Objective To assess the effectiveness of acupuncture combined with selective serotonin reuptake inhibitors (SSRIs) for patients with depression in hospital using a pragmatic randomised controlled trial.
Methods 76 patients with depression were randomly divided into two groups (randomisation ratio 2:1 for treatment and control groups (CGs), respectively) and 71 patients completed the study. The 45 patients in the treatment group (TG) underwent acupuncture and received an SSRI and the 26 patients in the CG received an SSRI only. The 17-item Hamilton Depression Rating Scale (HDRS-17) was used to quantitatively assess patients after 1, 2, 4 and 6 weeks of treatment.
Results The mean (SD) baseline total HDRS scores were 22.2 (0.60) and 22.1 (0.33) in the TG and CG, respectively. After the first week of treatment the HDRS score for the TG was reduced to 15.6 (0.81), significantly different from the score of 18.3 (0.55) for the CG, p<0.05. This significant difference was maintained to the end of the 6-week treatment period, when HDRS scores had fallen to 6.3 (0.49) and 8.2 (0.35) for the TG and CG, respectively.
Conclusions Acupuncture combined with an SSRI showed a statistically significant benefit for patients with depression in hospital over the 6-week period compared with SSRIs alone. This reduction in symptoms started in the first week and continued throughout the 6 weeks of treatment.
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Depression is a major public health problem that affects 8–20% of the worldwide population.1 According to WHO reports, depression is predicted to become the second leading contributor to disease worldwide by 2020, affecting at least 350 million people,2 and the leading cause of the global disease burden by 2030.3
Antidepressants, typically selective serotonin reuptake inhibitors (SSRIs), have provided successful treatment for depression.4 However, a significant proportion (50–60%) of patients with depression do not respond fully to these drugs and many patients have undesirable side effects such as nausea, anxiety and dizziness.5 ,6
Acupuncture has been used for treatment of depression for more than 20 years.7 ,8 Increasing popularity of complementary medicines has seen greater application of acupuncture for the treatment of depression,9 with favourable clinical outcomes. Some authors remain sceptical and have commented on poor investigative study design, such as lack of sham controls and a high risk of bias.8 ,10
This pragmatic randomised controlled trial compares the effectiveness of acupuncture combined with antidepressants with that of antidepressants used alone, for the treatment of severe depression in hospital, using the Hamilton Depression Rating Scale (HDRS) as the assessment method.
The Nanjing University of Chinese Medicine research board and ethics committee approved the study protocol. Participants with major depression were recruited from the inpatient department of medical psychology of Nanjing Brain Hospital between April and November 2006. The inclusion criteria were adults diagnosed with major depressive disorder by the qualified psychiatrist using the ICD-9 (International Classification of Diseases V.9)—current at the time of the research; and with a total score of the HDRS-17 of ≥18. Patients were excluded if they had received SSRIs or acupuncture treatment for depression in the past 3 months; had a severe medical disease; had a history of brain stroke or other mental health disorders; were pregnant or breast feeding. The patients were recruited to the study soon after their admission for depression. All eligible patients gave informed consent to participate.
Patients were randomised into either an acupuncture treatment group (TG) or a control group (CG). Randomisation was conducted using sequentially numbered and sealed opaque envelopes, prepared in advance (randomisation ratio 2:1 for TGs and CGs, respectively). Healthcare staff, apart from the acupuncturist, were blinded to the group allocation before each participant was enrolled.
Outcome measures and timing
Treatment outcomes were measured using the HDRS-17, with scores ranging from 0 to 5411; scores of 0–6 indicate a normal person without depression; 7–17, mild depression, 18–24, moderate depression; >24, severe depression. Baseline assessments were carried out before randomisation and allocation of patients to the groups (W0). Repeated assessments were made after intervention at 1 (W1), 2 (W2), 4 (W4) and 6 weeks (W6) as study endpoints. All assessments were carried out by trained psychiatrists who were blinded to the group allocation (κ=0.87). Routine health examinations, including liver and renal function tests, were carried out weekly.
