Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

BACKGROUND: Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. METHODS/DESIGN: The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. DISCUSSION: Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. TRIAL REGISTRATION: ClinicalTrials.gov NCT02475538 .

What predicts a positive response to acupuncture? A secondary analysis of three randomised controlled trials of insomnia.

OBJECTIVE: Few studies have investigated the predictors of the specific and non-specific effects of acupuncture. The aim of this secondary analysis was to determine patient characteristics that may predict a better treatment response to acupuncture for insomnia. METHODS: We pooled the data of three randomised, double-blind, placebo-controlled trials of acupuncture for insomnia to examine sociodemographic variables, clinical characteristics, baseline sleep-wake variables, and treatment expectancy in relation to acupuncture response. Subjects with an improvement in insomnia severity index (ISI) scores of ≥8 points from baseline to 1 week post-treatment were classified as responders. Factors were compared between responders and non-responders, and also by univariate and multivariate logistic regression analysis. RESULTS: A total of 116 subjects who received traditional needle acupuncture were included, of which 37 (31.9%) were classified as responders. Acupuncture responders had a higher educational level (p<0.01) and higher baseline ISI score (p<0.05), compared to non-responders. In the multivariate logistic regression analysis, only the number of years spent in full-time education remained significant as a predictor of treatment response (OR 1.21, 95% CI 1.06 to 1.38, p<0.01). CONCLUSIONS: Consistent with previous studies, our data suggest that the response to acupuncture is difficult to predict. Although the predictive power of educational level is weak overall, our findings provide potentially valuable information that could be built upon in further research (including a larger sample size), and may help to inform patient selection for the treatment of chronic insomnia with acupuncture in the future. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: #NCT00839592; Results, #NCT00838994; Results, and #NCT01707706; Results.

Acupuncture for residual insomnia associated with major depressive disorder: a placebo- and sham-controlled, subject- and assessor-blind, randomized trial.

OBJECTIVE: To evaluate the efficacy and safety of acupuncture for residual insomnia and other residual symptoms associated with major depressive disorder (MDD). METHOD: 150 participants having significant insomnia for more than 3 months and a history of MDD (both based on DSM-IV-TR criteria) were recruited from 4 psychiatric outpatient clinics in Hong Kong from May 2011 to August 2013 to receive 9 sessions of treatment over 3 weeks. They were randomized to receive acupuncture, minimal acupuncture, or placebo acupuncture. Primary outcome was sleep diary-derived sleep efficiency. Secondary outcomes included other sleep diary parameters, actigraphy, anxiety and depressive symptoms, daytime functioning, and adverse events. RESULTS: The mean difference in sleep diary-derived sleep efficiency at 1-week posttreatment was -1.40 (95% CI, -7.08 to 4.28) between the acupuncture and minimal acupuncture groups and was 3.10 (95% CI, -3.64 to 9.84) between the acupuncture and placebo acupuncture groups. A χ(2) test showed that acupuncture produced a significantly higher proportion of participants achieving sleep-onset latency ≤ 30 minutes than did minimal acupuncture at 1-week posttreatment (P = .04). However, there was no significant between-group difference in most of the other outcomes. Treatment blinding was successful, as a majority of participants did not know which treatment they had received. CONCLUSIONS: Acupuncture was well tolerated, but the efficacy was only mild and similar to that of minimal acupuncture and placebo acupuncture. A high proportion of patients remained clinically significantly affected by insomnia after treatment. The finding raises certain doubts about the value of acupuncture and underscores the difficulties in the treatment of residual insomnia in MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01707706.

Prescription of Chinese Herbal Medicine in Pattern-Based Traditional Chinese Medicine Treatment for Depression: A Systematic Review.

Traditional Chinese medicine (TCM) treatments are often prescribed based on individuals' pattern diagnoses. A systematic review of randomized controlled trials in Chinese and English literatures on TCM pattern-based treatment for depression has therefore been conducted. A total of 61 studies, 2504 subjects, and 27 TCM patterns were included. Due to the large variation of TCM pattern among participants, we only analyzed the top four commonly studied TCM patterns: liver qi depression, liver depression and spleen deficiency, dual deficiency of the heart, and spleen and liver depression and qi stagnation. We found that Xiaoyao decoction was the most frequently used herbal formula for the treatment of liver qi depression and liver depression with spleen deficiency, while Chaihu Shugan decoction was often used for liver depression and qi stagnation. Bai Shao (Paeonia lactiflora Pall.) and Chai Hu (Bupleurum chinense DC.) were commonly used across different TCM patterns regardless of the prescribed Chinese herbal formulas. The rationale underlying herb selection was seldom provided. Due to the limited number of studies on TCM pattern-based treatment of depression and their low methodological quality, we are unable to draw any conclusion regarding which herbal formulas have higher efficacy and which TCM patterns respond better to CHM.

