1027332

research-article2021
CRE0010.1177/02692155211027332Clinical RehabilitationWang et al.

CLINICAL
Original Article REHABILITATION

Clinical Rehabilitation

Effects of mirror therapy on 1­–12

© The Author(s) 2021
Article reuse guidelines:
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DOI: 10.1177/02692155211027332
https://doi.org/10.1177/02692155211027332

phantom limb pain in amputees: A journals.sagepub.com/home/cre

systematic review and meta-analysis

of randomized controlled trials

Fengyi Wang1,2 , Rengang Zhang1,2, Jiaqi Zhang3, Dinggen Li1,2,

Yu Wang1, Yong-Hong Yang1,2 and Quan Wei1,2

Abstract
Objective: This systematic review and meta-analysis aimed to evaluate the effects of mirror therapy on
phantom limb sensation and phantom limb pain in amputees.
Data sources: Nine electronic databases (PubMed, EMBASE, MEDLINE, Web of Science, the Cochrane
Library, CINAHL, PsycInfo, PreQuest, PEDro) were searched from their inception to May 10th, 2021.
Methods: Two authors independently selected relevant studies and extracted the data. The effect sizes
were calculated under a random-effects model meta-analysis, and heterogeneity was assessed using the I2
test. The risk of bias was evaluated by the Cochrane risk of bias tool, and the methodological quality was
appraised by the PEDro scale. The GRADE approach was applied to assess the confidence of the effect.
Results: A total of 11 RCTs involving 491 participants were included in this review and nine RCTs involving
372 participants were included in meta-analysis. The quality of these studies was from poor to good with
scores ranging from 2 to 8 points according to PEDro scale. The pooled SMD showed that mirror therapy
reduced the pain with a large effect size (−0.81; 95% CI = −1.36 to −0.25; P = 0.005; I2 = 82%; n = 372)
compared with other methods (four covered mirror, one phantom exercise, three mental visualization, one
sensorimotor exercise, one transcutaneous electrical nerve stimulation, one tactile stimuli). The quality of
evidence for the outcome pain intensity was determined to be fair according to GRADE approach.
Conclusion: There is fair-quality evidence that MT is beneficial for reducing phantom limb pain.

Keywords
Mirror therapy, amputation, phantom limb sensation, phantom limb pain, meta-analysis
Received: 1 February 2021; accepted: 21 May 2021

