Acupuncture for depression

Caroline A Smith; Mike Armour; Myeong Soo Lee; Li‐Qiong Wang; Phillipa J Hay

doi:10.1002/14651858.CD004046.pub4

. 2018 Mar 4;2018(3):CD004046. doi: 10.1002/14651858.CD004046.pub4

Acupuncture for depression

Caroline A Smith ^1,^✉, Mike Armour ¹, Myeong Soo Lee ², Li‐Qiong Wang ³, Phillipa J Hay ^4,⁵

Editor: Cochrane Common Mental Disorders Group

PMCID: PMC6494180 PMID: 29502347

Abstract

Background

Depression is recognised as a major public health problem that has a substantial impact on individuals and on society. People with depression may consider using complementary therapies such as acupuncture, and an increasing body of research has been undertaken to assess the effectiveness of acupuncture for treatment of individuals with depression. This is the second update of this review.

Objectives

To examine the effectiveness and adverse effects of acupuncture for treatment of individuals with depression.

To determine:

• Whether acupuncture is more effective than treatment as usual/no treatment/wait list control for treating and improving quality of life for individuals with depression.

• Whether acupuncture is more effective than control acupuncture for treating and improving quality of life for individuals with depression.

• Whether acupuncture is more effective than pharmacological therapies for treating and improving quality of life for individuals with depression.

• Whether acupuncture plus pharmacological therapy is more effective than pharmacological therapy alone for treating and improving quality of life for individuals with depression.

• Whether acupuncture is more effective than psychological therapies for treating and improving quality of life for individuals with depression.

• Adverse effects of acupuncture compared with treatment as usual/no treatment/wait list control, control acupuncture, pharmacological therapies, and psychological therapies for treatment of individuals with depression.

Search methods

We searched the following databases to June 2016: Cochrane Common Mental Disorders Group Controlled Trials Register (CCMD‐CTR), Korean Studies Information Service System (KISS), DBPIA (Korean article database website), Korea Institute of Science and Technology Information, Research Information Service System (RISS), Korea Med, Korean Medical Database (KM base), and Oriental Medicine Advanced Searching Integrated System (OASIS), as well as several Korean medical journals.

Selection criteria

Review criteria called for inclusion of all published and unpublished randomised controlled trials comparing acupuncture versus control acupuncture, no treatment, medication, other structured psychotherapies (cognitive‐behavioural therapy, psychotherapy, or counselling), or standard care. Modes of treatment included acupuncture, electro‐acupuncture, and laser acupuncture. Participants included adult men and women with depression diagnosed by Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM‐IV), Research Diagnostic Criteria (RDC), International Statistical Classification of Diseases and Related Health Problems (ICD), or Chinese Classification of Mental Disorders Third Edition Revised (CCMD‐3‐R). If necessary, we used trial authors' definitions of depressive disorder.

Data collection and analysis

We performed meta‐analyses using risk ratios (RRs) for dichotomous outcomes and standardised mean differences (SMDs) for continuous outcomes, with 95% confidence intervals (CIs). Primary outcomes were reduction in the severity of depression, measured by self‐rating scales or by clinician‐rated scales, and improvement in depression, defined as remission versus no remission. We assessed evidence quality using the GRADE method.

Main results

This review is an update of previous versions and includes 64 studies (7104 participants). Most studies were at high risk of performance bias, at high or unclear risk of detection bias, and at low or unclear risk of selection bias, attrition bias, reporting bias, and other bias.

Acupuncture versus no treatment/wait list/treatment as usual

We found low‐quality evidence suggesting that acupuncture (manual and electro‐) may moderately reduce the severity of depression by end of treatment (SMD ‐0.66, 95% CI ‐1.06 to ‐0.25, five trials, 488 participants). It is unclear whether data show differences between groups in the risk of adverse events (RR 0.89, 95% CI 0.35 to 2.24, one trial, 302 participants; low‐quality evidence).

Acupuncture versus control acupuncture (invasive, non‐invasive sham controls)

Acupuncture may be associated with a small reduction in the severity of depression of 1.69 points on the Hamilton Depression Rating Scale (HAMD) by end of treatment (95% CI ‐3.33 to ‐0.05, 14 trials, 841 participants; low‐quality evidence). It is unclear whether data show differences between groups in the risk of adverse events (RR 1.63, 95% CI 0.93 to 2.86, five trials, 300 participants; moderate‐quality evidence).

Acupuncture versus medication

We found very low‐quality evidence suggesting that acupuncture may confer small benefit in reducing the severity of depression by end of treatment (SMD ‐0.23, 95% CI ‐0.40 to ‐0.05, 31 trials, 3127 participants). Studies show substantial variation resulting from use of different classes of medications and different modes of acupuncture stimulation. Very low‐quality evidence suggests lower ratings of adverse events following acupuncture compared with medication alone, as measured by the Montgomery‐Asberg Depression Rating Scale (MADRS) (mean difference (MD) ‐4.32, 95% CI ‐7.41 to ‐1.23, three trials, 481 participants).

Acupuncture plus medication versus medication alone

We found very low‐quality evidence suggesting that acupuncture is highly beneficial in reducing the severity of depression by end of treatment (SMD ‐1.15, 95% CI ‐1.63 to ‐0.66, 11 trials, 775 participants). Studies show substantial variation resulting from use of different modes of acupuncture stimulation. It is unclear whether differences in adverse events are associated with different modes of acupuncture (SMD ‐1.32, 95% CI ‐2.86 to 0.23, three trials, 200 participants; very low‐quality evidence).

Acupuncture versus psychological therapy

It is unclear whether data show differences between acupuncture and psychological therapy in the severity of depression by end of treatment (SMD ‐0.5, 95% CI ‐1.33 to 0.33, two trials, 497 participants; low‐quality evidence). Low‐quality evidence suggests no differences between groups in rates of adverse events (RR 0.62, 95% CI 0.29 to 1.33, one trial, 452 participants).

Authors' conclusions

The reduction in severity of depression was less when acupuncture was compared with control acupuncture than when acupuncture was compared with no treatment control, although in both cases, results were rated as providing low‐quality evidence. The reduction in severity of depression with acupuncture given alone or in conjunction with medication versus medication alone is uncertain owing to the very low quality of evidence. The effect of acupuncture compared with psychological therapy is unclear. The risk of adverse events with acupuncture is also unclear, as most trials did not report adverse events adequately. Few studies included follow‐up periods or assessed important outcomes such as quality of life. High‐quality randomised controlled trials are urgently needed to examine the clinical efficacy and acceptability of acupuncture, as well as its effectiveness, compared with acupuncture controls, medication, or psychological therapies.

Plain language summary

Acupuncture for depression

Why is this review important?

Depression is widely experienced in our communities. People with clinical depression report lack of interest in life and activities that they otherwise normally enjoy. Some people who are depressed use complementary therapies, and some prefer these therapies over medication. Acupuncture treatment involves insertion of fine needles into different parts of the body to correct the imbalance of energy within the body.

Who will be interested in this review?

Adolescents and adults; healthcare practitioners, including general practitioners working with or involved in the treatment of individuals with depression; and providers and commissioners of healthcare services will be interested in this review.

What questions does this review aim to answer?

This review, which is an update of a previous Cochrane review (published in 2010), aims to answer the following questions.

• Is acupuncture better than no treatment or usual care?

• Is acupuncture better than control acupuncture (a treatment that looks similar to acupuncture)?

• Is acupuncture better than pharmacological therapies such as antidepressant medication?

• Is acupuncture combined with antidepressant medication better than antidepressant medication alone?

• Is acupuncture better than psychological therapies?

• Is acupuncture safer than other types of treatment for depression?

Which studies were included in the review?

Included were 64 randomised controlled trials (with 7104 participants) that measured changes in depression symptoms.

What does evidence from the review tell us?

Review authors rated the quality of evidence from most included studies as very low or low, and the effects described below should be interpreted with caution.

Acupuncture may result in a moderate reduction in the severity of depression when compared with treatment as usual/no treatment. Use of acupuncture may lead to a small reduction in the severity of depression when compared with control acupuncture. Effects of acupuncture versus medication and psychological therapy are uncertain owing to the very low quality of evidence. Risks of adverse events with acupuncture are also unclear, as most trials have not reported on adverse events.

What should happen next?

Review authors recommend that additional high‐quality randomised controlled trials should be undertaken. These trials should use suitable blinding (by which people do not know which treatment they are receiving) when appropriate and should incorporate quality of life measures, assessment of treatment acceptability, and medium‐ and long‐term follow‐up.

Summary of findings

Background

Description of the condition

Clinical depression is characterised by behavioural, cognitive, and emotional features. Depressed patients often exhibit signs of dysphoric mood, loss of interest in normally enjoyable pursuits, self‐neglect and social withdrawal, poor appetite or overeating, insomnia or hypersomnia, fatigue or loss of energy, low self‐esteem, poor concentration or difficulty making decisions, and feelings of hopelessness.

Depression is recognised as a major public health problem that has a substantial impact on individuals and on society. Depressive disorders are common in the general population. In the United States, the lifetime prevalence of a major depressive disorder (MDD) has been reported at 16.2% (Kessler 2007). The World Health Organization has described depression as an "unseen burden" (Murray 1996). MDD is associated with a significant loss of workdays (Kessler 2007), as well as substantial role impairment in relation to household responsibilities, social life, and personal relationships (Kessler 2003). It has been demonstrated that those in the community who have depressive disorders experience reduced physical and mental functioning ‐ similar to those seen with chronic diseases such as diabetes (Hays 1995; Wells 1989). In addition, mood disorders have been shown to have a greater impact on quality of life when compared with conditions such as hypertension and cardiac disease (Spitzer 1995). Depression is associated with considerable financial costs for health services and for society. The economic burden in England is estimated to exceed £9 billion per annum, with approximately £370 million accounting for direct costs of treatment (Thomas 2003).

Description of the intervention

Major depression is a discrete episode of severe depression; when it is gone, the person is described as being in remission and feeling completely normal. Dysthymia is a pervasive 'low‐level' depression that lasts a long time ‐ frequently for a few years. Treatment approaches are the same for both conditions. Most depressed patients are treated in primary care and do not require hospitalisation. In primary care, depression is most often managed with antidepressants (Goldman 1999). A range of psychological interventions, including cognitive‐behavioural therapies, interpersonal therapy, psychotherapy, and counselling, are also available. Surveys have shown that Australians report a preference for self‐help and complementary therapies for depression (Jorm 1997;Jorm 2000), and depressed persons in the United States report greater use of complementary therapies (Kessler 2000).

Acupuncture has a long history of use in China, Japan, and Korea. Contemporary acupuncture practice is commonly undertaken as part of the medical hospital system in modern China (Robinson 2012), as part of traditional Korean medicine in South Korea (Woo 2014), and as a mix of hospital and private practice in the United Kingdom (Hopton 2012). Traditional Chinese Medicine theory describes a state of health maintained by a balance of energy within the body. Acupuncture involves insertion of fine needles into different parts of the body to correct the imbalance of energy within the body. Styles of acupuncture range from traditional/classical acupuncture to auricular acupuncture, to trigger point acupuncture, to single‐point acupuncture. Acupuncture is practised under several theoretical frameworks. Traditional Chinese Medicine (TCM) and Classical Acupuncture are based on theoretical concepts of Yin and Yang and the Five Elements and explain disease and physiological function. A westernised medical application of acupuncture involves use of trigger points, segmental points, and commonly used formula points. Medical acupuncture may involve application of acupuncture based on the principles of neurophysiology and anatomy, rather than on TCM principles and philosophy. Auricular therapy involves using the ear to make a diagnosis and subsequent needling to points on the ear. Electro‐acupuncture is defined as application of a small current through acupuncture needles. Laser acupuncture is a non‐penetrative form of acupuncture that uses low‐power laser light to stimulate acupuncture points. The rationale for treatment will determine the needling details (e.g. selection of points, number of needles used) and the method of stimulation (e.g. manual acupuncture, electro‐acupuncture, laser acupuncture). Different styles of acupuncture may differ in their effectiveness, but little research has been conducted to directly examine effects on clinical outcomes when these parameters are changed (Armour 2016; Lin 2016).

Acupuncture is not entirely free of adverse events. Two large prospective surveys have been undertaken in the United Kingdom (MacPherson 2004; White 2001). White 2001 reported an incidence of 684 adverse events per 10,000 consultations. Most were minor events such as bleeding, needling pain, or aggravation of symptoms, and investigators have reported a low rate of significant adverse events (14 per 10,000). MacPherson 2004 reported a rate of 107 adverse events per 1000 participants (95% confidence interval (CI) 100 to 115). Three participants reported a serious adverse event. Events most commonly reported were severe tiredness and exhaustion, pain at the site of needling, and headache. White 2004 summarised the range and incidence of adverse events associated with acupuncture. Twelve prospective studies undertaken in the UK, Germany, Singapore, Japan, and Sweden surveyed more than a million treatments and found that risk of a serious adverse event with acupuncture was estimated to be 0.05 per 10,000 treatments, and 0.55 per 10,000 individual patients. Data from these studies suggest that the risks associated with acupuncture are few ‐ a point reinforced by Vincent 2001, which concluded that acupuncture is safe in competent hands.

How the intervention might work

The cause of depression appears to be multi‐factorial, and biological and psychosocial factors are involved (Davidson 2002). Various interdependent biological components have been implicated in the onset and maintenance of MDD. Current models suggest that changes in the hypothalamic‐pituitary‐adrenal (HPA) axis, dysfunction among stress hormones, and disequilibrium in neurotransmitters such as noradrenaline, serotonin, and dopamine may be key factors (Hou 2016).

Several mechanisms may explain the therapeutic effects of acupuncture within the current model of depression. Strong evidence obtained over the past three decades indicates that effects of acupuncture are mediated by various neurotransmitters, predominantly the endogenous opioid mechanism (EOM), catecholamines, and serotonin, and that an estimated 20 to 30 other neuropeptides are affected (Leung 2014). Results from animal experiments suggest that, similar to antidepressant medications, acupuncture is capable of affecting neurotransmitter levels of serotonin and noradrenaline, along with the adenylate cyclase‐cyclic adenosine monophosphate‐protein kinase A (AC‐cAMP‐PKA) cascade within the central nervous system (Leung 2014). In addition, acupuncture has produced structural and functional magnetic resonance imaging (fMRI) changes (as described by Huang 2012) in the default mode network, anterior cingulate cortex, and amygdala‐hippocampal formation (Liu 2009). Dysfunction in these areas of the brain has been previously implicated in depressive disorders (Hamilton 2015). Manual acupuncture causes a broad range of central nervous system responses involving the amygdala, hippocampus, hypothalamus, cerebellum, and other limbic structures as seen on fMRI and electroencephalography (EEG) (Napadow 2005). Electro‐acupuncture is thought to deliver a greater 'dose' of acupuncture compared with manual acupuncture, as a result of the duration and intensity of stimulation, and to cause greater activation of endogenous opoid mechanisms (Mayor 2013). This may or may not lead to greater clinical effects in non‐pain‐related conditions (Langevin 2015;Mayor 2013). The mechanism of laser acupuncture remains unclear, but proposed models involve changes in gene expression mediated via changes in nitric oxide (Chung 2012).

