Elsevier

Journal of Affective Disorders

Volume 176, 1 May 2015, Pages 106-117
Journal of Affective Disorders

Review
The benefit of combined acupuncture and antidepressant medication for depression: A systematic review and meta-analysis

https://doi.org/10.1016/j.jad.2015.01.048Get rights and content

Abstract

Acupuncture, one of the most popular complementary therapies, is best known for its ability to provide pain relief. Accumulating evidence suggests that acupuncture may also be beneficial in depression, although its effectiveness remains uncertain in this condition. We conducted a meta-analysis of randomized trials in which the effects of acupuncture combined with antidepressant medications were compared with those of antidepressant medications alone in adults with a diagnosed depressive disorder. Thirteen randomized controlled trials involving 1046 subjects were included in the meta-analysis. Our results confirmed that the pooled standardized mean difference of the ‘endpoint scores of the 17-item Hamilton rating scale for depression’ was −3.74 (95% CI, −4.77 to −2.70, p<0.001) in week 1 and −2.52 (95% CI, −4.12 to −0.92; p<0.01) in week 6, indicating a significant difference in favor of acupuncture combined with selective serotonin reuptake inhibitors (SSRIs). Moreover, therapeutic response rates were statistically significantly different between the two groups (risk ratio [RR], 1.23; 95% CI, 1.10 to 1.39; p<0.001; I2=68%) in favor of the combined treatment group. This systematic review and meta-analysis suggest that acupuncture combined with antidepressant medication is effective, has an early onset of action, safe and well-tolerated over the first 6-week treatment period. Moreover, this treatment combination appears to result in greater therapeutic efficacy than SSRI therapy alone. More high-quality randomized clinical trials are needed to evaluate the clinical benefit and long-term effectiveness of acupuncture in the treatment of depression.

Introduction

Depressive disorders are among the most common psychiatric disorders in adults and are associated with a substantial loss of quality of life for patients and their relatives (Saarni et al., 2007), huge social and financial burdens (Greenberg and Birnbaum, 2005, Simon et al., 2001), and result in a considerable public health disease burden (Mathers and Loncar, 2006). The 2010 Global Burden of Disease (GBD) study identified major depressive disorder as the second leading cause of disability worldwide and a major contributor to the burden of suicide and ischemic heart disease (Ferrari et al., 2013). These findings reinforce the importance of treating depressive disorders as a public health priority and of implementing cost-effective interventions to reduce its huge burden.

The symptoms of depression generally include depressed mood, fatigue, sleep difficulties, anxiety, irritability, poor concentration, poor appetite and a loss of interest in people or activities. Effective treatments are available for depression, including several types of antidepressant medication and psychotherapy (Bauer, 2007). The American Psychiatric Association 2000 Practice Guideline for the Treatment of Patients with major depressive disorder indicates that antidepressant medications may be provided as an initial primary treatment for depressive disorder. The most important classes of antidepressants are the selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MOIs). In regard to SSRIs, approximately 60% of patients respond well to active treatment, but approximately 30% are nonresponders (Arroll et al., 2005, Baghai et al., 2006, Ruhe et al., 2006). The effectiveness of SSRIs is consistently reduced by a lack of therapeutic effect in some depressed patients who are unable to tolerate adverse effects, and by high dropout rates. Thus, a large proportion of depressed patients cannot obtain a full remission and they experience relapse and functional impairment (Arroll et al., 2005, Blier and de Montigny, 1994). Moreover, the delayed onset of antidepressant action with SSRIs prolongs feelings of depression in patients (Blier, 2003).

This reality has led patients or researchers to search for alternative treatments that may better treat depression, particularly in the early phase of the disease (Adell et al., 2005, Pilkington et al., 2006). Acupuncture is one of the most popular complementary therapies in the West and good evidence shows that acupuncture is efficacious for various types of depressive disorders (Smith et al., 2010, Wang et al., 2008, Zhang et al., 2010). Acupuncture involves puncturing the skin with thin, sterile needles at defined acupuncture points. In manual acupuncture (MA), the needles are twisted back and forth by practitioner until DeQi is achieved, which is described as a feeling of numbness, soreness or heaviness. The effect of MA differs by the number of the needles, treatment duration and methods of manipulation. In electroacupuncture (EA), the needles are connected to an electrical stimulator delivering either high or low frequency impulses, or a combination of both. The effect of EA differs by the frequency and intensity of the electrical stimulation. Recent studies have found that EA has immediate and short-term effects in alleviating pain, autonomic dysfunction, and mood symptoms (Dhond et al., 2007, Ulett et al., 1998, Zhao, 2008). A biochemical hypothesis for the effectiveness of acupuncture in the treatment of depression is that the intervention stimulates afferent Group III nerve fibers that transmit impulses to various parts of the central nervous system and induce the release of norepinephrine, serotonin, substance P, dopamine, β-endorphin, enkephalin and dynorphins, primarily in the hypothalamus (Siedentopf et al., 2005, Ulett et al., 1998), all of which play a principal role in the pathophysiology of major depression (Belmaker and Agam, 2008).