1
 epartment of Rehabilitation Medicine, West China Hospital,
D Corresponding authors:
Sichuan University, Chengdu, Sichuan Province, China
2
Key Laboratory of Rehabilitation Medicine of Sichuan
Province, Chengdu, Sichuan Province, China
3
Department of Rehabilitation Sciences, The Hong Kong
Polytechnic University, Hung Hom, Hong Kong
Yonghong Yang, Department of Rehabilitation Medicine, West
China Hospital, Sichuan University, No. 37, Guoxuexiang,
Wuhou District, Chengdu, Sichuan Province 610041, China.
Email: nicole308@126.com
Quan Wei, Department of Rehabilitation Medicine, West
China Hospital, Sichuan University, No. 37, Guo-xue-xiang
Street, Chengdu 610041, China.
Email: weiquan@scu.edu.cn
2 Clinical Rehabilitation 00(0)
Introduction
Pain felt in the amputated limb is common, and one
method of trying to control it is to use the mirror
reflected image of the other limb, known as mirror
therapy. The neurophysiological basis of mirror
therapy has been extensively studied,1,2 but it is still
unclear whether the therapy is clinically effective.
As an alternative treatment approach, mirror ther-
apy has been proposed as potentially beneficial for
reducing phantom limb pain introduced by
Ramachandran and Rogers-Ramachandran.3 Mirror
therapy is based on visual feedback stimulation in
which the mirror reflection of voluntary movements
performed by the remaining limb create an illusion
of normal movement of the phantom limb. During
mirror therapy, the impaired coherence between
motor command and sensory feedback after ampu-
tation are enhanced.
Phantom limb sensation refers to the vivid pres-
ence of the missing limb with normal or distortion of
shape, length, position, and telescoping, these may
vary in intensity and change over time.4 Phantom
limb pain is known as the pain perceived by the
body part that no longer exists. Phantom limb pain is
accompanied by pain of different properties and
degrees based on phantom limb sensation, and it
occurs in up to 80% of amputees.5–7 Phantom limb
pain is a kind of neuropathic pain, the pain can be
knife-like, needle-like, burning, throbbing, shoot-
ing, squeezing, tingling, jabbing, cramping, crush-
ing, itching, and tearing.4–7 Phantom limb problems
troubles amputees with a serious impact on sleep
quality, mood, mobility, activity of daily living,
work, and quality of life.8,9
Recently, there has been an increasing number
of studies investigating the role of mirror therapy
in reducing phantom limb sensation and phantom
limb pain, but its effectiveness remains unclear. A
systematic review10 of mirror therapy for phantom
limb pain published in 2016 shown that the evi-
dence of efficacy of mirror therapy on phantom
limb pain is inadequate and those studies are het-
erogeneous in terms of their methodologies and
findings. No meta-analysis investigating the effect
of mirror therapy for phantom limb pain has been
performed yet. Consequently, this systematic
review with meta-analyses aimed to evaluate the
updated evidence to identify the effects of mirror
therapy on phantom limb pain at both short-term
and long-term. Due to high heterogeneity observed
in the forms of control therapy, subgroup analysis
was performed to identify whether the type of con-
trol therapy had a confounding effect on the esti-
mation of the effect size.
Method
This systematic review and meta-analysis was
undertaken in accordance with the PRISMA
(Preferred Reporting Items for Systematic Reviews
and Meta-Analysis) statements.11 The registration
number in PROSPERO is CRD42021225854.
Electronic literature searches were conducted
on PubMed, EMBASE, MEDLINE, Web of
Science, the Cochrane Library, CINAHL, PsycInfo,
PreQuest, PEDro databases from their inception to
May 10th, 2021. When searched databases allowed
limits, searches were restricted to human beings,
clinical trials, English, and Chinese. The following
keywords were used to obtain potential articles:
amputation, loss limb, pain, phantom limb, mirror
therapy, visual feedback. We also screened the ref-
erence lists of the potentially eligible articles that
were identified in database searches. The full search
strategy is available in Supplemental Appendix 1.
One author searched the nine databases and
removed the duplicates. Two authors independently
screened all titles, abstracts, and full-text articles
generated by the electronic database searches for
selecting eligible studies. When it was necessary, a
third author would discuss any disagreements with
the two authors. The included articles met the fol-
lowing inclusion criteria: (1) participants with diag-
nosed amputation with phantom limb sensation or
phantom limb pain; (2) designed randomized con-
trolled trial (RCT); (3) intervention based on mirror
therapy, that is, patients can observe the mirror vis-
ual feedback of their intact limb superimposing on
the amputated side; (4) control therapy without any
form of mirror visual feedback applied; (5) reported
at least one of outcome measures, such as pain
intensity, phantom limb pain severity, total daily
time experiencing phantom limb pain; and (6) pro-
vided sufficient data to calculate the effect size. The
Wang et al. 3
studies were excluded if: (1) duplicated studies; (2)
only abstract was available or numerical scores of
outcomes were not reported; and (3) published in
language other than either English or Chinese
language.12
Two authors independently extracted data
from the studies using standard data extraction
forms adapted from Cochrane Collaboration.13
The following data from each included study
were extracted: first author, year of publication,
participants population, gender and mean age of
the participants, mirror therapy and control group
intervention performed, outcome measures, and
adverse effect. Both authors were required to
achieve a consensus on each item on the data
extraction form. If disagreement occurred, a third
arbitrator participated in the determination.
The methodological assessment for each
included article was independently assessed by two
authors using the Physiotherapy Evidence Database
(PEDro) scale.14 This scale contained 11 parts: eli-
gibility criteria, random allocation, concealed allo-
cation, baseline comparability, blind subjects, blind
therapists, blind assessors, adequate follow-up,
intention-to-treat analysis, between-group compar-
isons, point estimates, and variability. The maxi-
mum score of PEDro scale was 10 points (eligibility
criteria item does not contribute to total score), and
the score of 9–10 points, 6–8 points, 4–5 points,
and <4 points were categorized as excellent, good,
fair, and poor quality respectively.14
The Cochrane risk of bias tool was adopted to
assess the risk of bias of the included studies.13 This
scale contained seven parts: sequence generation
and allocation sequence concealment (selection
bias), masking of participants, personnel and out-
come assessment (detection bias and performance
bias), selective reporting (reporting bias), incom-
plete outcome data (attrition bias), and other bias
(e.g. fund assistance and baseline comparability).
Each part was evaluated for low risk of bias, unclear,
or high risk of bias. The risk of bias and applicabil-
ity was analyzed using RevMan 5.4 (Cochrane
Collaboration’s Information Management System).
The Grading of Recommendations Assessment,
Development, and Evaluation (GRADE) approach15
were applied to assess the confidence of the effect
estimates on the basis of the following criteria:
presence of study limitations (RoB), indirectness of
evidence, inconsistency of results/unexplained het-
erogeneity, imprecision of results, and high proba-
bility of publication bias. This process was
independently performed by two authors, with the
participation of a third one when discrepancy
occurred.
The RevMan 5.4 was employed to perform the
meta-analysis. A minimum of three studies judged
similar enough in terms of the comparator and out-
come measures were considered sufficient for
pooling data for the meta-analysis. If the data
reported in articles could not be used for data pool-
ing, the authors of the articles were contacted to
request the necessary data. If we could not get the
data from the authors, estimates were made based
on the sample size, median, interquartile range, and
95% confidence interval (CI).16–18
For continuous outcome measures of the inter-
vention, effects were evaluated through the Mean
Difference (MD) or the Standardized Mean
Difference (SMD) along with the 95% Confidence
Interval (CI), of post-intervention values. The
Q-test and the I2 were employed to rate heterogene-
ity of combined studies. The values for I2 at 25%,
50%, and 75% indicate low, moderate, and high
heterogeneity, respectively. If I2 > 50%, a random-
effects model was conducted to calculate the pooled
effect size (ES) of SMD, otherwise a fixed-effect
model was used.19 SMD of >0.8 were considered
to represent a large effect size, and SMD ranging
from 0.5 to 0.8 and from 0.2 to 0.5 were considered
to represent moderate and small effect sizes, respec-
tively.20 Subgroup analyses were used to explore
the source of heterogeneity and to investigate the
potentially differential effects when comparing mir-
ror therapy with different forms of control therapy.
A negative value for ES indicates more favorable
outcome scores for the group of intervention, a pos-
itive ES indicates a more favorable outcome for the
control group. The synthesized results were pre-
sented in forest plots and the funnel plot was
employed to examine the publication bias.19
Result
We retrieved 2397 articles from nine electric data-
bases and manual searches from bibliography lists
4 Clinical Rehabilitation 00(0)
Figure 1.  PRISMA flow diagram.
following the PRISMA guideline (Figure 1). There
were 1640 articles after removing duplicates (n =
757). The titles and abstracts of these records were
then screened, the potentially relevant articles (n =
20) were further assessed for eligibility according to
their full-texts. Finally, 11 comparative studies.21–31
met the inclusion criteria and were selected for qual-
itative analysis. The reference list of excluded
studies after full-text checking can be found in
Supplemental Appendix 2.
The remaining 11 randomized controlled trials
were fully analyzed, approved by both reviewers
and the data were extracted. The characteristics of
the included studies were summarized in Table 1.
The 11 studies were published between 2003 and
2020, including a total of 491 subjects with 417
Table1.  The characteristics of included studies.
Study Sample size n Age of years Gender Mean months Amputation Intervention (dosage) Outcome Side
(EG/CG) (mean ± SD) (M/F) since amputation site measures effect
EG CG
Wang et al.