Why it is important to do this review

An increasing body of research is focussed on assessing the effectiveness of acupuncture. In 2005, we published the first version of this systematic review and concluded that evidence was insufficient for determination of the efficacy of acupuncture. An update was published in 2010. Since that time, new trials have been published and we have gained comprehensive access to a large body of relevant literature from China.

Objectives

To examine the effectiveness and adverse effects of acupuncture for treatment of individuals with depression.

To determine whether acupuncture is more effective than treatment as usual/no treatment/wait list control for treating and improving quality of life for individuals with depression.
To determine whether acupuncture is more effective than control acupuncture for treating and improving quality of life for individuals with depression.
To determine whether acupuncture is more effective than pharmacological therapies for treating and improving quality of life for individuals with depression.
To determine whether acupuncture plus pharmacological therapy is more effective than pharmacological therapy alone for treating and improving quality of life for individuals with depression.
To determine whether acupuncture is more effective than psychological therapies for treating and improving quality of life for individuals with depression.
To determine adverse effects of acupuncture compared with treatment as usual/no treatment/wait list control, control acupuncture, pharmacological therapies, and psychological therapies for treatment of individuals with depression.

Methods

Criteria for considering studies for this review

Types of studies

We sought to include all relevant published and unpublished randomised controlled trials (RCTs). We excluded cross‐over trials owing to uncertainty regarding the period allowed for washout before acupuncture treatment. We included cluster‐randomised trials and excluded quasi‐randomised trials that used non‐random methods of treatment assignment such as date of admission (see Differences between protocol and review).

Types of participants

Characteristics

We included studies of people of either gender and of any ethnicity, aged 16 years or older, with clinically diagnosed depression as the primary condition or as a comorbidity.

Diagnosis

We included studies in which investigators diagnosed depression using one or more of the following criteria: depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Third Edition (DSM‐III), Fourth Edition (DSM‐IV), or Fifth Edition (DSM‐5); APA 2015), or the Research Diagnostic Criteria (RDC; Spitzer 1977), or the International Statistical Classification of Diseases and Related Health Problems (ICD; WHO 1993), or the Chinese Classification of Mental Disorders (Second Edition (CCMD‐2) or Third Edition (CCMD‐3); Chinese Psychiatric Society 2001). If necessary, we used trial authors' definitions of depressive disorder. We included both major depression and dysthymia.

Comorbidities

As long as depression was the main focus of the trial, studies that involve participants with comorbid physical or common mental disorders were eligible for inclusion.

Treatment setting

All settings ‐ primary, secondary, tertiary, and community ‐ were eligible for inclusion.

Types of interventions

Experimental interventions

Manual acupuncture: involves stimulation of anatomical points on the body through penetration of the skin with thin, solid, metallic needles that are manipulated by the hands. Also included is auricular acupuncture ‐ insertion of needles into points located on the ear
Electro‐acupuncture: involves passing a pulsed current through the body through acupuncture needles
Laser acupuncture: use of a low‐level laser beam instead of an acupuncture needle to stimulate an acupuncture point

Comparator interventions

We included in this review five main categories of trial comparison groups. We excluded trials that did not include one of the following comparison groups. We classified the comparator group in each study as follows.

Wait list control/treatment as usual/no treatment.
Control acupuncture.
- Invasive acupuncture control.
  - Sham acupuncture, which consists of insertion of a needle into a non‐acupuncture point.
  - Minimal acupuncture, in which needles are inserted into non‐acupuncture points but more superficially, without stimulation or manipulation, to avoid the needling sensation known as 'de qi'.
- Non‐invasive acupuncture control: includes use of the placebo needle, which is a blunted needle that looks as if it is piercing the skin yet does not; two forms are available (Park 2002;Streitberger 1998).
- Mock electro‐acupuncture: involves using a de‐commissioned acupuncture stimulation unit and fixing electrodes to the skin with the switch turned off.
- Mock laser acupuncture.
Antidepressants ‐ organised into classes for the purposes of this review.
- Selective serotonin reuptake inhibitors (SSRIs): zimelidine, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram.
- Tetracyclic antidepressants (TCAs): amitriptyline, imipramine, trimipramine, doxepin, desipramine, protriptyline, nortriptyline, clomipramine, dothiepin, lofepramine.
- Heterocyclic antidepressants: mianserin, trazodone, amoxapine, maprotiline.
- Monoamine oxidase inhibitors (MAOIs): irreversible: phenelzine, tranylcypromine, izocarboxazid; reversible: brofaromine, moclobemide, tyrima.
- Other antidepressants: noradrenaline reuptake inhibitors (NARIs): reboxetine, atomoxetine; norepinephrine‐dopamine reuptake inhibitors (NDRIs): amineptine, bupropion; serotonin‐norepinephrine reuptake inhibitors (SNRIs): trazodone; unclassified: agomelatine, vilazodone.
Combination therapy by which the same adjunct therapy was delivered to all study groups.
- Acupuncture plus medication versus medication.
Psychological therapies.
- Cognitive‐behavioural therapy (CBT).
- Behavioural therapy (BT).
- Psychotherapy.
- Counselling.

Types of outcome measures

Primary outcomes

Reduction in the severity of depression, measured at the end of the intervention primarily as a continuous variable on self‐rating scales such as the Beck Depression Inventory (BDI) (Beck 1961), or on clinician‐rated scales, such as the Hamilton Depression Rating Scale (HAMD) ‐ as discussed in Hamilton 1960
Total numbers of adverse events

Secondary outcomes

Remission of depression as defined in trial reports and based on the HAMD or another clinician‐rated scale of depression severity and reported as a binary outcome
Quality of life indices (e.g. Short Form Health Survey (SF‐36); Ware 1994), with individual domains related to quality of life, for example, physical and emotional well‐being, reported
Change in use of medication or use of other support systems, measured as additional treatment provided, number of appointments attended, etc.
Dropouts from treatment, defined as failure to complete, including number of individuals leaving each study early and reasons for early dropout

Timing of outcome assessment

The primary time frame for reporting primary and secondary outcomes is at completion of the intervention. If a study reported several time points during the time frame (i.e. during treatment), we reported the last observation before treatment completion. We included all time frames and grouped them as follows.

During the treatment period.
At the conclusion of the treatment period.
Between zero and six months after conclusion of the treatment period (short term).
Between six and 12 months after conclusion of the treatment period (medium term).
Longer than 12 months after conclusion of the treatment period (long term).

Hierarchy of outcome measures

We treated equally five scales commonly used for assessment of depression: the Beck Depression Inventory (BDI; Beck 1961); the Hamilton Depression Rating Scale (HAMD; Hamilton 1960); the Patient Health Questionnaire (PHQ; Spitzer 1999); the Montgomery‐Asberg Depression Rating Scale (MADRS; Montgomery 1979); and the Clinical Global Impression‐Severity Scale (CGI‐S). We rated all other depression scales lower. If investigators used two or more of these scales, we applied the following hierarchy: (1) HAMD; (2) MADRS; (3) CGI‐S; (4) BDI; (5) PHQ; and (6) all other depression scales. Owing to the difficulty of participant blinding often seen in acupuncture trials, we gave preference to clinician‐rated scales when both clinician‐rated and self‐reported outcomes were provided.

If a study employed more than one quality of life measure, we applied the following hierarchy of scales: (1) World Health Organization Quality of Life (WHOQOL; WHO 1998); (2) Short Form Health Survey (SF‐36; Ware 1994); and (3) any other quality of life measures used.

We included both clinician‐rated and self‐reported outcomes in the same analysis; however, if investigators reported both, we used clinician‐rated scales in preference. If investigators presented no clinician‐rated outcomes, we used a self‐reported outcome. Each group did not include enough trials for these outcomes to be reported separately via subgroup analysis.

Search methods for identification of studies

Cochrane Specialised Registers: Cochrane Common Mental Disorders Clinical Trials Register (CCMD‐CTR)

The Cochrane Common Mental Disorders Group maintains a specialised register of randomised controlled trials ‐ the CCMD‐CTR. This register contains more than 39,000 reference records (reports of RCTs) on depression, anxiety, and other common mental disorders. A percentage of the reference records have been tagged to 12,500 individual, PICO‐coded study records (with coding based on the EU‐PSI (Evidence‐Based Treatment in Mental Health and Optimised Use of Databases) Coding Manual). Reports of RCTs for inclusion in the Register are collated from (weekly) generic searches of MEDLINE, Embase, and PsycINFO; quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL); and review‐specific searches of additional databases. Reports of trials were also derived from international trial registries and drug companies; through handsearching of key journals; and via electronic searches of conference proceedings and other (non‐Cochrane) systematic reviews and meta‐analyses. Details of core CCMD search strategies can be found on the CCMD Group website.

Electronic searches

We searched the CCMD‐CTR (studies and references) (all years to 10 June 2016) using the following terms:  ((acupunct* or acupress* or acupoints* or electroacupunct* or electro‐acupunct* or auriculotherap* or auriculoacupunct* or moxibust*) and (depress* or "affective disorder*" or "affective symptoms" or mood)):ti,ab,kw,ky,emt,mh,mc.

We did not systematically search Chinese language‐only databases for this version of the review; therefore trials meeting our selection criteria beyond those identified may exist. We identified a significant number of Chinese language trials through other search strategies (reported above), and a large number did not meet the inclusion criteria.

We searched the following eight electronic Korean medical databases using the same terms as above, without restricting language, from their respective inceptions up to June 2016: the Korean Studies Information Service System (KISS), Korean article database website (DBPIA), Korea Institute of Science and Technology Information, the Research Information Service System (RISS), Korea Med, the Korean Medical Database (KM Base), and the Oriental Medicine Advanced Searching Integrated System (OASIS). In addition, we searched the following Korean language journals: Journal of Korean Medicine, Korean Journal of Acupuncture, Journal of Pharmacopuncture, Journal of Acupuncture and Meridian Studies, Korean Journal of Joongpoong, Journal of Korean Acupuncture & Moxibustion Medicine Society, Journal of Korean Oriental Internal Medicine, Journal of Oriental Obstetrics and Gynecology, Journal of Society of Korean Medicine for Obesity Research, Journal of Oriental Neuropsychiatry, and Journal of Sasang Constitutional Medicine.

We applied no restrictions on publication date or status when conducting these searches.

We searched international trial registries via the World Health Organization trials portal (ICTRP), the Chinese clinical trial registry (www.chictr.org.cn), and the US National Library of Medicine database (ClinicalTrials.gov) to identify unpublished and ongoing studies.

Searching other resources

Grey literature

We searched sources of grey literature including dissertations and theses, clinical guidelines, and reports from regulatory agencies (when appropriate).

ProQuest Dissertations and Theses Database.
National Guideline Clearing House (http://guideline.gov).
OpenGrey (http://www.opengrey.eu/).

Handsearching

We handsearched relevant conference proceedings by referring to lists of publications in manuscripts.

Reference lists

We checked the reference lists of all included studies and relevant systematic reviews to identify additional studies missed by the original electronic searches (e.g. unpublished or in‐press citations). We conducted a cited reference search on the Web of Science.

Correspondence

We contacted trialists and subject experts to ask for information on unpublished or ongoing studies, or to request additional trial data.

Data collection and analysis

Selection of studies

Two review authors (of CS, MA, PH, HM, MS, L‐QW) reviewed all articles. Review authors independently screened titles and abstracts for potential inclusion of all studies identified as a result of the search and coded them as 'retrieve' (eligible or potentially eligible) or 'do not retrieve'. We retrieved full‐text study reports/publications, and two review authors (for all authors of the review) independently screened full‐texts, identified studies for inclusion, and identified and recorded reasons for exclusion of ineligible studies. We resolved disagreements through discussion or, if required, consulted a third review author (of PH, HM, CS). We identified and excluded duplicate records and collated multiple reports related to the same study, so that each study rather than each report is the unit of interest in the review. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram.

Data extraction and management

Following assessment for inclusion, we assessed the methods used by each trial. All review authors independently extracted onto hard copy data sheets trial data on participants, methods, interventions, outcomes, and results. We sought missing data or clarification of study details from respective trial authors by mail or by email.

Main planned comparisons

Acupuncture versus wait list control/treatment as usual/no treatment
Acupuncture versus control acupuncture
Acupuncture versus pharmacological therapies
Acupuncture plus medication versus medication alone
Acupuncture versus psychological therapies (including counselling)

Assessment of risk of bias in included studies

Two or more review authors independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved disagreements by discussion or by consultation with a third party, when necessary. We assessed risk of bias according to the following domains.

Random sequence generation.
Allocation concealment.
Blinding of participants and personnel.
Blinding of outcome assessment.
Incomplete outcome data.
Selective outcome reporting.
Other bias.

We judged each potential source of bias as high, low, or unclear and provided a supporting quotation from the study report together with a justification for our judgement in the 'Risk of bias' table. We summarised risk of bias judgements across different studies for each of the domains listed. We considered blinding separately for different key outcomes when necessary (e.g. for unblinded outcome assessment). When information on risk of bias was related to unpublished data or correspondence with a trialist, we noted this in the 'Risk of bias' table.

When considering treatment effects, we took into account the risk of bias for studies that contributed to that outcome. For assessments of overall quality of the evidence for each outcome that included pooled data, we used the GRADE method to determine evidence quality, downgrading evidence from high quality by one level for serious (or two for very serious) issues with risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias.

Measures of treatment effect

We performed statistical analysis using Review Manager 5 (Revman 2014) software.

We undertook a statistical summary of the data and expressed dichotomous data as risk ratios (RRs) with corresponding 95% confidence intervals (95% CIs). We expressed continuous data as mean differences (MDs) with 95% CIs, or as standardised mean differences (SMDs) if outcomes were conceptually the same but were measured in different ways, for example, by using different instruments (e.g. BDI, HAMD).

Unit of analysis issues

Trials with multiple groups

We included trials with multiple groups and described them in the Characteristics of included studies table. For example, acupuncture might be compared with sham acupuncture, and with no acupuncture in another study group. If investigators included two acupuncture groups, we combined data from both treatment groups. For studies using a sham control and including no treatment control group, we evenly divided shared interventions between groups, as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). When outcomes were repeated measures, we conducted analysis of outcomes at completion of the intervention.

Cluster‐randomised trials

We included cluster‐randomised trials in analyses along with individually randomised trials. We adjusted their[sample sizes or standard errors] using methods described in the Cochrane Handbook for Systematic Reviews of Interventions [Section 16.3.4 or 16.3.6] and provided an estimate of the intracluster correlation coefficient (ICC) derived from trial data (if possible), from a similar trial, or from a study of a similar population. If we used ICCs from other sources, we reported this and conducted sensitivity analyses to investigate effects of variation in the ICC. If we identified both cluster‐randomised and individually randomised trials, we planned to synthesise relevant information. We considered it reasonable to combine results from both types of trials if we noted little heterogeneity between study designs, and if we considered interaction between effects of the intervention and choice of the randomisation unit unlikely. We also acknowledged heterogeneity in the randomisation unit and performed a subgroup analysis to investigate effects of the randomisation unit.

