Acupuncture for depression

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

doi:10.1002/14651858.CD004046.pub4

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Figure 1

Study flow diagram.

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Figure 2

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

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Figure 3

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

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Figure 4

Forest plot of comparison: 1 Acupuncture versus no treatment/wait list/TAU, outcome: 1.1 Severity of depression at the end of treatment.

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Figure 5

Forest plot of comparison: 2 Acupuncture versus control acupuncture, outcome: 2.1 Severity of depression at the end of the intervention.

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Figure 6

Forest plot of comparison: 3 Acupuncture versus medication, outcome: 3.1 Severity of depression at the end of treatment.

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Figure 7

Forest plot of comparison: 4 Acupuncture plus medication vs medication, outcome: 4.1 Severity of depression at the end of treatment.

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Figure 8

Funnel plot of comparison: 2 Acupuncture versus control acupuncture, outcome: 2.1 Severity of depression at the end of the intervention.

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Figure 9

Funnel plot of comparison: 3 Acupuncture versus medication, outcome: 3.1 Severity of depression at the end of treatment.

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Figure 10

Funnel plot of comparison: 4 Acupuncture plus medication vs medication, outcome: 4.1 Severity of depression at the end of treatment.

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Analysis 1.1

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 1 Severity of depression at the end of treatment.

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Analysis 1.2

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 2 Adverse events.

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Analysis 1.3

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 3 Severity of depression during treatment.

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Analysis 1.4

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 4 Severity of depression 0‐6 months after treatment.

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Analysis 1.5

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 5 Severity of depression 6‐12 months after treatment.

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Analysis 1.6

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 6 Remission of depression.

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Analysis 1.7

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 7 Change in use of medication at the end of treatment.

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Analysis 1.8

Comparison 1 Acupuncture versus no treatment/wait list/TAU, Outcome 8 Dropout from treatment.

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Analysis 2.1

Comparison 2 Acupuncture versus control acupuncture, Outcome 1 Severity of depression at the end of the intervention.

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Analysis 2.2

Comparison 2 Acupuncture versus control acupuncture, Outcome 2 Adverse events.

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Analysis 2.3

Comparison 2 Acupuncture versus control acupuncture, Outcome 3 Severity of depression during treatment.

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Analysis 2.4

Comparison 2 Acupuncture versus control acupuncture, Outcome 4 Severity of depression at 0‐6 months' follow‐up.

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Analysis 2.5

Comparison 2 Acupuncture versus control acupuncture, Outcome 5 Remission of depression.

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Analysis 2.6

Comparison 2 Acupuncture versus control acupuncture, Outcome 6 Quality of life (emotional) during treatment.

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Analysis 2.7

Comparison 2 Acupuncture versus control acupuncture, Outcome 7 Quality of life (emotional) at the end of treatment.

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Analysis 2.8

Comparison 2 Acupuncture versus control acupuncture, Outcome 8 Quality of life (physical) during treatment.

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Analysis 2.9

Comparison 2 Acupuncture versus control acupuncture, Outcome 9 Quality of life (physical) at the end of treatment.

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Analysis 2.10

Comparison 2 Acupuncture versus control acupuncture, Outcome 10 Change in medication.

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Analysis 2.11

Comparison 2 Acupuncture versus control acupuncture, Outcome 11 Dropout from treatment.

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Analysis 3.1

Comparison 3 Acupuncture versus medication, Outcome 1 Severity of depression at the end of treatment.

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Analysis 3.2

Comparison 3 Acupuncture versus medication, Outcome 2 Adverse events.

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Analysis 3.3

Comparison 3 Acupuncture versus medication, Outcome 3 Severity of depression during treatment.

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Analysis 3.4

Comparison 3 Acupuncture versus medication, Outcome 4 Severity of depression 0‐6 months after treatment.

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Analysis 3.5

Comparison 3 Acupuncture versus medication, Outcome 5 Remission of depression.

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Analysis 3.6

Comparison 3 Acupuncture versus medication, Outcome 6 Dropout from treatment.

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Analysis 4.1

Comparison 4 Acupuncture plus medication versus medication, Outcome 1 Severity of depression at the end of treatment.

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Analysis 4.2

Comparison 4 Acupuncture plus medication versus medication, Outcome 2 Adverse events.

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Analysis 4.3

Comparison 4 Acupuncture plus medication versus medication, Outcome 3 Severity of depression during treatment.

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Analysis 4.4

Comparison 4 Acupuncture plus medication versus medication, Outcome 4 Remission of depression.

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Analysis 4.5

Comparison 4 Acupuncture plus medication versus medication, Outcome 5 Quality of life (physical).

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Analysis 4.6

Comparison 4 Acupuncture plus medication versus medication, Outcome 6 Quality of life (emotional).