Brodie 21 (11/10) 51.5 ± 12.5 16/5 189 ULLA MT (NR) CM (NR) Description of PL NO
et al.21 control
Brodie 80 (41/39) 53.3 ± 15.8 63/17 108 ULLA MT (NR) CM (NR) VAS, MPQ, PLP NO
et al.22 frequency
Chan et al.23 18 (6/12) NR NR NR ULLA MT (15 minutes/day, 8 CG1: CM (15 minutes/day, 4 weeks) VAS YES
weeks) + MT (15 minutes/day, 4 weeks)
CG2: MV (15 minutes/day, 4 weeks)
+ MT (15 minutes/day, 4 weeks)
Tung et al.24 20 (11/9) 26.7 ± 5.6 20/0 5.7 BLLA MT (20 minutes/day, one MV (20 minutes/day, one month) VAS, MPQ NR
month)
Tilak et al.25 25 (12/13) 39 ± 10.4 23/2 0.4 UU/LLA MT (20 minutes/day, 4 days) TENS (20 minutes/day, 4 days) VAS, UPS NO
Finn et al.26 15 (9/6) 28.7 ± 14.9 15/0 4.5 UULA MT (15 minutes/day, 5 days/ CG: CM (15 minutes/day, 5 days/ VAS, TDTEP YES
week, 4 weeks) week, 4 weeks) or MV (15 minutes/
day, 5 days/week, 4 weeks)
Ramadugu 60 (32/28) 17–62a 60/0 NR UU/LLA MT (15 minutes/day, 4 CM (15 minutes/day, 4 weeks) + MT VAS, MPQ, PLP NO
et al.28 weeks) (15 minutes/day, 4 weeks) frequency and
duration
Ol et al.27 45 (15/30) 55.7 ± 6.7 45/0 275 ULLA MT (5 minutes × 2/day, 4 CG1: TS (5 minutes × 2/day, 4 VAS NR
weeks) weeks)
CG2: MT (5 minutes × 2/day, 4
weeks) + TS (5 minutes × 2/day, 4
weeks)
Rothgangel 75 (51/24) 61.1 ± 14.2 52/23 66.7 ULLA MT1 (30 minutes × 10, SE (30 minutes × 10, 4 weeks) + NRS, PLP frequency YES
et al.29 4 weeks) + teleMT (⩾5 selfSE (⩾5 minutes × 10, 6 weeks) and duration, NPSI,
minutes × 10, 6 weeks) PSFS, PDI, PSEQ,
MT2 (30 minutes × 10, GPE, EQ-5D-5L
4 weeks) + selfMT (⩾5
minutes × 10, 6 weeks)
Anaforoglu 40 (20/20) 31.1 ± 7.2 23/17 20.4 ULLA MT (15 minutes/day, 4 PE (15 repetitions/day, 4 weeks) VAS, SF-36, BDI NR
Kulunkoglu weeks)
et al.30
Mallik et al.31 92 (46/46) 34.8 ± 12.5 73/19 NR UU/LLA MT (first 30 minutes in MV (first 40 minutes in hospital, then VAS NO
hospital, then at home) at home)