Dealing with missing data

We contacted investigators or study sponsors to verify key study characteristics and to obtain missing numerical outcome data when possible (e.g. when we identified a study in abstract format only). We documented all correspondence with trialists and reported in the full report which trialists responded. When it was unclear whether an intention‐to‐treat (ITT) analysis was performed, we contacted trial authors to request confirmation. In most cases, we obtained extracted data directly from the study itself; these data may represent available case data only. If possible, we calculated data using methods that enable this (e.g. if standard deviations are missing, it may be possible to calculate these from confidence intervals, standard errors, t values, or the like, using methods outlined in Higgins 2011, Section(s) 7.7.3.2 and 7.7.3.3). We sought statistical advice on imputation and attempted this only if most trials in the meta‐analysis provided complete statistics (Higgins 2011).

Assessment of heterogeneity

We investigated heterogeneity between studies by using the I² statistic (I² greater than or equal to 50% was considered indicative of heterogeneity). We formally tested heterogeneity by examining the P value of the I² statistic. When determining the importance of heterogeneity, we took into account the magnitude and direction of effects; and the strength of evidence for heterogeneity (the P value from the Chi² test or the width of the confidence interval for the I² statistic).

We interpreted the I² statistic as follows.

10% to 40%: might not be important.
30% to 60%: may represent moderate heterogeneity.
50% to 90%: may represent substantial heterogeneity.
75% to 100%: considerable heterogeneity.

When we detected heterogeneity greater than 75%, we rechecked the data and if necessary contacted study authors to confirm the accuracy of data as reported in the journal article.

Assessment of reporting biases

Reporting biases arise when dissemination of research findings is influenced by the nature and direction of results (Higgins 2011). We investigated potential biases of publication using the funnel plot or another analytical method (Egger 1997). If we included 10 or more studies in the meta‐analysis, we investigated reporting biases (such as publication bias) by assessing funnel plot asymmetry visually. If asymmetry was suggested by visual assessment, we explored possible reasons by performing the tests proposed in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Data synthesis

We used a random‐effects model to pool the results of all studies because this model is more conservative than a fixed‐effect model, and it incorporates both within‐study and between‐study variance. This change from the original protocol was due to the heterogeneity of studies.

If data were not reported in a form that would allow inclusion in the meta‐analysis, we reported the findings narratively.

Subgroup analysis and investigation of heterogeneity

Effects of acupuncture may be influenced by mode of stimulation and style of acupuncture administered. We planned to undertake prespecified subgroup analysis to examine effects of the mode of acupuncture stimulation used (i.e. manual, electro‐acupuncture, or laser); and different acupuncture styles applied (e.g. classical/traditional acupuncture vs single‐point therapy, auricular acupuncture). We also planned to conduct a subgroup analysis of different forms of acupuncture by using a classification of invasive and non‐invasive controls that may be influenced by bias derived from unblinding and physiological activity.

When we identified other psychological and pharmacological interventions, we planned to conduct subgroup analysis for the control groups (i.e. CBT vs BT or TCA vs SSRI). We planned to conduct other subgroup analyses to explore effects of treatment among people with different diagnoses (e.g. major depression, dysthymia) and people of different ages (< 65 years and ≥ 65 years).

We planned to conduct an a posteriori subgroup analysis to examine effects of the number of acupuncture treatment sessions provided (< 20 sessions and ≥ 20 sessions) and another analysis to examine outcomes of clinician‐rated versus self‐rated depression scales. We were unable to perform any of the subgroup analyses planned, as all subgroups included too few studies (fewer than five studies).

Sensitivity analysis

A priori, we planned to perform sensitivity analyses of results to look at the possible contribution of:

excluding trials that did not clearly report the randomisation process;
excluding trials with unclear concealment of random allocation; and
excluding trials reporting dropout greater than 20%.

We planned to perform an a posteriori sensitivity analysis to examine the contribution of overall trial quality by excluding trials rated as having overall high risk. We defined trials as having overall high risk if they had high risk of bias in any two or more domains. We defined trials as having overall low risk if they had low risk of bias for randomisation, allocation, and both performance and detection blinding.

'Summary of findings' tables

We prepared 'Summary of findings' tables using GRADEproGDT. These tables present the overall quality of the body of evidence for five comparisons reporting on primary review outcomes at completion of the intervention (severity of depression, adverse events), according to GRADE criteria (study limitations, consistency of effect, imprecision, indirectness, and publication bias). We justified, documented, and incorporated into reporting of results judgements about evidence quality (high, moderate, low) for each outcome.

Results

Description of studies

Results of the search

In total, we retrieved 559 articles through updated searches, and 559 remained after de‐duplication. Two review authors (CS, HM) read the titles and abstracts of all articles retrieved in English, one review author read those provided in Korean (MSL), and another review author read those written in Chinese (LQW). Another review author (PH) resolved discrepancies. We excluded 268 articles on the basis of title or abstract and retained 291 articles for inspection of the full‐text article for eligibility. We excluded a total of 227 studies after reading the full text; we have included in the Excluded studies section only studies reviewed on the basis of title or abstract that did not meet the review inclusion criteria. We included 34 new trials and excluded another 42 studies.

The previous version of this review included 30 trials and excluded 11 trials. See Characteristics of included studies, Characteristics of excluded studies, Characteristics of studies awaiting classification, and Characteristics of ongoing studies. This update includes 64 studies with 7104 participants and excludes 53 studies. See Figure 1.

Included studies

Design

All trials used a parallel‐group design, 43 trials included two groups (acupuncture plus a control group), and 21 trials included three groups. We adjusted the unit of analysis for trials including multiple groups on the basis of the description of study methods provided.

Control groups varied between studies according to the research question. A total of 43 trials used medication alone, and four used control acupuncture combined with medication. Two trials used counselling, one trial usual care, and three trials a wait list. Control acupuncture groups included in four trials used sham inactive laser or electro‐acupuncture technique, four used the non‐invasive placebo sham needle, and three used both minimal and sham types of acupuncture.

Sample size

Sample sizes of studies included in this review ranged from 19 in Whiting 2008 to 755 in MacPherson 2013, with a median of 75 participants in each study.

Setting

A total of 51 studies were undertaken in China, three in the USA, three in Hong Kong, three in Germany, two in Australia, and two in the United Kingdom. Eleven studies recruited participants from both inpatient and outpatient hospital settings, 20 from inpatient settings, 16 from outpatient settings only, and six from the community via advertising or primary care settings; in 11 trials, the setting was unclear.

Participants

Trials recruited participants who met the diagnostic criteria for depression, or who had a clinical presentation of depression as defined by trial authors. Thirteen trials used the DSM (II, III, IV, or V), 33 used the CCMD (2 or 3), and eight used ICD Tenth Revision (ICD‐10) criteria. Ten trials recruited participants on the basis of a clinical presentation of depression. Two trials recruited participants only on the basis of BDI scores ≥ 12, and four used HAMD scores alone. Two trials used the Zung Self‐rating Depression Scale (SDS), one used the Clinical Interview Schedule Revised (CIS‐R; Whiting 2008), and one used Chinese Neuroscience Society diagnostic guidelines (He 2005). Inclusion criteria in addition to ICD‐10, DSM, or CCMD diagnosis were specified as HAMD score > 18 in 29 trials and HAMD score < 18 in five trials; remaining trials did not report a specific required HAMD score for entry.

Interventions

Trials delivered acupuncture that varied in terms of point selection, frequency of treatment, and total number of treatments administered. Most trials (46) used a standardised treatment protocol with a fixed selection of points administered at each acupuncture session. Selection of points varied and included acupuncture points located on arms, legs, abdomen, and head. Fourteen trials used a semi‐standardised treatment protocol consisting of a predefined set of acupuncture points used in combination with acupuncture points selected on the basis of diagnosis and identification of symptomatic patterns. Four trials administered individualised treatment for study participants on the basis of their diagnosis.

A total of 42 trials reported needling duration between 20 and 30 minutes. Needling duration was 30 to 60 minutes in 10 trials. Twelve trials provided no or unclear details.

Three trials provided fewer than 10 sessions, 19 trials between 12 and 18 sessions, and 38 trials between 21 and 60 sessions; four trials did not report the number of sessions. Included trials provided a median of 30 sessions.

One trial provided twice‐daily treatment (He 2007), and 12 trials reported daily treatment. Nineteen trials treated participants five or six days per week. Twenty‐six trials treated participants one to three times a week, and in six trials, treatment frequency was unclear. Some trials started with more frequent treatments before reducing frequency to weekly sessions.

Twenty‐five trials were of six weeks' duration, 17 were of six and a half to 12 weeks' duration, and 17 were of less than six weeks' duration. Duration of treatment was unclear in five trials.

Most trials (42) used manual acupuncture, 13 used electro‐acupuncture, seven used a combination of manual and electro‐acupuncture, and two used laser acupuncture.

Outcomes

Most trials assessed depression using HAMD as the primary outcome measure. Fifty‐four trials used HAMD as the primary outcome measure. Two trials used BDI as the primary outcome, two used CGI‐S, two used SDS, one used Symptom Checklist‐90 (SCL‐90), one used PHQ‐9, and two used a custom scale.

Excluded studies

We excluded 53 trials (see Characteristics of excluded studies). Fourteen studies did not meet the inclusion criteria for the control group (as specified in the methods) owing to a suboptimal dose of medication, lack of a suitable comparison group (as outlined under Types of interventions), or the fact that a non‐specified control group was used. Twenty trials provided data from participants who did not meet the diagnosis for depression. Three trials were duplicate publications in another language or used the same data set as included trials. One trial examined the effect of acupuncture on autonomic function in patients with depression or anxiety, and one trial examined the effect of acupuncture on menopausal symptoms in women with depression. Neither of these studies treated or evaluated the effect of acupuncture on depression. Three trials were quasi‐randomised; five used an intervention that was combined with another active intervention such as herbs; and six were identified as not randomised. We have presented further background information on these trials in the Characteristics of excluded studies section.

Ongoing studies

We identified 14 trials from clinical trial registries as ongoing (see Characteristics of ongoing studies).

Studies awaiting classification

We classified 17 trials as awaiting classification. Fourteen trials were awaiting confirmation of randomisation details, results of two studies were not available, the diagnosis was unclear in one study, and details of treatment required clarification in another trial (see Studies awaiting classification).

New studies found at this update

This update includes 34 new trials (Andreescu 2011;Bosch 2015;Chung 2015;Du 2005;Duan 2011;Fan 2013;Feng 2011;Fu 2006;He 2012;Huang 2013;Li 2008;Li 2011b;Lin 2012;Liu 2006;Liu 2013a; Liu 2015;Lv 2015;Ma 2011;Ma 2012;MacPherson 2013;Pei 2006;Qiao 2007;Qu 2013;Quah‐Smith 2013;Sun 2010;Sun 2013;Sun 2015b;Wang 2014;Wang 2015;Xiao 2014;Xu 2011;Yeung 2011b;Zhang 2005a;Zhang 2007a;Zhang 2009;Zhang 2012), for a total of 64 included trials. We excluded 42 trials since the last update (Arvidsdotter 2014; Bennett 1997; Bergmann 2014; Bin 2007; Carvalho 2013; Chang 2009; Chang 2010, Cocchi 1977; Deng 2013; Dormaemen 2011; Duan 2009;Fan 2015b;Guo 2009;He 2011; Hmwe 2015; Honda 2012; Hou 1996; Hu 2013; Huang 2003;Huo 2013; Khang 2002; Kim 2015; Li 2011; Liu 2013;Man 2014; Mischoulon 2012; Niu 2006; Shi 2014;Sun 2012; Tang 2003b; Tse 2010; Wang 2003; Wang 2006; Wang 2015; Wu 2010; Xie 2009; Xie 2012; Yeung 2011; Zhang 2004; Zhang 2004b; Zhao 2014; Zhou 2015), for a total of 53 excluded trials.

Risk of bias in included studies

See Figure 2 and Figure 3 for a graphical summary of risk of bias assessments performed by review authors for the 64 included studies, based on the seven risk of bias domains. Trial authors described three trials as having low risk of bias for all domains (Andreescu 2011;Chung 2015; Yeung 2011b). Four trials were at low risk of bias for five domains.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Review authors' judgements about each 'risk of bias' domain for each included study.

Investigators described all trials as randomised.

Allocation

Using Cochrane criteria that rate the adequacy of random allocation concealment, we rated most trials as having low risk (75%; n = 48) and rated no trials as having high risk of bias.

A total of 22 trials used a randomisation sequence that was computer generated, 30 used random tables, two used lot drawing, and Quah‐Smith 2005 used coded beans.

A total of 18 trials assessed allocation concealment as being at low risk of bias; in most trials (46), this was unclear. Five trials performed central randomisation, and 11 trials reported using sealed opaque envelopes. Forty‐six trials did not report the method of allocation, or we assessed their risk as unclear.

Blinding

We assessed blinding as providing low risk of performance bias in 14 trials. Most trials involved comparisons of acupuncture versus medication and could not be blinded; this contributed to assessment of high risk. We assessed a total of 48 trials as having high risk for performance bias. For studies comparing acupuncture versus a sham or placebo acupuncture control, we sought evidence of verification of blinding of participants. We rated 10 trials as having low risk of detection bias. Most trials (35) did not report on blinding of the assessor/clinician or the analyst or used patient‐reported outcome measures.

Incomplete outcome data

We assessed most (37) trials as having low risk of bias for outcome reporting. Eight trials were at high risk owing to dropout or incomplete data ,and reporting bias was unclear in 19 trials. We rated trials as having high risk of bias if dropout rates were uneven between groups and the reason for dropout was related or suspected to be related to group allocation. We also rated trials as having high risk for bias if investigators reported a dropout rate > 20% and did not report how they dealt with this (e.g. ITT analysis, last observation carried forward).

Selective reporting

We rated risk of bias from selective reporting as unclear for most trials owing to no available study protocol. We rated two trials as having high risk of bias and found that Li 2007 did not report data on all included outcomes.

Other potential sources of bias

Risk of bias was unclear for most trials (31). We rated risk from other sources of bias as low for 29 trials. We assessed an imbalance at randomisation in eight trials (Allen 1998;Ding 2003;Fan 2005;Fu 2008;Luo 1988;Luo 1998;Whiting 2008;Xiujuan 1994). We rated trials at high risk of bias if we noted significant baseline imbalance between groups, and at unclear risk if trial authors did not report a baseline analysis.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4; Table 5

Summary of findings for the main comparison. Acupuncture compared with no treatment/wait list/treatment as usual for depression.

