The effectiveness of hypnosis for pain relief: A systematic review and meta-analysis of 85 controlled experimental trials

Abstract

The current meta-analysis aimed to quantify the effectiveness of hypnosis for reducing pain and identify factors that influence efficacy. Six major databases were systematically searched for trials comparing hypnotic inductions with no-intervention control conditions on pain ratings, threshold and tolerance using experimentally-evoked pain models in healthy participants. Eighty-five eligible studies (primarily crossover trials) were identified, consisting of 3632 participants (hypnosis nö=ö2892, control nö=ö2646). Random effects meta-analysis found analgesic effects of hypnosis for all pain outcomes (gö=ö0.54-0.76, p's<.001). Efficacy was strongly influenced by hypnotic suggestibility and use of direct analgesic suggestion. Specifically, optimal pain relief was obtained for hypnosis with direct analgesic suggestion administered to high and medium suggestibles, who respectively demonstrated 42% (pö<ö.001) and 29% (pö<ö.001) clinically meaningful reductions in pain. Minimal benefits were found for low suggestibles. These findings suggest that hypnotic intervention can deliver meaningful pain relief for most people and therefore may be an effective and safe alternative to pharmaceutical intervention. High quality clinical data is, however, needed to establish generalisability in chronic pain populations.

Full text

HYPNOSIS AND PAIN
1
The effectiveness of hypnosis for pain relief: A systematic
review and meta-analysis of 85 controlled experimental trials
Trevor Thompsona, Devin B. Terhuneb, Charlotte Orama, Joseph Sharangparnia, Rommana
Roufa, Marco Solmic, Nicola Veronesed, Brendon Stubbsef
aFaculty of Education and Health, University of Greenwich, London SE9 2UG, UK
bDepartment of Psychology, Goldsmiths, University of London, London, UK
cDepartment of Neuroscience, University of Padova, Padova, Italy
dNational Research Council, Neurosciences Department, Aging Branch, Padova, Italy
ePhysiotherapy Department, South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK
fDepartment of Psychological Medicine, King's College, De Crespigny Park, London SE5 8AF, UK
Corresponding Author:
Trevor Thompson, t.thompson@gre.ac.uk, +4420 8331 9632
Number of manuscript pages: 29
Number of figures: 3
Number of tables: 2
Online supplementary material: 2 (search strings and study validity ratings)
Word count (exc. abstract, references, tables): 4803
Declaration of interest
Declarations of interest: none

HYPNOSIS AND PAIN
2
ABSTRACT
The current meta-analysis aimed to quantify the effectiveness of hypnosis for
reducing pain and identify factors that influence efficacy. Six major databases were
systematically searched for trials comparing hypnotic inductions with no-
intervention control conditions on pain ratings, threshold and tolerance using
experimentally-evoked pain models in healthy participants. Eighty-five eligible
studies (primarily crossover trials) were identified, consisting of 3632 participants
(hypnosis n=2892, control n=2646). Random effects meta-analysis found analgesic
effects of hypnosis for all pain outcomes (g=0.54-0.76, p’s<.001). Efficacy was
strongly influenced by hypnotic suggestibility and use of direct analgesic suggestion.
Specifically, optimal pain relief was obtained for hypnosis with direct analgesic
suggestion administered to high and medium suggestibles, who respectively
demonstrated 42% (p<.001) and 29% (p<.001) clinically meaningful reductions in
pain. Minimal benefits were found for low suggestibles. These findings suggest that
hypnotic intervention can deliver meaningful pain relief for most people and
therefore may be an effective and safe alternative to pharmaceutical intervention.
High quality clinical data is, however, needed to establish generalisability in chronic
pain populations.
Keywords: pain; hypnosis; analgesia; review; meta-analysis; suggestion

