacupuncture can relieve the depressive symptoms. There were also a lot of basic researches on the mechanism of electroacupuncture for depression ^[9]. The authors believe that electroacupuncture has potential advantages in the treatment of post-schizophrenic depression. Therefore, randomized controlled trial is designed to observe the clinical efficacy difference between electroacupuncture at Băihuì (百会GV 20) and Yìntáng (印堂EX-HN3) and oral administration of sertraline hydrochloride for post-schizophrenic depression, which can provide scientific basis and guidance for the treatment method into the field of severe mental diseases treatment.

CLINICAL DATA

General information

The inpatients with post-schizophrenic depression in Zhongshan Third People's Hospital (psychiatric hospital) from March to September 2017 were recruited by two psychiatric doctors. Sixty patients with post-schizophrenic depression who conformed to the inclusion criteria were randomly divided into electroacupuncture group and western medicine group. The randomization method is as follows: sixty number cards were put into empty envelopes, and the order was disrupted. Each included patient was asked to extract one envelope randomly. The patients who extracted odd number were assigned into electroacupuncture group, and the patients with even number were assigned into western medicine group. In electroacupuncture group (30 cases), there were 16 males and 14 females with a mean age of (29.6±11.2) years old; in western medicine group (30 cases), there were 17 males and 13 females with a mean age of (29.2±10.5) years old. The differences in age and gender of patients in the two groups were not statistically significant (both P＞0.05). In the process of study, there were 2 drop-out cases in electroacupuncture group because they cannot bear the pain of acupuncture, and 3 drop-out cases in western medicine group for the reason that depressive symptom aggravated, associated with aggravating hallucination and delusion symptoms. The 5 drop-out cases withdrew from the study within the first 2 weeks after inclusion, they were considered as drop-out cases because they cannot accept the treatment, or they need other combined therapy. Per-protocol analysis was adopted in the study.

Diagnostic criteria

The symptoms conformed to the diagnostic criteria of "post-schizophrenic depression" in the international diagnostic criteria of diseases in International Classification of Diseases (ICD-10): The patients suffered from schizoid disease which conformed to the general criteria of schizophrenia within the past 12 months. ‚The patients used to have schizoid symptom. ƒThe patients with obvious depressive symptoms which conformed to the diagnostic criteria of “depressive disorder” in ICD-10, and the symptoms have lasted for at least 2 weeks.

Inclusion criteria

① The patients with the age of 18—45 years old. ② The patients with HAMD-17 score higher than 17 points. ③ The patients who graduated from middle school or above, with the ability of completing the scale independently. ④ The patients with the informed consents from themselves or family members. ⑤ The patients without severe physical disease or infectious disease. ⑥ The patients without the history of psychoactive drug dependence.

Exclusion criteria

① The patients who were taking antidepressants or in the wash-out period of antidepressants. ② The patients who were taking anti-arrhythmia agents, antidiabetics or tryptophan. ③ Pregnant women or lactating women. ④ The patients with severe heart, liver or kidney diseases or other systemic diseases. ⑤ The patients with organic diseases in brain. ⑥ The patients with the score of Nurses' Global Assessment of Suicide Risk (NGASR) lower than 11 points.

Elimination criteria

① Incorrect inclusion; ② misdiagnose; ③ without taking any drugs; ④ without any inspection record. The elimination causes should be stated clearly, and their case report forms should be kept for review.

Criteria for drop-out cases

① The patients withdrew from the study for themselves. ② The patient who loss to follow-up visit. ③ The patients who have poor compliance. ④ The patients with complications or changes of the illness who were asked to withdraw from the study by the physician (the patients may be turn to mania, or concomitantly with psychotic symptoms for more than 2 weeks, or with obvious suicide attempt).

TREATMENT METHODS

The patients in the two groups were all given antipsychotics as basic treatment, that is, to maintain the original (in acute phase) antipsychotic treatment schedule.

Electroacupuncture group

The patients were asked in supine position. Acupoint selection: GV 20 and EX-HN3. Manipulations: 0.32 mm×25 mm disposable acupuncture needles were adopted. GV 20: slowly and backward transverse insertion with a depth of 13-20 mm. EX-HN3: slowly and upward perpendicular insertion with a depth of 13-20 mm. No lifting and thrusting was performed at GV 20 and EX-HN3, and even twirling was carried out to the extent of sore and swollen sensation. After deqi, Han's stimulus device LH-202H was connected with GV 20 connecting to the positive electrode and EX-HN3 connecting to the negative electrode. 2/15 Hz dilatational wave was applied, and the current intensity was controlled within the tolerance scope of patients (slight shaking of skin). Electroacupuncture was conducted for 30 min one time. The patients in electroacupuncture group were given treatment for once every other day, 3 times per week, and the treatment for 6 weeks was needed. The acupuncturists who participated in the study must be educated in formal colleges of Chinese medicine and get bachelor's degree or above, and have the qualification of clinical practicing physician, with more than 3 years' experience in clinical practice of acupuncture. The acupuncturists participating in the subject should accept the standardized operation training before the beginning of the study.