Acupuncture compared with no treatment/wait list/treatment as usual for depression
Patient or population: clinical diagnosis of depression  Setting: community/outpatient/inpatient  Intervention: acupuncture  Comparison: no treatment/wait list/treatment as usual
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Risk with no treatment/wait list/treatment as usual	Risk with acupuncture
Severity of depression at the end of treatment  assessed with various clinician‐rated and self‐rated outcome measures (lower score indicates less severe depression)		SMD 0.66 lower  (1.06 lower to 0.25 lower)	‐	488  (5 RCTs)	⊕⊕⊝⊝  LOW^a,b	As a rule of thumb, 0.2 SMD represents a small difference, 0.5 moderate, and 0.8 large.
Adverse events	Study population		RR 0.89  (0.35 to 2.24)	302  (1 RCT)	⊕⊕⊝⊝  LOW^c,d
	60 per 1000	53 per 1000  (21 to 134)
Quality of life (physical)	‐	‐	‐	‐	‐	Cannot estimate the effect of acupuncture as no studies reported on this outcome
Quality of life (emotional)	‐	‐	‐	‐	‐	Cannot estimate the effect of acupuncture as no studies reported on this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference.
GRADE Working Group grades of evidence.  High quality: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Acupuncture compared with control acupuncture for depression
Patient or population: clinical diagnosis of depression  Setting: community/outpatient/inpatient  Intervention: acupuncture  Comparison: control acupuncture
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Risk with control acupuncture	Risk with acupuncture
Severity of depression at the end of the intervention as measured by the Hamilton Depression Rating Scale (HAMD) scored from 0 to 54 (lower score indicates less severe depression)	In the study population, average severity of depression at the end of treatment was 11.4 in clinician‐rated HAMD scores.	MD 1.69 lower  (3.33 lower to 0.05 lower)	‐	841  (14 RCTs)	⊕⊕⊝⊝  LOW^a,b
Adverse events	Study population		RR 1.63  (0.93 to 2.86)	300  (5 RCTs)	⊕⊕⊕⊝  MODERATE^c
	162 per 1000	264 per 1000  (151 to 463)
Quality of life (physical) at the end of treatment (higher scores indicate greater quality of life)	Mean quality of life (physical) at the end of treatment was 37.	MD 5.12 lower  (10.38 lower to 0.13 higher)	‐	150  (1 RCT)	⊕⊕⊝⊝  MODERATE^d
Quality of life (emotional) at the end of treatment (higher scores indicate greater quality of life)	Mean quality of life (emotional) at the end of treatment was 44.6.	MD 2.25 lower  (5.89 lower to 1.39 higher)	‐	167  (2 RCTs)	⊕⊕⊕⊝  MODERATE^e
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; HAMD: Hamilton Depression Rating Scale; MD: mean difference; RCTs: randomised controlled trials; RR: risk ratio.
GRADE Working Group grades of evidence.  High quality: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Acupuncture compared with medication for depression
Patient or population: clinical diagnosis of depression  Setting: community/outpatient/inpatient  Intervention: acupuncture  Comparison: medication
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Outcomes	Risk with medication	Risk with acupuncture	Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Severity of depression at the end of treatment  assessed with various clinician‐rated and self‐rated outcome measures (lower score indicates less severe depression)		SMD 0.23 lower  (0.4 lower to 0.05 lower)	‐	3127  (31 RCTs)	⊕⊝⊝⊝  VERY LOW^a,b	As a rule of thumb, 0.2 SMD represents a small difference, 0.5 moderate, and 0.8 large.
Adverse events (measured with Asberg Antidepressant Side Effect Scale)	Mean number of adverse events was 6.2.	MD 4.32 lower  (7.41 lower to 1.23 lower)	‐	481  (3 RCTs)	⊕⊝⊝⊝  VERY LOW^c,d
Quality of life (physical)	‐	‐		No studies reported on this outcome.	‐	Cannot estimate the effect of acupuncture as no studies reported on this outcome
Quality of life (emotional)	‐	‐		No studies reported on this outcome.	‐	Cannot estimate the effect of acupuncture as no studies reported on this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; MD: mean difference; RCTs, randomised controlled trials; SMD: standardised mean difference.
GRADE Working Group grades of evidence.  High quality: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Acupuncture plus medication compared with medication for depression
Patient or population: clinical diagnosis of depression  Setting: community/outpatient/inpatient  Intervention: acupuncture plus medication  Comparison: medication
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Outcomes	Risk with medication	Risk with acupuncture plus medication	Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Severity of depression at the end of treatment  assessed with various clinician‐rated and self‐rated outcome measures (lower score indicates less severe depression)		SMD 1.15 lower  (1.63 lower to 0.66 lower)	‐	813  (11 RCTs)	⊕⊝⊝⊝  VERY LOW^a,b	As a rule of thumb, 0.2 SMD represents a small difference, 0.5 moderate, and 0.8 large.
Adverse events (measured with Asberg Antidepressant Side Effect Scale and Toxic Exposure Surveillance System)		SMD 1.32 lower  (2.86 lower to 0.23 higher)	‐	200  (3 RCTs)	⊕⊝⊝⊝  VERY LOW^c,d	As a rule of thumb, 0.2 SMD represents a small difference, 0.5 moderate, and 0.8 large.
Quality of life (physical) at the end of treatment (higher scores indicate greater quality of life)	Quality of life (physical) score in the single included study was 14.9.	MD 1.19 higher  (0.33 higher to 2.05 higher)	‐	127  (1 RCT)	⊕⊝⊝⊝  VERY LOW^e,f
Quality of life (emotional) at the end of treatment (higher scores indicate greater quality of life)	Mean quality of life (emotional) score was 17.2.	MD 0.25 higher  (0.9 lower to 1.4 higher)	‐	219  (2 RCTs)	⊕⊝⊝⊝  VERY LOW^f,g
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; MD: mean difference; RCTs: randomised controlled trials; SMD: standardised mean difference.
GRADE Working Group grades of evidence.  High quality: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Acupuncture compared with psychological therapy for depression
Patient or population: clinical diagnosis of depression  Setting: community  Intervention: acupuncture  Comparison: psychological therapy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Risk with psychological therapy	Risk with acupuncture
Severity of depression at the end of treatment as measured by self‐rated depression scores (lower score indicates less severe depression)		SMD 0.5 lower  (1.33 lower to 0.33 higher)	‐	497  (2 RCTs)	⊕⊕⊝⊝  LOW^a,b	As a rule of thumb, 0.2 SMD represents a small difference, 0.5 moderate, and 0.8 large.
Adverse events measured during study treatment	Study population		RR 0.62  (0.29 to 1.33)	453  (1 RCT)	⊕⊕⊝⊝  LOW^c,d
	86 per 1000	53 per 1000  (25 to 115)
Quality of life (physical)	‐	‐	‐	No studies reported on this outcome.	‐	Cannot estimate the effect of acupuncture as no studies reported on this outcome
Quality of life (emotional)	‐	‐	‐	No studies reported on this outcome.	‐	Cannot estimate the effect of acupuncture as no studies reported on this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; RCTs: randomised controlled trials; RR: risk ratio; SMD: standardised mean difference.
GRADE Working Group grades of evidence.  High quality: We are very confident that the true effect lies close to that of the estimate of the effect.  Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.  Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Date	Event	Description
14 December 2016	New citation required and conclusions have changed	The previous version of this review did not show evidence of benefit for acupuncture. Low‐quality evidence now suggests a small reduction in severity of depression with acupuncture compared with no treatment/wait list/treatment as usual and control acupuncture.
12 October 2016	New search has been performed	34 new studies have been added.

Date	Event	Description
14 December 2009	Amended	Slight clarification and copyediting provided for the 'Acknowledgements' section of the review
26 April 2009	New citation required and conclusions have changed	New search undertaken and review updated
1 November 2008	Amended	Review converted to new format
24 February 2005	Amended	Minor updates provided
17 March 2004	New citation required and conclusions have changed	Substantive amendments made

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment	5	488	Std. Mean Difference (IV, Random, 95% CI)	‐0.66 [‐1.06, ‐0.25]
1.1 Manual acupuncture	5	458	Std. Mean Difference (IV, Random, 95% CI)	‐0.56 [‐0.98, ‐0.15]
1.2 Electro‐acupuncture	1	30	Std. Mean Difference (IV, Random, 95% CI)	‐1.26 [‐2.10, ‐0.43]
2 Adverse events	1	302	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.35, 2.24]
2.1 Manual acupuncture	1	302	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.35, 2.24]
3 Severity of depression during treatment	2	137	Mean Difference (IV, Random, 95% CI)	‐6.75 [‐9.12, ‐4.38]
3.1 Manual acupuncture	2	107	Mean Difference (IV, Random, 95% CI)	‐7.04 [‐11.08, ‐3.00]
3.2 Electro‐acupuncture	1	30	Mean Difference (IV, Random, 95% CI)	‐6.24 [‐9.86, ‐2.62]
4 Severity of depression 0‐6 months after treatment	1	237	Mean Difference (IV, Random, 95% CI)	‐1.90 [‐3.01, ‐0.79]
4.1 Manual acupuncture	1	237	Mean Difference (IV, Random, 95% CI)	‐1.90 [‐3.01, ‐0.79]
5 Severity of depression 6‐12 months after treatment	1	235	Mean Difference (IV, Random, 95% CI)	‐1.0 [‐2.53, 0.53]
5.1 Manual acupuncture	1	235	Mean Difference (IV, Random, 95% CI)	‐1.0 [‐2.53, 0.53]
6 Remission of depression	2	94	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.77, 3.65]
6.1 Manual acupuncture	2	94	Risk Ratio (M‐H, Random, 95% CI)	1.67 [0.77, 3.65]
7 Change in use of medication at the end of treatment	1	302	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.73, 1.14]
7.1 Manual acupuncture	1	302	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.73, 1.14]
8 Dropout from treatment	1	302	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.21, 4.88]
8.1 Manual acupuncture	1	302	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.21, 4.88]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of the intervention	14	841	Mean Difference (IV, Random, 95% CI)	‐1.69 [‐3.33, ‐0.05]
1.1 Manual acupuncture vs invasive control	7	418	Mean Difference (IV, Random, 95% CI)	‐2.97 [‐6.26, 0.31]
1.2 Electro‐acupuncture vs invasive control	5	251	Mean Difference (IV, Random, 95% CI)	0.43 [‐0.54, 1.40]
1.3 Electro‐acupuncture vs non‐invasive electro‐control	2	99	Mean Difference (IV, Random, 95% CI)	0.17 [‐2.14, 2.48]
1.4 Laser acupuncture vs non‐invasive control	2	73	Mean Difference (IV, Random, 95% CI)	‐5.51 [‐8.30, ‐2.73]
2 Adverse events	5	300	Risk Ratio (M‐H, Random, 95% CI)	1.63 [0.93, 2.86]
2.1 Manual acupuncture vs invasive control	1	17	Risk Ratio (M‐H, Random, 95% CI)	2.5 [0.15, 40.37]
2.2 Electro‐acupuncture vs invasive control	4	244	Risk Ratio (M‐H, Random, 95% CI)	1.79 [0.99, 3.25]
2.3 Electro‐acupuncture vs non‐invasive control	1	39	Risk Ratio (M‐H, Random, 95% CI)	0.4 [0.05, 3.08]
3 Severity of depression during treatment	6	413	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.81, 0.90]
3.1 Manual acupuncture vs invasive control	2	117	Mean Difference (IV, Random, 95% CI)	0.09 [‐2.55, 2.74]
3.2 Electro‐acupuncture vs invasive control	4	197	Mean Difference (IV, Random, 95% CI)	0.16 [‐0.92, 1.24]
3.3 Electro‐acupuncture vs non‐invasive control	2	99	Mean Difference (IV, Random, 95% CI)	‐0.45 [‐2.71, 1.80]
4 Severity of depression at 0‐6 months' follow‐up	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
4.1 Manual acupuncture vs invasive control	1	95	Mean Difference (IV, Random, 95% CI)	‐0.85 [‐0.98, ‐0.72]
5 Remission of depression	10	601	Risk Ratio (M‐H, Random, 95% CI)	1.91 [1.14, 3.21]
5.1 Manual acupuncture vs invasive control	5	368	Risk Ratio (M‐H, Random, 95% CI)	1.89 [0.75, 4.75]
5.2 Electro‐acupuncture vs invasive control	2	87	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.35, 4.29]
5.3 Electro‐acupuncture vs non‐invasive electro‐control	1	73	Risk Ratio (M‐H, Random, 95% CI)	2.15 [0.60, 7.67]
5.4 Laser acupuncture vs non‐invasive control	2	73	Risk Ratio (M‐H, Random, 95% CI)	3.00 [1.48, 6.09]
6 Quality of life (emotional) during treatment	1	150	Mean Difference (IV, Random, 95% CI)	‐1.98 [‐5.41, 1.45]
6.1 Electro‐acupuncture vs invasive control	1	90	Mean Difference (IV, Random, 95% CI)	‐2.09 [‐6.54, 2.36]
6.2 Electro‐acupuncture vs non‐invasive control	1	60	Mean Difference (IV, Random, 95% CI)	‐1.81 [‐7.18, 3.56]
7 Quality of life (emotional) at the end of treatment	2	167	Mean Difference (IV, Random, 95% CI)	‐2.25 [‐5.89, 1.39]
7.1 Manual acupuncture vs invasive control	1	17	Mean Difference (IV, Random, 95% CI)	‐5.0 [‐36.47, 26.47]
7.2 Electro‐acupuncture vs invasive control	1	90	Mean Difference (IV, Random, 95% CI)	‐2.55 [‐7.38, 2.28]
7.3 Electro‐acupuncture vs non‐invasive control	1	60	Mean Difference (IV, Random, 95% CI)	‐1.76 [‐7.38, 3.86]
8 Quality of life (physical) during treatment	1	150	Mean Difference (IV, Random, 95% CI)	‐0.99 [‐4.74, 2.77]
8.1 Electro‐acupuncture vs invasive control	1	90	Mean Difference (IV, Random, 95% CI)	‐2.62 [‐7.07, 1.83]
8.2 Electro‐acupuncture vs non‐invasive control	1	60	Mean Difference (IV, Random, 95% CI)	1.26 [‐4.12, 6.64]
9 Quality of life (physical) at the end of treatment	1	150	Mean Difference (IV, Random, 95% CI)	‐5.12 [‐10.38, 0.13]
9.1 Electro‐acupuncture vs invasive control	1	90	Mean Difference (IV, Random, 95% CI)	‐7.61 [‐12.38, ‐2.84]
9.2 Electro‐acupuncture vs non‐invasive control	1	60	Mean Difference (IV, Random, 95% CI)	‐2.23 [‐7.81, 3.35]
10 Change in medication	1	70	Mean Difference (IV, Random, 95% CI)	‐0.39 [‐1.71, 0.93]
10.1 Electro‐acupuncture vs non‐invasive control	1	70	Mean Difference (IV, Random, 95% CI)	‐0.39 [‐1.71, 0.93]
11 Dropout from treatment	7	501	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.62, 1.75]
11.1 Manual acupuncture vs invasive control	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.6 [0.16, 2.29]
11.2 Electro‐acupuncture vs invasive control	4	224	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.51, 2.02]
11.3 Electro‐acupuncture vs non‐invasive control	4	217	Risk Ratio (M‐H, Random, 95% CI)	1.48 [0.56, 3.91]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment	31	3127	Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.40, ‐0.05]
1.1 Manual acupuncture vs SSRI	16	1570	Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.50, 0.04]
1.2 Electro‐acupuncture vs SSRI	5	197	Std. Mean Difference (IV, Random, 95% CI)	‐0.47 [‐0.85, ‐0.10]
1.3 Manual acupuncture vs TCAs	3	397	Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐1.25, 0.69]
1.4 Electro‐acupuncture vs TCAs	5	801	Std. Mean Difference (IV, Random, 95% CI)	‐0.20 [‐0.42, 0.01]
1.5 Manual acupuncture vs other antidepressant	1	60	Std. Mean Difference (IV, Random, 95% CI)	‐0.22 [‐0.73, 0.29]
1.6 Electro‐acupuncture vs heterocyclic antidepressants	1	61	Std. Mean Difference (IV, Random, 95% CI)	0.30 [‐0.21, 0.80]
1.7 Electro‐acupuncture vs other antidepressant	1	41	Std. Mean Difference (IV, Random, 95% CI)	0.09 [‐0.52, 0.70]
2 Adverse events	3	481	Mean Difference (IV, Random, 95% CI)	‐4.32 [‐7.41, ‐1.23]
2.1 Manual acupuncture vs SSRI	3	481	Mean Difference (IV, Random, 95% CI)	‐4.32 [‐7.41, ‐1.23]
3 Severity of depression during treatment	9	552	Mean Difference (IV, Random, 95% CI)	‐1.67 [‐2.91, ‐0.43]
3.1 Manual acupuncture vs SSRI	5	340	Mean Difference (IV, Random, 95% CI)	‐1.38 [‐3.20, 0.45]
3.2 Electro‐acupuncture vs SSRI	3	112	Mean Difference (IV, Random, 95% CI)	‐2.58 [‐4.38, ‐0.78]
3.3 Manual acupuncture vs TCAs	1	100	Mean Difference (IV, Random, 95% CI)	‐0.80 [‐3.65, 2.05]
4 Severity of depression 0‐6 months after treatment	1	60	Mean Difference (IV, Random, 95% CI)	‐5.60 [‐7.60, ‐3.60]
4.1 Manual acupuncture vs other antidepressant medication	1	60	Mean Difference (IV, Random, 95% CI)	‐5.60 [‐7.60, ‐3.60]
5 Remission of depression	25	2918	Risk Ratio (M‐H, Random, 95% CI)	1.16 [1.05, 1.29]
5.1 Manual acupuncture vs SSRI	14	1332	Risk Ratio (M‐H, Random, 95% CI)	1.16 [0.98, 1.37]
5.2 Electro‐acupuncture vs SSRI	4	188	Risk Ratio (M‐H, Random, 95% CI)	1.28 [0.94, 1.75]
5.3 Manual acupuncture vs TCAs	4	620	Risk Ratio (M‐H, Random, 95% CI)	1.32 [1.03, 1.69]
5.4 Electro‐acupuncture vs TCAs	4	778	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.88, 1.21]
6 Dropout from treatment	5	246	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.20, 3.71]
6.1 Manual acupuncture vs SSRI	2	134	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.03, 2.47]
6.2 Electro‐acupuncture vs SSRI	3	112	Risk Ratio (M‐H, Random, 95% CI)	1.82 [0.43, 7.79]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment	11	813	Std. Mean Difference (IV, Random, 95% CI)	‐1.15 [‐1.63, ‐0.66]
1.1 Manual acupuncture plus SSRI vs SSRI	8	539	Std. Mean Difference (IV, Random, 95% CI)	‐1.32 [‐2.09, ‐0.55]
1.2 Electro‐acupuncture plus SSRI vs SSRI	5	274	Std. Mean Difference (IV, Random, 95% CI)	‐0.84 [‐1.16, ‐0.51]
2 Adverse events	3	200	Std. Mean Difference (IV, Random, 95% CI)	‐1.32 [‐2.86, 0.23]
2.1 Manual acupuncture plus SSRI vs SSRI	2	150	Std. Mean Difference (IV, Random, 95% CI)	‐0.37 [‐1.20, 0.47]
2.2 Electro‐acupuncture plus SSRI vs SSRI	1	50	Std. Mean Difference (IV, Random, 95% CI)	‐3.39 [‐4.27, ‐2.50]
3 Severity of depression during treatment	6	514	Std. Mean Difference (IV, Random, 95% CI)	‐1.60 [‐2.45, ‐0.76]
3.1 Manual acupuncture plus SSRI vs SSRI	6	432	Std. Mean Difference (IV, Random, 95% CI)	‐1.81 [‐2.83, ‐0.80]
3.2 Electro‐acupuncture plus SSRI vs SSRI	1	82	Std. Mean Difference (IV, Random, 95% CI)	‐0.70 [‐1.19, ‐0.21]
4 Remission of depression	9	618	Risk Ratio (M‐H, Random, 95% CI)	1.21 [0.85, 1.73]
4.1 Manual acupuncture plus SSRI vs SSRI	5	299	Risk Ratio (M‐H, Random, 95% CI)	1.33 [0.65, 2.73]
4.2 Electro‐acupuncture plus SSRI vs SSRI	5	273	Risk Ratio (M‐H, Random, 95% CI)	1.17 [0.75, 1.80]
4.3 Manual acupuncture plus heterocyclic antidepressant vs medication alone	1	46	Risk Ratio (M‐H, Random, 95% CI)	4.36 [0.53, 36.12]
5 Quality of life (physical)	1	127	Mean Difference (IV, Fixed, 95% CI)	1.19 [0.33, 2.05]
5.1 Manual acupuncture plus SSRI vs SSRI	1	64	Mean Difference (IV, Fixed, 95% CI)	1.40 [0.15, 2.65]
5.2 Electro‐acupuncture plus SSRI vs SSRI	1	63	Mean Difference (IV, Fixed, 95% CI)	1.0 [‐0.18, 2.18]
6 Quality of life (emotional)	2	219	Mean Difference (IV, Random, 95% CI)	0.25 [‐0.90, 1.40]
6.1 Manual acupuncture plus SSRI vs SSRI	2	111	Mean Difference (IV, Random, 95% CI)	0.10 [‐1.46, 1.65]
6.2 Electro‐acupuncture plus SSRI vs SSRI	2	108	Mean Difference (IV, Random, 95% CI)	0.35 [‐2.00, 2.70]
7 Change in use of medication	2	236	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.22, 0.67]
7.1 Manual acupuncture plus SSRI vs SSRI	2	154	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.20, 0.72]
7.2 Electro‐acupuncture plus SSRI vs SSRI	1	82	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.13, 1.30]
8 Dropout from treatment	5	426	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.35, 1.42]
8.1 Manual acupuncture plus SSRI vs SSRI	3	234	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.18, 1.15]
8.2 Electro‐acupuncture plus SSRI vs SSRI	3	192	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.43, 3.51]