EG: experimental group; CG: control group; M: male; F: female; ULLA: unilateral lower limb amputees; BLLA: bilateral lower limb amputees; UU/LLA: unilateral upper limb or lower limb amputees;
UULA: unilateral upper limb amputees; PL: phantom limb; PLS: phantom limb sensation; PLP: phantom limb pain; MT: mirror therapy; CM: covered mirror; MV: mental visualization; TENS:
transcutaneous electrical nerve stimulation; TS: tactile stimuli; SE: sensomotor exercises (sensory stimuli + phantom exercises); PE: phantom exercises; teleMT: teletreatment of mirror therapy;
selfMT: self-conducted mirror therapy; selfSE: self-conducted sensomotor exercises; VAS: visual analog scale; MPQ: McGill Pain Questionnaire; UPS: universal pain score; TDTEP: total daily time
experiencing pain; NRS: numeric rating scale; NPSI: neuropathic pain symptom inventory; PSFS: patient-specific functional scale; PDI: pain disability index; PSEQ: pain self-efficacy questionnaire; GPE:
global perceived effect scale; EQ-5D-5L: 5-dimensional EuroQol questionnaire; SF-36: short-form 36; BDI: beck depression inventory; NR: not reported.
a
The study only reported the age of patients ranged from 17 to 62 years
5
6 Clinical Rehabilitation 00(0)

Table 2.  Methodological quality of the included studies (PEDro scale).

