Electrical acupoint stimulation for psychiatric sequelae in women victims of domestic violence: study protocol for an assessor-blind randomized controlled trial

Abstract

Background

Domestic violence is a global public health problem linked to mental illness morbidity. A significant proportion of domestic violence victims have been found to exhibit unsatisfactory response rates to first-line treatments and display low acceptance levels towards psychological interventions. To improve the therapeutic effectiveness for this population, we aim to develop an electrical acupoint stimulation modality that integrates clinic-based and home-based therapies, with the goal of improving the psychiatric symptoms experienced by women victims of domestic violence.

Methods

This is an assessor-blinded randomized controlled trial, consisting of 110 women victims diagnosed with depression. The patients will be randomly assigned to either the treatment group or the routine care group in a 1:1 ratio. The treatment group will receive electrical acupoint stimulation over a period of 12 consecutive weeks, in addition to their routine care. On the other hand, the routine care group will not receive any electrical acupoint stimulation until the end of the 12-week study. The primary outcome of the study is the mean change in the score of Beck Depression Inventory–II (BDI-II) from baseline to the end of the 12-week treatment. Secondary outcomes will include the 17-item Hamilton Depression Rating Scale (HAMD-17), 10-Item Perceived Stress Scale (PSS-10), PTSD Check List-Civilian Version (PCL-C), Insomnia Severity Index (ISI), 12-Item Short Form Survey (SF-12), as well as any observed adverse events.

Discussion

If effective, this electrical acupoint stimulation modality could have significant clinical and research implications for women victims of domestic violence with psychiatric sequelae.

Trials registration

ClinicalTrials.gov as NCT05102253. Registered 1 November 2021. https://www.clinicaltrials.gov/study/NCT05102253.

Background

Domestic violence is a serious global public health problem that has been linked to impaired mental health conditions. Among these mental health problems, depression is one of the most common psychiatric sequelae. In Hong Kong, the lifetime prevalence rates of depression among women range from 2.44 to 8.4% [1]. A previous review of 18 studies found that among women victims, the weighted mean prevalence of depression was as high as 47.6% [2], which was much higher than the lifetime prevalence rates. A large proportion of victims were unable to obtain a satisfactory response to the first-line treatments, and had low acceptance of psychological interventions. This seems to be particularly apparent among Asian women [3].

Electrical acupoint stimulation includes both invasive and non-invasive forms, and is designed to produce therapeutic effects through electrical stimulation on specified acupoints. Previous researches have demonstrated its efficacy and safety for depression [4, 5]. However, there is insufficient evidence to determine the efficacy and safety of electrical acupoint stimulation for relieving depression and other mental health issues related to domestic violence.

Therefore, we plan to conduct an assessor-blinded randomized controlled trial to assess the efficacy and safety of a 12-week electrical acupoint stimulation on improving the mental health of women exposed to domestic violence. The aims of this study are: (1) to evaluate the effectiveness of electrical acupoint stimulation on depression associated with domestic violence; (2) to evaluate the effectiveness of electrical acupoint stimulation across other psychiatric sequelae associated with domestic violence, including stress, post-traumatic stress disorder (PTSD), sleep disturbance and quality of life; and (3) to evaluate the safety of electrical acupoint stimulation for women victims with psychiatric sequelae. Based on previous findings [4, 5] and the clinical experience of colleagues, it is hypothesised that the participants in treatment group will be safe and receive greater therapeutic benefits on depression and other psychiatric sequelae associated with domestic violence than routine care group. In addition, blood biomarkers will be recorded to further evaluate the potential mechanisms of action of this treatment modality.

Methods

Design

This study is an assessor-blind randomized controlled trial. This study protocol is designed in accordance with the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) checklist [6]. Eligible subjects (n = 110) will be randomly assigned to one of two treatment conditions: the treatment group and the routine care group in a 1:1 ratio. The study flow chart are presented in Fig. 1. This study has been approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (Ref no: UW 21–238) and the Research Ethics Committee of Kowloon central/ Kowloon east (Ref no: KC/KE-22-0072). And previously registered at ClinicalTrials.gov as NCT05102253. Registered 1 November 2021. https://www.clinicaltrials.gov/study/NCT05102253.

Fig. 1.

Study flow chart. Abbreviations: T, timepoint; TEAS, transcutaneous electrical acupoint stimulation; DCEAS, dense cranial electroacupuncture stimulation

Participants

Participants with an experience of domestic violence and complaints of depression will be referred from Harmony House, H.K.S.K.H. Lady Maclehose Center and Tung Wah Group of Hospitals Community Services Division by social workers. To further facilitate recruitment, multiple promotions (e.g., adding more sites, advertisements on local/social media) will also be considered. Applicants will be provided with an explanatory statement describing the project, either verbally or in writing, after being screened by the researcher in an face-to-face or telephone interview. Following confirmation by the applicants, the researcher will invite those who have expressed a desire to participate to sign an informed consent form for the clinical trial and the blood collection.

