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Effect of Acupuncture on Physical Symptoms and Quality of Life in Treatment-Resistant Major Depressive Disorder and Bipolar Disorder: a Single-Arm Longitudinal Study

Yuto Matsuura1,* , Seiji Hongo2 , Hiroshi Taniguchi1 , Fumiko Yasuno1 , Tomomi Sakai1

1Department of Acupuncture and Moxibustion, Tokyo Ariake University of Medical and Health Sciences, Tokyo, Japan
2Himorogi Psychiatric Institute, Tokyo, Japan

Correspondence to:
Yuto Matsuura
Department of Acupuncture and Moxibustion, Tokyo Ariake University of Medical and Health Sciences, Tokyo, Japan
E-mail matsuuray@tau.ac.jp
Received: January 23, 2022; Revised: March 22, 2022; Accepted: October 4, 2022

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

J Acupunct Meridian Stud 2022; 15(6): 336-346

Published December 31, 2022 https://doi.org/10.51507/j.jams.2022.15.6.336

Copyright © Medical Association of Pharmacopuncture Institute.

Abstract

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Background: Acupuncture is a non-pharmacological therapy used clinically for mood disorders. Relief of physical symptoms with acupuncture treatment may lead to relief of depressive symptoms and improvement of quality of life (QoL). Few studies have examined the effect of acupuncture on the physical symptoms and QoL of patients with mood disorders.
Objectives: To examine the effect of acupuncture on physical symptoms and QoL of patients with treatment-resistant major depressive disorder (MDD) and bipolar disorder (BD).
Methods: This prospective, single-arm, longitudinal study included patients with MDD and BD from an outpatient psychiatric clinic. Acupuncture was performed weekly for 12 weeks in combination with regular treatment, with fixed acupoints and individualized treatment for each patient. Psychiatric symptoms were evaluated using the Himorogi Self-Rating Depression Scale (HSDS) and Himorogi Self-Rating Anxiety Scale (HSAS). Physical symptoms such as physical pain, gastrointestinal symptoms, and sleep disorders were evaluated using the Japanese version of the Somatic Symptom Scale-8 (SSS-8) and Visual Analog Scale (VAS). QoL was evaluated using the 8-item Short-Form (SF-8) Health Survey.
Results: A total of 36 patients (15 MDD and 21 BD patients) were analyzed. After 12 weeks of acupuncture, HSDS and HSAS scores significantly decreased (p < 0.05). Physical symptoms evaluated using SSS-8 and VAS scores also significantly improved (p < 0.05). In particular, neck pain and insomnia improved at an early stage. Among the SF-8 subscales, scores of bodily pain, general health perception, role limitations due to emotional problems, and mental health significantly increased (p < 0.05).
Conclusion: Acupuncture may improve not only psychiatric symptoms but also physical symptoms and QoL in patients with treatment-resistant mood disorders. Further studies are required for confirmation of the preliminary data collected thus far.

Keywords

Acupuncture, Bipolar disorder, Case series, Major depressive disorder, Physical symptom, Quality of life

INTRODUCTION

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Major depressive disorder (MDD) and bipolar disorder (BD) are mood disorders that involve major depressive episodes (MDE) [1]. MDD only exhibits a depressive state, whereas BD presents as a manic or hypomanic state in addition to depression. The prevalence of mood disorders is increasing worldwide [2]. MDD is expected to be the second-most prevalent disease in 2020 hindering daily life [3]. BD is the sixth leading cause of disability worldwide [4], with a lifetime prevalence of 3% in the general population [5].

Medication and non-pharmacological therapies such as cognitive behavioral therapy (CBT) are standard treatments for mood disorders. However, medication therapy has the following problems: i) the effectiveness rate of antidepressants in MDD, at first use, is approximately 60%-70% [6], which decreases further with MDE recurrence [7]; ii) side effects often prevent continuation of the medication [8]; and iii) patients with mood disorders have many physical symptoms during MDE and remission periods [9]. It is, therefore, difficult to manage mood disorders using medication therapy alone [10]. In particular, physical symptoms reduce the quality of life (QoL) and increase the risk of recurrence [11-13]. Considering the risk of overdose, treatment using medication alone is not recommended. Therefore, effective guidelines to administer non-pharmacological therapies should be established.

Various non-pharmacological therapies, such as CBT, have been attempted in response to problems caused by medication for mood disorders [14]. However, CBT usually requires multiple interviews and takes time, effort, and money. Moreover, because of the limited number of formally trained therapists, only a few patients benefit from CBT [15]. CBT provision did not increase even after its coverage in Japan’s National Health Insurance scheme [16]. Recently, internet-delivered CBT is being used to compensate for the limitations of conventional CBT, but high dropout rates during the course of therapy has been an issue [17]. Thus, patients with mood disorders need more accessible non-pharmacological therapies.

Acupuncture as a non-pharmacological therapy can be expected to complement medication therapy and is more effective at reducing depressive symptoms than medication therapy [18] and sham acupuncture treatment [19]. Furthermore, the combined use of conventional care and acupuncture is more effective in relieving depressive symptoms in MDD patients than usual care alone [20]. Acupuncture treatment has unique characteristics not found in other psychiatric treatments wherein the treatment approach is from the patient’s body surface. This means that acupuncture treatment can directly intervene in the physical symptoms of mood disorder patients. Relief of physical symptoms may lead to relief of depressive symptoms and improvement of QoL. However, few studies have examined the effect of acupuncture on the physical symptoms and QoL of patients with mood disorders. Therefore, it is necessary to observe changes in symptoms through acupuncture interventions at clinical sites and collect preliminary data. This exploratory study aimed to examine the effect of acupuncture on physical symptoms and QoL of patients with MDD and BD and to facilitate future confirmatory studies.

MATERIALS AND METHODS

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1. Ethical approval

This study was approved by the Research Ethics Committee of the Himorogi Psychiatric Institute (201704-02) on April 19, 2017. Participants were provided written and verbal explanations on freedom of study participation/withdrawal, consent, and protection of privacy. They then provided written consent. All study procedures were performed per the principles of the Declaration of Helsinki. The trial ID was UMIN000030714.

2. Study design

The study design was a single-arm, longitudinal study with a combination of acupuncture and standard treatment.

3. Participants

The setting was an outpatient psychiatric clinic in Ichigaya, Tokyo. Data were collected between April 2017 and March 2020. Outpatients of the clinic who consented to participate in the study and met the requisite criteria were included.

The inclusion criteria were as follows: i) having a diagnosis of MDD or BD as per the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5); ii) age ≥ 18 years; iii) no improvement or remission despite sufficient administration with more than two types of medications for 4 weeks, including SSRI, SNRI, mirtazapine, TCA/non-TCA, lithium, lamotrigine, sodium valproate, carbamazepine, and atypical antipsychotics, before administering acupuncture treatment; and iv) Himorogi Self-Rating Depression Scale (HSDS) [21] score ≥ 10 points or Himorogi Self-Rating Anxiety Scale (HSAS) [22] score ≥ 8 points. The exclusion criteria were as follows: i) depression or depressive state caused by organic brain damage; ii) severe disorders of the liver, kidney, blood, or circulation; iii) malignancy or previous history of malignancy; iv) pregnancy, nursing, or expecting (or planning) pregnancy in the near future; v) strong suicidal tendency, previous history of suicidal ideation, or suicide attempt; vi) personality disorder or intellectual disability; vii) substance dependence or drug abuse; and viii) non-completion of acupuncture treatment for 3 months.