HYPNOSIS AND PAIN
3
1 INTRODUCTION
Pain affects up to 1.5 billion adults worldwide (Yaqub, 2015) and has a substantial
negative impact on quality of life. In addition to becoming one of the leading causes
of years lived with disability (GBD Causes of Death Collaborators, 2017), pain also
incurs a massive economic burden. Pain-related health care and lost productivity
incur annual costs of up to $635 billion in the US alone (Gaskin and Richard, 2012),
greater than that of heart disease, cancer or diabetes. Increasing concern over the
side effects, addictive properties and costs of opioid medication has led to an urgent
need to identify non-pharmacological interventions for pain that are effective, safe,
and inexpensive.
One popular psychological intervention for pain management is hypnosis, which
typically involves relaxation, focused attention and targeted verbal suggestion to
alter perceptual experience and behaviour (Jensen and Patterson, 2014). Hypnosis is
easily administered, has few or no side effects, and is inexpensive if delivered in a
pre-recorded format (e.g., audio recording) that does not require the presence of a
practitioner (Jensen et al., 2015). Recent research has indicated that hypnotic
suggestion produces altered activity in key regions of the brain involved in pain
regulation, including the anterior cingulate, prefrontal and insular cortices (Del
Casale et al., 2015), and this could provide a basis for possible analgesic effects.
Exaggerated claims of hypnotic analgesia have, however, created scepticism over its
efficacy (Larkin, 1999), and a rigorous evaluation of controlled trials is needed to
properly evaluate and quantify its effectiveness for reducing pain.
A recent meta-analysis of 14 trials of people with chronic pain (Adachi et al., 2014)
concluded that hypnosis was effective for managing pain. However, this conclusion
was based primarily on a subset of 4 studies comparing hypnosis with standard care
(d=.60, CI95[0.03, 1.17]) that was largely unreplicated in other subset comparisons.
Individual study findings were inconsistent, probably resulting from variation in pain
conditions, control comparisons (e.g. treatment-as-usual, no intervention) and
hypnotic suggestibility of study samples, and thus this meta-analysis provides an

HYPNOSIS AND PAIN
4
unclear overall picture of the analgesic benefits of hypnosis. Other reviews have
indicated beneficial effects of hypnosis on labour pain (Madden et al., 2016), and
fibromyalgia (Bernardy et al., 2011), but have all concluded that supporting clinical
evidence is of low methodological quality.
The effect of hypnosis on pain has also been examined using experimental
paradigms to provide a level of methodological control difficult to achieve in clinical
settings. A meta-analysis of 18 studies that included 12 experimental and 6 clinical
trials (Montgomery et al., 2000) found significant moderate analgesic effects of
hypnosis (d=.67). While this represents an important finding, several important
limitations driven primarily by a lack of available data should be noted. First,
determining the level of meaningful analgesia from hypnosis is difficult given the
absence of a metric on which meaningful clinical change can be mapped (e.g. 0-10
numerical ratings). Second, estimates of hypnotic analgesia were complicated by
considerable heterogeneity in control comparators. Third, factors such as hypnotic
suggestibility and the use of direct analgesic suggestion that may be critical to
treatment success (Patterson and Jensen, 2003) could not be adequately assessed. A
large number of experimental studies have been published since this meta-analysis
from almost 20 years ago, thereby providing a new opportunity for more reliable
estimates of the effectiveness of hypnosis for pain reduction and to assess potential
moderating factors.
To fill the gap in current knowledge regarding the efficacy of hypnosis for pain, we
conducted a meta-analysis comparing hypnotic interventions with no-treatment
control in studies using experimental pain models in healthy participants. Specific
aims were to obtain precise estimates of: (1) the magnitude of hypnotic analgesia on
standardized and unstandardized scales (e.g. 0-10 ratings); and (2) the degree to
which intervention effectiveness is dependent upon both hypnotic suggestibility and
the inclusion of direct suggestions of pain relief.