Psychiatrists prescribed one SSRI to each patient, as shown in table 1, and patients received normal hospital inpatient care in the Nanjing Brain Hospital. Patients in the TG additionally received Chinese acupuncture diagnosis and intervention given by a senior acupuncturist (TW), with 15 years’ clinical experience and certified by the China Association of Acupuncture and Moxibustion.
The key points used for all patients in the TG were GV24 (Shenting), GV20 (Baihui), GV14 (Dazhui) and GV4 (Mingmen). Additional points were used according to traditional Chinese medicine (TCM) differentiation for depression with the four diagnostic methods including tongue and pulse once a week, and the additional points were changed accordingly: Liver depression and Spleen deficiency, add LR3 (Taichong), SP9 (Yinlingquan); Liver Qi stagnation, add LR3, LR14 (Qimen); Heart and Spleen deficiency, add HT7 (Shenmen) and ST36 (Zusanli); Liver and Kidney Yin deficiency, add KI3 (Taixi) and LR3; Spleen and Kidney Yang deficiency, add CV4 and CV6. In addition, according to the individual symptoms, other extra points could be applied: insomnia and forgetfulness, add HT7 and An'mian (Ext); palpitations and chest tightness, add PC6 (Neiguan); constipation, add ST25 (Tianshu) and ST37 (Shangjuxu). The total number of needles used for each patient varied from six to10.
The needle size was 0.25×40 mm (Huatuo Suzhou China) and the depth of insertion 10–30 mm. After achieving de qi needling sensation, Dao qi technique acupuncture was applied at the four key acupuncture points. This manipulation involved lifting-thrusting and rotating the needle with light and smooth stimulation. The amplitude was 1–2 mm; needle rotation angle <90° and frequency 60–100 times per minute for 1–2 min. GV14 and GV4 were needled in a sitting position, with 5 min retention before the needles were removed. Participants were then placed in the supine position for the other points, which were needled to achieve de qi sensation only, with retention for 30 min. Treatment was given daily in the mornings, 5 days a week for 6 weeks.
Statistical analysis was undertaken using SPSS commercial statistics package V.13.0 (SPSS Inc, USA). The mean HDRS scores of the groups, and the patients’ demographic and baseline characteristics, were analysed by analysis of variance A two-sided p value of <0.05 was considered statistically significant.
Patients were aged between 22 and 73 years; other baseline characteristics, TCM patterns and HDRS total scores of the participants are shown in table 1. There was no significant difference (p>0.05) between the two groups.
Eighty-six patients with depression were screened—the total number available during the study period. Nine patients did not meet the inclusion criteria and one withdrew from fear of acupuncture, leaving 76 patients for inclusion in the study. Five patients did not complete the study—two from the TG and three from the CG—owing to lack of financial support (two), family problems (one) and fear of needle sensation (two). Finally, a total of 71 patients completed the study and were included in the analysis. The overall flow chart of the study design is shown in figure 1.
Patients’ HDRS total scores before and after intervention, with estimated differences, are shown in table 2. A statistically significant reduction in mean HDRS score was found for the TG compared with the CG receiving SSRIs only. Acupuncture plus SSRIs showed a reduction of 17 total scores (p<0.05) after 6 weeks (−1.83, 95% CI −2.07 to −1.58) and this difference was evident from the first week of intervention (−2.52, 95% CI −2.14 to −2.92). Figure 2 shows the trend of HDRS total scores of each group.
Routine health investigations, including liver and renal function tests, were carried out at baseline and every week during treatment for all subjects. During the 6-week study no concerns about safety were evident. In addition, no adverse reaction to acupuncture, such as needle fainting and internal organ injury, was reported.
We showed that acupuncture combined with SSRIs produces statically significantly larger reductions of HDRS values than SSRIs alone. This additional benefit was evident from the first week and continued throughout 6 weeks of treatment.
These findings are in line with those of a recent study, which was conducted in an outpatient setting.12 Most Western studies of acupuncture for depression recruit participants from primary healthcare and the community, whereas study of hospital inpatients is typical among most Chinese studies.10 The hospital setting has the advantage of enabling close monitoring of participants and minimising the variables.