4. Acupuncture treatment

The details of acupuncture treatment were reported based on the STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) guidelines [23] (Supplementary Table).

The acupuncture style was a combination of the common treatment with fixed acupoints and individualized treatment for each patient. This is based on the acupuncture method commonly used in Japan. In Japanese acupuncture therapy, careful detection of the acupoints of individual patients by palpation and fine-needling technique with comfortable subjective sensation is considered important [24]. Governor vessels 20 (GV20), gallbladder 20 (GB20), pericardium 6 (PC6), large intestine 4 (LI4), stomach 36 (ST36), spleen 6 (SP6), liver 3 (LR3), bladder 15 (BL15), bladder 18 (BL18), and bladder 20 (BL20) were selected as common acupoints based on the review of acupoints frequently used in randomized controlled trials of MDD patients [25] and our clinical experience with mood disorders [26,27]. The common acupoints GV20 and GB20 on the head and neck and PC6, LI4, ST36, SP6, and LR3 on the limbs were selected because they reportedly improve brain function and increase regional cerebral blood flow through acupuncture stimulation [28-33]. Acupuncture stimulation of BL15, BL18, and BL20 on the back improves circulation and gastrointestinal reactions via the somato-visceral reflex [34]. The acupuncture needle was inserted at a depth of 10-20 mm and left indwelling for 10 min.

In addition, individualized acupuncture treatment was administered for the physical symptoms of each patient. Treatment was administered based on physical conditions, which were evaluated through the physical examination (medical interview, palpation/manual examination) of each patient. When deciding on the acupoints or treatment site, emphasis was placed on palpation and the decision was made by confirming the patient’s reaction. We also performed electroacupuncture by applying electrical stimulation to the inserted needle when there were severe symptoms based on the patient’s condition or remarkable musculoskeletal symptoms. The equipment used for electroacupuncture was an Ohms pulsar (ZENRYOUKI Co., Fukuoka, Japan); a frequency of 1 Hz was used, with an energization time of 10 min. Stimulus intensity was set such that the muscle contraction did not cause discomfort to the patient.

Acupuncture treatment was performed once a week for 12 weeks. There was no limit on the number of needle insertions per participant per session. For treatment, a sterilized single-use needle of 0.16 × 40 mm or 20 × 60 mm was used (SEIRIN Co., Shizuoka, Japan). We did not use moxibustion therapy. Acupuncture was performed by an acupuncturist with a clinical experience of 5 years. During the acupuncture treatment, standard therapies such as medication and psychotherapy were not limited.

5. Outcome measures

1) Depressive and anxiety symptoms

Depression symptoms were assessed using the HSDS [21], and anxiety symptoms were assessed using the HSAS [22]. These are self-evaluation questionnaires that allow easy evaluation of psychiatric symptoms, even outside psychiatric specialties. The HSDS was created by extracting frequently asked questions from the Hamilton Depression Rating Scale (HDRS). The procedure for score allocation was similar to that of total score evaluation using the HDRS (correlation coefficient: 0.94). The HSDS cut-off scores are as follows: 0-5 points, no problem; 6-13 points, very mild; 14-23 points, mild; 24-30 points, moderate; and 31-39 points, severe. The HSAS was created based on the comparison between the Hamilton Rating Scale for Anxiety Interview Guide and Sheehan Patient-Rated Anxiety Scale. The HSAS cut-off scores are as follows: 0-4 points, no problem; 5-9 points, very mild; 10-14 points, mild; 15-19 points, moderate; and 20-39 points, severe. The HSDS and HSAS have 10 items each; the total score ranges from 0 to 39 points, and a higher score indicates more severe symptoms. The score validities were then verified. Cronbach’s α for the HSDS and HSAS was 0.85 (95% confidence interval [CI], 0.82-0.88) and 0.87 (95% CI, 0.85-0.90), respectively. Using these tools, it is possible to record and evaluate patients’ symptoms in a short time.

2) Physical symptoms

The Japanese version of the Somatic Symptom Scale-8 (SSS-8) [35] was used as an index of somatization, and the visual analog scale (VAS) was used as an index of subjective symptoms. The SSS-8 can quantify somatization that occurs because of stress response and evaluates eight symptoms using a scale from 0 (not at all) to 4 (very much) points. VAS was used to evaluate malaise, insomnia, stomach discomfort, anorexia, diarrhea, constipation, headache, neck pain, and low back pain, which are symptoms associated with mood disorders. The left end (0 mm) of the straight line (length of 100 mm) was evaluated as “no symptoms at all” and the right end (100 mm) as “maximum chaoticity.” If the VAS score of a patient’s particular physical symptom was 0 mm during the first assessment, that physical symptom was excluded from the analysis.

3) Quality of life

The Japanese version of the 8-item Short-Form Health Survey (SF-8) [36] was used to evaluate QoL. SF-8 can measure health-related QoL on eight subscales: physical function, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social function, role limitations due to emotional problems, and mental health.

4) Equivalent conversion value of medication use

The equivalent conversion value of the amount of medication used was evaluated from the 1st to 12th week. That is, the conversion value of chlorpromazine was used for antipsychotics; the conversion value of imipramine was used for antidepressants; and the conversion value of diazepam was used for anxiolytics.

6. Statistical analysis

The data are shown as mean ± standard deviation (S.D.) for participant characteristics, and outcome measures are shown as mean ± standard error (S.E.). Changes in each outcome measure were statistically analyzed using repeated measures analysis of variance (ANOVA). Dunnett’s test was used as a posthoc test when significant difference was observed. Changes in the equivalent conversion value of medication use were analyzed using a paired t-test. For items that showed significant differences at the 12th week, the mean difference (MD), 95% CI, and effect size (ES) from the 1st to 12th week were calculated. Statistical analyses were performed using GraphPad PRISM 6.0 (GraphPad Software, San Diego, USA). Statistical tests were conducted using a two-sided significance level of 0.05. The ES was calculated using Microsoft Excel (Microsoft 365 Apps for enterprise, USA) with repeated measures ANOVA as partial eta squared (partial η2) and posthoc test as Cohen’s d (0.20-0.49 = small, 0.50-0.79 = medium, and ≥ 0.8 = large effects) [37]. Loss to follow-up was not included in the statistical analysis.

RESULTS

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1. Participants

The enrollment rate at our psychiatric clinic was 91% (52/57). Of all patients who enrolled and started acupuncture treatment, 80% (16/20) of MDD patients and 71% (23/32) of BD patients completed the acupuncture treatment. After excluding three patients with data loss (one MDD and two BD patients), 75% (15/20) and 66% (21/32) of MDD and BD patients, respectively, were analyzed (Fig. 1). Table 1 shows age, sex, BD classification, disease duration, number of MDE, and number of complaints of physical symptoms in the 36 patients with MDD and BD.