Study Score Methodological PEDro item number

quality
1 2 3 4 5 6 7 8 9 10 11
Brodie et al.21 2 Poor ＋ ＋ ＋  
Brodie et al.22 5 Fair ＋ ＋ ＋ ＋ ＋ ＋
Chan et al.23 3 Poor ＋ ＋ ＋
Tung et al.24 5 Fair ＋ ＋ ＋ ＋ ＋ ＋
Tilak et al.25 7 Good ＋ ＋ ＋ ＋ ＋ ＋ ＋ ＋
Finn et al.26 6 Good ＋ ＋ ＋ ＋ ＋ ＋ ＋
Ramadugu et al.28 7 Good ＋ ＋ ＋ ＋ ＋ ＋ ＋ ＋
Rothgangel et al.29 8 Good ＋ ＋ ＋ ＋ ＋ ＋ ＋ ＋ ＋
Ol et al.27 5 Fair ＋ ＋ ＋ ＋ ＋ ＋
Anaforoglu Kulunkoglu 6 Good ＋ ＋ ＋ ＋ ＋ ＋ ＋
et al.30
Mallik et al.31 5 Fair ＋ ＋ ＋ ＋ ＋ ＋

Studies were classified as having excellent (9–10), good (6–8), fair (4–5), or poor (<4) quality. Scale of item score: +, present.
The PEDro scale criteria are (1) eligibility criteria; (2) random allocation; (3) concealed allocation; (4) similarity at baseline on
key measures; (5) participant blinding; (6) instructor blinding; (7) assessor blinding; (8) more than 85% retention rate of at least
one outcome; (9) intention-to-treat analysis; (10) between-group statistical comparison for at least one outcome; and (11) point
estimates and measures of variability provided for at least one outcome.

unilateral lower limb amputees, 54 unilateral
upper limb amputees, and 20 bilateral lower limb
amputees. The sample size of the included studies
ranged from 15 to 92 patients. The reasons for
amputation include diabetes, dysvascular, tumor,
trauma, and other medical conditions. As the main
outcome measure for pain intensity, Visual Analog
Scale (VAS) was used by nine studies,22–28,30
Numeric Rating Scale (NRS) was used by one
study.29 One study only measured for phantom
limb sensation.21 The intervention included the use
of traditional mirror therapy,21–23,25–30 teletreat-
ment of mirror therapy delivered in tele mode29 or
action observation of others’ movements,24 and the
comparison contained covered mirror,21–23,26,28
mental visualization,23,24,26,31 phantom exercise,30
tactile stimuli,27 sensorimotor exercise,29 and
Transcutaneous Electrical Nerve Stimulation.25
Supplemental Appendix 3 shows the details about
intervention performed in studies.
The methodological quality of the randomized
controlled trials was evaluated using the PEDro
scale and the quality of included studies was from
poor to good with score ranging from 2 to 8 points
(Table 2).
See Figure 2 for risk of bias and applicability
concerns judged by authors about each domain for
each included study and Figure 3 for risk of bias
and applicability concerns judged by authors about
each domain presented as percentages across
included studies (the tool recommended in the
Cochrane Handbook for Systematic Reviews of
Interventions).
Among the 11 involved RCTs in qualitative
synthesis, one study21 only reported about phan-
tom limb sensation and did not do use any out-
come measurement of phantom limb pain, and
another study23 did not report appropriate numeri-
cal outcomes of phantom limb pain. Therefore,
nine RCTs22,24–30 involving 372 participants were
included in quantitative synthesis, the quality of the
nine studies were from fair to good with scores rang-
ing from 5 to 8 points according to PEDro scale. In
the nine involved RCTs, two 2-arm studies22,28 com-
pared mirror therapy with covered mirror, one
2-arm study30 compared mirror therapy with
phantom exercise, two 2-arm study24,31 compared
mirror therapy with mental visualization, one
2-arm26 study compared mirror therapy with cov-
ered mirror or mental visualization, one 2-arm
Wang et al. 7

Questionnaire was used in three studies22,24,28

Blinding of participants and personnel (performance bias)

while one28 did not report enough data of the
results, and the frequency of phantom limb pain

Blinding of outcome assessment (detection bias)

Random sequence generation (selection bias)
was assessed in three studies22,28,29 with a numeri-

Incomplete outcome data (attrition bias)

Allocation concealment (selection bias)
cal scale or the number of episodes per day.