HYPNOSIS AND PAIN
5
2 METHOD
This systematic review was conducted in accordance with the PRISMA-P 2015
statement for systematic review and meta-analysis protocols (Moher et al., 2015).
An a priori but unpublished protocol was followed (available from the authors upon
request).
2.1 Eligibility Criteria
Inclusion criteria were: (1) a hypnotic induction; (2) a non-hypnosis control condition
with no active intervention; (3) an experimental pain stimulus administered to
healthy participants; and (4) a quantitative assessment of pain. Although there is no
established consensus for a definition of a hypnotic induction (Terhune and Cardeña,
2016), we used the conceptualisation by Jensen and Patterson (2014) of suggestions
offered to another person to alter perceptual experience and voluntary action that
typically involves relaxation, focused attention and/or imagery. Exclusion criteria
were: (1) hypnosis induced by a pharmacological agent (e.g. ketamine); or (2) co-
administration of hypnosis with other intervention(s).
2.2 Search Strategy
PubMed, EMBASE, PsycINFO, CINAHL, CENTRAL and Web of Science databases were
searched independently by two reviewers (RR, JS) for potentially eligible studies
indexed from database inception until 21st May, 2018.
The search string consisted of three elements related to hypnosis AND pain AND
experimental noxious stimuli (see Appendix S1). Specific free text words chosen for
experimental pain methods were derived from Gracely (2005) and our previous
meta-analyses (Thompson et al., 2017a; Thompson et al., 2017b). Searches were
applied to all database fields where possible, or title/abstract/keywords where this
restriction was imposed by the database. Results were limited a posteriori to ‘human
studies’ and searches were augmented through manual searches of reference lists of
included articles and reviews.

HYPNOSIS AND PAIN
6
2.3 Study selection
Titles and abstracts of articles returned by initial searches were independently
screened by two reviewers (RR, JS) who rejected articles not meeting eligibility
criteria. The full-text of remaining articles was independently examined by the same
reviewers to reach a final list of articles. Disagreements at either screening stage
were resolved through discussion with a third reviewer (TT). When an eligible article
provided insufficient data for inclusion, corresponding authors were contacted up to
3 times over an 8-week period to request additional data. Of 20 author groups
contacted, 6 (30%) provided data sufficient to permit study inclusion (see
acknowledgements section).
2.4 Pain outcomes
Outcome variables were: (1) self-reported pain ratings (e.g. 0-10 rating scale), (2)
pain tolerance and (3) pain threshold. Pain threshold is the point at which pain is first
detected and tolerance is the point at which pain can no longer be endured, with
both measures typically quantified as stimulus intensity (e.g. temperature) or
exposure time.
Pain ratings were included to provide a clinically meaningful measure of pain, with
threshold and tolerance included as they represent behavioural responses to
minimal and maximal pain respectively.
2.5 Study quality
Two raters (RR, JS) independently rated each study for methodological quality on a
15-item validity scale assessing methodological rigour, selection and reporting bias
(Table S1). Items were based on Cochrane criteria and PRISMA recommendations,
and were adapted from Thompson et al. (2017a) for the current review.
2.6 Data Extraction
Extraction and coding of study data were performed by three authors (CO, RR, JS) on
a standardized template (Thompson et al., 2017a), with all data entry checked by

HYPNOSIS AND PAIN
7
another reviewer (TT). The following data were extracted: (1) pain outcomes; (2)
sample characteristics: age, gender, hypnotic suggestibility; (3) study characteristics:
location, design, pain induction method; (4) hypnotic induction: method (e.g.
Stanford procedure), format (e.g. verbal, virtual reality), direct suggestions of
analgesia (present, absent), number/duration of sessions, control condition (nothing,
placebo). For pain outcomes, when a study did not report Ms and SDs, effect sizes
were calculated from any other statistics that allowed their computation based on
standardised formulae (Cooper et al., 2009).
When a study provided data for multiple effect sizes (e.g. across different time
points), all such data were extracted. In addition, the following extraction decisions
were made: (1) for a few studies that did not report Ms/SDs but did report
significance thresholds (e.g. p<.01), we conservatively rounded these to absolute p-
values (e.g. p=.01) to compute effect size; (2) for a few studies that reported use of
hyperalgesic (pain increasing) and analgesic suggestions across different hypnotic
conditions, only analgesic data were extracted; (3) data from a few studies (k=3) that
used control conditions involving reading, relaxation or a simple cognitive task were
included, as although not entirely inactive, these were considered unlikely to have
substantial analgesic effects; (4) for a few studies (k=5) that collected pain ratings
using a tolerance model (where stimulus intensity/exposure time can potentially
vary across groups), pain outcome data were included. This was a conservative
strategy, as all studies reported longer exposure times for hypnosis, so pain ratings
in this condition would not be expected to be reduced due to the use of a tolerance
model. For (1), (3) and (4), sensitivity analyses were conducted to examine their
impact on effect size.
2.7 Hypnotic suggestibility
Hypnotic suggestibility is the degree of responsiveness to suggestions made within a
hypnotic induction. Scoring is typically based on the aggregation of behavioural
responses to a series of individual suggestions (e.g. whether suggestions of
heaviness or tiredness in the arm produce lowering of the hand by 6 inches or more)