Western medicine group

The patients in western medicine group were asked to take sertraline hydrochloride tablets orally. The dosage should followed the drug instructions. The initial dose was 50 mg/day in the first week of the treatment for once a day. The dosage was adjusted to 100 mg/day from the second week to the end of treatment for once a day. Sertraline hydrochloride tablets were orally taken after breakfast for 6 consecutive weeks.

EFFICACY OBSERVATION

Outcomes

 (1) Global Assessment Scale (GAS): GAS refers to a comprehensively overall evaluation of the severity of mental symptoms and the level of social function of a patient conducted by a clinician, ranging from level 1 to level 100. The lower the score, the severer the disease. Evaluation was performed before and after the treatment.

 (2) Hamilton Depression Scale-17 (HAMD-17): HAMD-17 was formulated by Hamilton in 1960, which is composed of 17 items. HAMD-17 is the most commonly used scale in clinical evaluation of depression. The higher the total score, the severer the depressive condition. Evaluation was performed before treatment, after treatment for 1 week, 2 weeks and 4 weeks, after treatment as well as during follow-up visit in the 4^th week after treatment.

Statistical methods

   SPSS17.0 statistical software was adopted to analyze data. Measurement data were expressed as , independent-samples t test was applied to intergroup comparison, and paired-samples t test was adopted for intra-group comparison. Enumeration data was analyzed by adopting chi-square test. The difference was statistically significant when P＜0.05.

Results

 (1) Comparison of GAS scores of the patients with post-schizophrenic depression in the two groups before and after treatment

The difference in the GAS scores of patients in electroacupuncture group and western medicine group before treatment was not statistically significant (P >0.05). The GAS scores of patients in the two groups after treatment were all higher than that before treatment (both P<0.05). The difference in the GAS scores of patients in electroacupuncture group and western medicine group after treatment was not statistically significant (P >0.05). The details are shown in Table 1.   

Table 1 Comparison of GAS scores of the patients with post-schizophrenic depression in the two groups before and after treatment                              (, point)

Note: Compared with the same group before treatment, ^1）P＜0.05.

(2) Comparison of HAMD-17 scores of the patients with post-schizophrenic depression in the two groups before and after treatment as well as during follow-up visit

The HAMD-17 scores of patients in electroacupuncture group reduced gradually in the 6 time points of before treatment, after treatment for 1 week, 2 weeks and 4 weeks, after treatment as well as during follow-up visit, and the differences of scores between two adjacent time points were statistically significant (all P<0.05). The HAMD-17 scores of patients in western medicine group reduced gradually in the 6 time points of before treatment, after treatment for 1 week, 2 weeks and 4 weeks, after treatment as well as during follow-up visit, and the differences of scores between two adjacent time points among after treatment for 2 weeks and 4 weeks, and after treatment were statistically significant (both P<0.05). The HAMD-17 scores of patients in electroacupuncture group were lower than that in western medicine group after treatment for 1 week, 2 weeks and 4 weeks, and the differences were statistically significant (all P<0.01). The details are shown in Table 2.

Table 2 Comparison of HAMD-17 scores of the patients with post-schizophrenic depression in the two groups before and after treatment as well as during follow-up visit    (, point)

Note: Compared with the previously adjacent time point in the same group, ^1）P<0.05; compared with the same time point in western medicine group, ^2）P<0.05.

DISCUSSION

Post-schizophrenic depression is a group of depressive symptoms occurred in the schizophrenic patients. Its complexity is that we cannot distinguish whether these depressive symptoms are the sequelae after the alleviation of the original psychotic symptoms (rather than new depression onset) or the intrinsic components of schizophrenia (rather than psychological reactions to schizophrenia). Thus it's hard for us to determine which symptoms are derived from depression, and which are derived from nerve blocker therapy or mental disorders and insipid emotion of schizophrenia. Therefore, it seems to be impossible to surmount this barrier based on the precise treatment in western medicine. We believe the holistic treatment concept in traditional Chinese medicine may be a way to solve the problems. This disease belongs to the depressive psychosis and mania in traditional Chinese medicine. The patients may suffer from depressive symptoms secondary to the old illness with down mood, decreased interest, reduced activity and other decreased functions, and this disease belongs to yin disease in traditional Chinese Medicine. Suffering from yin disease, the patients may have deficient yang or excess yin, while depressive psychosis and mania are mainly caused by exogenous or endogenous pathogenic qi, thus disharmony of the brain and mind may lead to abnormal behaviors. The treatment principle should be regulating the balance of yin and yang and restoring consciousness and opening the orifices for treating the original of the disease, and inspiring yang to bring yang into yin for treating the symptoms. In this study, electroacupuncture was performed at GV 20 and EX-HN3 which are the key acupoints for treatment of mania and depression. GV 20 locates on the top of the head, and it is the intersection of three yang meridians of the hand and foot, governor vessel and the foot-jueyin liver meridian. As the intersection of all the vessels, GV 20 can regulate the meridian qi of yang meridians, restore consciousness and open the orifices, calm the mood and regulate the mind, therefore, GV 20 is one of the most commonly used acupoints for treatment of emotional diseases in traditional Chinese medicine, such as mania and depression. EX-HN3 is the acupoint governor vessel pass through on the forehead with the functions of calming the mind and arresting convulsion, restoring consciousness and opening the orifices. Combination of paired-acupoints can play the role of restoring consciousness and relieving depression together. Perpendicular insertion was carried out at EX-HN3 in order to bring qi to the upper side to GV 20. Transverse insertion was performed at GV 20 in order to bring yang into yin, so as to treat yin diseases.