Methods	Randomised controlled trial of 50 participants comparing manual acupuncture vs wait‐list control
Participants	Diagnosis: depression Method of diagnosis: ICD F33.2 Age: 48.68 years (experimental), 46.32 years (control) Participant information: 3 males, 22 females (experimental), 2 males 23 females (control) Location: Germany (psychiatric clinic) Inclusion/Exclusion: Inclusion criteria: not specified, apart from the diagnosis of depression Exclusion criteria: addiction (other than nicotine), epilepsy or other neurological disorders, other co‐morbid psychiatric disorders
Interventions	(1) Duration: 12 weeks (12 sessions) Frequency of treatment: 1/week Treatment protocol: TCM‐style acupuncture/manual acupuncture. Needles were retained for 60 minutes. Point selection was individualised with the following points being most common (% of all treatments): Hegu (LI4) (96%), Sanyinjiao (SP6) (96%), Yinlingquan (SP9) (96%), Shenmen (HT7) (95%), Taixi (KI3) (95%), Sishencong (EX‐HN1) (92%), Zusanli (ST36) (91%), Taichong (LR3) (78%), Quchi (LI11) (53%), Zhaohai (KI6) (53%), Guanyuan (CV4) (46%), Yanglingquan (GB34) (36%), Gongsun (SP4) (34%), Xuehai (SP10) (34%), and Lieque (LU7) (32%). All acupuncture was performed by a licensed Oriental medical practitioner with more than 5 years of clinical experience. (2) Duration: 12 weeks Frequency of treatment: N/A Treatment protocol: Wait‐list control
Outcomes	Time points for assessment: end of intervention Outcomes: Beck Depression Inventory (BDI)
Notes	ITT not undertaken
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number generator was used.
Allocation concealment (selection bias)	Unclear risk	This was not reported.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	No blinding was attempted.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Patient‐reported outcomes were used; therefore blinding was not applicable.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Dropout rate was high (> 20%).
Selective reporting (reporting bias)	Unclear risk	Insufficient details were provided.
Other bias	Unclear risk	Insufficient details were provided.

Methods	Randomised controlled trial of abdominal acupuncture vs electro‐acupuncture and standard care
Participants	Diagnosis: major depressive disorder Method of diagnosis: depression diagnosed by CCMD and DSM‐II Age: 60 to 85 years Participant information: 60 participants Location: inpatients at the Department of Neurology at the First Hospital Affiliated to Changchun China Inclusion/Exclusion: Inclusion criteria: cerebral infarction or cerebral haemorrhage; no history of depression or abuse of medication or alcohol and no known allergies to medications; no severe heart, lung, liver, or kidney disease; no loss of speech Exclusion criteria: history of mental disorders; taking antidepressants in past 2 weeks; severe depression; HAMD > 35; allergic to alcohol or medications; cardiovascular, cerebral, liver, kidney, or blood pathology conditions; do no meet inclusion criteria; not taking medication as advised or dropped out halfway; fainting during acupuncture; infection at acupuncture points
Interventions	(1) Duration: 6 weeks (21 treatments) Frequency of treatment: every second day Treatment protocol: The treatment group received abdominal acupuncture, with stimulation to acupuncture points CV12 Zhong Wan, CV10 Xia Wan, CV6 Qi Hai, CV4 Guan Yuan, ST24 Hua Rou Men (on both sides), ST26 Wai Ling, and Tai Heng. Acupuncture needles were inserted perpendicular to a depth before the muscle layer. Needles were inserted quickly ‐ only twirling no lifting, and de qi sensation was not obtained. Needles were left in for 30 minutes. Needles used were of the Hwato brand and were manufactured at Suzhouby Tai xin san lI medical product company, H model, 0.35 mm × 40 mm, 0.30 mm × 25 mm, 0.30 mm × 50 mm. (2) Duration: 6 weeks (21 treatments) Frequency of treatment: every second day Treatment protocol: Electro‐acupuncture to points DU 20 Baihui, DU24 Shen Ting, M‐HN‐3 Yintang, M‐NH‐1 Shishenchong, LIV 3 Taichong, and HT 7 Shenmen. Baihui was needled 1 cun parallel to the skin, Shenting was needled 0.5 cun parallel to the skin, Yintang was needled 0.5 cun parallel to the skin, Shishenchong was needled parallel to the skin, Taichong was needled perpendicular 0.5 to 1 cun, Shenmen was needled perpendicular 0.5 cun. The electro‐acupuncture machine was connected to needles administered at a frequent pulse frequency at 4 Hz and intermittent pulse at 20 Hz. Positive pulse amplitude at 50 V and negative pulse amplitude at 35 V. During treatment, patients should feel an achey numbness, a sensation of fullness, or twitching of muscle. Needles were left in for 30 minutes. Electro‐machine model GD6805X, manufactured by Xia xi san yuan medical equipment company, was used. (3) Duration: 6 weeks Frequency of treatment: treatment administered every second day. Treatment protocol: The control was standard care for stroke rehabilitation.
Outcomes	Time points for assessment: 2, 4, and 6 weeks after the start of the study Outcomes: Hamilton Depression Rating Scale (HAMD)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details of randomisation were provided.
Allocation concealment (selection bias)	Unclear risk	No information could be obtained from trial authors.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	The participant and the therapist were not blind.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	It was unclear whether analysts and assessing clinicians were blind to group allocation.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No losses to follow‐up were reported. Data on all participants were analysed.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	Data show no imbalance in randomisation at baseline between groups. The study appears free of other sources of bias.

Methods	Randomised controlled trial comparing 2 types of manual acupuncture with medication (fluoxetine)
Participants	Diagnosis: clinical depression Method of diagnosis: CCMD‐3, HAMD score ≥ 20 Age: not stated Participant information: 103 women Location: outpatient setting, China Inclusion/Exclusion: Exclusion criteria: schizophrenia; interstitial disease; physical illness that can cause symptoms of depression; schizophrenia and other psychotic disorders; heart, liver, and kidney system diseases; glaucoma
Interventions	(1) Duration: 6 weeks (42 sessions) Frequency of treatment: daily Treatment protocol: Harmonize spirit soothe liver acupuncture group Points needled: Baihui (DU20); Fengfu (DU16); Shuigou (DU26); Yintang (EX‐HN 3); Sishencong (EX‐HN 1);Taichong (LR 3); Ganshu (BL18) (2) Duration: 6 weeks (42 sessions) Frequency of treatment: daily Treatment protocol: Regular acupuncture group Points needled: Qimen (LV14); Taichong (LR 3); Yanglingquan (GB34); Zhigou (SJ6); Neiguan (PC6); Zusanli (ST36) (3) Duration: 6 weeks Frequency of treatment: daily treatment. Treatment protocol: Control group: fluoxetine 20 mg/d for 6 weeks
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD) SDS SCL‐90 Cured rate based on HAMD score
Notes	No ITT
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number table was used.
Allocation concealment (selection bias)	Unclear risk	This was not stated.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	No blinding was attempted.
Blinding of outcome assessment (detection bias)   All outcomes	High risk	No blinding was attempted.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Reason for missing outcome data is likely to be related to true outcomes, with imbalance in numbers or reasons for missing data across intervention groups.
Selective reporting (reporting bias)	Unclear risk	Reporting was insufficient.
Other bias	High risk	Sample size calculation was not provided.

