Differences in Symptoms Following Acupuncture Treatment in Three Case Presentations of Bipolar Disorder: Type 2, Comorbid Anxiety Disorder, and Rapid Cycling Type

Abstract

Background:

This study reports the effects of acupuncture treatment on depression and anxiety symptoms for 3 different bipolar disorder (BD) pathologies.

Case:

Case 1: A 35-year-old man was diagnosed with BD type 2. His depressive symptoms appeared 17 years ago. He did not meet the diagnostic criteria for anxiety disorder (AD) in the Mini International Neuropsychiatric Interview (MINI). Case 2: A 32-year-old woman was diagnosed with BD type 2 with AD. Her depressive symptoms appeared 5 years ago. MINI indicated panic-, social anxiety-, and generalized AD. Case 3: A 42-year-old woman was diagnosed with rapid cycling BD. She developed depressive and hypomanic symptoms and visited our hospital 18 years ago. Acupuncture treatment was performed weekly for 12 weeks. Depression and anxiety symptoms were evaluated using the Himorogi Self-Rating Depression Scale (HSDS) and Himorogi Self-Rating Anxiety Scale (HSAS), respectively.

Results:

Case 1: The HSAS score did not improve significantly, but the HSDS score decreased from 22 points at baseline to 9 points at the 12th visit. Case 2: The HSDS score did not improve, and the HSAS score remained high from 26 points at baseline to 25 points at the 12th visit. Case 3: During the acupuncture period, both HSDS and HSAS scores fluctuated greatly, and the patient experienced repeated episodes of depression and hypomania.

Conclusions:

The response to acupuncture treatment may differ according to the classification and pathology of BD, and it may be desirable to perform the acupuncture treatment after evaluating the pathology and estimating the prognosis.

BACKGROUND

Bipolar disorder (BD) is a mental disorder characterized by alternating mania and depression. BD is a common, life-long, and disabling psychiatric disorder, characterized by the presence of 1 or more recurrent manic (BD type I), and hypomanic and depressive (BD type II) episodes, which may alternate rapidly. Medication therapy for BD has high treatment discontinuation and conversion rates due to problems including side effects, high recurrence rate, and high cost.¹ Moreover, the complexity of BD pathology renders a significant proportion of patients, refractory.²

A randomized controlled trial that evaluated the efficacy and safety of adjunctive acupuncture to treat BD reported that all patients' symptoms improved after treatment, although the results were nonsignificant.³ Furthermore, the retrospective longitudinal study has reported depressive, anxious, and physical symptoms associated with depression were reduced through the combination of acupuncture and the usual standard treatment for patients with mood disorder including BD.⁴ As an adjunctive treatment, acupuncture may be useful in stabilizing the mood in BD patients. However, BD treatment requires separate consideration of specific and different treatments for manic, hypomanic, mixed, bipolar depressive episodes, and unipolar depressive episodes.² Presently, no studies have been reported that have observed the course of acupuncture toward BD pathology; it is unclear how the course of acupuncture treatment differs with pathology.

This study reports the effects of acupuncture treatment on depression and anxiety symptoms for cases of 3 different BD pathologies: BD type 2, BD with combined anxiety disorder (AD), and rapid cycling type BD.

CASE DESCRIPTIONS

Table 1 shows the characteristics of 3 cases.

Table 1.

Characteristics of the 3 Cases

	Case 1	Case 2	Case 3
Age, years	35	32	42
Sex	Male	Female	Female
Duration disease, years	17	5	18
Diagnosis	BD type 2	BD type 2 Panic disorder Social AD Generalized anxiety disorder	BD rapid cycling
Medication	Lamotrigine 200 mg/day Brexpiprazole 0.5 mg/day	Lamotrigine 100 mg/day Escitalopram Oxalate 10 mg/day Ramelteon 4 mg/day	Flunitrazepam 2 mg/day Zolpidem Tartrate 10 mg/day Diazepam 2 mg/day Lamotrigine 100 mg/day Escitalopram Oxalate 20 mg/day Aripiprazole 1 mg/day Olanzapine 1.25 mg/day Famotidine 10 mg/day
Individualized acupuncture treatment	Electroacupuncture was added to GB21 and BL10 for the treatment of neck pain, and BL25 and BL52 for the treatment of low back pain.	ST25, ST27, BL25, and CV4 were added for the treatment of diarrhea.	ST7, ST8, and BL2 was added for the treatment of headache. Electroacupuncture was added to GB20 and GB21 for the treatment of neck pain, and BL25 and BL53 for the treatment of low back pain.

AD, anxiety disorder; BD, bipolar disorder.