Table 1 . Characteristics of participants

MDD (n = 15)BD (n = 21)Total (n = 36)
Age, yrs, mean (S.D.)50.3 (13.5)41.8 (12.3)45.3 (13.3)
SexFemale: 10, male: 5Female: 13, male: 8Female: 23, male: 13
Type I-11
Type II-1616
Unspecified-44
Duration disease, yrs, mean (S.D.)5.3 (5.0)9.3 (6.0)7.6 (5.9)
Number of major depressive episode
Single episode505
Recurrent episode102131
Complaint of physical symptom, n (%)
Neck pain15 (100%)20 (95%)35 (97%)
Insomnia14 (93%)19 (90%)33 (92%)
Stomach discomfort14 (93%)18 (85%)32 (88%)
Malaise15 (100%)17 (81%)32 (88%)
Anorexia13 (86%)18 (85%)31 (86%)
Headache14 (93%)16 (76%)30 (83%)
Diarrhea or constipation11 (73%)18 (85%)29 (81%)
Low back pain13 (86%)15 (71%)28 (78%)

MDD = Major depressive disorder; BD = Bipolar disorder.
Figure 1.The flow diagram of the participants 4. MDD = major depressive disorder; BD = bipolar disorder.

2. Depressive and anxiety symptoms

Repeated measures ANOVA showed significantly different HSDS and HSAS scores (p < 0.001, ES: 0.71; p = 0.001, ES: 0.78). The HSDS score significantly decreased after the 8th week of acupuncture (MD: 5.1, 95% CI: 2.1-8.1, ES: 0.74) (Fig. 2A). The HSAS score significantly decreased after the 9th, 10th, and 12th week (MD: 4.1, 95% CI: 0.9-7.1, ES: 0.55) (Fig. 2B).

Figure 2.Changes of (A) Himorogi self-rating depression scale (HSDS), (B) Himorogi self-rating anxiety scale (HSAS) and (C) somatic symptom scale-8 (SSS-8) in the patients during 12 weeks of acupuncture treatments. Patients were treated once a week (See Materials and Methods for details of acupuncture treatment). Data point and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.

3. Physical symptoms

The SSS-8 score was significantly different with repeated measures ANOVA (p < 0.001, ES: 0.68), and it significantly decreased after the 3rd and 5th week and thereafter (MD: 4.6, 95% CI: 2.7-6.5, ES: 1.35) (Fig. 2C).

The VAS score significantly decreased for neck pain (p = 0.001, ES: 0.64), insomnia (p < 0.001, ES: 0.51), stomach discomfort (p < 0.0004, ES: 0.44), malaise (p < 0.001, ES: 0.57), anorexia (p = 0.008, ES: 0.50), headache (p < 0.001, ES: 0.52), and diarrhea/constipation (p = 0.027, ES: 0.57) as shown by repeated measures ANOVA. Neck pain significantly decreased after the 2nd, 4th, and 7th week and thereafter (MD: 19.1, 95% CI: 2.9-35.3, ES: 0.68). Insomnia significantly decreased after the 2nd week and thereafter (MD: 26.9, 95% CI: 9.4-44.4, ES: 0.97). Stomach discomfort significantly decreased after the 5th and 7th week and thereafter (MD: 26.0, 95% CI: 9.8-42.1, ES: 0.88). Malaise significantly decreased after the 9th, 10th, and 12th week and thereafter (MD: 18.7, 95% CI: 1.6-35.9, ES: 0.67). Anorexia significantly decreased after the 12th week (MD: 18.4, 95% CI: 0.5-36.2, ES: 0.64). Headache significantly decreased after the 11th and 12th week and thereafter (MD: 21.8, 95% CI: 2.0-41.6, ES: 0.77). Diarrhea/constipation significantly decreased after the 7th and 9th week and thereafter (MD: 24.3, 95% CI: 2.8-45.8, ES: 0.78). There was no significant change regarding low back pain (Fig. 3).

Figure 3.Changes in visual analogue scale (VAS) scores for physical symptoms in the patients during 12 weeks of acupuncture treatments. Patients were individually treated with acupuncture (See Materials and Methods for details of the treatment). Data point and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.

4. Quality of life

The SF-8 subscale scores significantly decreased for bodily pain (p = 0.003, ES: 0.61), general health perception (p = 0.001, ES: 0.31), role limitation due to emotional problems (p = 0.009, ES: 0.49), and mental health (p < 0.001, ES: 0.46) with repeated measures ANOVA. Bodily pain significantly decreased after the 12th week (MD: –5.2, 95% CI: –9.4 to –0.9, ES: 0.61). General health perception significantly decreased after the 11th and 12th week (MD: –7.1, 95% CI: –11.9 to –2.3, ES: 1.07). Role limitation due to emotional problems significantly decreased after the 10th week or thereafter (MD: –6.6, 95% CI: –12.2 to –0.9, ES: 0.73). Mental health significantly decreased after the 7th, 8th, 11th, and 12th week (MD: –5.1, 95% CI: –10.1 to –0.1, ES: 0.61). There were no significant changes in vitality, social function, role limitations due to physical problems, or physical function (Fig. 4).

Figure 4.Changes in subscale on the 8-item Short-Form Health Survey (SF-8) evaluated for quality of life in the patients during 12 weeks of acupuncture treatments. Data and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.

5. Equivalent conversion value

Changes in the equivalent conversion value of medication use 12 weeks after baseline were 59.7 (17.9) to 54.6 (18.2) mg for chlorpromazine conversion, 117.3 (28.3) to 115.7 (24.8) mg for imipramine conversion, and 10.4 (1.6) to 8.6 (1.7) mg for diazepam conversion. There were no significant changes during the acupuncture treatment period.

6. Safety

No patient required medical treatment for complaints of worsening psychiatric symptoms and adverse events during the acupuncture treatment period.

DISCUSSION

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In this exploratory, prospective, single-arm, longitudinal study, we focused on the effects of acupuncture on physical symptoms and QoL. The physical symptoms and QoL of patients with mood disorders were assessed to help improve them with acupuncture treatment. Our exploratory study showed that even for treatment-resistant mood disorders, treatment of physical symptoms and QoL through acupuncture is feasible and acceptable.

Our study also showed that acupuncture effectively improved physical symptoms associated with mood disorders. Mood disorders are strongly associated with physical symptoms, especially pain, which co-exists in approximately 35% of MDD patients [38]. Chronic pain can cause anxiety and depression, and negative emotions can induce and increase pain [39]. Acupuncture can be expected to be effective in reducing symptoms related to pain-centric mood disorders. A clinical controlled trial on electroacupuncture and SSRIs aimed at more detailed symptom evaluation using HAMD-24 showed that electroacupuncture significantly alleviated anxiety/somatization, which consists of mental and physical anxiety, gastrointestinal and general physical symptoms, hypochondriasis, and insights [40], compared with SSRI with factor analysis [41]. Moreover, a systematic review and meta-analysis of acupuncture for chronic pain-related depression reported that acupuncture is an effective and safe treatment for chronic pain-related depression, and acupuncture combined with medication therapy is more effective in reducing pain intensity than medication therapy alone [42]. In our study, improvements in physical symptoms preceded improvements in depressive symptoms. In particular, insomnia and neck pain were alleviated during the early stage. Physical symptoms of insomnia and pain have been shown to adversely affect the prognosis of mood disorders [43-46]. Our findings suggest that acupuncture treatment improves physical symptoms and can help mitigate psychiatric symptoms in mood disorders. It is worth noting that because our study did not analyze causal relationships, results should be interpreted as trends.