Methods	Randomised controlled trial of electro‐acupuncture, medication (fluoxetine), and electro‐acupuncture plus medication
Participants	Diagnosis: clinical depression Method of diagnosis: CCMD‐3 and HAMD score of 20 to 35 Age: 18 to 60 years Participant information: 75 participants Location: inpatients or day patients at the Department of Neurology, PLA General Hospital, Beijing, China Inclusion/Exclusion: Inclusion criteria: history of severe neurological or physical disease, no history of mental illness; willingness to participate in this study Exclusion criteria: schizophrenia and other mental disorders; central nervous system organic disease; pregnancy or breastfeeding, or planning pregnancy during treatment; severe depression with HAMD score of 35; suicidal tendencies; known allergies to fluoxetine
Interventions	(1) Duration: 6 weeks (36 sessions) Frequency of treatment: 6/week Treatment protocol: Electro‐acupuncture plus medication. Acupuncture points Baihui DU 20, M‐HN‐3 Yintang were stimulated. Additional points were added based on differential patterns: Liver qi stagnation type add LIV3 Taichong, LI4 Hegu; Fire due to qi stagnation type add LIV2 Xing jian; Melancholy injuring the spirit type add Anmian, Shenmen HT7, Neiguan PC6; heart and spleen deficiency add SP6 Sanyinjiao, Zhusanl ST36; Yin deficiency with excess fire type add KD3 Taixi and KD6 Zhaohai. GV20 Baihu and DU24 Shen ting were connected to electro‐acupuncture machine model G 6805‐1, using continuous pulse, frequency set at 120 to 250 times per minute. Strength was set at a comfort level for the participant. Electro‐acupuncture was administered over 30 minutes, and needles were retained for 1 hour. Medication consisted of fluoxetine 20 mg per day, administered over 6 weeks. (2) Duration: 6 weeks (36 sessions) Frequency of treatment: 6/week Treatment protocol: Electro‐acupuncture only. Acupuncture points Baihui DU 20, M‐HN‐3 Yintang were stimulated. Additional points were added based on differential patterns: Liver qi stagnation type add LIV3 Taichong, LI4 Hegu; Fire due to qi stagnation type add LIV2 Xing jian; Melancholy injuring the spirit type add Anmian, Shenmen HT7, Neiguan PC6; heart and spleen deficiency add SP6 Sanyinjiao, Zhusanl ST36; Yin deficiency with excess fire type add KD3 Taixi and KD6 Zhaohai. GV20 Baihu and DU24 Shen ting were connected to electro‐acupuncture machine model G 6805‐1, using continuous pulse, frequency set at 120 to 250 times per minute. Strength was set at a comfort level for the participant. Electro‐acupuncture was administered over 30 minutes, and needles were retained for 1 hour. (3) Duration: 6 weeks Frequency of treatment: daily Treatment protocol: Medication only, fluoxetine 20 mg per day
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation sequence was computer generated.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was unclear.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Participants and therapists were not blind to group allocation.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Assessing clinicians were blind, but it was unclear whether analysts were blind to group allocation.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Five (6%) participants dropped out from the trial ‐ 2 in the medication group owing to side effects, 2 in the electro‐acupuncture group owing to work commitments and a family member death, and 1 in the acupuncture plus medication group owing to side effects attributed to the medication.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	No imbalances in randomisation were evident at baseline. The study appears free of other sources of bias.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment	2	497	Std. Mean Difference (IV, Random, 95% CI)	‐0.50 [‐1.33, 0.33]
1.1 Manual acupuncture	2	497	Std. Mean Difference (IV, Random, 95% CI)	‐0.50 [‐1.33, 0.33]
2 Adverse events	1	453	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.29, 1.33]
2.1 Manual acupuncture	1	453	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.29, 1.33]
3 Severity of depression 0‐6 months after treatment	1	453	Mean Difference (IV, Random, 95% CI)	0.5 [‐0.51, 1.51]
3.1 Manual acupuncture	1	453	Mean Difference (IV, Random, 95% CI)	0.5 [‐0.51, 1.51]
4 Severity of depression 6‐12 months	1	453	Mean Difference (IV, Random, 95% CI)	0.60 [‐0.80, 2.00]
4.1 Manual acupuncture	1	453	Mean Difference (IV, Random, 95% CI)	0.60 [‐0.80, 2.00]
5 Remission of depression	0		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
5.1 Manual acupuncture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Change in use of medication	1	453	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.61, 1.10]
6.1 Manual acupuncture	1	453	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.61, 1.10]
7 Dropout from treatment	1	453	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.08, 0.90]
7.1 Manual acupuncture	1	453	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.08, 0.90]

Methods	Single‐blind randomised controlled trial of acupuncture, non‐specific acupuncture, and a wait‐list control
Participants	Diagnosis: major depressive disorder Method of diagnosis: DSM‐IV Age: 18 to 45 years Participant information: 38 women Location: United States (community) Inclusion/Exclusion: Exclusion criteria: dysthymia or chronic depression, history of psychosis or mania, substance abuse, current treatment, endocrine abnormalities, history of central nervous system lesions or any medical condition causing depression, pregnancy, suicide potential
Interventions	(1) Duration: 8 weeks (12 sessions) Frequency of treatment: The intervention involved 2 sessions a week for the first 4 weeks, followed by 1 session a week thereafter. Treatment protocol: Acupuncture ‐ no details provided (2) Duration: 8 weeks (12 sessions) Frequency of treatment: The intervention involved 2 sessions a week for the first 4 weeks, followed by 1 session a week thereafter. Treatment protocol: Non‐specific acupuncture ‐ no details provided (3) Duration: 8 weeks Frequency of treatment: N/A Treatment protocol: The wait list control received acupuncture at 8 weeks.
Outcomes	Time points for assessment: baseline, 8 and 16 weeks Outcomes: Hamilton Depression Rating Scale (HAMD) Beck Depression Inventory (BDI)
Notes	A power calculation was not reported.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was computer generated.
Allocation concealment (selection bias)	Low risk	Randomisation was undertaken centrally.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Participants in the 2 acupuncture groups and the therapist were blind. It remains possible that the acupuncture therapists developed some awareness between treatments.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	The assessing clinician was blind. It was unclear whether the analyst was blind.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Five women dropped out (13%) ‐ 2 from the acupuncture group, 2 from non‐specific acupuncture, and 1 from wait‐list control.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Unclear risk	Insufficient information was presented to examine other sources of bias, for example, imbalance at randomisation.

Methods	Acupuncture vs control acupuncture
Participants	Diagnosis: major depressive disorder Method of diagnosis: DSM‐IV and SCID with score > 14, mild to moderate depression Age: not stated Participant information: 53 participants Location: University of Pittsburgh Medical Center (UPMC) Shadyside, Center for Complementary Medicine, Pittsburgh, Pennsylvania, USA Inclusion/Exclusion: Exclusion criteria: severe MDD, suicidal, seizure disorder, psychosis, bipolar disorder, chronic MDD (i.e. duration > 2 years), treatment‐resistant MDD, history of substance abuse within past 6 months
Interventions	All medication was tapered before randomisation and participants remained free of psychotropic medication during the study. No other interventions were used. (1) Duration: 6 weeks (12 sessions) Frequency of treatment: 2/week Treatment protocol: Each session was administered over 30 minutes. Points Du 20 and Yingtang were needled. Electro‐acupuncture (EA) was administered. 0.22 × 30 mm needles were inserted. Electro‐stimulator 4C connected current 3 to 5 mA had a frequency of 2 Hz. Treatment was administered by a practitioner with 4 years of training who had completed Masters of Acupuncture and TCM and was certified by NCCAOM, had been in practice for 5 years, and had clinical practice with treatment of patients with anxiety and depression. (2) Duration: 6 weeks (12 sessions) Frequency of treatment: 2/week Treatment protocol: Control group: non‐scalp points with sham EA. Needles were inserted at 2 points away from classical points near channels, and no current was applied to the needle. Needles were inserted obliquely to 1 cm.
Outcomes	Time points for assessment: unclear for HAMD, weekly for side effects rating scale; SF‐36 2 weeks post intervention Outcomes: Hamilton Depression Rating Scale (HAMD) Comparison of responders in each group defined as a score ≤ 10 with relative decrease of 50% from baseline Side effects rating scale SF‐36
Notes	ITT was undertaken.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence was used.
Allocation concealment (selection bias)	Low risk	Envelopes were sealed/opaque.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Blinding of participants and key study personnel was ensured; it is unlikely that blinding could have been broken.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	The trained research associate undertaking measurement was blind.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Reasons for missing outcome data were unlikely to be related to true outcomes (for survival data, censoring was unlikely to introduce bias). Treatment group: 4 were attrition, 1 could not be contacted, 2 preferred a different treatment regimen, 1 withdrew owing to physical health. Control group: All 3 could not be contacted.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	The study appears free of other sources of bias.

Methods	Electro‐acupuncture vs minimal acupuncture vs control acupuncture controlled trial
Participants	Diagnosis: major depressive disorder Method of diagnosis: DSM‐IV and clinician assessment via structured interview Age: not stated Participant information: 150 participants Location: 4 regional psychiatric outpatient clinics in Hong Kong Inclusion/Exclusion: Inclusion criteria: age 18‐70 years, insomnia >3 nights /week for last 3 months, Insomnia severity index score >15, fixed dose of antidepressants in last 3 months Exclusion criteria: HAMD score > 18, apnoea hypopnoea index ≥ 10 or periodic limb movement disorder ≥ 15, significant suicidal risk, previous diagnosis of schizophrenia, psychotic disorder, bipolar disorder, alcoholism, substance abuse, pregnancy or breastfeeding, infection close to acupuncture points, serious illness, acupuncture in previous 12 months, CHM within 2 weeks before baseline measurements, increased dose of hypnotics within 4 weeks of baseline measures
Interventions	Acupuncture experience of person administering treatment: registered acupuncturist with at least 3 years' experience (1) Duration: 3 weeks (9 sessions) Frequency of treatment: 3/week Treatment protocol: TCM‐style acupuncture. Choice of points used: bilateral ear shenmen, Sishencong Anmian, PC6, Ht7, SP6 Yintang GV20 Mode of stimulation:depth of insertion 2 to 25 mm. De qi obtained if possible. Electro‐stimulator attached to all needles, current 0.4 ms at 4 Hz needles left for 30 minutes (2) Duration: 3 weeks (9 sessions) Frequency of treatment: 3/week Treatment protocol: Minimal: at points thought to have no effect and avoidance of de qi. Points on forearm 1 inch lateral to HE3 and HE7, I inch lateral to Lu3, and 0.5 inch dorsal to GB29, pony forehead, and ear. Electro‐stimulator the same (3) Duration: 3 weeks (9 sessions) Frequency of treatment: 3/week Treatment protocol: Placebo: Streitberger placebo needle placed at 1 inch beside acupuncture points used in acupuncture group connected to electro‐stimulator with no current
Outcomes	Time points for assessment: Outcome assessment at 1 and 5 weeks post treatment Adverse events assessed after 3rd, 6th, and 9th treatments Outcomes: Hamilton Depression Rating Scale (HAMD) Secondary outcomes: quality of life based on SF‐36
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated assignment was used.
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes were used.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Blinding of participants and key study personnel was ensured, and it is unlikely that the blinding could have been broken. Credibility and blinding of treatment were assessed.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Study personnel were blinded.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Missing outcome data were balanced in numbers across intervention groups, with similar reasons provided for missing data across groups; 16 (10%) dropped out during treatment, and 18 (12%) withdrew at 5 weeks.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	The study appears free of other sources of bias.

Methods	Acupuncture vs medication (fluoxetine)
Participants	Diagnosis: post‐stroke depression Method of diagnosis: Diagnoses were based on DSM‐II‐R and HAMD scales. Age: not stated Participant information: 62 participants Location: Beijing Hospital of Integration of Chinese and Western Medicine, China Inclusion/Exclusion: Exclusion criteria: none specified
Interventions	(1) Duration: unclear (40 sessions) Frequency of treatment: daily for 10 days, then 2‐ to 3‐day break Treatment protocol: Acupuncture points on the Du meridian were needles including DU 20 Baihui, DU 24 Shenting, DU 16 Feng fu. Additional points were used including PC6 Neiguan (both sides), LI4 Hegu (both sides), GB20 Feng chi (both sides). Needles of 30 gauge 1 to 1.5 cun (Chinese unit of measurement) long were used, needled to a depth of 0.5 to 1 cun. Needles were manipulation using reinforcing reducing method. Once de qi was obtained, needles were left in for 30 minutes. (2) Duration: 60 days Frequency of treatment: daily Treatment protocol: The control group received medication including fluoxetine 20 mg/d for 60 days.
Outcomes	Time points for assessment: before treatment, 30 days into treatment, 60 days into treatment Outcomes: Hamilton Depression Rating Scale (HAMD)
Notes	Two participants dropped out owing to adverse effects.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation schedule was computer generated.
Allocation concealment (selection bias)	Unclear risk	No information could be obtained from the trial author.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	The study participant and the therapist were not blind.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	It was unclear whether the assessing clinician(s) and the analyst were blind to the study group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Two participants (1 from each group) were excluded post randomisation with no details reported. Data on primary outcome were available for 60 participants.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Unclear risk	It was unclear whether baseline characteristics were comparable.

Methods	Three‐arm randomised controlled trial of electro‐acupuncture vs acupuncture vs medication (fluoxetine) among participants with post‐stroke depression
Participants	Diagnosis: post‐stroke depression Method of diagnosis: depression according to DSM‐IV, CCMD‐3, and HAMD score > 20 Age: not stated Participant information: 108 participants Location: inpatients or day patients from the Heilongjiang Provincial Academy of TCM Hospitial, China Inclusion/Exclusion: Exclusion criteria: a severe health condition, pregnancy or breastfeeding, long‐term medication, plasma 5‐HT and SSRI‐type medications taken together in the past 2 weeks, lack of willingness or suitability to be participants in this clinical trial, severe suicidal ideation or behaviour not suitable for patient to be medicated, organic mental disorder, depression caused by psychoactive substances or non‐addictive medications
Interventions	(1) Duration: 30 days (30 sessions) Frequency of treatment: daily Treatment protocol: Electro‐acupuncture. Points stimulated include GB5 Xuan Lu, DU17 Nao Hu, GV18 Qiang Jian, GB15 Tou lin qi, GB14 Yang Bai, GB 8 Shuai Gu, GB 7 Qu Bin, GV24 Shen Ting, M‐HN‐3 Yin Tang. Each acupuncture needle was inserted to a depth of 40 to 50 mm, stimulation used a fast but small angled twirling manipulation method, at 200 twirls per minute, with each needle manipulated for 1 minute. Needles were then connected to an electro‐acupuncture device, model G6805‐I. A continuous pulse was used, with frequency set at 120 to 250 pulse per minute. Intensity was set at a level tolerable to the participant. Stimulation was given over 30 minutes, with needles retained for 1 hour. (2) Duration: 30 days (30 sessions) Frequency of treatment: daily Treatment protocol: Manual acupuncture of non‐point‐through‐point (NON). Acupuncture was administered to points GV20 Baihui, M‐HN‐3 Yintang, M‐HN‐1 Shishencong, PC6 Neiguan, HT7 Shenmen, SP6 Sanyinjiao, LI4 Hegu, and LIV3 Taichong. Needles were inserted and de qi obtained, needles were manipulated using either lifting twirling reinforcing‐dispersing method or reinforcing‐dispersing manipulation methods. Needles were retained for 1 hour. Hwato acupuncture needles, manufactured by Suzhou medical product company, with dimensions 0.38 mm × 40 mm to 40 mm were used. (3) Duration: 30 days Frequency of treatment: daily Treatment protocol: The medication group received fluoxetine. Participants initially were given a 20‐mg/d dose; after 2 weeks with no severe side effects observed, the dose was increase to 80 mg/d.
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details on randomisation were reported.
Allocation concealment (selection bias)	Unclear risk	No communication was received from trial authors in response to a letter requesting further details on study methods.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Participants and therapists were not blind to their group allocation.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	No details on the blinding status of the assessing clinician(s) and analyst were reported.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Exclusions and loss of data were not explained. Data on one primary outcome are complete. Data on secondary outcomes are incomplete.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	Groups were comparable at baseline. The study appears free of other sources of bias.