Eligibility criteria

Subjects will be included in this study if they: (1) are Chinese women aged 18–65 years; (2) have experienced domestic violence in the previous two years, confirmed with the abuse assessment screen (AAS) questionnaire; (3) are currently experiencing a major depressive episode and fulfil the diagnostic criteria for major depressive disorder (MDD) of the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5); (4) are with a Beck depression inventory–II (BDI- II) score of at least 14; (5) have ability to understand the nature of the study and willingness to give informed consent; and (6) have ability to provide responses during outcome measurement.

Subjects will be excluded if they are experiencing or have: (1) serious medical conditions or any life-threatening situation that may limit their participation; (2) a history of brain injury or surgery; (3) pregnancy or lactation; (4) investigational intervention in the previous 6 months; (5) heart pacemaker or other metal or electrical devices implanted in the body; (6) serious suicidal ideation or behaviours; (7) history of manic, hypomanic or mixed episodes; (8) history of alcohol or drug abuse in the past year; (9) history of regular electrical acupoint stimulation in previous 6 months; or (10) severe needle phobia.

Randomization/masking

Participants will be assigned to 2 groups, the treatment group or the routine care group, in a 1:1 ratio. Block randomization with random block sizes of 4 and 6 will be used for code generation. An independent research assistant will generate the codes and use it to make opaque, sealed envelopes with a treatment allocation number. Also, a participant-specific randomisation identification number will be marked on the envelope. After completing the baseline assessments, therapists and patients will receive their treatment allocation number and randomisation identification number. The assessors will be blinded to patients’ allocation through the whole treatment period. Also, patients will be told not to talk about their allocation with other participants and assessors.

Intervention

All patients participating in this study will continue their original routine care regardless of the group to which the patient is assigned. The routine care may include pharmacotherapy, psychotherapy and advocacy intervention, etc.

Treatment group

For patients in this group, electrical acupoint stimulation, which includes both transcutaneous electrical acupoint stimulation (TEAS) and dense cranial electroacupuncture stimulation (DCEAS), will be additionally offered on top of the existing routine care.

TEAS procedure is based on our previously published studies [5, 7]. The intervention consists of 3 sessions per week for 12 weeks. Participants will conduct this treatment themselves at home after a training workshop introducing the use of the TEAS stimulator. During the treatment, the patient is relaxed in a supine or sitting position. The treatment will be performed with a pair of electrodes equipped with TEAS apparatus (SDP-330, Yuwell, Suzhou Medical Appliances Co, Ltd., Suzhou, China). Two electrode pads will be adhered onto the bilateral Nei-Guan (PC6) skin (see Fig. 2b). Neuroimaging has shown that acupoint stimulation on Nei-Guan can modulate a wide range of cortical and limbic brain region activity [8]. The stimulation frequency will be set at 50 Hz, which has been proved to have a robust effect in inducing the release of endogenous opiate neuropeptides in the central nervous system [9]. A pulse width increasing from 30 to 100 µs, and keeping in 100 µs at treatment stage will be set to provide the patient a better adaptation to the stimulus. The pulse amplitude will be adjusted to a level that patients have the perception of strong but comfortable. Each session of treatment will last 30 min. Patients will be assigned a log sheet and required to record their TEAS sessions on a daily basis. The researcher will follow up on participants who do not complete their treatments on time and will supplement the missing session if necessary. Meanwhile, researchers will send reminders to participants, monitor their TEAS treatment, answer their questions, and receive their emergency report by mobile.

Fig. 2.

Schematic representation for Dense Cranial Electroacupuncture Stimulation (DCEAS) and Transcutaneous Electrical Acupoint Stimulation (TEAS). (a) The location of acupoints used in DCEAS and (b) the placement of electrode pads for TEAS