Selective reporting (reporting bias)

Furthermore, the duration of phantom limb pain
was assessed using the total minutes per day,26
quality of life using Short-Form 36 (SF-36),30
psychological status using the Beck depression
inventory (BDI).30 As a minimum of three studies

Other bias
judged similar enough in terms of the comparator
+ + – ? + + +
and outcome measures were considered sufficient
Anaforaglu 2019
for pooling data for the meta-analysis, pain inten-
Brodie 2003 ? ? – ? ? ? +
sity was the only outcome measure we pooled in
Brodie 2007 ? ? – ? ? ? + this meta-analysis. And subgroup analyses in
terms of the type of control intervention were
Chan 2007 + ? – ? ? ? ?
made to contrast the outcomes of mirror therapy
Finn 2017 + ? – ? + + + with other forms of interventions for amputees
Mallik 2020 + ? ? ? + + ?
with phantom limb pain.

Ol 2018 + – – – + + +

Ramadugu 2017 + + – + + + + Immediate treatment effects at

Rothgangel 2018 + + – + + + + intervention endpoint: Phantom limb
Tilak 2016 + + – + ? + +
pain intensity – mirror therapy versus
+ ? – ? + + +
control
Tung 2014

Compared with the findings for the control group

in the nine included studies,22,24–30 the pooled SMD
Figure 2.  Risk of bias graph: review authors’
showed that the differences were statistically sig-
judgments about each risk of bias item presented as
percentages across all included studies. nificant between the two groups for alleviating
pain intensity (−0.81; 95% CI = −1.36 to −0.25;
P = 0.005; I2 = 82%; n = 372) (Figure 4(a)). The
study29 compared mirror therapy with sensorimo- funnel plot was not symmetrical which indicated
tor exercise, one 2-arm study25 compared mirror that publication bias was observed on pain of
therapy with transcutaneous electrical nerve stim- amputees (Figure 5). It was likely that the limited
ulation, one 3-arm study27 compared mirror ther- number of included studies and the heterogeneity
apy with tactile stimuli and mirror therapy between studies caused the unsymmetrical plot. To
combined with tactile stimuli. Multiple outcome observe whether the outliers could have influenced
measures were used among the included studies. the overall significance and heterogeneity, the
Pain intensity assessed with the Visual Analog studies by Anaforoglu Kulunkoglu et al.30 and
Scale or Numeric Rating Scale was selected as Mallik et al.31 were excluded, and the significance
our targeted measures. In total, the Visual Analog of the pooled SMD for pain intensity still remained
Scale was used in eight studies22,24–28,30,31 and the (−0.40; 95% CI = −0.66 to −0.14; P = 0.003; n =
Numeric Rating Scale was used in one study29 to 240), with low heterogeneity (I2 = 0%) (Figure 1
measure pain intensity. The multidimensional in Supplemental Appendix 4) and symmetrical fun-
assessment of pain measured by McGill Pain nel plot (Figure 2 in Supplemental Appendix 4).
8 Clinical Rehabilitation 00(0)

Random sequence generation (selection bias)

Allocation concealment (selection bias)

Blinding of participants and personnel (performance bias)

Blinding of outcome assessment (detection bias)

Incomplete outcome data (attrition bias)

Selective reporting (reporting bias)

Other bias

0% 25% 50% 75% 100%

Low risk of bias Unclear risk of bias High risk of bias

Figure 3.  Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages
across all included studies.