In our study, the SF-8 QoL evaluation, including general health perception, role limitations due to emotional problems, and mental health, improved after 3 months of acupuncture treatment. Pain intensity is a factor in predicting physical and psychosocial QoL changes for 3 months [47]. This means that QoL can be improved by alleviating physical pain. Our results showed that improvements in physical symptoms had a positive effect on QoL. Therefore, alleviation of physical symptoms in mood disorders is important for alleviating psychiatric symptoms and improving QoL. These findings imply that acupuncture therapy may contribute toward preventing medication overdose when treating physical symptoms and reducing medicine dosage.

Improvement of the above symptoms can also be explained by the mechanism that acts on the central and local pathologies of acupuncture. Acupuncture activates the analgesic, circulatory, and autonomic nervous systems [24]. These reactions occur mainly in the central nervous system. In particular, the effects of acupuncture have been used in clinical settings to treat physical symptoms, such as chronic pain caused by central sensitization [48]. Similarly, some of the physical symptoms in mood disorders reflect somatization due to brain dysfunction [49]. In this study, the SSS-8 scores used to assess the burden of physical symptoms due to somatization were reduced by acupuncture. This suggests that acupuncture contributed to the improvement of the pathology of the higher central nervous system.

On the other hand, acupuncture may also play an important role in improving symptoms even in the treatment of local pathologies. Notably, an important feature of the Japanese-style acupuncture method used in this study is that acupuncture was applied to different participants based on individual symptoms and physical findings. Japanese acupuncture and moxibustion characteristics stem from a cultural and historical background that prioritizes less painful treatment methods, such as acupuncture using a guide tube [50]. Treatment is adjusted according to the patient’s susceptibility. Palpation is emphasized when selecting acupuncture points, and individual treatment is performed according to individual physical findings. Acupuncture can address not only the pathology of central effects but also the physical symptoms of individual patients. This is a feature of acupuncture that is not found in other non-pharmacological treatments, such as psychotherapy.

This study has several limitations. First, the placebo effect could have been involved in improvements related to acupuncture considering the absence of a control group. Mental illness has been shown to be susceptible to placebo effects [51]. Typically, it is desirable to include a placebo group in clinical trials on acupuncture. However, sham acupuncture has no single and definite definition [52]. Sham acupuncture, such as non-acupoint stimulation and shallow needling, can elicit physiological activity. The next step after this exploratory study is to conduct a practical clinical trial that includes a placebo group to compare the presence or absence of individualized treatment. In the future, we wish to clarify the effectiveness of acupuncture treatment by conducting a placebo-controlled clinical trial using double-blind acupuncture needles in which the acupuncture needle tip does not come into contact with the skin [53]. Second, this study does not describe the causal relationship between physical symptoms and the improvement of depression due to the lack of a control group. Our findings should be confirmed in a larger, randomized study. Third, the standard treatment for study participants was not limited. Medication therapy was confirmed to have no significant change in use by the equivalent conversion value of medications. On the other hand, the use of psychotherapy may have contributed to symptom relief in participants, but this could not be quantified in this study. Our results also included the effects of medication therapy adjustments and other psychotherapies. This study presents the effects of addition of acupuncture treatment to general practice. Fourth, although individualized treatment was used in this study, it lacks detailed reports on the individualized acupuncture methods employed. To obtain reproducibility, it is necessary to report the results of more detailed interventions, such as the number of acupuncture needles and site of electrical stimulation. Fifth, MDD and BD have similar MDE but are defined as different diseases in the DSM-5. In this preliminary study, both MDD and BD patients with treatment-resistant MDE were recruited to broaden the scope of the study. Considering that BD had a higher dropout rate, a detailed analysis including comparison by disease and BD type will be required in the future. Sixth, although no adverse events requiring treatment occurred, minor adverse events such as post-treatment drowsiness, dullness, and discomfort at the acupuncture site occurred in a few cases. Because we were unable to obtain the specific number of occurrences of these minor adverse events, future studies are required for detailed safety reporting.

CONCLUSIONS

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Acupuncture was tolerated by patients with treatment-resistant mood disorders, and the effect of acupuncture on this population could be observed. In addition, acupuncture may improve not only mood symptoms but also physical symptoms and improve QoL in patients with treatment-resistant mood disorders. Based on this preliminary data, we need to conduct comparative tests with control groups to clarify the effectiveness of acupuncture treatment for mood disorders. The results of this study provide valuable preliminary data for future confirmatory studies.

SUPPLEMENTARY MATERIAL

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Supplementary data to this article can be found online at https://doi.org/10.51507/j.jams.2022.15.6.336

jams-15-6-336-supple.pdf

ACKNOWLEDGEMENTS

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The authors express thanks to Arisa Mukou and Eriko Kobayashi for acupuncture treatment assistance.

FUNDING

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This work was supported by a research grant to TS by Tokyo Ariake University of Medical and Health Sciences, Tokyo, Japan.

AUTHORS' CONTRIBUTIONS

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YM, FY, and TS contributed to conceptualization. SH contributed to patient eligibility assessment and recruitment. YM and FY contributed to data collection and wrote the original draft of the manuscript. HT contributed to the analysis and interpretation of data, assisted in the preparation of the manuscript, and critically reviewed and edited the manuscript. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

CONFLICT OF INTEREST

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The authors declare no conflict of interest.

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More Related Articles

Article

Research Article

J Acupunct Meridian Stud 2022; 15(6): 336-346

Published online December 31, 2022 https://doi.org/10.51507/j.jams.2022.15.6.336

Copyright © Medical Association of Pharmacopuncture Institute.

Effect of Acupuncture on Physical Symptoms and Quality of Life in Treatment-Resistant Major Depressive Disorder and Bipolar Disorder: a Single-Arm Longitudinal Study

Yuto Matsuura1,* , Seiji Hongo2 , Hiroshi Taniguchi1 , Fumiko Yasuno1 , Tomomi Sakai1

1Department of Acupuncture and Moxibustion, Tokyo Ariake University of Medical and Health Sciences, Tokyo, Japan
2Himorogi Psychiatric Institute, Tokyo, Japan

Correspondence to:Yuto Matsuura
Department of Acupuncture and Moxibustion, Tokyo Ariake University of Medical and Health Sciences, Tokyo, Japan
E-mail matsuuray@tau.ac.jp