DCEAS consists of 2 sessions per week for 12 consecutive weeks. The procedure is based on our previously published studies [4, 10]. A trained registered Chinese medicine practitioner (RCMP) will be responsible for the operation of acupuncture and will introduce the specific procedure of DCEAS treatment to patients before the treatment begins. Electrical stimulation will be conducted on up to 12 forehead acupoints (see Fig. 2a), including: Bai-Hui (GV20), Yin-Tang (EX-HN3), bilateral Si-Shen-Cong (EX-HN1), bilateral Tou-Lin-Qi (GB15), bilateral Shuai-Gu (GB8), bilateral Tai-Yang (EX-HN5), and bilateral Tou-Wei (ST8). The patient should be relaxed and placed in a supine position. The acupoints are first disinfected with 75% alcohol swabs. The acupuncturist will then insert sterilized disposable acupuncture needles (25 mm long and 0.22 mm in diameter) with a guiding tube to the specific acupoints. The needles inserted will then be adjusted to make patients achieve a sense of De-Qi, which is defined as the sensation of soreness, numbness, swelling, aches or heaviness around the needle-inserted region [11]. Electrodes from the electric stimulator will be connected to the end of the needles. The output peak current and voltage of the machine are 6 V and 48 mA, respectively, with constant wave at frequency of 2 Hz and phase duration of 100 µs for 30 min. The low frequency could produce broader neuromodulation compared to higher frequency [12]. The stimulation intensity will be adjusted to a level at which patients feel strong but comfortable. Once the needles are removed, the acupuncturist will immediately apply pressure to the appropriate area with a sterile dry cotton ball to avoid bleeding. Participation in each treatment will be recorded and those who fail to participate on time will be followed up and provided the supplementary session if necessary.

Routine care group

For this group, patients will continue all their routine care and are allowed to take any type of treatment desired other than electrical acupoint stimulation. TEAS and DCEAS will not be provided to them during the 12-week treatment period. After the treatment period, patients in this group may choose to have 12 weeks of compensatory TEAS and/or DCEAS treatment.

Regardless of the group, participants are also allowed to contact the researcher at any working hours when feel unwell and need our recourses. The researcher will send the patient information about relevant routine care resources if needed, including Chinese medicine clinics, psychological services, and domestic violence centres. They will decide on the uptake of the services according to their own needs. The list of resources we provide is generally government-regulated institutions, university-affiliated agencies, and partner domestic violence centres. However, patients are prohibited from undergoing other electrical acupoint stimulation while participating in the study, which may affect the psychiatric symptoms during the treatment period. The participants will be asked to inform the research investigators of any new treatments that they would like to perform in advanced after entry into the trial.

Participant timeline

The BDI-II, 17-item Hamilton depression rating scale (HAMD-17), 10-item perceived stress scale (PSS-10), PTSD check list-civilian version (PCL-C), insomnia severity index (ISI) and 12-item short form survey (SF-12) will be assessed by trained research assistants at baseline, week 3, week 6 and week 12. Abuse assessment screen (AAS) and adverse events (AEs) will also be recorded at each timepoint. During visits 2–4, the questions on the AAS that aim to assessing long-term status will be omitted. Instead, only the items that assess the participant’s status within the past month will be preserved. This modification is intended to provide a more focused understanding of the domestic violence encountered by individuals at each stage of the assessment. Patients will also undergo blood collection procedures at both baseline and endpoint (week 12), with 10 ml of blood being procured on each occasion. To avoid the bias from participants, such as feelings of loss and negativity after being assigned to the control group, all participants will be told in advance that the difference in the order of treatment, assessment and waiting time is due to the limited number of acupuncturists. In addition, if participants express a strong desire to be immediately assigned to electrical acupoint stimulation treatment, they will be advised to seek alternative treatment, such as Chinese herbal medicine. The SPIRIT diagram of all assessments at enrolment, allocation, and different time points can be found in Fig. 3.

Fig. 3.

SPIRIT schedule of enrolment, interventions, and assessments. Abbreviations: BDI-II, Beck depression inventory–II; AAS, abuse assessment screen; HAMD-17, 17-item Hamilton depression rating scale; PCL-C, PTSD check list-civilian version; PSS-10, 10-item perceived stress scale; ISI, insomnia severity index; SF-12, 12-item short form survey

Primary and secondary outcomes

The primary outcome will be the mean change of the score of BDI-II from baseline to the end of 12-week treatment. The secondary outcome includes: (1) the mean change in the BDI-II score at other time points; (2) the response rate, which is defined as the proportion of subjects with ≥ 50% reduction from the baseline BDI-II score; (3) the remission rate, which is defined as the proportion of subjects with BDI-II score less than 10; (4) change of HAMD-17 score from baseline; (5) change of PSS score from baseline; (6) change of PCL-C score from baseline; (7) change of ISI score from baseline; (8) change of SF-12 score from baseline.

Measures

BDI-II is a validated self-report questionnaire. The 21-item BDI-II [13], rated on a 4-point Likert scale, has been reported as a valid tool for depression measurement with high internal consistency reliability (Cronbach’s alpha > 0.91) [14]. It quantifies cognitive, affective, and somatic components of depression. The range of BDI-II score is 0–63, and a higher score indicates a more severe condition.