Figure 4.  Forest plot for the effect of mirror therapy on pain intensity: (a) forest plot for the effect of mirror
therapy compared with control group, (b) forest plot for the effect of mirror therapy compared with covered
mirror, and (c) forest plot for the effect of mirror therapy compared with mental visualization.
Wang et al. 9
Figure 5.  Funnel plot for the effect of mirror therapy
on pain intensity.
Immediate treatment effects at
intervention endpoint: Phantom limb
pain intensity – mirror therapy versus
covered mirror
Compared with the findings for the covered mirror
in three included studies,22,26,28 the pooled SMD
showed that the differences were not statistically
significant between the two groups for alleviating
pain intensity (−0.25; 95% CI = −0.73 to 0.24;
P = 0.32; I2 = 14%; n = 90) in the mirror therapy
group (Figure 4(b)).
Immediate treatment effects at
intervention endpoint: Phantom limb
pain intensity – mirror therapy versus
mental visualization
Compared with the findings for the mental visuali-
zation (including the phantom exercise, which was
performed the same as mental visualization) in four
included studies,24,26,30,31 the pooled SMD showed
that the differences were statistically significant
between the two groups for alleviating pain inten-
sity (−1.47; 95% CI = −2.42 to −0.52; P = 0.002;
I2 = 82%; n = 167) in the mirror therapy group
(Figure 4(c)).
Treatment effects at mid-term follow-up:
Phantom limb pain intensity – mirror
therapy versus control
Four included studies28–31 reported the treatment
effect at mid-term follow up (about three months),
the pooled SMD showed that the differences were
statistically significant between the two groups for
alleviating pain intensity (−0.59; 95% CI = −1.16
to −0.03; P = 0.046; I2 = 786%; n = 254) in the
mirror therapy group (Figure 6(a)).
Treatment effects at long-term follow-
up: Phantom limb pain intensity – mirror
therapy versus control
Four included studies28–31 reported the treatment
effect at long-term follow up (about six months),
the pooled SMD showed that the differences were
statistically significant between the two groups for
alleviating follow-up pain intensity (−1.21; 95%
CI = −2.22 to − 0.20; P = 0.02; I2 = 92%; n =
164) in the mirror therapy group (Figure 6(b)).
The quality of evidence according to the
GRADE system is presented in Supplemental
Appendix 5 Table S1. We found fair-quality evi-
dence that mirror therapy has a moderate effect on
pain reduction after the end of the intervention. The
quality of evidence was downgraded by high het-
erogeneity, small sample size, and/or wide 95% CI.
Supplemental Appendix 5 shows the summary of
findings.
Three studies24,27,30 did not report information
about adverse effect, five studies21,22,25,28,31 reported
that there was no increase in the phantom pain or
any other adverse effects occurred in any of the
subjects in both group, one study23 reported that
there were two patients had brief reactions (<2
minutes) of grief on viewing the reflected intact
lower limb, one26 reported that one subject experi-
enced an increase in pain during mirror therapy
treatment, one29 pointed out that four patients in the
mirror therapy group reported short events of
increased phantom limb pain during treatment and
two patients from the mirror therapy group exhib-
ited minor degrees of nausea, emotional reactions,
and increased transpiration at the beginning of the
treatment.
Discussion
Our findings suggested that mirror therapy was
effective for reducing phantom limb pain for ampu-
tees when compared with other control therapies.
10 Clinical Rehabilitation 00(0)

Figure 6.  Forest plot for the mid-term and long-term effect of mirror therapy on pain intensity: (a) forest plot for
the mid-term (about three months) effect of mirror therapy on pain intensity and (b) forest plot for the long-term
(about six months) effect of mirror therapy on pain intensity).

