Efficacy of Electroacupuncture Combined with Auricular Point Pressing in Improving Mental Well-Being among Individuals with Heroin Use Disorder: A Randomized Controlled Crossover Trial and Pilot Study

Objective To evaluate the clinical efficacy of combining electroacupuncture with auricular point pressing in improving quality of life of individuals with heroin use disorder undergoing methadone maintenance treatment. Design A randomized controlled crossover trial. Subjects 50 participants were recruited from Taipei City Hospital, Linsen Chinese Medicine and Kunming branches, and randomly allocated to treatment groups. Method The 36-Item Short Form Health Survey (SF-36) was used. Group A received electroacupuncture at the Hegu (LI4) and Zusanli (ST36) and auricular point pressing on Ear Shenmen, and Group B received only auricular point pressing on Ear Shenmen biweekly for 4 weeks. After a 1-week washout period, crossover of the groups was performed. Results The SF-36 mental component scores of the combined treatment group improved relative to the single treatment group (11.09 vs. 10.33, p=0.023). Methadone dosage was reduced in both groups (combined therapy group: 8.58 ± 4.17/7.76 ± 4.11 (baseline/posttreatment) vs. single therapy group: 8.36 ± 4.20/8.30 ± .28, p=0.001). Conclusion Combined therapy of high-frequency electroacupuncture with auricular point pressing had better efficacy in enhancing quality of life, especially for mental well-being, and in gradually reducing methadone dosage.


Introduction
Heroin use disorder is a prominent public health problem worldwide and a chronic medical illness. is disorder is associated with not only spreading of infectious diseases, such as HIV and hepatitis B and C, but also loss of productivity, disruption of personal relationships, crime, and violence [1]. However, opiate use disorders cause multiple types of damage to the normal functioning of individuals and thus require a multiaspect approach to the treatment process to improve their quality of life [2].
Treatment and prevention of heroin use disorder are a substantial public health concern [3]. Methadone and buprenorphine/naloxone are considered not only first-line treatments for heroin use disorder but also opioid substitution treatments. ey can both alleviate opioid withdrawal symptoms and reduce opioid cravings, drug use, and mortality by reducing opioid use and improving quality of life [4,5].
In 2006, an HIV/AIDS outbreak among people who use heroin intravenously in Taiwan had a considerable na-MMT may have poorer physical and psychological health than the general population, with a mental status similar to that of clinically depressed patients [9]. Approaches to improving the quality of life of individuals should include physiology and psychology [10,11]. Low quality of life can easily lead to nonadherence to MMT [12]. e application of acupuncture has proven significant clinical effects on anxiety and depression, both physiologically and psychologically [13]. Patients undergoing MMT who received acupuncture treatment experienced significant improvement in quality of life, [14,15] especially with treatment by biweekly application of electroacupuncture at Hegu on the hand, Zusanli on the leg, and Shenmen on the ear. With electroacupuncture as an adjunctive treatment for their withdrawal syndrome, these patients were able to reduce their methadone dosage [16,17].
Auricular point pressing treatment, an alternative to electroacupuncture, is an easily accessible adjunct therapeutic method for treating withdrawal symptoms during opiate detoxification. is treatment is beneficial in MMT for managing disorders related to drug use and follows theories and principles of Traditional Chinese Medicine (TCM) [24][25][26][27].
Reduction in quality of life related to poor physical and psychological health is closely associated with sleep quality in individuals who are dependent on heroin [28,29].
In the treatment of individuals with opiate use disorders, improved quality of life is among the efficacies associated with both acupuncture and auricular point pressing. However, the efficacy of a combination treatment of electroacupuncture and auricular point pressing is unknown. Hence, the aim of this study was to evaluate the clinical efficacy of combined electroacupuncture and auricular point pressing in improving the quality of life of individuals with heroin use disorder undergoing MMT.

Study Participants.
e study was conducted from June 23, 2017, to December 28, 2018. We invited 72 individuals in clinics of the Linsen Chinese Medicine and Kunming branches of Taipei City Hospital (Taipei, Taiwan), which offers standard methadone therapy, to participate.
Inclusion criteria were as follows: (1) the participant was between 20 and 65 years of age and (2) received a diagnosis of heroin disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Exclusion criteria involved the following: (1) pregnancy, (2) refusal to receive electroacupuncture or auricular point pressing treatment, (3) appearance of major physical or mental disorders, and (4) apparently irregular or fluctuating dosage of methadone or apparent morphine withdrawal syndrome. During their first clinic visit, participants were interviewed by a research assistant and signed informed consent forms approved by the Research Ethics Committee of Taipei City Hospital (IRB number: TCHIRB-10601106). Baseline assessments were conducted in Taipei City Hospital, Linsen Chinese Medicine and Kunming branches, clinics. e trial was registered with ClinicalTrials.gov (Identifier: NCT03881618).