Adverse Events Related to Acupuncture: Development and Testing of a Rating Scale.

OBJECTIVES: Mild adverse events (AEs) are common with acupuncture, but the collection of AEs is generally poor. The objective of this study was to develop and test a new instrument for acupuncture-related AEs. MATERIALS AND METHODS: After literature review, consultation with experts, and pilot-testing, the acupuncture-related AE report form (AcupAE), a 20-item scale on local and systemic AEs was tested in 150 adults who were randomized to receive acupuncture, minimal acupuncture, and placebo acupuncture. AE was assessed using open-ended questioning, followed by the AcupAE after the third, sixth, and ninth treatment. RESULTS: The incidence of any AEs per patient, as derived from the AcupAE, was 42.4% with acupuncture, 42.2% with minimal acupuncture, and 16.7% with placebo acupuncture; the respective incidence was 6.8%, 5.1%, and 3.3% with open-ended questioning. There was a significant difference in the incidence of any AEs between the 3 groups based on the AcupAE, and the incidence rates of any AEs were significantly higher when assessed by the AcupAE than by open-ended questioning in the acupuncture and minimal acupuncture groups. DISCUSSION: The AcupAE was able to detect differences in AE between true, minimal, and simulated acupuncture, whereas the open-ended questioning was not sensitive enough. The results support the use of AcupAE as an effective instrument for the assessment of acupuncture-related AEs. Although the checklist approach can result in overreporting and the causality may be unclear for some events, it is the first step for collecting standardized information and allowing comparison between different acupuncture approaches and patient groups in future studies.

The use of conventional and complementary therapies for insomnia among Hong Kong Chinese: a telephone survey.

OBJECTIVE: To examine the prevalence and utilization pattern of complementary and alternative medicine (CAM) for insomnia in Hong Kong. METHODS: Respondents were selected from the general population and interviewed by telephone Their sleep was assessed by a Chinese version of the Brief Insomnia Questionnaire (BIQ) and CAM use by a checklist. Prevalence findings were weighted by the BIQ insomnia diagnosis, age, and sex. RESULTS: 402 respondents completed the survey. The population-weighted prevalence of any treatment in the past 12 months was 21.3%, any CAM use at 12.3%, any conventional treatment at 6.5%, and alcohol use at 1.6%; however, 46.6% of the BIQ insomnia cases did not seek treatment. The most commonly used CAM modalities was Chinese herbal medicine (7.9%), followed by acupuncture (1.7%) and Western herbal products (1.7%). Most CAM therapies were used infrequently and without consultation of healthcare professionals. Only BIQ insomnia diagnosis and being female were found predictive of CAM use. CONCLUSIONS: Apart from Chinese herbal medicine and acupuncture, the use of conventional treatments, CAM, and alcohol for trouble sleeping was all less common in Hong Kong. Public education on the consequences of insomnia and various treatment modalities is needed.

Risk factors associated with adverse events of acupuncture: a prospective study.

OBJECTIVE: Mild adverse events (AEs) are common with acupuncture, but the risk factors remain unclear. A prospective study using a standardised AE assessment and acupuncture protocol was undertaken to address the question. METHODS: A 20-item AE report form investigated local and systemic AEs in 150 adults with insomnia randomised to receive traditional, minimal and non-invasive sham acupuncture. Sociodemographic, clinical and psychological variables at baseline and past history and perceived credibility of acupuncture were assessed. RESULTS: The incidence of any AEs per patient was 42.4% with traditional acupuncture, 40.7% with minimal acupuncture and 16.7% with non-invasive sham acupuncture. Traditional and minimal acupuncture were associated with a greater number of local AEs, while the presence of a chronic medical condition was predictive of fewer local and systemic AEs. Greater severity of insomnia, anxiety, depression, somatic symptoms and pain catastrophising thoughts were associated with lower risk, but most of the significant correlations disappeared after logistic regression. Divorce and widowhood were the only significant sociodemographic variables, while previous acupuncture treatment and perceived credibility of acupuncture were found to be unrelated. The risk of any AEs was higher in participants receiving traditional acupuncture (OR 4.26) and minimal acupuncture (OR 4.27) and in those without medical comorbidity (OR 3.39). CONCLUSIONS: The prevalence of AEs was higher than usual, probably due to the low threshold in our definition of AEs and the systematic collection from the patients' perspective. Baseline variables were largely unable to predict AEs associated with acupuncture. Further studies should explore the roles of practitioners, patients' anxiety during treatment and patient-practitioner interactions. TRIAL REGISTRATION NUMBER: NCT01707706.