Received: January 23, 2022; Revised: March 22, 2022; Accepted: October 4, 2022

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Acupuncture is a non-pharmacological therapy used clinically for mood disorders. Relief of physical symptoms with acupuncture treatment may lead to relief of depressive symptoms and improvement of quality of life (QoL). Few studies have examined the effect of acupuncture on the physical symptoms and QoL of patients with mood disorders.
Objectives: To examine the effect of acupuncture on physical symptoms and QoL of patients with treatment-resistant major depressive disorder (MDD) and bipolar disorder (BD).
Methods: This prospective, single-arm, longitudinal study included patients with MDD and BD from an outpatient psychiatric clinic. Acupuncture was performed weekly for 12 weeks in combination with regular treatment, with fixed acupoints and individualized treatment for each patient. Psychiatric symptoms were evaluated using the Himorogi Self-Rating Depression Scale (HSDS) and Himorogi Self-Rating Anxiety Scale (HSAS). Physical symptoms such as physical pain, gastrointestinal symptoms, and sleep disorders were evaluated using the Japanese version of the Somatic Symptom Scale-8 (SSS-8) and Visual Analog Scale (VAS). QoL was evaluated using the 8-item Short-Form (SF-8) Health Survey.
Results: A total of 36 patients (15 MDD and 21 BD patients) were analyzed. After 12 weeks of acupuncture, HSDS and HSAS scores significantly decreased (p < 0.05). Physical symptoms evaluated using SSS-8 and VAS scores also significantly improved (p < 0.05). In particular, neck pain and insomnia improved at an early stage. Among the SF-8 subscales, scores of bodily pain, general health perception, role limitations due to emotional problems, and mental health significantly increased (p < 0.05).
Conclusion: Acupuncture may improve not only psychiatric symptoms but also physical symptoms and QoL in patients with treatment-resistant mood disorders. Further studies are required for confirmation of the preliminary data collected thus far.

Keywords: Acupuncture, Bipolar disorder, Case series, Major depressive disorder, Physical symptom, Quality of life

INTRODUCTION

Major depressive disorder (MDD) and bipolar disorder (BD) are mood disorders that involve major depressive episodes (MDE) [1]. MDD only exhibits a depressive state, whereas BD presents as a manic or hypomanic state in addition to depression. The prevalence of mood disorders is increasing worldwide [2]. MDD is expected to be the second-most prevalent disease in 2020 hindering daily life [3]. BD is the sixth leading cause of disability worldwide [4], with a lifetime prevalence of 3% in the general population [5].

Medication and non-pharmacological therapies such as cognitive behavioral therapy (CBT) are standard treatments for mood disorders. However, medication therapy has the following problems: i) the effectiveness rate of antidepressants in MDD, at first use, is approximately 60%-70% [6], which decreases further with MDE recurrence [7]; ii) side effects often prevent continuation of the medication [8]; and iii) patients with mood disorders have many physical symptoms during MDE and remission periods [9]. It is, therefore, difficult to manage mood disorders using medication therapy alone [10]. In particular, physical symptoms reduce the quality of life (QoL) and increase the risk of recurrence [11-13]. Considering the risk of overdose, treatment using medication alone is not recommended. Therefore, effective guidelines to administer non-pharmacological therapies should be established.

Various non-pharmacological therapies, such as CBT, have been attempted in response to problems caused by medication for mood disorders [14]. However, CBT usually requires multiple interviews and takes time, effort, and money. Moreover, because of the limited number of formally trained therapists, only a few patients benefit from CBT [15]. CBT provision did not increase even after its coverage in Japan’s National Health Insurance scheme [16]. Recently, internet-delivered CBT is being used to compensate for the limitations of conventional CBT, but high dropout rates during the course of therapy has been an issue [17]. Thus, patients with mood disorders need more accessible non-pharmacological therapies.

Acupuncture as a non-pharmacological therapy can be expected to complement medication therapy and is more effective at reducing depressive symptoms than medication therapy [18] and sham acupuncture treatment [19]. Furthermore, the combined use of conventional care and acupuncture is more effective in relieving depressive symptoms in MDD patients than usual care alone [20]. Acupuncture treatment has unique characteristics not found in other psychiatric treatments wherein the treatment approach is from the patient’s body surface. This means that acupuncture treatment can directly intervene in the physical symptoms of mood disorder patients. Relief of physical symptoms may lead to relief of depressive symptoms and improvement of QoL. However, few studies have examined the effect of acupuncture on the physical symptoms and QoL of patients with mood disorders. Therefore, it is necessary to observe changes in symptoms through acupuncture interventions at clinical sites and collect preliminary data. This exploratory study aimed to examine the effect of acupuncture on physical symptoms and QoL of patients with MDD and BD and to facilitate future confirmatory studies.

MATERIALS AND METHODS

1. Ethical approval

This study was approved by the Research Ethics Committee of the Himorogi Psychiatric Institute (201704-02) on April 19, 2017. Participants were provided written and verbal explanations on freedom of study participation/withdrawal, consent, and protection of privacy. They then provided written consent. All study procedures were performed per the principles of the Declaration of Helsinki. The trial ID was UMIN000030714.

2. Study design

The study design was a single-arm, longitudinal study with a combination of acupuncture and standard treatment.

3. Participants

The setting was an outpatient psychiatric clinic in Ichigaya, Tokyo. Data were collected between April 2017 and March 2020. Outpatients of the clinic who consented to participate in the study and met the requisite criteria were included.

The inclusion criteria were as follows: i) having a diagnosis of MDD or BD as per the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5); ii) age ≥ 18 years; iii) no improvement or remission despite sufficient administration with more than two types of medications for 4 weeks, including SSRI, SNRI, mirtazapine, TCA/non-TCA, lithium, lamotrigine, sodium valproate, carbamazepine, and atypical antipsychotics, before administering acupuncture treatment; and iv) Himorogi Self-Rating Depression Scale (HSDS) [21] score ≥ 10 points or Himorogi Self-Rating Anxiety Scale (HSAS) [22] score ≥ 8 points. The exclusion criteria were as follows: i) depression or depressive state caused by organic brain damage; ii) severe disorders of the liver, kidney, blood, or circulation; iii) malignancy or previous history of malignancy; iv) pregnancy, nursing, or expecting (or planning) pregnancy in the near future; v) strong suicidal tendency, previous history of suicidal ideation, or suicide attempt; vi) personality disorder or intellectual disability; vii) substance dependence or drug abuse; and viii) non-completion of acupuncture treatment for 3 months.

4. Acupuncture treatment

The details of acupuncture treatment were reported based on the STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) guidelines [23] (Supplementary Table).

The acupuncture style was a combination of the common treatment with fixed acupoints and individualized treatment for each patient. This is based on the acupuncture method commonly used in Japan. In Japanese acupuncture therapy, careful detection of the acupoints of individual patients by palpation and fine-needling technique with comfortable subjective sensation is considered important [24]. Governor vessels 20 (GV20), gallbladder 20 (GB20), pericardium 6 (PC6), large intestine 4 (LI4), stomach 36 (ST36), spleen 6 (SP6), liver 3 (LR3), bladder 15 (BL15), bladder 18 (BL18), and bladder 20 (BL20) were selected as common acupoints based on the review of acupoints frequently used in randomized controlled trials of MDD patients [25] and our clinical experience with mood disorders [26,27]. The common acupoints GV20 and GB20 on the head and neck and PC6, LI4, ST36, SP6, and LR3 on the limbs were selected because they reportedly improve brain function and increase regional cerebral blood flow through acupuncture stimulation [28-33]. Acupuncture stimulation of BL15, BL18, and BL20 on the back improves circulation and gastrointestinal reactions via the somato-visceral reflex [34]. The acupuncture needle was inserted at a depth of 10-20 mm and left indwelling for 10 min.