Randomization.
After completion of the baseline assessment, all eligible participants received a sealed envelope containing a computer-generated random number collected by the author who did not have direct contact with participants. Allocation was concealed until completion of all baseline assessments. Participants were randomly allocated to one of the two groups in a 1 : 1 ratio (Group A, n � 25 and Group B, n � 25) and started receiving treatment according to their assignment.

Interventions.
Acupuncture points for the electroacupuncture intervention were selected on the basis of studies examining the efficacy of acupuncture for the treatment of opioid addiction [13,16,17,[30][31][32][33]. Hegu and Zusanli were chosen as two acupoints. ey consisted of four bilateral acupuncture points on the hands and legs, and electroacupuncture was administered using an electroacupuncture machine (Model D0310K, Ching Ming Medical Device Co. Ltd., Taiwan) delivering a frequency of 100 Hz (dense and disperse, DD). Electroacupuncture was dispersed at automatic 2-second intervals for 20 minutes to lead to "DeQi" (revealed as numbness, soreness, and heaviness), with increasing 1 mA increments of intensity to the maximum tolerable intensity as reported by the participant. In addition, bilateral Shenmen auricular acupoints were fixed with cowherb seed by a breathable tape and stimulated by manual pressing every five minutes for a total of 20 minutes, in accordance with relevant research [24][25][26]. All TCM interventions and care were provided in quiet, private clinics of the Linsen Chinese Medicine and Kunming branches of Taipei City Hospital, Taipei, Taiwan, by the same attending clinician with 10 years of acupuncture experience, and all interventions were performed in the evening (between 5:00 and 8:00 pm). e needles and cowherb seeds were removed immediately afterward by the same clinician after intervention.

Study Process.
After the exclusion of ineligible individuals, 50 (69%) patients aged between 20 and 65 years were included in the parallel intervention. Group A received combined therapy (electroacupuncture at the Hegu (LI4) and Zusanli (ST36) and auricular point press on Ear   In methadone maintenance treatment, opioid withdrawal syndrome may be observed among patients with irregular adherence, causing poor quality of life. erefore, a gradual and smooth methadone dosage tapering without heroin relapse is inevitably a vivid goal for individuals with heroin use disorder.
2.6. Sample Size. Sample size was calculated using the following input parameters: two tails, an error probability � 0.05, and power (1 − b error probability) � 0.8. e required size was calculated to be 35. With a 20% dropout rate, approximately 44 participants were required.

Statistical
Analysis. Statistical analysis was performed by another researcher who was unaware of treatment allocation. Demographic and other data for age, sex, occupation, marital status, and history of methadone use, hepatitis B, hepatitis C, HIV, and syphilis were collected and analyzed using SPSS (version 22.0). e demographic characteristics were first analyzed using descriptive statistics, including the mean, standard deviation, and percentage. Inferential statistics, including the independent t-test, were used to verify homogeneity and the effect of electroacupuncture among groups. e paired t-test was used to evaluate within-group differences. Statistical significance was set at a p value of 0.05, two-tailed. Figure 1 presents the study flowchart. Among 72 eligible participants, 22 were excluded as they did not wish to try acupuncture. In total, 50 participants were enrolled, of whom 37 completed both stages of the study. During the study period, five participants (20%) in Group A dropped out. Four were afraid of needle treatment in Stage I and one participant was unwilling to accept Stage II treatment. Eight participants in Group B (32%) dropped out (three because they were unwilling to complete the questionnaire at Stage I and five because they were afraid of needle treatment at Stage II). Demographic data revealed no significant differences between these groups (Table 1).  Table 2).

Treatment Outcome on
We divided data for treatment groups for comparison (Table 3). Significant differences in vitality (VT: p � 0.012) and mental health (MH: p < 0.001) subscales were observed.
Data collected using the SF-36 were also analyzed by the physical component score (PCS) and mental component score (MCS) for evaluation. We uncovered a significantly higher percentage of improvement in the MCS score of the combined treatment group vs. the single treatment group (11.09 vs. 10.33, p � .023; Figure 2).