HAMD-17

is a widely used validated questionnaire which is assessed by clinicians [15]. This is a reliable assessment of depression with good internal consistency (Cronbach’s alpha = 0.789), inter-rater reliability, test-retest reliability [16]. The range of HAMD-17 score is 0–52. A higher score indicates a more severe condition. Training workshops led by at least one experienced psychiatrist will be held regularly to ensure the accuracy and consistency of the HAMD-17 assessment across the study.

PSS-10

is a 10-item self-report questionnaire that is used to provide a global measure of perceived stress [17]. This questionnaire has good ability in measuring life-events stress and social anxiety, and has robust reliability (Cronbach’s alpha = 0.84–0.86) [18]. Each item ranges on a 5-point Likert scale ​​from 0 (never) to 4 (very often), with a total score of 0–40. A higher score indicates a more severe condition.

PCL-C

is a 17-item self-report valid tool used for the measurement of PTSD symptoms [19, 20]. PCL-C has a good internal consistency reliability (Cronbach’s alpha = 0.89) [21]. The range of the total score of PCL-C is 17 to 85. Also, The three subscales are defined by the author that correspond to the DSM-IV symptom clusters; they are: reexperiencing, avoidance/numbing, and arousal [22–24].

ISI

is a 7-item self-report questionnaire devised to measure the severity of insomnia [25]. ISI has adequate internal consistency (Cronbach’s alpha = 0.74) [26]. The total score ranges from 0 to 28.

SF-12

is a 12-item self-report tool used to measure health-related quality of life [27, 28]. This score is with good internal consistency (Cronbach’s alpha = 0.91) [29] and a total score ranging from 0 (lowest level of health) to 100 (highest level of health) [30]. The measurement of SF-12 includes both the mental component scale (MCS) and physical component scale (PCS).

AAS

a self-report questionnaire measuring severity, frequency and perpetrator of abuse [31]. This is used to measure the patient’s experience of domestic violence at each timepoint.

Safety assessment

For each visit to treatment, an acupuncture and adverse event record form will be used to record patients’ AEs, including whether any AE has occurred, occurrence time, duration, type of event, severity, management, and its outcome. Also, whether the adverse events are caused by acupuncture would be assessed. The Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria will be used to evaluate the severity of each adverse event [32]. All associated research staffs are trained to recognize and respond to all the adverse events. If an adverse event is regarded as a serious adverse event, it will be reported to project investigators (ZJZ) and Ethics Committee to review immediately. They will decide whether the patient will be temporarily/permanently interrupted from their current treatment, whether the patient will withdraw from this clinical trial and whether this trial needs to be adjusted or terminated.

Data management

Data will be collected by blinded independent assessors and entered into a password-protected computer using a double entry method. Each participant will be assigned an identification number for data processing and communication. Personal data will be stored and protected in accordance with the requirements of the Hong Kong Personal Data (Privacy) Ordinance (CAP 486). The de-identified data will be used for analysis and publication. The publication of any results will not reveal the identity of any participant. The results will be provided to the participants and social workers in a short summary after the publication of the trial if required. To prevent patient attrition, research assistants will confirm appointment information with participants and send a reminder before the scheduled appointment. In addition, a transport allowance will be provided to each participant upon completion.

Blood sample collection

Patients will have blood draws at baseline and endpoint (week 12), with 10 ml of blood collected each time. Serum and peripheral blood mononuclear cells (PBMCs) will be immediately separated and stored for the following tests. The details of biomarker analysis will be report in a separate article.

Sample size

The sample size for this trial was estimated based on our preliminary trials [5, 33]. According to previous established HAMD-17 to BDI-II conversion metrics [34], the results indicating an approximately difference of 6.55 in the BDI-II score between two groups. A sample size of 55 in each group will be sufficient with a 95% level of significance (α), 80% power (1 − β), and a conservatively assumed standard deviation of 12.1, and a dropout rate of 20%. Therefore, this trial will include 110 subjects.

Statistical analysis

One biostatistician who is blinded to interventions will be responsible for statistical analysis. Descriptive statistics tables will be used to present basic information on all variables. For continuous variables, the mean and standard deviation (or medians, 25th, and 75th percentiles) will be presented; while for categorical variables, the number of participants in each category and its percentage will be presented separately. The analysis will be carried out on the intention-to-treat (ITT) population. All eligible participants will be included in the analysis. Missing data on the primary outcome will be imputed using the multiple imputation method under the missing at random (MAR) assumption or last observation carried forward (LOCF) method, depending on the condition of missing values. A sensitivity analysis will be conducted.