We therefore conducted a meta-analysis using data from all relevant randomized clinical trials that had compared the effectiveness of antidepressants alone and in combination with acupuncture in the treatment of various depressive conditions. We also reviewed the quality of the study design, types of acupuncture applied, and selected acupoints or sites of the body.

Section snippets

Search strategy

In March 2014, we searched three electronic bibliographic databases (PubMed, Ebsco and the Cochrane database of randomized trials) using the search terms ‘acupuncture OR electroacupuncture’ and ‘depression OR depressive disorder OR major depression’. The search was restricted to English- and Chinese-language studies.

Inclusion criteria

We included studies that met the following criteria: (1) randomized control trials (RCTs) that adopted a double-blind, single-blind, or non-blind design and (2) patients met

Description of the studies

The search yielded 661 potential article titles for review, 616 of which were excluded for reasons of irrelevance (Fig. 1). Fifty clinical trials assessing the application of acupuncture for depression were retrieved for further assessment. Among these 50 trials, 14 were excluded due to diagnosis of post-stroke depression, postpartum depression, depression during pregnancy and depression relating to Parkinson׳s disease. Twenty-two trials did not compare antidepressants alone with acupuncture in

Discussion

This meta-analysis reveals clear evidence of greater antidepressant activity with acupuncture combined with an SSRIs compared with SSRIs alone over the initial six weeks of treatment. In six trials, the combination of acupuncture and SSRI resulted in a greater mean reduction in HAMD-17 scores in the first week of treatment than that seen with SSRIs alone, which indicates that the addition of acupuncture may cause an earlier onset of action with SSRIs. Research has not yet been able to clarify

Conclusion

In conclusion, this meta-analysis of data from 13 RCTs indicates that combined acupuncture and antidepressant treatment is more effective than antidepressants alone in the first 6 weeks of treatment. Acupuncture has the potential to be an effective, safe and well-tolerated therapy with early onset in depression and may help to reduce side effects of antidepressants. There are no reports regarding the use of acupuncture for preventing recurrence after recovery from a depressive episode. Further

Role of funding source

The funding sources for the study (China Medical University and the Ministry of Science and Technology, Taiwan) had no role in study design, data analysis, writing of the manuscript or decision to submit the paper for publication.

Conflict of interest

The authors have no competing conflicts of interest.

Acknowledgments

We would like to thank Ms. Iona MacDonald for her input into the preparation of this manuscript. This work was supported by grant of A-4-1-a from China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan and by grants of MOST103-2320-B-039-008- and 102-2320-B-039-029- from the Ministry of Science and Technology, Taipei, Taiwan.

References (88)

  • J.H. Kim et al.

    The difference between electroacupuncture only and electroacupuncture with manipulation on analgesia in rats

    Neurosci. Lett.

    (2000)
  • R.J. Leo et al.

    A systematic review of randomized controlled trials of acupuncture in the treatment of depression

    J. Affect. Disord.

    (2007)
  • L.Y. Liu et al.

    Influence of electro-acupuncture on the side effects of fluoxetine on depression patients

    J. Tradit. Chin. Med.=Chung i tsa chih ying wen pan

    (2009)
  • W.E. Mehling et al.

    Symptom management with massage and acupuncture in postoperative cancer patients: a randomized controlled trial

    J. Pain Symptom Manag.

    (2007)
  • C.M. Pariante et al.

    The HPA axis in major depression: classical theories and new developments

    Trends Neurosci.

    (2008)
  • S.S. Qu et al.

    A 6-week randomized controlled trial with 4-week follow-up of acupuncture combined with paroxetine in patients with major depressive disorder

    J. Psychiatr. Res.

    (2013)
  • J. Roschke et al.

    The benefit from whole body acupuncture in major depression

    J. Affect. Disord.

    (2000)
  • M. Sairanen et al.

    Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat

    Neuroscience

    (2007)
  • G.A. Ulett et al.

    Electroacupuncture: mechanisms and clinical application

    Biol. Psychiatry

    (1998)
  • H. Wang et al.

    Is acupuncture beneficial in depression: a meta-analysis of 8 randomized controlled trials?

    J. Affect. Disord.

    (2008)
  • K. Wang et al.

    A randomised, placebo-controlled trial of manual and electrical acupuncture for the treatment of tinnitus

    Complement. Ther. Med.

    (2010)
  • A. Watanabe et al.

    Chronic buspirone treatment normalizes regional serotonin synthesis in the olfactory bulbectomized rat brain: an autoradiographic study

    Brain Res. Bull.

    (2006)
  • Z.J. Zhang et al.

    The effectiveness and safety of acupuncture therapy in depressive disorders: systematic review and meta-analysis

    J. Affect. Disord.

    (2010)
  • Z.Q. Zhao

    Neural mechanism underlying acupuncture analgesia

    Prog. Neurobiol.

    (2008)
  • B. Arroll et al.

    Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis

    Ann. Fam. Med.

    (2005)
  • T.C. Baghai et al.

    Recent progress in pharmacological and non-pharmacological treatment options of major depression

    Curr. Pharm. Des.

    (2006)
  • M. Bauer

    Updated WFSBP guidelines for the biological treatment of unipolar depressive disorders in primary care

    World J. Biol. Psychiatry: Off. J. World Fed. Soc. Biol. Psychiatry

    (2007)
  • R.H. Belmaker et al.

    Major depressive disorder

    N. Engl. J. Med.

    (2008)
  • S. Ceniceros et al.

    Acupuncture: a review of its history, theories, and indications

    South. Med. J.

    (1998)
  • J. Chen et al.

    Acupuncture/electroacupuncture enhances anti-depressant effect of Seroxat: the Symptom Checklist-90 scores

    Neural Regen. Res.

    (2014)
  • R. Cheng et al.

    Electroacupuncture elevates blood cortisol levels in naive horses; sham treatment has no effect

    Int. J. Neurosci.

    (1980)
  • W. Dai et al.

    Effect of electroacupuncture on hippocampal apoptosis and JNK signal pathway in chronic stress depression rats

    Zhen ci yan jiu=Acupunct. Res.

    (2010)
  • R.P. Dhond et al.

    Neuroimaging acupuncture effects in the human brain

    J. Altern. Complement. Med.

    (2007)
  • J.P. Dong et al.

    Clinical observation on head point-through-point electroacupuncture for treatment of poststroke depression

    Zhongguo zhen jiu=Chin. Acupunct. Moxib.

    (2007)
  • D. Duan et al.

    Hippocampal gene expression in a rat model of depression after electroacupuncture at the Baihui and Yintang acupoints

    Neural Regen. Res.

    (2014)
  • D.M. Duan et al.

    Assessment of effectiveness of electroacupuncture and fluoxetine for treatment of depression with physical symptoms

    Zhongguo zhen jiu=Chin. Acupunct. Moxib.

    (2008)
  • D.M. Duan et al.

    The relevance between symptoms and magnetic resonance imaging analysis of the hippocampus of depressed patients given electro-acupuncture combined with Fluoxetine intervention—a randomized, controlled trial

    Chin. J. Integr. Med.

    (2011)
  • P.F. Engelhardt et al.

    Acupuncture in the treatment of psychogenic erectile dysfunction: first results of a prospective randomized placebo-controlled study

    Int. J. Impot. Res.

    (2003)
  • A.J. Ferrari et al.

    Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010

    PLoS Med.

    (2013)
  • P.E. Greenberg et al.

    The economic burden of depression in the US: societal and patient perspectives

    Expert Opin. Pharmacother.

    (2005)
  • C.S. Han et al.

    The role of central 5-hydroxytryptamine in acupuncture analgesia

    Sci. Sin.

    (1979)
  • J.S. Han

    Electroacupuncture: an alternative to antidepressants for treating affective diseases?

    Int. J. Neurosci.

    (1986)
  • J.S. Han et al.

    Neurochemical basis of acupuncture analgesia

    Annu. Rev. Pharmacol. Toxicol.

    (1982)
  • Y.J. Han et al.

    Effect of electroacupuncture on hippocampal NO-cGMP signaling pathway in depression rats

    Zhen ci yan jiu=Acupunct. Res.

    (2009)
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