Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2018-021484 on 20 April 2019. Downloaded from Efficacy and safety of electroacupuncture on treating depression-related insomnia: a study protocol for a multicentre randomised controlled trial Xuan Yin,1 Bo Dong,1 Tingting Liang,1 Ping Yin,1 Xia Li,2 Xiang Lin,2 Shuang Zhou,3 Xiaolu Qian,3 Lixing Lao,4 Shifen Xu 1 To cite: Yin X, Dong B, Liang T, ABSTRACT Strengths and limitations of this study et al. Efficacy and safety Introduction Sleep disorders including insomnia occur of electroacupuncture on frequently in depressive patients. Acupuncture is a widely ► This is a strictly designed, single-blinded, ran- treating depression-related recognised therapy to treat depression and sleep disorders insomnia: a study protocol domised controlled trial with long intervention and in clinical practice. This multicentre randomised controlled for a multicentre randomised follow-up period. trial (RCT) is aimed to investigate the efficacy and safety controlled trial. BMJ Open ► Sleep indicators in the actigraphy will be used as of electroacupuncture (EA) in the treatment of depression 2019;9:e021484. doi:10.1136/ objective outcomes of patients’ sleep quality. bmjopen-2018-021484 patients with insomnia. ► We will do comprehensive evaluation about the effi- Methods and analysis We describe a protocol for a cacy of acupuncture treatment. ► Prepublication history for multicentre RCT. A total of 270 eligible patients in three this paper is available online. ► Rigorous central randomisation and allocation con- different healthcare centres in Shanghai will be randomly To view these files, please visit cealment methods will be applied. assigned to one of these three groups: treatment the journal online (http:// dx. doi. ► This cannot be designed as a double-blinded trial group (EA + standard care), control A group (sham org/ 10. 1136/ bmjopen- 2018- because acupuncturists cannot be blinded to the electroacupuncture + standard care) and control B group 021484). group assignment. (standard care). Treatment will be given three times per Received 4 January 2018 week for 8 consecutive weeks. The primary outcome is the Revised 31 January 2019 Pittsburgh Sleep Quality Index. The secondary outcomes http://bmjopen.bmj.com/ Accepted 22 February 2019 are sleep parameters recorded in the actigraphy, Hamilton depressive patients’ health. Insomnia may 3 Rating Scale for Depression score and Self-rating Anxiety occur in 60%–80% of patients with MDDs ; Scale score. Daily dose of patients’ antidepressant and it is one of the most frequent residual symp- sedative-hypnotic medication will be recorded in the dairy. toms of depression,4 and may persist even © Author(s) (or their All adverse effects will be assessed by the Treatment after depressive mood symptoms have been employer(s)) 2019. Re-use Emergent Symptom Scale. Outcomes will be evaluated relieved.5 permitted under CC BY-NC. No at baseline, 4 weeks post-treatment and 8 weeks post- Insomnia is characterised by persistent commercial re-use. See rights treatment, as well as at 1-month, 3-month and 6-month dissatisfaction with sleep quantity or quality on October 3, 2021 by guest. Protected copyright. and permissions. Published by follow-up. BMJ. Ethics and dissemination The trial has been approved for at least 4 weeks, with specific complaints 1 Shanghai Municipal Hospital of by the Ethics Committee of Shanghai Municipal Hospital of difficulty falling asleep, frequent nighttime Traditional Chinese Medicine, of Traditional Chinese Medicine (2017SHL-KY-04). Written awakenings and/or awakening earlier in the Shanghai University of 6 informed consent will be obtained from all participants. morning than desired. It may be triggered by Traditional Chinese Medicine, Shanghai, China The results of this study will be published in peer-reviewed different factors including psychiatric disor- 2Shanghai Mental Health Center, journals or presented at academic conferences. ders, organic diseases and the intake of drugs 7 Shanghai Jiaotong University of Trial registration number NCT03122080; Pre-results. or alcohol. In fact, depressive symptoms are Medicine, Shanghai, China the largest and most consistent risk factors 3 Changhai Hospital, Second for insomnia because it affects the normal Military Medical University, INTRODUCTIon 8 9 Shanghai, China sleep–wake cycle. Previous meta-analysis 4School of Chinese Medicine, Depression and its related sleep disorders indicated moderate to large effect size (ES) The University of Hong Kong, are becoming serious public health problems improvement in depression as measured Hong Kong worldwide. The global point prevalence of with the Hamilton Depression Rating major depressive disorder (MDD) is 4.7%,1 Scale (ES=−1.29, 