Some studies have revealed the effectiveness of electroacupuncture at GV 20 and EX-HN3 for treatment of depression. For example, Dong Yu-ping^[4] adopted electroacupuncture at GV 20 and EX-HN3 for treatment of 101 cases of depression, and the total effective rate was 84.2%. Some domestic scholars also explored the mechanism of electroacupuncture for treatment of depression through animal experiments, for instance, Chen Ze-qin, et al. ^[10] found that electroacupuncture treatment can effectively improve the core symptom of behaviors of Wistar-Kyoto (WKY) depression model rats through the observation of the effect of electroacupuncture at GV 20 and EX-HN3 on the behaviors of WKY depression model rats. According to the study of the effect of electroacupuncture at GV 20 and EX-HN3 on hypothalamic–pituitary–adrenal axis (HPA) and GR-NMDAR pathway of depression model rats, Zhao Li-jie et al. ^[12] found that: (1) electroacupuncture can antagonize the abnormal hyperfunction of HPA; (2) electroacupuncture can antagonize the sensitivity reduction of hippocampal GA, NMDAR and NMAB of model rats. Our study group participated in a multi-center clinical study from 2008 to 2011 in order to explore the optimum proposal of acupuncture for treatment of mild or moderate depression. The results of the study showed that electroacupuncture at GV 20 and EX-HN3 can rapidly improve the depressive symptoms of patients in early stage (the first 2 weeks), while its efficacy was not good as the combination of electroacupuncture and oral administration of antidepressants in the first 6 weeks; the observed results of resting state functional magnetic resonance imaging (RS-fMRI) before and after treatment revealed that the mechanism of electroacupuncture at GV 20 and EX-HN3 for treatment of depression may be the electroacupuncture at GV 20 and EX-HN3 can act on the encephalic region, middle temporal gyrus and caudate nucleus related with the onset of depression^[11-13]. What is more, the follow-up visit in this study was not conducted in western medicine group because of the ethical considerations. It has been pointed out in Guidelines for Prevention and Treatment of Depression in China ^[14] that: "The relapse rate of depression is common in the initial 6 months during treatment, which is up to 85% in the patients with discontinued therapy (drug therapy and ECT). Therefore, for the patients who are cured by antidepressants in acute stage, consolidation treatment for 4-9 months is strongly recommended when their symptoms are well controlled. In principle, the effective drugs in acute phase can be used continuously with the same dose". Therefore, the observation of drug withdrawal for 4 weeks was not conducted in western medicine group, and the follow-up data were not comparable with that in electroacupuncture group. One of the possible pathogenic factors of post-schizophrenic depression patients is "the sense of shame", namely after the patients' psychotic symptoms such as hallucinations and delusions are eliminated, and their mind recovers. The patients feel ashamed for suffering from the mental illness, which leads to the emergence of depression. Therefore, there is a close relationship between the psychotic symptoms (hallucinations, delusions, etc.) of such patients and their depressive symptoms.

In this study, GAS was adopted for evaluation of the general curative effect of patients with post-schizophrenic depression, and HAMD-17 was applied to evaluate the degree of depression. It was found that both of the foresaid indicators were improved, indicating that electroacupuncture at GV 20 and EX-HN3 can promote the improvement of the overall mental conditions and social functions at the same time of alleviating the depressive symptoms. The study showed that electroacupuncture at GV 20 and EX-HN3 can relieve the depressive symptoms. In this study, we assumed that electroacupuncture at GV 20 and EX-HN3 which was effective on the treatment of depression was also effective on post-schizophrenic depression, and according to the comparison with the curative effect of sertraline hydrochloride tablets recommended in the Guidelines for Prevention and Treatment of Depression in China ^[14], it was found that the overall conditions were improved effectively and the difference was not statistically significant between the groups. Electroacupuncture takes effect more rapidly in the treatment of depression, and its effect can last for a longer time. In conclusion, electroacupuncture at GV 20 and EX-HN3 is an effective therapy of post-schizophrenic depression.

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