Methods	Randomised placebo‐controlled trial of acupuncture vs control acupuncture
Participants	Diagnosis: minor depression Method of diagnosis: ICD‐10 F32.0, 32.1 Age: unclear Participant information: 56 participants with depression Location: inpatient and outpatient clinic setting in Germany Inclusion/Exclusion: Exclusion criteria: compulsory detained, alcohol or drug intoxication, subcutaneous long‐acting medication taken in the previous 30 days, mania, bipolar disorder, schizophrenia, blood clot disorder, impaired wound healing, organic disease, seizures, pregnancy or breastfeeding, study participation in the past 30 days, knowledge of acupuncture
Interventions	Before the intervention was commenced, a 2‐week washout was undertaken. A total of 11 points was used for both groups. (1) Duration: 2 weeks (14 sessions) Frequency of treatment: daily Treatment protocol: Participants were administered body acupuncture via acupuncture points known from the literature to have a regulating effect. These included Du20 Baihui, Bl62 Shenmai, PC6 Naiguan, HT 7 Shenman, and EX‐HN1 Sishencong. (2) Duration: 2 weeks (14 sessions) Frequency of treatment: daily Treatment protocol: The control group used sham points at non‐specific points with minimal insertion, located on the hand, head, and foot.
Outcomes	Time points for assessment: end of intervention Outcomes: Global Clinical Improvement Scale
Notes	Reported results may have been limited because data were presented for depression combined with general anxiety.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details of the randomisation schedule were reported.
Allocation concealment (selection bias)	Unclear risk	No details of the randomisation schedule were reported.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Participants were blind to group allocation, and therapists were aware of group allocation.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Assessing clinicians were blinded. It is unclear whether analysts were blind to group allocation.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up was reported.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	No differences in baseline characteristics were evident. The study appears free of other sources of bias.

Methods	Randomised controlled trial of acupuncture, medication (Prozac), and control acupuncture
Participants	Diagnosis: depressive neurosis Method of diagnosis: CCMD‐2 Age: 18 to 65 years Participant information: 81 participants Location: Guangdong Hospital, Guangdong, China Inclusion/Exclusion: Inclusion criteria: needed not to have taken medication in the previous 2 weeks Exclusion criteria: liver, kidney, blood, gastrointestinal disorders; infectious diseases; current pregnancy or breastfeeding
Interventions	(1) Duration: 3 months Frequency of treatment: unclear Treatment protocol: Acupuncture was administered to 4 acupuncture points, Baihi Du 20, M‐HN‐3 Yintang, 4 gates, ear seeds to auricular points liver and heart. These points were rotated between the left and right ear twice a week. Other points were retained for 30 minutes. (2) Duration: 3 months Frequency of treatment: daily Treatment protocol: The first control group received 20 mg of fluoxetine daily for 3 months. (3) Duration: 3 months Frequency of treatment: unclear Treatment protocol: The second control group received sham acupuncture at non‐acupuncture points; the ear points were administered.
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation sequence was computer generated.
Allocation concealment (selection bias)	Low risk	Randomisation was concealed by the use of opaque envelopes.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Participants and therapists were not blind to group allocation.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Assessing clinicians were blind, and it is unclear whether analysts were blind to group allocation.
Incomplete outcome data (attrition bias)   All outcomes	High risk	Four participants (5%) from the medication group withdrew from the study owing to side effects.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Unclear risk	Reported information was insufficient for assessment of other sources of bias.

Methods	Randomised parallel controlled trial of acupuncture vs acupuncture with shallow needling vs acupuncture vs control
Participants	Diagnosis: depression Method of diagnosis: CCMD‐3 Age: not stated Participant information: 163 participants Location: outpatient at Guangdong Provincial Hospital of TCM, China Inclusion/Exclusion: Inclusion criteria: HAMD score < 20, meeting TCM criteria for stagnation of liver qi, qi depression transforming into fire, aged 18 to 70 years, not taking antidepressant medication in the past 2 weeks Exclusion criteria: organic somatic disease, e.g. psychosis, schizophrenia; HAMD score > 35; other TCM diagnostic criteria met; epilepsy; serious cerebro‐cardiovascular hepatic, renal gastrointestinal disease
Interventions	(1) Duration: 12 weeks (24 sessions) Frequency of treatment: 2/week Treatment protocol: Acupuncture delivered with the aim of soothing the liver and regulating the mind Acupuncture points: LI4 and LR3, GV20 and Yintang, GV29 Mode of stimulation: 0.35 mm × 25 mm needles, insertion 10 to 12 mm, even lifting, thrusting and rotating manipulation until arrival of de qi. Moxa on Bl17, Bl19, 5 cones/point interdermal needling Bl15, Bl18 (2) Duration: 12 weeks (24 sessions) Frequency of treatment: 2/week Treatment protocol: Control group: non‐acupuncture points with invasive shallow needling 10 mm away from Li4, LR3, GV20 Gv29; shallow but same needling techniques Moxa 10 mm away from points; intradermal needles 10 mm away from points
Outcomes	Time points for assessment: end of intervention Outcomes: Symptom Checklist‐90 Adverse events Dropout from treatment
Notes	ITT not undertaken Groups 1 and 2 combined
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence was used.
Allocation concealment (selection bias)	Unclear risk	This was not reported.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Participants and some key study personnel were not blinded; non‐blinding of others was likely to introduce bias.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Patient‐reported outcomes were reported; therefore blinding was not applicable.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Six dropped out from acupuncture, 8 from shallow needling, 6 from control. Reasons for missing outcome data were unlikely to be related to true outcomes.
Selective reporting (reporting bias)	Unclear risk	Reporting was insufficient, but no adverse events were reported.
Other bias	Unclear risk	No differences were evident between baseline characteristics.

Methods	Parallel randomised controlled trial of acupuncture vs medication (fluoxetine)
Participants	Diagnosis: depression Method of diagnosis: SDS (Self‐rating Depression Scale) score > 50, Hamilton Depression Rating Scale (HAMD) score > 7, PSQI score ≥ 8 Age: 18 to 75 years Participant information: 80 participants Location: outpatient and inpatient ward of Traditional Chinese Medicine (TCM) Department or Acupuncture Department of Chinese PLA General Hospital, China, from October 2008 to October 2010 Inclusion/Exclusion: Inclusion criteria: no intellectual or mental disorders, ability to self‐judge the sleep condition and other common conditions, ability to accomplish the scale independently, expected survival time longer than 3 months Exclusion criteria: taking antidepressant drugs at the present time, Karnofsky score < 30
Interventions	(1) Duration: 30 days Frequency of treatment: daily Treatment protocol: In treatment group, participants were treated with acupuncture on the acupoints of Fenglong (ST 40), Yinlingquan (SP 9), Xuehai (SP 10), Sanyinjiao (SP 6), Yintang (EX‐HN3), Baihui (DU 20), Sishencong (EX‐HN1), Neiguan (PC 6), and Shenmen (TF 4). When needling, method of neutral supplementation and drainage was used. Participants were treated for 20 to 30 minutes, and the acupuncturist performed needling manipulation at intervals of 5 to 10 minutes. (2) Duration: 30 days Frequency of treatment: daily Treatment protocol: Participants in the control group received fluoxetine hydrochloride capsules (trade name: Prozac, produced by Patheon, in France) 20 mg per day.
Outcomes	Time points for assessment: end of intervention Outcomes: HAMD reduced rate (%) = (score before treatment － score after treatment)/score before treatment × 100% Cure rate (reduced rate > 75%), effective rate (reduced rate 50% to 75%), improved rate (reduced rate 25% to 49%), invalid rate (reduced rate < 25%)
Notes	ITT was not mentioned.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number tables were used.
Allocation concealment (selection bias)	Unclear risk	This was not reported.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Participants were not blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Blinding status was not reported.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No dropouts were reported.
Selective reporting (reporting bias)	Unclear risk	No protocol was available and reporting was insufficient.
Other bias	Unclear risk	Reporting was insufficient.

PERMALINK

Acupuncture for depression

Caroline A Smith

Mike Armour

Myeong Soo Lee

Li‐Qiong Wang

Phillipa J Hay

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Characteristics

Diagnosis

Comorbidities

Treatment setting

Types of interventions

Experimental interventions

Comparator interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Timing of outcome assessment

Hierarchy of outcome measures

Search methods for identification of studies

Cochrane Specialised Registers: Cochrane Common Mental Disorders Clinical Trials Register (CCMD‐CTR)

Electronic searches

Searching other resources

Grey literature

Handsearching

Reference lists

Correspondence

Data collection and analysis

Selection of studies

Data extraction and management

Main planned comparisons

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Trials with multiple groups

Cluster‐randomised trials

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

'Summary of findings' tables

Results

Description of studies

Results of the search

1.

Included studies

Design

Sample size

Setting

Participants

Interventions

Outcomes

Excluded studies

Ongoing studies

Studies awaiting classification

New studies found at this update

Risk of bias in included studies

2.

Methods	Three‐armed randomised controlled trial comparing acupuncture, medication, and control acupuncture for treatment of individuals with depression
Participants	Diagnosis: depression Method of diagnosis: CCMD‐2‐R Age: not stated Participant information: 201 participants were randomised into acupuncture group (n = 78), medication (Prozac) group (n = 82), and sham‐acupuncture group (n = 41). Location: outpatient, China Inclusion/Exclusion: Exclusion criteria: schizophrenia; physical diseases or organic diseases that can cause similar symptoms of depression; age > 65; severe cardiovascular, liver, kidney, haematopoietic system diseases; pregnancy; haematic disease; antidepressant drugs taken within the past 2 weeks
Interventions	(1) Duration: 12 weeks (24 sessions) Frequency of treatment: twice per week Treatment protocol: TCM style of acupuncture. Acupoints used were Taichong (LR 3), Hegu (LI 4), Baihui (GV 20), Yintang (EX‐HN 3), to point Liver and Heart. For sham acupuncture group, punctured spots were those 0.5 cm to LR 3 and LI4 on the radial side, 0.5 cm to GV 20 on the left side, 0.5 cm to EX‐HN 3 on the left side. Manual acupuncture treatment lasted 30 minutes. (2) Duration: 12 weeks Frequency of treatment: daily Treatment protocol: Participants in medication group were ordered to take Prozac 20 mg/d, continuously for 12 weeks.
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD) Self‐rating Depression Scale (SDS)
Notes	ITT was not stated.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence was used.
Allocation concealment (selection bias)	Low risk	Sealed envelopes were used.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Acupuncture and sham participants were blinded.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	It was unclear whether assessing clinicians and analysts were blinded.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Details were insufficient; 28 were lost to follow‐up, but no details of group allocation were provided.
Selective reporting (reporting bias)	Unclear risk	Information presented was insufficient.
Other bias	Unclear risk	Information presented was insufficient.

Methods	Multi‐centred randomised controlled trial of acupuncture vs control acupuncture vs medication (fluoxetine)
Participants	Diagnosis: depression Method of diagnosis: CCMD‐2 and score > 20 on the HAMD Age: 18 to 65 years Participant information: 440 participants Location: mixed inpatients and outpatients from 4 different hospitals between October 2004 and December 2006, in China Inclusion/Exclusion: Inclusion criteria: conscious, no loss of speech, preserved intelligence, minimum primary education level, TCM diagnostic criteria of ‘yu bing’ depressive disease due to liver qi stagnation or qi stagnation causing fire, no antidepressant medication taken in the previous 2 weeks Exclusion criteria: schizophrenia; organic or somatic disease that can trigger depression; < 18 years or > 65 years of age; severe cardiovascular, neurological, liver, kidney, or blood function disease; pregnancy; non‐co‐operative during needling; not taking medication on time; antidepressants taken in the past 2 weeks
Interventions	(1) Duration: 12 weeks (24 sessions) Frequency of treatment: twice per week Treatment protocol: Treatment group received acupuncture administered to LIV3 Taichong, LI 4 Hegu, DU 20 Baihui, and M‐HN‐3 Yin tang. The 4 gates were needled first, to a depth of 15 mm; the needle was stimulated by lifting twirling manipulation until de qi was obtained. Bai hui was needled at a 30º angle in a quick motion. Yintang was needled by pinching the skin, then inserting to a depth of 15 mm parallel to the skin surface. Baihui and Yintang were twirled until de qi was obtained. The needles were left in for 30 minutes. Two auricular acupuncture points were used ‐ liver and heart points. Ear press tacks were placed on points and secured with small strips of bandage. These points were left in for 3 days, then were repeated in alternate ears. (2) Duration: 12 weeks Frequency of treatment: daily Treatment protocol: The control group received fluoxetine 20 mg/d (Prozac capsule, manufactured by Eli Lilly and Company). These were taken orally once in the morning after meals for a total of 12 weeks. (3) Duration: 12 weeks (24 sessions) Frequency of treatment: twice per week Treatment protocol: The sham acupuncture group involved needling of points in the region of Taichong, Baihui, Yintang, but roughly 0.5 cun away from actual points. The needle was inserted and manipulated in the same way as for the acupuncture group. The auricular acupuncture points were used in the same way as in the active group.
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD) Assessment of cure and marked effect > 75% change from baseline Reports of adverse events
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation allocation sequence was computer generated.
Allocation concealment (selection bias)	Low risk	The allocation sequence was concealed with the use of opaque envelopes.
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Blinding of participants in acupuncture and sham groups was unclear, and no testing was reported. The therapist was not blind to group allocation.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Assessing clinicians were blind, and the blinding status of analysts was unclear.
Incomplete outcome data (attrition bias)   All outcomes	High risk	A total of 64 (15%) participants did not complete the trial. No further details were reported.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	High risk	Potential bias was evident with imbalance in characteristics at randomisation, including previous psychiatric medication use and history of psychiatric care, for which no adjustments were made in the analysis.

Methods	Acupuncture vs standard medication (maprotiline)
Participants	Diagnosis: depression Method of diagnosis: ICD‐10 and score > 20 on the Hamilton Depression Rating Scale Age: 18 to 55 years Participant information: 66 men and women Location: outpatients from the Beijing University Mental Health Institute, China Inclusion/Exclusion: Exclusion criteria: none specified.
Interventions	(1) Duration: 6 weeks (36 sessions) Frequency of treatment: 6/week Treatment protocol: Electro‐acupuncture was administered for 45 minutes, 6 times a week, over 6 weeks, through unspecified numerous standardised points. (2) Duration: 6 weeks Frequency of treatment: daily Treatment protocol: The medicated group received daily maprotiline at doses ranging from 75 to 250 mg for 6 weeks.
Outcomes	Time points for assessment: baseline and 14, 28, and 42 days from trial entry Outcomes: Hamilton Depression Rating Scale (HAMD) Clinical Global Impression Scale Ashberg Rating Scale for side effects
Notes	ITT was performed.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details on how the allocation sequence was generated could be obtained from the trial author.
Allocation concealment (selection bias)	Unclear risk	No details on the method of concealment used could be obtained from the trial author.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	The study participant and the therapist were not blind.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	It was unclear whether assessing clinicians and analysts were blinded to the study group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Complete follow‐up was obtained.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	Baseline characteristics show no imbalance between groups. Intention‐to‐treat analysis was performed. The study appears free of other sources of bias.