HYPNOSIS AND PAIN
8
(Weitzenhoffer and Hilgard, 1962). Study samples were classified as low, medium or
high in hypnotic suggestibility if scores on standardised measures fell within the
following ranges: (a) Harvard Group Scale of Hypnotic Suggestibility:Form A
(HGSHS:A) and Stanford Hypnotic Suggestibility Scale (SHSS) forms A and C: low (0-
4), medium (5-7), high (8-12) (Shor and Orne, 1963; Weitzenhoffer and Hilgard,
1962); (b) Carleton University Responsiveness to Suggestion Scale: Objective
dimension (CURSS:O): low (0-2), medium (3-4), high (5-7) (Spanos et al., 1983b); and
(c) Stanford Hypnotic Arm Levitation Induction and Test (SHALIT): low (0-3), medium
(4-7), high (8-12) (Hilgard et al., 1979).
Classifications were made using two different methods. First, a study sample was
classified as low, medium or high suggestibility if the reported study range fell within
the above normative boundaries (k=40). Second, as sometimes only mean scores
were reported or ranges did not precisely match normative ranges, we used an
alternative, less stringent classification to maximise study inclusion (k=67) for
moderation analysis. Specifically, we made additional classifications when (a) the
mean suggestibility score fell within normative boundaries (and range was not
reported), or (b) reported study ranges closely approximated normative guidelines
(e.g. when 0-5, rather than 0-4, was reported for the Stanford scale). We employed
the less stringent classification in moderation analysis, but performed sensitivity
analysis to evaluate the impact of this decision.
2.8 Effect size
The standardized mean difference (SMD) for hypnosis vs. control was computed with
Hedges' g formula (Cooper et al., 2009), where 0.20, 0.50 and 0.80 can be broadly
translated as small, medium and large effects (Cohen, 1988). SMDs for all studies
were computed using original (unadjusted) standard deviations, but effect size
variance was computed dependent upon study design (Morris and DeShon, 2002).
Effect sizes were coded so that positive values indicated beneficial effects of
hypnosis (i.e. a decrease in pain ratings or an increase in threshold/tolerance).

HYPNOSIS AND PAIN
9
2.9 Meta-analysis
A random-effects model was used as heterogeneity in effect size due to variation in
study methodology is likely. As studies typically report multiple effect size data (e.g.
from the same subjects across multiple time points), we used a robust variance
estimation (RVE) method (Hedges et al., 2010) to account for within-study
dependency of effect sizes. In RVE, individual weights are based on the true common
correlation of within-study effect sizes. Although this value is usually unknown,
simulation studies have shown that different correlations tend to have little impact
on results (Tanner-Smith and Tipton, 2014; Hedges et al., 2010). We used r=0.65 as
our estimated correlation as this approximated that typically reported by studies
employing repeated testing, but conducted sensitivity analysis using lower (r=.40)
and higher (r=.90) correlations to examine the effect on parameter estimates. RVE
meta-analysis estimates are most reliable when 10 or more studies are available
(Tanner-Smith and Tipton, 2014). A few studies collected pain ratings on scales other
than 0-10 (e.g. 0-20), and these were transformed to a 0-10 scale.
2.10 Meta-regression
RVE meta-regression analyses were performed to identify potential sources of
heterogeneity size if moderate or greater inconsistency was found, as indicated by
I2>50% (Higgins et al., 2003) and 40 or more studies were available (Tanner-Smith
and Tipton, 2014).
Primary moderators were: (1) hypnotic suggestibility (low/medium/high), and (2)
direct analgesic suggestion (present/absent), with the hypothesis that hypnosis
would produce greater analgesia when participants were higher in hypnotic
suggestibility and direct suggestions of pain relief were present.
Secondary moderators were examined to provide preliminary data on any
moderating influence of hypnosis method, format (audio recording/live), comparison
group (control/placebo), study age, gender composition and pain induction method.
Where the endorsement of important study validity criteria varied across studies,