The significant improvement of HDRS scores was seen from the first week with acupuncture combined with SSRIs, as also found by other studies.12 ,13 It seems that combined treatment may overcome the well-documented delay before the onset of the therapeutic action of SSRIs.14 ,15
The benefit of acupuncture for the treatment of depression has not been found by all studies,16–18 possibly through failure to use appropriate acupuncture points, inadequate needle stimulation and inadequate frequency of treatment sessions.19 ,20 Insufficient acupuncture needle sensation and stimulation might influence response in acupuncture trials.19 ,21 In our study the acupuncture treatment was carried out by one single practitioner, providing standardisation of acupuncture techniques and, in particular, sufficient ‘dosage’ of stimulation.
The design of this pragmatic randomised controlled trial comparing the effectiveness of combined treatments with conventional antidepressants alone did not include a non-treated group or placebo control. We acknowledge that acupuncture may have a placebo effect.22 In addition, the SSRIs given within the two study groups varied and might have influenced treatment effectiveness, but such pragmatic trial designs test the overall effect of acupuncture and generate evidence within everyday clinical situations.10 Such trials could facilitate decision-making for patient management and provide evidence to the public health service for guidance and referral policies.23 ,24
All patients were diagnosed with major depression, as confirmed by their HDRS score of >17, indicative of moderate or severe status. Patients with serious depression cannot ethically be treated by complementary medicine such as acupuncture alone.10 The cost-effectiveness of acupuncture for depression may be a concern in many healthcare services and some patients may not be able to afford the costs of private care.25 However, this should be balanced against the enhanced improvement which might reduce days of hospitalisation, offsetting the higher cost of this therapeutic approach.
This study has several limitations, particularly the small sample size and lack of long-term follow-up. In addition, the acupuncture practitioner and patients were not blinded to the treatment, which might have led to bias. However, the clinical assessor and psychiatrist who rated the HDRS were blinded to the treatment given.
The overall evidence on use of acupuncture for depression was insufficient to reach conclusions about its effectiveness, according to the 2010 Cochrane review.8 Giving the positive outcome of our study, the combination of acupuncture and an antidepressant might be a valuable solution, potentially allowing reduction of the dose of antidepressants and their associated adverse clinical outcome.
Acupuncture combined with SSRIs shows a statistically significant benefit over a 6-week period compared with SSRI administration only. This reduction in symptoms starts from the first week and continues throughout the 6 weeks of treatment. Earlier intervention with acupuncture might contribute to the treatment of depression, with reduction of adverse effects. However, doubt remains about the contribution of non-specific effects. Further trials with large patient groups and lower doses of medication are now warranted.
Selective serotonin reuptake inhibitors (SSRIs) for treatment of depression may have side effects and may not be effective.
Acupuncture combined with SSRIs was compared with SSRIs alone for depression.
The acupuncture group showed a significantly better response, from week 1.
We sincerely thank all the patients for their involvement in the study. We also thank the psychiatrists from the inpatient department of medical psychology of Nanjing Brain Hospital for their contributions for the prescription of selective serotonin reuptake inhibitors, routine healthcare and Hamilton Depression Rating Scale scores. We thank reader Sally Cutler, Professor Olivia Corcoran, Dr Stefano Casalotti, Dr Barbara Pendry and Patsy Savage from the University of East London contributed to the proof reading and manuscript preparation.
Correction notice This article has been corrected since it was published Online First. The word ‘Results’ has been included in the abstract.
Contributors TW substantially contributed to the conception and design; drafted the article and revised it critically for important intellectual content; analysed and interpreted the data and gave final approval of the version to be published. LW and LC planned the design; TW, LC and WT arranged and carried out the acupuncture and collected the clinical data.
Funding Opening Projects from the Laboratory of Acupuncture-Medicine, Nanjing University of Chinese Medicine (No JKA200505).
Competing interests None.
Ethics approval Nanjing University of Chinese Medicine research board and the ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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