The primary outcome will be analyzed by a linear mixed-effects model with repeated-measures [35], with adjustment for the baseline; visit, treatment, and the visit × treatment interaction as a fixed effect, and individual subject as the random effect. A significant two-way interaction will be considered to demonstrate whether the treatment group has a greater change in the BDI-II score from baseline to assessing points than the routine care group. The effect of the treatment will be estimated by the difference between treatments, and will be presented together with its associated 95% confidence intervals (CIs). A similar approach will be applied to other continuous outcomes.

For the response rate and remission rate, logistic regression, with adjustment for baseline scores, will be used. The definition of responder is subjects with ≥ 50% reduction from the baseline BDI-II score; the definition of remission is subjects with BDI-II score less than 10. The response or non-response at each assessing point except for the baseline will be regarded as dependent variable. Subjects who discontinue treatment prior to having a post-baseline BDI-II score will be considered non-responders/not remission. A significant two-way interaction will be considered to be used for the comparison between two groups.

Subgroup analysis will be further conducted to detect whether demographic and baseline clinical variables are associated with outcomes. Student t-test will be used to detect differences in continuous baseline variables between the two groups. Categorical baseline variables, including discontinuation and incidence of adverse events will be analysed using Chi-square (χ²) test. For all statistical analyses, R studio software (version 4.4.1) will be used. Statistical significance is defined as a two-tailed P < 0.05.

Discussion

Acceptance of and satisfaction with current frontline treatments for victims of domestic violence still require improvement. A previous study on Major Depressive Disorder (MDD) demonstrated that transcutaneous cranial auricular acupoint stimulation demonstrated greater efficacy in individuals with previous psychological trauma [36]. Interestingly, this difference in effectiveness was not observed with the standard depression treatment, escitalopram. These findings suggest that a tailored treatment approach may be necessary for individuals who have experienced domestic violence, a form of psychological trauma, to effectively address their mental health issues. Therefore, this study aims to explore the therapeutic effect of electrical acupoint stimulation in improving mental health problems related to domestic violence in conjunction with routine therapy.

This study adopt an assessor-blind, randomized controlled design and included a relatively large sample size to compare the efficacy differences between the treatment group and the routine care group. Several strengths of this study should be identified. The level of depression will be evaluated by both self-assessment and clinician evaluation, which can eliminate the influence of patients’ disease self-awareness on their self-evaluation scores, making the results more convincing. In addition, we will also evaluate other common mental sequalae after domestic violence, such as PTSD, stress, insomnia, as well as participants’ quality of life, to more comprehensively demonstrate the efficacy of electrical acupoint stimulation. Moreover, we will explore depression-related blood biomarkers of participants in the follow-up study, hoping to further understand the mechanism of this treatment plan.

This combination of clinical and home treatment effectively simulates real-life situations and is conducive to the promotion in relevant practitioners. If the proposed study can prove that combining TEAS and DCEAS is effective in treating psychiatry sequelae caused by domestic violence, it will become a potential powerful additional intervention for the victims.

Abbreviations

AEs

Adverse events

BDI-II

Beck depression inventory–II

CIs

Confidence intervals

CTCAE

Common terminology criteria for adverse events

DCEAS

Dense cranial electroacupuncture stimulation

DSM-5

Diagnostic and statistical manual of mental disorders, fifth edition

HAMD-17

17-item Hamilton Depression Rating Scale

ISI

Insomnia severity index

ITT

Intention-to-treat

LOCF

Last observation carried forward

MAR

Missing at random

MCS

Mental component scale

MDD

Major depressive disorder

PBMCs

Peripheral blood mononuclear cells

PCL-C

PTSD check list-civilian version

PCS

Physical component scale

PSS-10

10-item perceived stress scale

PTSD

Post-traumatic stress disorder

RCMP

Registered chinese medicine practitioner

SF-12

12-item short form survey

SPIRIT

Standard protocol items: recommendations for intervention trials

TEAS

Transcutaneous electrical acupoint stimulation

Author contributions

SCY drafted the manuscript. ZJZ, SCY, AT, DSTC, CPWC, MYC, HYC involved in the design of the project. SCY developed the statistical analysis plan. All authors approved the final manuscript.

Funding

This study is funded by the Health and Medical Research Fund provided by the Government of the Hong Kong Special Administrative Region of China (Ref no: 18191451). The funding body does not involve in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This research has been approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (Ref no: UW 21–238) and the Research Ethics Committee of Kowloon central/ Kowloon east(Ref no: KC/KE-22-0072). After reading and understanding the project in detail, the research assistant will send a written informed consent form to all participants. The participants will sign the form before they join the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.