A systematic review on the efficacy, safety and types of Chinese herbal medicine for depression.

Chinese herbal medicine (CHM) is one of the commonly used complementary and alternative medicine therapies for major depressive disorder. The objective of this study was to review the efficacy, safety and types of CHM for depression. We systematically searched key databases (9 Chinese and 7 English) up until May 2013 for randomized controlled trials (RCTs) and examined 7 systematic reviews for additional articles. Methodological quality was assessed by modified Jadad scale and Cochrane's risk of bias assessment. Only studies with moderate methodological quality, defined as modified Jadad scale score ≥3, were included in meta-analysis for efficacy. Of the 296 RCTs that were assessed in details, 278 (93.9%) had modified Jadad scale score < 3, and only 21 scored ≥ 3. The frequently used formulas were Xiao Yao decoction, Chaihu Shugan decoction and Ganmai Dazao decoction; while Chaihu, Bai Shao and Fu Ling were the frequently used single herb. Meta-analyses showed that CHM monotherapy was better than placebo and as effective as antidepressants in reducing Hamilton Depression Rating Scale (HDRS) score (CHM vs. placebo: mean difference: -7.97, 95% CI: -10.25 to -5.70, P < 0.00001, 2 studies; CHM vs. antidepressants: mean difference: 0.01, 95% CI: -0.28 to 0.30, P = 0.95, 7 studies). CHM were associated with less adverse events than antidepressants, and adding CHM to antidepressants reduced adverse events. Despite the overall positive results, due to the small number of studies with sufficient methodological quality, it is premature to accurately conclude the benefits and risks of CHM for depression.

A meta-analysis of the efficacy and safety of traditional Chinese medicine formula Ganmai Dazao decoction for depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganmai Dazao (GMDZ) decoction is a traditional Chinese herbal formula commonly used for the treatment of depression. The objective of this study was to assess the efficacy and safety of GMDZ, either alone or as co-therapy, for depression. MATERIALS AND METHODS: We systematically searched key databases (9 Chinese and 7 English) up until May 2013 for randomized controlled trials (RCTs). The primary outcomes were effective rate and self-rated or clinician-rated severity of depression. The secondary outcome was the occurrence of adverse events. Methodological quality of the RCTs was assessed by the Cochrane׳s risk of bias assessment. RESULTS: Ten RCTs were included. All were written in Chinese and the methodological quality was generally low. Pooled analysis of 5 studies which compared GMDZ with antidepressants showed that GMDZ was significantly more efficacious than antidepressants in effective rate (risk ratio: 1.14, 95% CI: 1.02 to 1.27, P=0.02, I(2)=0%), but comparable in Hamilton Depression Rating Scale (HDRS) score (mean difference: -2.10, 95% CI: -4.62 to -0.41, P=0.10, I(2)=92%). With regard to the other 5 studies which compared GMDZ plus antidepressants with antidepressants alone, there was no significant difference in effective rate (risk ratio: 1.24, 95% CI: 0.99 to 1.55, P=0.07, I(2)=93%), but the end-point HDRS score was significantly lower in GMDZ antidepressants combination (mean difference: -4.25, 95% CI: -6.50 to -2.00, P=0.0002, I(2)=96%). Adverse events were more common with antidepressants than GMDZ (rate ratio: 0.52, 95% CI: 0.32 to 0.82, P=0.005, I(2)=37%) and in antidepressants alone compared to GMDZ antidepressants combination (rate ratio: 0.23, 95% CI: 0.08 to 0.68, P=0.08, I(2)=0%). CONCLUSION: The overall results suggest that GMDZ has few side effects and the potential as an antidepressant. Adding GMDZ to antidepressants reduces side effects and enhances efficacy of antidepressants. However, due to the small number of studies and their limitations, further studies with better methodological quality and more comprehensive safety assessment are needed to determine the benefits and risks of GMDZ in the treatment of depression.