In addition, individualized acupuncture treatment was administered for the physical symptoms of each patient. Treatment was administered based on physical conditions, which were evaluated through the physical examination (medical interview, palpation/manual examination) of each patient. When deciding on the acupoints or treatment site, emphasis was placed on palpation and the decision was made by confirming the patient’s reaction. We also performed electroacupuncture by applying electrical stimulation to the inserted needle when there were severe symptoms based on the patient’s condition or remarkable musculoskeletal symptoms. The equipment used for electroacupuncture was an Ohms pulsar (ZENRYOUKI Co., Fukuoka, Japan); a frequency of 1 Hz was used, with an energization time of 10 min. Stimulus intensity was set such that the muscle contraction did not cause discomfort to the patient.

Acupuncture treatment was performed once a week for 12 weeks. There was no limit on the number of needle insertions per participant per session. For treatment, a sterilized single-use needle of 0.16 × 40 mm or 20 × 60 mm was used (SEIRIN Co., Shizuoka, Japan). We did not use moxibustion therapy. Acupuncture was performed by an acupuncturist with a clinical experience of 5 years. During the acupuncture treatment, standard therapies such as medication and psychotherapy were not limited.

5. Outcome measures

1) Depressive and anxiety symptoms

Depression symptoms were assessed using the HSDS [21], and anxiety symptoms were assessed using the HSAS [22]. These are self-evaluation questionnaires that allow easy evaluation of psychiatric symptoms, even outside psychiatric specialties. The HSDS was created by extracting frequently asked questions from the Hamilton Depression Rating Scale (HDRS). The procedure for score allocation was similar to that of total score evaluation using the HDRS (correlation coefficient: 0.94). The HSDS cut-off scores are as follows: 0-5 points, no problem; 6-13 points, very mild; 14-23 points, mild; 24-30 points, moderate; and 31-39 points, severe. The HSAS was created based on the comparison between the Hamilton Rating Scale for Anxiety Interview Guide and Sheehan Patient-Rated Anxiety Scale. The HSAS cut-off scores are as follows: 0-4 points, no problem; 5-9 points, very mild; 10-14 points, mild; 15-19 points, moderate; and 20-39 points, severe. The HSDS and HSAS have 10 items each; the total score ranges from 0 to 39 points, and a higher score indicates more severe symptoms. The score validities were then verified. Cronbach’s α for the HSDS and HSAS was 0.85 (95% confidence interval [CI], 0.82-0.88) and 0.87 (95% CI, 0.85-0.90), respectively. Using these tools, it is possible to record and evaluate patients’ symptoms in a short time.

2) Physical symptoms

The Japanese version of the Somatic Symptom Scale-8 (SSS-8) [35] was used as an index of somatization, and the visual analog scale (VAS) was used as an index of subjective symptoms. The SSS-8 can quantify somatization that occurs because of stress response and evaluates eight symptoms using a scale from 0 (not at all) to 4 (very much) points. VAS was used to evaluate malaise, insomnia, stomach discomfort, anorexia, diarrhea, constipation, headache, neck pain, and low back pain, which are symptoms associated with mood disorders. The left end (0 mm) of the straight line (length of 100 mm) was evaluated as “no symptoms at all” and the right end (100 mm) as “maximum chaoticity.” If the VAS score of a patient’s particular physical symptom was 0 mm during the first assessment, that physical symptom was excluded from the analysis.

3) Quality of life

The Japanese version of the 8-item Short-Form Health Survey (SF-8) [36] was used to evaluate QoL. SF-8 can measure health-related QoL on eight subscales: physical function, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social function, role limitations due to emotional problems, and mental health.

4) Equivalent conversion value of medication use

The equivalent conversion value of the amount of medication used was evaluated from the 1st to 12th week. That is, the conversion value of chlorpromazine was used for antipsychotics; the conversion value of imipramine was used for antidepressants; and the conversion value of diazepam was used for anxiolytics.

6. Statistical analysis

The data are shown as mean ± standard deviation (S.D.) for participant characteristics, and outcome measures are shown as mean ± standard error (S.E.). Changes in each outcome measure were statistically analyzed using repeated measures analysis of variance (ANOVA). Dunnett’s test was used as a posthoc test when significant difference was observed. Changes in the equivalent conversion value of medication use were analyzed using a paired t-test. For items that showed significant differences at the 12th week, the mean difference (MD), 95% CI, and effect size (ES) from the 1st to 12th week were calculated. Statistical analyses were performed using GraphPad PRISM 6.0 (GraphPad Software, San Diego, USA). Statistical tests were conducted using a two-sided significance level of 0.05. The ES was calculated using Microsoft Excel (Microsoft 365 Apps for enterprise, USA) with repeated measures ANOVA as partial eta squared (partial η2) and posthoc test as Cohen’s d (0.20-0.49 = small, 0.50-0.79 = medium, and ≥ 0.8 = large effects) [37]. Loss to follow-up was not included in the statistical analysis.

RESULTS

1. Participants

The enrollment rate at our psychiatric clinic was 91% (52/57). Of all patients who enrolled and started acupuncture treatment, 80% (16/20) of MDD patients and 71% (23/32) of BD patients completed the acupuncture treatment. After excluding three patients with data loss (one MDD and two BD patients), 75% (15/20) and 66% (21/32) of MDD and BD patients, respectively, were analyzed (Fig. 1). Table 1 shows age, sex, BD classification, disease duration, number of MDE, and number of complaints of physical symptoms in the 36 patients with MDD and BD.

MDD = Major depressive disorder; BD = Bipolar disorder..

&md=tbl&idx=1' data-target="#file-modal"">Table 1

Characteristics of participants.

MDD (n = 15)BD (n = 21)Total (n = 36)
Age, yrs, mean (S.D.)50.3 (13.5)41.8 (12.3)45.3 (13.3)
SexFemale: 10, male: 5Female: 13, male: 8Female: 23, male: 13
Type I-11
Type II-1616
Unspecified-44
Duration disease, yrs, mean (S.D.)5.3 (5.0)9.3 (6.0)7.6 (5.9)
Number of major depressive episode
Single episode505
Recurrent episode102131
Complaint of physical symptom, n (%)
Neck pain15 (100%)20 (95%)35 (97%)
Insomnia14 (93%)19 (90%)33 (92%)
Stomach discomfort14 (93%)18 (85%)32 (88%)
Malaise15 (100%)17 (81%)32 (88%)
Anorexia13 (86%)18 (85%)31 (86%)
Headache14 (93%)16 (76%)30 (83%)
Diarrhea or constipation11 (73%)18 (85%)29 (81%)
Low back pain13 (86%)15 (71%)28 (78%)

MDD = Major depressive disorder; BD = Bipolar disorder..
Figure 1. The flow diagram of the participants 4. MDD = major depressive disorder; BD = bipolar disorder.