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Analysis 4.7

Comparison 4 Acupuncture plus medication versus medication, Outcome 7 Change in use of medication.

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Analysis 4.8

Comparison 4 Acupuncture plus medication versus medication, Outcome 8 Dropout from treatment.

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Analysis 5.1

Comparison 5 Acupuncture versus psychological therapy, Outcome 1 Severity of depression at the end of treatment.

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Analysis 5.2

Comparison 5 Acupuncture versus psychological therapy, Outcome 2 Adverse events.

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Analysis 5.3

Comparison 5 Acupuncture versus psychological therapy, Outcome 3 Severity of depression 0‐6 months after treatment.

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Analysis 5.4

Comparison 5 Acupuncture versus psychological therapy, Outcome 4 Severity of depression 6‐12 months.

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Analysis 5.6

Comparison 5 Acupuncture versus psychological therapy, Outcome 6 Change in use of medication.

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Analysis 5.7

Comparison 5 Acupuncture versus psychological therapy, Outcome 7 Dropout from treatment.

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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.
^aDowngraded one level owing to high risk of performance bias across most included studies. ^bDowngraded one level owing to substantial heterogeneity (I² = 64%, Tau² = 0.14, P = 0.02). ^cDowngraded one level owing to high risk of performance bias. ^dDowngraded one level owing to small sample size for detecting relatively rare events.

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

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Summary of findings 2. Acupuncture compared with control acupuncture for depression

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.
^aDowngraded one level owing to high risk of bias in performance bias in five of the included studies and high risk of bias in at least one domain in most studies. ^bDowngraded one level owing to substantial heterogeneity (I² = 80%, Tau² = 7.80, P < 0.001). ^cDowngraded one level owing to small sample size for relatively rare events. ^dDowngraded one level because only one small study contributed to this outcome. ^eDowngraded one level for imprecision due to small sample size.

Summary of findings 2. Acupuncture compared with control acupuncture for depression

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Summary of findings 3. Acupuncture compared with medication for depression

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.
^aDowngraded two levels owing to very serious risk of bias. Of 31 trials, 30 were at high risk of bias owing to lack of blinding of participants, and 12 were at high risk of bias owing to lack of blinding of outcome assessors. ^bDowngraded one level owing to substantial heterogeneity (I² = 80%, Tau² = 0.19, P < 0.0001). ^cDowngraded two levels owing to very serious risk of bias in all three studies. ^dDowngraded two levels owing to considerable heterogeneity (I² = 97%, Tau² = 7.22, P < 0.001).

Summary of findings 3. Acupuncture compared with medication for depression

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Summary of findings 4. Acupuncture plus medication compared with medication for depression

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.
^aDowngraded two levels owing to very serious risk of bias. Of 11 trials, nine were at high risk of bias owing to lack of blinding of participants, and 6 were at high risk of bias owing to lack of blinding of outcome assessors. ^bDowngraded two levels owing to considerable heterogeneity (I² = 89%, Tau² = 0.70, P < 0.001). ^cDowngraded two levels owing to very serious risk of bias. ^dDowngraded two levels owing to considerable heterogeneity (I² = 95%, Tau² = 1.75, P < 0.001). ^eDowngraded one level owing to small sample size and only one study reporting on this outcome. ^fDowngraded two levels owing to very serious risk of bias. ^gDowngraded one level owing to substantial heterogeneity (I² = 71%, Tau² = 0.97, P < 0.0001).

Summary of findings 4. Acupuncture plus medication compared with medication for depression

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Summary of findings 5. Acupuncture compared with psychological therapy for depression

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.
^aDowngraded one level for serious risk of bias; both included trials have high risk of performance bias. ^bDowngraded one level owing to substantial heterogeneity (I² = 85%, Tau² = 0.31, P = 0.01). ^cDowngraded one level for imprecision as only a single study reported on this rare outcome. ^dDowngraded one level owing to high risk of performance bias.

Summary of findings 5. Acupuncture compared with psychological therapy for depression

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Comparison 1. Acupuncture versus no treatment/wait list/TAU

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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]

Comparison 1. Acupuncture versus no treatment/wait list/TAU

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Comparison 2. Acupuncture versus control acupuncture

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of the intervention Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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]

Comparison 2. Acupuncture versus control acupuncture

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Comparison 3. Acupuncture versus medication

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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]

Comparison 3. Acupuncture versus medication

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Comparison 4. Acupuncture plus medication versus medication

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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) Show forest plot	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) Show forest plot	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 Show forest plot	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 Show forest plot	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]

Comparison 4. Acupuncture plus medication versus medication

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Comparison 5. Acupuncture versus psychological therapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severity of depression at the end of treatment Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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 Show forest plot	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]

Comparison 5. Acupuncture versus psychological therapy

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