The pain-reduction effects showed durability at
both three- and six-month follow-up. The subgroup
analysis based on type of control therapy suggested
that mirror therapy was superior to mental visuali-
zation on alleviating postintervention phantom
limb pain intensity, but not superior to control ther-
apy using a covered mirror. The differential effect
might be attributed to the potential effect of direct
observation of intact limb movement on pain
reduction, thus eliminating the between-group dif-
ference in effect. Yet, evidence from subgroup
analysis should be interpreted cautiously due to the
limited number of included studies.
The latest systematic review published in 2016
by Barbin et al.10 also evaluated the current evi-
dence of the effectiveness of mirror therapy for
treating phantom limb pain. However, the review
just included two eligible RCTs23,25 and did not
perform meta-analysis, it could not provide effi-
cacy proof of recommendation of mirror therapy
on phantom limb pain. Our study adds new value to
the current evidence and updates the conclusions.
Be different from Barbin’ opinion, we recommend
mirror therapy as a first intention treatment in
phantom limb pain instead of other rehabilitation
methods. Because mirror therapy not only allows
patients’ limbs to become “unfrozen,” but allows
amputees to regain control over their phantom limb
and experience pain reduction.
Of particular note is the adverse effect, knowl-
edge about adverse effects needs to inform treat-
ment decisions. The potential adverse effects of
mirror therapy were frequently mentioned by ther-
apists in clinical practice, in some studies,23,26,29
adverse effects of mirror therapy were reported
such as aggravation of the phantom limb sensation
and/or phantom limb pain, telescopic distortion of
the phantom limb, nausea, dizziness, confusion,
the sensation of irritation, and grief. Therapists
should systematically evaluate for such negative
effects and sufficiently inform patients before start-
ing the mirror therapy, and the treatment should be
stopped when the adverse effects are too strong.
Strengths of our study include a comprehensive
search, assessment of eligibility, assessment of risk
of bias, and data abstraction independently. The
evidence is from fair quality evidence because of
risk of bias due to all studies were ranked as high
Wang et al. 11
risk of bias for blinding of participants and person-
nel, most of studies were ranked as high or unclear
risk of bias for allocation concealment and blinding
of outcome assessment. No trial was able to blind
instructor and blinding patients, this finding was
not surprising since it was unfeasible for mirror
therapy training.
There are several limitations in our systematic
review. First, the number of included RCTs was
small (n = 11) and relatively small sample sizes in
each study (ranging from 6 to 46 in mirror therapy
groups). Second, studies were implemented with
high heterogeneity: they differed from the dura-
tion and frequency of the mirror therapy sessions
delivered to the experimental group, from the
types of intervention delivered to the control
group, for example, covered mirror; mental visu-
alization; transcutaneous electrical nerve stimula-
tion; tactile stimuli and sensorimotor exercises,
and the time point to assess. Third, the effects at
long-term follow-up have to be considered with
caution since they were based only on three stud-
ies. In future studies, the procedure for mirror
therapy should be standardized, and larger sample
sizes are needed to determine the efficacy of mir-
ror therapy accurately.
In conclusion, the present study provides the
latest evidence to support the implementation of
mirror therapy as an alternative treatment to reduce
phantom limb pain in amputees compared with the
control in the short term. It is recommended that
further research including larger sample sizes and
longer follow-up period studies in consideration of
various covariates, such as frequency and duration
of pain, amputation level, and mirror therapy appli-
cation, should be performed.
Clinical messages
•• The meta-analysis found low to fair evi-
dence suggesting a positive effect of mir-
ror therapy for phantom limb pain in
amputation patients.
•• Further investigations are required to
determine the optimal mirror therapy
treatment parameters and to evaluate
long-term effects.
Author contributions
Conceptualization: Fengyi Wang, Rengang Zhang, Quan
Wei. Search strategy, study selection and data extrac-
tion: Fengyi Wang, Rengang Zhang, Dinggen Li, Yu
Wang. Articles assessment and statistical analysis:
Fengyi Wang, Rengang Zhang, Jiaqi Zhang, Yonghong
Yang. Project administration: Rengang Zhang.
Supervision: Yonghong Yang, Quan Wei.Writing – orig-
inal draft: Fengyi Wang, Rengang Zhang, Jiaqi Zhang.
Writing – review & editing: Jiaqi Zhang, Yonghong
Yang, Quan Wei. All authors analyzed the results and
have read and approved the final version of the
manuscript.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest
with respect to the research, authorship, and/or publica-
tion of this article.
Funding
The author(s) disclosed receipt of the following financial
support for the research, authorship, and/or publication
of this article: This work was supported by the Project of
the Science and Technology Department in Sichuan
province (Grant No. 2019YJ0119).
ORCID iDs
Fengyi Wang https://orcid.org/0000-0002-8137-1975
Quan Wei https://orcid.org/0000-0002-0541-905X
Supplemental material
Supplemental material for this article is available online.
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