95% CI [−2.11 to –0.47]), Correspondence to Prof. Lixing Lao; lxlao1@ hku. hk and the estimation of a 12-month cumu- supporting that treating insomnia by Cogni- and Dr Shifen Xu; lative incidence of depression in China is tive Behavioural Therapy for Insomnia xu_ teacher2006@ 126. com 5.23%,2 causing an urgent need to improve (CBTI) in patients with depression is effective Yin X, et al. BMJ Open 2019;9:e021484. doi:10.1136/bmjopen-2018-021484 1 Open access BMJ Open: first published as 10.1136/bmjopen-2018-021484 on 20 April 2019. Downloaded from and also have a positive effect on mood.10 11 With regard DESIGN to the current medical conditions in China, the need This is a multicentre, patient–assessor-blinded, for CBTI for patients with depression cannot be met. randomised and controlled trial, aimed at evaluating Although selective serotonin reuptake inhibitors (SSRIs) the efficacy and safety of EA for insomnia in depression and barbiturates have considerably improved the efficacy patients and comparing the effects between EA plus stan- and prognosis in the treatment of comorbid depression dard care, sham acupuncture plus standard care and with insomnia, their side effects such as nausea, vomiting, simple standard care. tolerance, addiction, excessive sedation and neurological The trial will be performed in three healthcare centres toxicity cannot be ignored.12–14 What makes the phar- in Shanghai: the acupuncture department in Shanghai macotherapy more difficult is that some antidepressant Municipal Hospital of Traditional Chinese Medicine, drugs may worsen insomnia or cause daytime sleepiness,15 the acupuncture department in Changhai Hospital of and high hypnotic dosages for insomnia is closely associ- Shanghai and the therapeutic department in Shanghai ated with worsened depressive outcomes.16 In these cases, Mental Health Center. We will recruit 270 patients who a drug-free alternative intervention is urgently needed as meet the inclusion criteria and randomly assign them to an effective and safe therapeutic approach for treating one of three groups, receiving EA, sham acupuncture insomnia and depression. and/or standard medical care. After a week baseline, Our previous study demonstrated that acupuncture participants will enter an 8-month observation period in is an effective treatment to improve patients’ sleep effi- this trial. All treatments will be given three times a week cacy, prolong total sleep time (TST) and relieve patients’ (every other day) for 8 weeks. Participants will be assessed depressive mood.17 The preliminary result of our pilot at the following time points: the baseline (1 week before study18 about the effect of electroacupuncture (EA) treatment), the middle of the treatment (4 weeks after for depression-related insomnia showed that the Pitts- treatment starts), the end of the treatment (8 weeks burgh Sleep Quality Index (PSQI) score in depression after treatment starts) and follow-up (1 month, 3 months patients with EA treatment obviously decreased (from and 6 months after treatment finishes). All participants 16.47±1.89 to 9.83±3.11), and there was significant differ- will complete the assessments by the PSQI, actigraphy, ence between EA and sham electroacupuncture (SA) Hamilton Rating Scale for Depression (HAMD), Self- (p<0.01). Meta-analysis also suggested that acupuncture rating Anxiety Scale (SAS) and Treatment Emergent combined with SSRIs is an effective and well-tolerated Symptom Scale (TESS) (detailed trial process seen in therapy for depression and adverse effects of antidepres- figure 1 and table 1). We will follow the Standards for sants.19 However, other studies showed that acupuncture Reporting Interventions in Clinical Trials of Acupunc- is not significantly effective in relieving residual insomnia ture22 throughout the trial. associated with depression.20 21 As a result, randomised clinical trials in high quality are needed to evaluate the http://bmjopen.bmj.com/ clinical effects and long-term effectiveness of acupunc- ture in the treatment of depression-related insomnia. PATIENTS We planned this patient-blinded, multicentre, The study will include 270 depression patients with randomised and controlled trial with a sufficient obser- insomnia. To ensure the precision of the results, we devel- vation period in three healthcare centres in Shanghai, oped the following eligibility criteria. China. We aim to observe the effects of EA treatment on sleep status, and eliminate the possible placebo effect by Inclusion criteria setting reasonable sham methods. All interventions will Participants meeting the following criteria will be on October 3, 2021 by guest. Protected copyright. be administrated by licensed acupuncturists and psychia- included: trists under the supervision