Case 1: A 35-year-old man diagnosed with BD type 2. His depressive symptoms appeared 17 years ago. He started medication therapy but had repeated episodes of depression and hypomania. He was diagnosed with BD type 2 6 years ago when he visited our hospital. He did not meet the diagnostic criteria of AD in the Mini International Neuropsychiatric Interview (MINI). At the time of the first acupuncture treatment, the patient was taking Lamotrigine 200 mg and Brexpiprazole 0.5 mg.

Case 2: A 32-year-old woman diagnosed with BD type 2 with AD. Her depressive symptoms appeared 5 years ago, and she was diagnosed 4 years ago while visiting our hospital. MINI indicated panic-, social anxiety-, and generalized ADs. The medications reported at the first acupuncture treatment were Lamotrigine 100 mg, Escitalopram Oxalate 10 mg, and Ramelteon 4 mg.

Case 3: A 42-year-old woman diagnosed with rapid cycling BD. She developed depressive and hypomanic symptoms and visited our hospital 18 years ago. She has severe mood swings and exhibits rapid cycling between depression and hypomania in a short period of time. At the first acupuncture treatment, the patient reported taking Flunitrazepam 2 mg, Zolpidem Tartrate 10 mg, Diazepam 2 mg, Lamotrigine 100 mg, Escitalopram Oxalate 20 mg, Aripiprazole 1 mg, Olanzapine 1.25 mg, and Famotidine 10 mg.

ACUPUNCTURE TREATMENTS

Acupuncture treatment was administered once a week over a span of 12 weeks. A survey conducted in Japanese acupuncture clinics reported that the frequency of acupuncture treatment typically ranges between 48 and 95 sessions per year; consequently, receiving acupuncture treatment once or twice weekly is common in Japan.⁵ The treatment adopted the Japanese-style acupuncture method, which is tailored based on individual symptoms and physical findings.

The selection of acupoints was a combination of fixed, commonly used acupoints, and treatment plans individualized for each patient. The commonly selected acupoints, including GV20, GB20, PC6, LI4, ST36, SP6, LR3, BL15, BL18, and BL20, were chosen based on the most frequently employed acupoints in interventions across 30 randomized controlled trials for major depressive disorder using acupuncture, as per a 2016 report published in Japan.⁶ The acupuncture needle was inserted at a depth of 10–20 mm and left indwelling for 10 minutes after obtaining a de qi sensation. The patient was left in place for 10 minutes because the treatment was started in the prone position; thereon, the patient was in the supine position and treated in each position. For treatment, a sterilized single-use needle of 0.16 × 40 mm or 20 × 60 mm was used (SEIRIN Co., Shizuoka, Japan). The total duration of the treatment ranged from 40 to 60 minutes.

Furthermore, individualized acupuncture treatment plans were administered for each of the physical symptoms of the patients. This was based on physical conditions, which were evaluated through a physical examination (medical interview, palpation/manual examination, etc.) of each patient. In Japanese acupuncture therapy, careful detection of the acupoints of individual patients by palpation and fine-needling technique with comfortable subjective sensation is key.⁷ Table 1 lists the acupoints used in the individual treatment of each patient. For individual treatments, the same acupoints were used in 12 sessions. The equipment used for the electroacupuncture was an Ohms pulsar (ZENRYOUKI Co., Fukuoka, Japan), at a frequency of 1 Hz and an energization time of 10 minutes. Stimulus intensity was set such that the muscle contraction did not cause discomfort to the patient.

OUTCOME MEASURES

Depressive symptoms were assessed using the Himorogi Self-Rating Depression Scale (HSDS),⁸ while anxiety symptoms were assessed by the Himorogi Self-Rating Anxiety Scale (HSAS).⁹ The HSDS was created by extracting frequently asked questions on 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, with the total score ranging from 0 to 39 points, and a higher score indicating more severe symptoms. The score validities were then confirmed. The HSDS and HSAS have Cronbach's α values of 0.85 (95% confidence interval [CI], 0.82–0.88) and 0.87 (95% CI, 0.85–0.90), respectively.

RESULTS

Figure 1 shows the changes of HSDS and HSAS scores for the 3 cases.

FIG. 1.

Changes in (A) HSDS and (B) HSAS scores. HSAS, Himorogi Self-Rating Anxiety Scale; HSDS, Himorogi Self-Rating Depression Scale.

Case 1: The HSDS score gradually decreased from 22 points at the baseline. By the fourth visit, the experience of his depressed mood had substantially improved, as reflected by the decreased score to 10 points. There was a reduction in physical symptoms such as neck and lower back pain, as well. Since the fifth visit, no exacerbation of depression or mania was observed, and his symptoms were manageable (within 7–14 points), settling at 9 points by the 12th visit. The HSAS scores fluctuated between 10 and 17 points, with a baseline of 12 points. Although not showing significant improvement relative to the baseline, no particular exacerbation of the anxiety state was observed.