Methods	Manual acupuncture vs medication (fluoxetine)
Participants	Diagnosis: post‐stroke depression Method of diagnosis: Chinese Neuroscience Society diagnostic guidelines Age: not stated Participant information: 170 participants Location: inpatients from Zhongshan Chinese Medicine Hospital, China Inclusion/Exclusion: Exclusion criteria: serious heart, liver, kidney conditions; glaucoma
Interventions	(1) Duration: 8 weeks (48 sessions) Frequency of treatment: 6/week Treatment protocol: The acupuncture intervention consisted of stimulation of the acupuncture points DU26 Ren Zhong, PC6 Neiguan, LIV3 Taichong, HT7 Shenmen, with xing nao kai qiao needling method, with dispersal and regulation of liver qi and calming shen. Additional acupuncture points were added according to the diagnosis. If liver stagnation, diagnosed points TH6 Zhi Gou, LIV 14 Qi men were added. Qi stagnation with stagnation fire, diagnosed points LIV 2 Xing Jian, GB43 Jai xi were used to clear liver and purge fire. Heart and spleen deficiency was diagnosed; points UB15 Xing Shu, UB20 Pi Shu, ST36 Zusanli, SP6 Sanyinjiao were used to strengthen the spleen and nourish the heart. If the spirit was depressed affecting shen, additional points ST36 Zusanli, SP6 Sanyinjiao, and tong li HT5 were used to nourish the heart and calm the shen. Ren zhong was needled towards the nose 5 fen deep using the pecking dispersing method. Zhigou and Neiguan were needled perpendicular 1 cun, via the lifting twirling dispersing method. Xing jian, Jaixi, and Taichong were needled perpendicular 0.5 cun via the twirling dispersing method. Tong li, Shenmen were needled perpendicular via the reinforcing‐reducing manipulation method. Qimen was needled perpendicular 1 cun with the twirling dispersing method. Xingshu and Pishu were needled towards the spine 1 cun, after de qi use of the twirling dispersing method. Zusanli and Sanyinjiao were needle perpendicular 1 cun via the lifting twirling reinforcing method. Needles were retained for 30 minutes. (2) Duration: 8 weeks Frequency of treatment: daily Treatment protocol: The control group received fluoxetine 20 mg/d, taken in the morning.
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD) Rates of recovery reported as "cured" and "marked" effects
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation schedule was computer generated.
Allocation concealment (selection bias)	Unclear risk	No additional details could be obtained from the trial author.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	The study participant and the therapist were not blind.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	It was unclear whether assessing clinicians and analysts were blind to study groups.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up was reported.
Selective reporting (reporting bias)	Unclear risk	No study protocol was available.
Other bias	Low risk	Data show no imbalance at randomisation. The study appears free of other sources of bias.

Methods	Randomised trial of acupuncture or medication (fluoxetine)
Participants	Diagnosis: depression Method of diagnosis: CCMD‐3 Age: not stated Participant information: 80 participants Location: outpatient clinic of Rehabilitation Department at Fosan Shunde Jun’an Hospital, China, from August 2010 to June 2011 Inclusion/Exclusion: Inclusion criteria: aged 18 to 65 years, no schizophrenia; no history and family history of mental disorders.  Exclusion criteria: family history of mental disorders; serious liver and kidney disease, heart failure, post‐schizophrenia depression, post‐cerebral apoplexy depression, post natal depression, depression related to the menopause.
Interventions	(1) Duration: 6 weeks (45 sessions) Frequency of treatment: daily with a 2‐day interval every 15 days Treatment protocol: Acupuncture group received points: Bihui GV20, YinTang, Sanyinjaio SP6, Taichong LIV3, Neiguan PC6, and Hegu LI4. Acupuncture was given once per day; needles remained for 30 minutes. (2) Duration: 6 weeks Frequency of treatment: daily Treatment protocol: Control received fluoxetine once per day, 20 mg/time.
Outcomes	Time points for assessment: end of intervention Outcomes: HAMD Cured: reduced rate ≥ 75%; remarkably effective: reduced rate ≥ 50% and < 75%; improved: reduced rate ≥ 25% and < 50%; failed: reduced rate < 25% HAMD was classified into 7 categories of factor structures. Of them, a score < 8 indicated normal, in the range from 8 to 18 indicated mild depression, from 18 to 24 indicated moderate depression, and > 24 indicated serious depression.
Notes	ITT was not stated.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number tables were used.
Allocation concealment (selection bias)	High risk	Participants were divided into an acupuncture group (40 cases) and a western medicine group (40 cases).
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Participants were not blind.
Blinding of outcome assessment (detection bias)   All outcomes	High risk	Assessing clinicians undertook measurements by observation and communication, and therefore were unlikely to be blinded.
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Six cases: 2 in the acupuncture group, 4 in the control group
Selective reporting (reporting bias)	Unclear risk	Reporting was insufficient.
Other bias	Unclear risk	Reporting was insufficient.

Methods	60 patients with depression were randomly assigned to the medication group (30 cases) and to the treatment plus medication group (30 cases).
Participants	Diagnosis: clinical depression Method of diagnosis: CCMD‐3 Age: not stated Participant information: 60 men and women Location: inpatients in China Inclusion/Exclusion: Exclusion criteria: depression with psychotic symptoms and organic psychosis; depression caused by mental activity substance and non‐addiction substance; serious physical ailments, organic brain disorder, drug‐ and alcohol‐dependent individuals, and those with allergies
Interventions	(1) Duration: 6 weeks (18 sessions) Frequency of treatment: once every other day, 3 out of 7 days Treatment protocol: Manual acupuncture was administered. Acupuncture points Baihui (GV 20), Yintang (EX‐HN 3), Fengfu (GV16), Dazhui (GV 14), Fengchi (GB 20), Neiguan (PC 6), and Sanyinjiao (SP 6) were administered. (3) Duration: 6 weeks Frequency of treatment: daily Treatment protocol: Control group: paroxetine hydrochloride 20 to 40 mg/d
Outcomes	Time points for assessment: end of intervention Outcomes: Hamilton Depression Rating Scale (HAMD), Self‐rating Depression Scale (SDS), Eisenberg Antidepressant Side Effects Scale (Asberg)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number table was used.
Allocation concealment (selection bias)	Unclear risk	This was not reported.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	No blinding was attempted.
Blinding of outcome assessment (detection bias)   All outcomes	High risk	No blinding was attempted.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No dropouts were reported.
Selective reporting (reporting bias)	Unclear risk	Insufficient details were reported.
Other bias	Unclear risk	Insufficient details were reported.

Methods	Electro‐acupuncture vs standard medication (fluoxetine or paroxetine)
Participants	Diagnosis: mild, moderate, or severe depression Method of diagnosis: CCMD‐3, HAMD, BDI Age: not stated Participant information: 56 participants Location: inpatients at The First Teaching Hospital of Tianjin Traditional Chinese Medicine College, China Inclusion/Exclusion: Exclusion criteria: none specified
Interventions	(1) Duration: variable ‐ from 2 to 6 weeks Frequency of treatment: daily Treatment protocol: Particpants were randomly allocated to receive electro‐acupuncture or fluoxetine or paroxetine (adequate dose defined). The following acupuncture points were used: GB20 Feng chi, Anmien, M‐HN‐1 Shishencong, M‐HN‐3 Yintang, DU20 Baihui, Ht 7 Shenmen, PC5 Jian Shi, LI4 Hegu, LIV3 Taichong, SP6 Sanyinjiao, GB40 Quixu, GB 8 Shuaigu, and ST36 Zhusanli. All needles were manipulated by a twirling method, with gentle insertion applied on Shenmen. Zhong wan used as a breathing purging method, and electro‐acupuncture was applied to Yintang and Baihui, with the level of stimulation determined by the participant. Needles were left in for 30 minutes, and participants were needled once a day. (2) Duration: 6 weeks Frequency of treatment: daily Treatment protocol: The control group received oral fluoxetine or paroxetine 20 mg once a day in the morning.
Outcomes	Time points for assessment: 18 weeks Outcomes: Hamilton Depression Rating Scale Rates of recovery reported as "cured" and "marked" effects
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information could be obtained from the trial author on how the allocation sequence was generated.
Allocation concealment (selection bias)	Unclear risk	The trial author did not respond to letters sent.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Study participants and therapists were not blind.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	It was unclear whether assessing clinicians and analysts were blind to the study group.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No loss to follow‐up was reported, and all participants were included in the analysis.
Selective reporting (reporting bias)	High risk	Data from the Hamilton Depression Rating Scale ‐ but not the Beck Depression Inventory ‐ were reported.
Other bias	Low risk	Data show no imbalance in participant characteristics at baseline. The study appears free of other sources of bias.

Methods	Randomised controlled trial of TCM manual acupuncture (30 participants) vs control acupuncture (30 participants) via 'off channel' points
Participants	Diagnosis: depression Method of diagnosis: CCMD‐2‐R Age: not stated Participant information: 60 participants Location: unclear setting, China Inclusion/Exclusion: Exclusion criteria: organic cause for depression including schizophrenia, psychosis, or reactive depression; epilepsy; cardiovascular, liver, kidney, circulatory, or gastrointestinal disorders; pregnancy or lactation; any ear infection or damage to the ear; long‐term use of benzodiazepines for insomnia
Interventions	(1) Duration: 12 weeks (24 sessions) Frequency of treatment: 2/week Treatment protocol: Verum acupuncture was performed at Taichong (LR3), Hegu (LI4), Baihui (GV20), and Yintang (EX‐HN3). Ear acupuncture was performed on liver and heart auricular points. Manual stimulation was used for all points and was retained for 30 minutes. (2) Duration: 12 weeks (24 sessions) Frequency of treatment: 2/week Treatment protocol: Sham acupuncture was performed at 'off channel' points, 1 cm to the side of LR3, LI4, GV20, and EX‐HN3, and was retained for 30 minutes. Ear acupuncture was performed on liver and heart auricular points.
Outcomes	Time points for assessment: end of the intervention Outcomes: Hamilton Depression Rating Scale (HAMD) "Cured" rate measured by HAMD reduction > 75%
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A random number table was used.
Allocation concealment (selection bias)	Unclear risk	This was not reported.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Blinding of participants and key study personnel was ensured; it is unlikely that the blinding could have been broken.
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	It was unclear whether assessing clinicians and analysts were blinded.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Missing outcome data were balanced in numbers across intervention groups, and reasons for missing data were similar across groups.
Selective reporting (reporting bias)	Unclear risk	Reporting in the paper was insufficient.
Other bias	Unclear risk	Reporting in the paper was insufficient.

Methods	Acupuncture vs control acupuncture in a double‐blind controlled trial
Participants	Diagnosis: depression Method of diagnosis: DSM‐IV Age: not stated Participant information: 43 men and women (23 to acupuncture and 20 to sham acupuncture) Location: unclear setting, China Inclusion/Exclusion: Exclusion criteria: stroke patients with aphasia, language barrier, cognitive impairment, previous history of depression, needle phobia
Interventions	Both groups were able to continue taking fluoxetine. (1) Duration: 6 weeks (30 sessions) Frequency of treatment: 5 out of 7 days Treatment protocol: Acupuncture: TCM acupuncture. Each treatment lasted 30 minutes. Points Baihui (GV 20), Yintang (EX‐HN 3), Sishencong (EX‐HN 1), Taichong (LR 3), Shenmen (HT7), Neiguan (PC 6), Sanyinjiao (SP 6), Taixi (K 3), and Xinshu (BL 15) were administered. (2) Duration: 6 weeks (30 sessions) Frequency of treatment: 5 out of 7 days Treatment protocol: Sham acupuncture: applied to non‐acupoint points (5 mm lateral to acupoints) via shallow needling technique
Outcomes	Time points for assessment: end of the intervention Outcomes: Hamilton Depression Rating Scale (HAMD) Asberg Antidepressant Side Effect Scale
Notes	ITT was not reported.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number tables were used.
Allocation concealment (selection bias)	Unclear risk	This was not reported.
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Participants were blind to group allocation.
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Assessing clinicians were blinded; it is unlikely that blinding would have been broken.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No dropouts were reported.
Selective reporting (reporting bias)	Unclear risk	Reporting of details was insufficient.
Other bias	Unclear risk	Reporting of details was insufficient.

Methods	Randomised controlled trial of medication, manual acupuncture plus medication, and electro‐acupuncture plus medication
Participants	Diagnosis: depression Method of diagnosis: ICD‐10 plus a score ≥ 17 on the Hamilton Depression Rating Scale Age: not stated Participant information: 102 men and women (34 cases allocated to each group) Location: China, unclear setting. Inclusion/Exclusion: Exclusion criteria: previous enrolment in other clinical studies within 4 weeks, currently using antidepressants or anxiolytics, suicidal behaviour, cognitive disorders, serious cerebrovascular disease, liver and kidney disease, pregnancy or lactation, inability to comply with research data requirements during intervention or follow‐up phases
Interventions	Both acupuncture groups received the medication. (1) Duration: 6 weeks (18 sessions) Frequency of treatment: once every other day, 3 out of 7 days Treatment protocol: TCM‐style acupuncture was administered. Manual acupuncture to points Baihui (GV 20), Yintang (EX‐HN 3), Fengfu (GV16), Fengchi (GB 20), Dazhui (GV 14), Neiguan (PC 6), and Sanyinjiao (SP 6). Supplementary acupoints were combined according to syndrome differentiation. (2) Duration: 6 weeks (18 sessions) Frequency of treatment: once every other day, 3 out of 7 days Treatment protocol: Electro‐acupuncture stimulation to points Baihui (GV 20) and Yintang (EX‐HN 3) No other needling details were reported. (3) Duration: 6 weeks Frequency of treatment: daily Treatment protocol: Medication group: Seroxat was prescribed for oral administration once per day.
Outcomes	Time points for assessment: end of the intervention Outcomes: Clinical Global Impression Scale (CGI) Quality of life assessed by the WHOQOL
Notes	ITT was not reported.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number tables were used.
Allocation concealment (selection bias)	Unclear risk	This was not reported.
Blinding of participants and personnel (performance bias)   All outcomes	High risk	No blinding was attempted.
Blinding of outcome assessment (detection bias)   All outcomes	High risk	No blinding was attempted.
Incomplete outcome data (attrition bias)   All outcomes	Low risk	10 participants dropped out, numbers were balanced across groups, reasons were not reported.
Selective reporting (reporting bias)	Unclear risk	Reporting was insufficient to allow assessment.
Other bias	Unclear risk	Reporting was insufficient to allow assessment.