2. Depressive and anxiety symptoms

Repeated measures ANOVA showed significantly different HSDS and HSAS scores (p < 0.001, ES: 0.71; p = 0.001, ES: 0.78). The HSDS score significantly decreased after the 8th week of acupuncture (MD: 5.1, 95% CI: 2.1-8.1, ES: 0.74) (Fig. 2A). The HSAS score significantly decreased after the 9th, 10th, and 12th week (MD: 4.1, 95% CI: 0.9-7.1, ES: 0.55) (Fig. 2B).

Figure 2. Changes of (A) Himorogi self-rating depression scale (HSDS), (B) Himorogi self-rating anxiety scale (HSAS) and (C) somatic symptom scale-8 (SSS-8) in the patients during 12 weeks of acupuncture treatments. Patients were treated once a week (See Materials and Methods for details of acupuncture treatment). Data point and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.

3. Physical symptoms

The SSS-8 score was significantly different with repeated measures ANOVA (p < 0.001, ES: 0.68), and it significantly decreased after the 3rd and 5th week and thereafter (MD: 4.6, 95% CI: 2.7-6.5, ES: 1.35) (Fig. 2C).

The VAS score significantly decreased for neck pain (p = 0.001, ES: 0.64), insomnia (p < 0.001, ES: 0.51), stomach discomfort (p < 0.0004, ES: 0.44), malaise (p < 0.001, ES: 0.57), anorexia (p = 0.008, ES: 0.50), headache (p < 0.001, ES: 0.52), and diarrhea/constipation (p = 0.027, ES: 0.57) as shown by repeated measures ANOVA. Neck pain significantly decreased after the 2nd, 4th, and 7th week and thereafter (MD: 19.1, 95% CI: 2.9-35.3, ES: 0.68). Insomnia significantly decreased after the 2nd week and thereafter (MD: 26.9, 95% CI: 9.4-44.4, ES: 0.97). Stomach discomfort significantly decreased after the 5th and 7th week and thereafter (MD: 26.0, 95% CI: 9.8-42.1, ES: 0.88). Malaise significantly decreased after the 9th, 10th, and 12th week and thereafter (MD: 18.7, 95% CI: 1.6-35.9, ES: 0.67). Anorexia significantly decreased after the 12th week (MD: 18.4, 95% CI: 0.5-36.2, ES: 0.64). Headache significantly decreased after the 11th and 12th week and thereafter (MD: 21.8, 95% CI: 2.0-41.6, ES: 0.77). Diarrhea/constipation significantly decreased after the 7th and 9th week and thereafter (MD: 24.3, 95% CI: 2.8-45.8, ES: 0.78). There was no significant change regarding low back pain (Fig. 3).

Figure 3. Changes in visual analogue scale (VAS) scores for physical symptoms in the patients during 12 weeks of acupuncture treatments. Patients were individually treated with acupuncture (See Materials and Methods for details of the treatment). Data point and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.

4. Quality of life

The SF-8 subscale scores significantly decreased for bodily pain (p = 0.003, ES: 0.61), general health perception (p = 0.001, ES: 0.31), role limitation due to emotional problems (p = 0.009, ES: 0.49), and mental health (p < 0.001, ES: 0.46) with repeated measures ANOVA. Bodily pain significantly decreased after the 12th week (MD: –5.2, 95% CI: –9.4 to –0.9, ES: 0.61). General health perception significantly decreased after the 11th and 12th week (MD: –7.1, 95% CI: –11.9 to –2.3, ES: 1.07). Role limitation due to emotional problems significantly decreased after the 10th week or thereafter (MD: –6.6, 95% CI: –12.2 to –0.9, ES: 0.73). Mental health significantly decreased after the 7th, 8th, 11th, and 12th week (MD: –5.1, 95% CI: –10.1 to –0.1, ES: 0.61). There were no significant changes in vitality, social function, role limitations due to physical problems, or physical function (Fig. 4).

Figure 4. Changes in subscale on the 8-item Short-Form Health Survey (SF-8) evaluated for quality of life in the patients during 12 weeks of acupuncture treatments. Data and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.

5. Equivalent conversion value

Changes in the equivalent conversion value of medication use 12 weeks after baseline were 59.7 (17.9) to 54.6 (18.2) mg for chlorpromazine conversion, 117.3 (28.3) to 115.7 (24.8) mg for imipramine conversion, and 10.4 (1.6) to 8.6 (1.7) mg for diazepam conversion. There were no significant changes during the acupuncture treatment period.

6. Safety

No patient required medical treatment for complaints of worsening psychiatric symptoms and adverse events during the acupuncture treatment period.

DISCUSSION

In this exploratory, prospective, single-arm, longitudinal study, we focused on the effects of acupuncture on physical symptoms and QoL. The physical symptoms and QoL of patients with mood disorders were assessed to help improve them with acupuncture treatment. Our exploratory study showed that even for treatment-resistant mood disorders, treatment of physical symptoms and QoL through acupuncture is feasible and acceptable.

Our study also showed that acupuncture effectively improved physical symptoms associated with mood disorders. Mood disorders are strongly associated with physical symptoms, especially pain, which co-exists in approximately 35% of MDD patients [38]. Chronic pain can cause anxiety and depression, and negative emotions can induce and increase pain [39]. Acupuncture can be expected to be effective in reducing symptoms related to pain-centric mood disorders. A clinical controlled trial on electroacupuncture and SSRIs aimed at more detailed symptom evaluation using HAMD-24 showed that electroacupuncture significantly alleviated anxiety/somatization, which consists of mental and physical anxiety, gastrointestinal and general physical symptoms, hypochondriasis, and insights [40], compared with SSRI with factor analysis [41]. Moreover, a systematic review and meta-analysis of acupuncture for chronic pain-related depression reported that acupuncture is an effective and safe treatment for chronic pain-related depression, and acupuncture combined with medication therapy is more effective in reducing pain intensity than medication therapy alone [42]. In our study, improvements in physical symptoms preceded improvements in depressive symptoms. In particular, insomnia and neck pain were alleviated during the early stage. Physical symptoms of insomnia and pain have been shown to adversely affect the prognosis of mood disorders [43-46]. Our findings suggest that acupuncture treatment improves physical symptoms and can help mitigate psychiatric symptoms in mood disorders. It is worth noting that because our study did not analyze causal relationships, results should be interpreted as trends.

In our study, the SF-8 QoL evaluation, including general health perception, role limitations due to emotional problems, and mental health, improved after 3 months of acupuncture treatment. Pain intensity is a factor in predicting physical and psychosocial QoL changes for 3 months [47]. This means that QoL can be improved by alleviating physical pain. Our results showed that improvements in physical symptoms had a positive effect on QoL. Therefore, alleviation of physical symptoms in mood disorders is important for alleviating psychiatric symptoms and improving QoL. These findings imply that acupuncture therapy may contribute toward preventing medication overdose when treating physical symptoms and reducing medicine dosage.