Case 2: The HSDS scores varied between 18 and 25 points, from the baseline of 22 points. By the 12th visit, the score was 21 points, indicating no observable improvement in depressive symptoms as a result of acupuncture. The HSAS score at the baseline was 26 points, and it consistently ranged between 19 and 25 points thereafter. She continued to experience high anxiety, as reflected by a high score of 25 points even at the 12th visit. Despite implementing individualized acupuncture treatment to alleviate physical symptoms (such as diarrhea), no discernible improvement was noted.

Case 3: The HSDS score significantly fluctuated, changing from the baseline of 15 points to 0 points by the seventh visit, and later peaking at 23 points during the 11th and 12th visits. Similarly, the HSAS score changed dramatically; the baseline of 23 points substantially decreased to 2 points on the fourth and eighth visits, and finally to 21 points on the 12th visit. With such substantial variations in both scores, the patient experienced recurrent episodes of depression and hypomania.

DISCUSSION

In this 3 case reports, acupuncture was performed on 3 BD patients with different pathologies and followed up for 3 months. Consequently, we noted that depressive symptoms were reduced in patients having BD type 2 without comorbidities, whereas no significant effect was observed in patients with BD type 2 with comorbid AD and BD with rapid cycling. These preliminary observations may imply that the course of acupuncture treatment for patients with BD (presenting with depressive episodes) might vary based on the type of pathology; however, given the limited scope of our study, this interpretation is remains a hypothesis, as yet.

Case 1 showed a reduction in depressive symptoms. A combination of medication therapy and acupuncture reportedly reduces depressive symptoms in depressed patients.¹⁰ Furthermore, it has been reported that even for a long history of depressive episodes of BD, depressive symptoms can be alleviated by combining acupuncture with medication therapy.¹¹ In Case 1, where there were no comorbidities and the main symptom was a depressive episode, there is a possibility that acupuncture treatment may alleviate the depressive symptoms. By contrast, a review of complementary and alternative medicine for BD reported inconsistent evidence regarding the benefits of acupuncture.¹² Further research is needed on the efficacy of acupuncture for BD.

Conversely, for Case 2 with AD comorbidity, both depression and anxiety symptoms did not decrease. Coexisting anxiety in patients with BD is known to be an aggravating factor for mood state prognosis.¹³ Improvement of depressive and anxiety symptoms was not observed in Case 2, who had AD comorbidity and experienced anxiety. Our case report presents the novel suggestion that AD comorbidity could potentially serve as a predictive factor for the effect of acupuncture in patients with BD. However, given its novelty, further research is needed to confirm this finding. Similarly, high anxiety persisted even in Case 1, whose depressive symptoms were alleviated. Since we only observed short-term effects, it may be necessary to monitor anxiety states in patients with BD when following up over the long term.

In Case 3, the rapid cycling type, there was a large variation in symptoms over the 12 weeks of acupuncture treatment. Rapid cycling is the most malignant type of BD and has been shown to have a lifetime prevalence that ranges between 25.8% and 43% in patients with BD.¹⁴ Furthermore, most patients with rapid cycling are resistant to standard medication therapy.¹⁵ Thus, acupuncture may have limited efficacy for patients with rapid cycling BD.

The study was designed to include 3 BD manifestations, which are representative of most patient populations: with no comorbidities, with AD comorbidities, and with a more severe rapid cycling BD. To further investigate the insights of this study, future studies should focus on a greater sample size with varied BD manifestations.

CONCLUSION

In conclusion, the response to acupuncture treatment may differ depending on the classification and pathology of BD. Another preliminary suggestion of the study is that the evaluation of pathology and estimation of BD prognosis should be a prerequisite to acupuncture treatment. Based on the results of these various case reports, it shows that it is important to consider the type and pathophysiology of BD to carry out acupuncture therapy.

AUTHORs' CONTRIBUTIONS

Y.M. and S.H. contributed to conceptualization. S.H. contributed to patient eligibility assessment. Y.M. contributed to data collection and wrote the original draft of the article. S.H. contributed to the analysis and interpretation of data, assisted in the preparation of the article, and critically reviewed and edited the article. All authors approved the final version of the article 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.

ETHICAL APPROVAL

This study was approved by the Research Ethics Committee of the Himorogi Psychiatric Institute (201704-02) on April 19, 2017.

CONSENT

Written informed consent was obtained from the patient, following both written and verbal explanations about the freedom to participate in the present study/withdraw consent, privacy protection, and to publish the findings of this case study.

AUTHOR DISCLOSURE STATEMENT

No competing financial interests exist.

FUNDING INFORMATION

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