Discussion
Individuals with heroin use disorder may experience heroin relapse. erefore, relapse prevention approaches that improve the physical and mental health and well-being of individuals with heroin use disorder are vital during recovery. A low quality of life during MMT may be a latent risk factor for relapse [3]. Furthermore, the larger the amount of opiate used during MMT, the more severe the withdrawal syndrome symptoms are-especially its psychological symptoms [9]. A goal of improvement in client quality of life is decreased methadone dosage. When dosage is reduced gradually, withdrawal is less severe, creating a virtuous cycle with improved quality of life [3].
Our results indicate that combined therapy resulted in a larger decline in dosages (Table 4), which would also indirectly reduce the incidence of withdrawal syndrome through improving quality of life [38]. is improvement was more evident in MCS scores (combined therapy: 11.09 vs. single therapy: 10.33, p � 0.023) than in PCS scores (combined therapy: 15.29 vs. single therapy: 15.32, p � 0.079; Figure 2). e largest effects were observed in VT (combined therapy baseline : posttreatment (12.00 ± 1.90 : 13.29 ± 2.31) vs. single therapy baseline : posttreatment (11.78 ± 2.29 : 12.54 ± 2.04), p � .012) and RE (combined therapy: 4.45 ± 0.90 vs. single therapy: 4.97 ± 0.64, p � 0.007) subscales. e mechanism of electroacupuncture has been revealed to be associated with opioid receptors (kappa, delta, and mu) in brain regions known to interact with endogenous opioids and that are believed to play an essential role in life quality [39,40]. Exogenous opioids, such as morphine, bind to the same sites as endogenous opioids, suppressing the production of endogenous opioids. Withdrawal syndrome may appear when morphine exposure is suddenly stopped [41,42]. Acupuncture can compensate for the lack of a chemical cascade from neurotransmitters.  Evidence-Based Complementary and Alternative Medicine Auricular point pressing and electroacupuncture treatment follow theories and principles of TCM to improve Chi circulation [43]. Auricular point pressing was included in the design of both interventions because it is convenient and accessible at home by clients themselves, whereas invasive treatment must be executed at a clinic.
Little research has been conducted to study the clinical effect of high-frequency electroacupuncture. All that is known is that 100 Hz was more effective than 2 Hz in an animal study, owing to the promotion of endogenous opioids, such as dynorphin, which binds to kappa opioid receptors to ameliorate withdrawal syndrome. We demonstrated that high-frequency electroacupuncture reduced withdrawal syndrome among clients undergoing MMT as measured by SF-36, especially its mental domains. Furthermore, it may result in declining methadone dosage (Table 4).
Because auricular point pressing is a noninvasive, evidence-based, access-friendly TCM treatment, the related treatment program should be addressed by addiction specialists. TCM treatments are widely accepted in Taiwanese and Chinese culture, whether electroacupuncture or auricular point pressing. Auricular point pressing in a TCM clinic with adequate supervision by trained TCM clinicians improves quality of life, and combining it with high-frequency electroacupuncture further improves outcomes.
e clinical impact of the study is in its demonstration that TCM treatments, especially electroacupuncture with auricular point pressing, can be introduced as a routine facilitating treatment for patients undergoing MMT.

Limitations.
is study has several limitations. First, it included a small number of participants. However, through a randomized crossover controlled design, we could gather data with sufficient statistical power. Second, this was an open-label study and thus lacked blinding.
ird, the washout period was short, largely because participants undergoing MMT belonged to a particular ethnic group, making tracing and evaluation with a longer washout period too risky.

Conclusion
A combined therapy of electroacupuncture and auricular point pressing is more effective than only auricular point pressing in improving the quality of life of individuals with heroin use disorder undergoing MMT. TCM treatments, particularly electroacupuncture with auricular point pressing, can be introduced as a routine adjunctive treatment. Physical functioning RP:

Evidence-Based Complementary and Alternative Medicine
Data Availability e data used to support the findings of this study are available from the corresponding author upon request.

Ethical Approval
Data collection was approved by the Institutional Review Board of Taipei City Hospital (IRB number: TCHIRB-10601106; ClinicalTrials.gov Identifier: NCT03881618). Disclosure e funding sources had no role in any process of the study.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
Kai-Chiang Yu and Han-Ting Wei analyzed and interpreted patient data. Shang-Chih Chang collected patient data and designed the study. Prof. Chung-Hua Hsu led the TCM treatment team and constructed treatment protocols. All authors read and approved the manuscript.