Improvement of the above symptoms can also be explained by the mechanism that acts on the central and local pathologies of acupuncture. Acupuncture activates the analgesic, circulatory, and autonomic nervous systems [24]. These reactions occur mainly in the central nervous system. In particular, the effects of acupuncture have been used in clinical settings to treat physical symptoms, such as chronic pain caused by central sensitization [48]. Similarly, some of the physical symptoms in mood disorders reflect somatization due to brain dysfunction [49]. In this study, the SSS-8 scores used to assess the burden of physical symptoms due to somatization were reduced by acupuncture. This suggests that acupuncture contributed to the improvement of the pathology of the higher central nervous system.

On the other hand, acupuncture may also play an important role in improving symptoms even in the treatment of local pathologies. Notably, an important feature of the Japanese-style acupuncture method used in this study is that acupuncture was applied to different participants based on individual symptoms and physical findings. Japanese acupuncture and moxibustion characteristics stem from a cultural and historical background that prioritizes less painful treatment methods, such as acupuncture using a guide tube [50]. Treatment is adjusted according to the patient’s susceptibility. Palpation is emphasized when selecting acupuncture points, and individual treatment is performed according to individual physical findings. Acupuncture can address not only the pathology of central effects but also the physical symptoms of individual patients. This is a feature of acupuncture that is not found in other non-pharmacological treatments, such as psychotherapy.

This study has several limitations. First, the placebo effect could have been involved in improvements related to acupuncture considering the absence of a control group. Mental illness has been shown to be susceptible to placebo effects [51]. Typically, it is desirable to include a placebo group in clinical trials on acupuncture. However, sham acupuncture has no single and definite definition [52]. Sham acupuncture, such as non-acupoint stimulation and shallow needling, can elicit physiological activity. The next step after this exploratory study is to conduct a practical clinical trial that includes a placebo group to compare the presence or absence of individualized treatment. In the future, we wish to clarify the effectiveness of acupuncture treatment by conducting a placebo-controlled clinical trial using double-blind acupuncture needles in which the acupuncture needle tip does not come into contact with the skin [53]. Second, this study does not describe the causal relationship between physical symptoms and the improvement of depression due to the lack of a control group. Our findings should be confirmed in a larger, randomized study. Third, the standard treatment for study participants was not limited. Medication therapy was confirmed to have no significant change in use by the equivalent conversion value of medications. On the other hand, the use of psychotherapy may have contributed to symptom relief in participants, but this could not be quantified in this study. Our results also included the effects of medication therapy adjustments and other psychotherapies. This study presents the effects of addition of acupuncture treatment to general practice. Fourth, although individualized treatment was used in this study, it lacks detailed reports on the individualized acupuncture methods employed. To obtain reproducibility, it is necessary to report the results of more detailed interventions, such as the number of acupuncture needles and site of electrical stimulation. Fifth, MDD and BD have similar MDE but are defined as different diseases in the DSM-5. In this preliminary study, both MDD and BD patients with treatment-resistant MDE were recruited to broaden the scope of the study. Considering that BD had a higher dropout rate, a detailed analysis including comparison by disease and BD type will be required in the future. Sixth, although no adverse events requiring treatment occurred, minor adverse events such as post-treatment drowsiness, dullness, and discomfort at the acupuncture site occurred in a few cases. Because we were unable to obtain the specific number of occurrences of these minor adverse events, future studies are required for detailed safety reporting.

CONCLUSIONS

Acupuncture was tolerated by patients with treatment-resistant mood disorders, and the effect of acupuncture on this population could be observed. In addition, acupuncture may improve not only mood symptoms but also physical symptoms and improve QoL in patients with treatment-resistant mood disorders. Based on this preliminary data, we need to conduct comparative tests with control groups to clarify the effectiveness of acupuncture treatment for mood disorders. The results of this study provide valuable preliminary data for future confirmatory studies.

SUPPLEMENTARY MATERIAL

Supplementary data to this article can be found online at https://doi.org/10.51507/j.jams.2022.15.6.336

jams-15-6-336-supple.pdf

ACKNOWLEDGEMENTS

The authors express thanks to Arisa Mukou and Eriko Kobayashi for acupuncture treatment assistance.

FUNDING

This work was supported by a research grant to TS by Tokyo Ariake University of Medical and Health Sciences, Tokyo, Japan.

AUTHORS' CONTRIBUTIONS

YM, FY, and TS contributed to conceptualization. SH contributed to patient eligibility assessment and recruitment. YM and FY contributed to data collection and wrote the original draft of the manuscript. HT contributed to the analysis and interpretation of data, assisted in the preparation of the manuscript, and critically reviewed and edited the manuscript. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Fig 1.

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Figure 1.The flow diagram of the participants 4. MDD = major depressive disorder; BD = bipolar disorder.
Journal of Acupuncture and Meridian Studies 2022; 15: 336-346https://doi.org/10.51507/j.jams.2022.15.6.336

Fig 2.

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Figure 2.Changes of (A) Himorogi self-rating depression scale (HSDS), (B) Himorogi self-rating anxiety scale (HSAS) and (C) somatic symptom scale-8 (SSS-8) in the patients during 12 weeks of acupuncture treatments. Patients were treated once a week (See Materials and Methods for details of acupuncture treatment). Data point and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.
Journal of Acupuncture and Meridian Studies 2022; 15: 336-346https://doi.org/10.51507/j.jams.2022.15.6.336

Fig 3.

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Figure 3.Changes in visual analogue scale (VAS) scores for physical symptoms in the patients during 12 weeks of acupuncture treatments. Patients were individually treated with acupuncture (See Materials and Methods for details of the treatment). Data point and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.
Journal of Acupuncture and Meridian Studies 2022; 15: 336-346https://doi.org/10.51507/j.jams.2022.15.6.336

Fig 4.

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Figure 4.Changes in subscale on the 8-item Short-Form Health Survey (SF-8) evaluated for quality of life in the patients during 12 weeks of acupuncture treatments. Data and error bars represent mean ± SE. *p < 0.05 by repeated ANOVA and post hoc Dunnett’s multiple comparison test vs. 1st week.
Journal of Acupuncture and Meridian Studies 2022; 15: 336-346https://doi.org/10.51507/j.jams.2022.15.6.336

Table 1 . Characteristics of participants.

MDD (n = 15)BD (n = 21)Total (n = 36)
Age, yrs, mean (S.D.)50.3 (13.5)41.8 (12.3)45.3 (13.3)
SexFemale: 10, male: 5Female: 13, male: 8Female: 23, male: 13
Type I-11
Type II-1616
Unspecified-44
Duration disease, yrs, mean (S.D.)5.3 (5.0)9.3 (6.0)7.6 (5.9)
Number of major depressive episode
Single episode505
Recurrent episode102131
Complaint of physical symptom, n (%)
Neck pain15 (100%)20 (95%)35 (97%)
Insomnia14 (93%)19 (90%)33 (92%)
Stomach discomfort14 (93%)18 (85%)32 (88%)
Malaise15 (100%)17 (81%)32 (88%)
Anorexia13 (86%)18 (85%)31 (86%)
Headache14 (93%)16 (76%)30 (83%)
Diarrhea or constipation11 (73%)18 (85%)29 (81%)
Low back pain13 (86%)15 (71%)28 (78%)

MDD = Major depressive disorder; BD = Bipolar disorder..

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