HYPNOSIS AND PAIN
10
the influence of these criteria as potential moderators of effect size was also
assessed.
2.11 Publication bias
To assess potential publication bias, funnel plots of average study effect sizes against
standard errors were examined for asymmetry resulting from a relative lack of small
studies with small effect sizes (i.e. those most likely to be non-significant and remain
unpublished). Asymmetry was also tested statistically with Egger’s bias test (Egger et
al., 1997) with p<.05 indicating asymmetry. If evidence of asymmetry was present, a
revised effect size was computed using the trim and fill method (Duval and Tweedie,
2000).
All analyses were performed using the robumeta (Fisher and Tipton, 2014) and
metafor (Viechtbauer, 2010) packages in R (R Core Team, 2017).
3 RESULTS
3.1 Study inclusion
An initial pool of 4,801 unique studies were identified through database searches,
with 14 additional records acquired through manual searching of reference lists.
Screening of titles/abstracts identified 229 potentially eligible articles, with full-text
review resulting in a final list of 85 eligible studies (see Figure 1). Key characteristics
of these studies are presented in Table 1.
3.2 Participant characteristics
The 85 studies provided data for 3,632 participants (hypnosis n=2,892, control n=
2,646, with crossover trials primarily used). Mean study age (reported by k=28 of 85
studies) was 24.6 years (SD=4.5) for hypnosis and 25.4 years (SD =4.4) for controls.

HYPNOSIS AND PAIN
11
Mean gender composition (k=62) was 63.5% female (SD=22.4) for hypnosis and
63.1% female (SD =23.8) for controls.
3.3 Study characteristics
Study designs used were crossover (k=61), pre-post control (k=22) and parallel
groups (k=2). Study locations were USA (k=32), Italy (k=16), Canada (k=15), Germany
(k=4), UK (k=3), France (k=3), Belgium (k=3), Denmark (k=2), Israel (k=2), Netherlands
(k=1), Australia (k=1), New Zealand (k=1), Romania (k=1) and Switzerland (k=1).
3.4 Pain assessment and induction
Different pain assessment (ks: intensity ratings=66, affective ratings=24,
tolerance=18, threshold=16) and pain induction (ks: cold=23, electric=22,
pressure=19, heat=16, ischemic=5, laser=2) methods were used, with multiple
assessment and induction methods within a single study sometimes employed.
Noxious stimuli were most commonly applied to the hand (k=62) or forearm/upper
arm (k=12).
3.5 Hypnotic induction and suggestibility
Details of hypnotic induction procedures are provided in Table 1, which we broadly
categorised as standard/typical hypnotic procedures (k=55) and standardized (e.g.
HGSHS/SHSS) inductions (k=30) (both procedures typically include combinations of
eye fixation, progressive relaxation and suggestions of drowsiness). Direct analgesic
suggestions (e.g. ‘you cannot feel pain because the glove you are wearing prevents
you from feeling it’) were present (k=72) and/or absent (k=37) and hypnosis was
delivered in several formats (ks: live=68, recorded audio=19, virtual media=3).
Comparison conditions consisted of an inactive control (k=83) and/or a placebo
condition (k=8) such as a sham analgesic spray.
Hypnotic suggestibility was assessed in 78 studies primarily using the SHSS (k=35;
form C=28, form A=7), HGSHS:A (k=23), CURSS:O (k=19), SHALIT (k=2) and/or WSGC

HYPNOSIS AND PAIN
12
(k=2) tests. Most studies used a single session of hypnosis (k=74), with a small subset
using two (k=10) or three sessions (k=1) with sessions usually lasting 15-30 mins.
3.6 Study validity criteria
Study ratings for each validity criteria are shown in Appendix S2. Although most
study criteria were well met, several criteria were not. Perhaps most importantly,
only 42% of studies explicitly reported random allocation/counterbalancing. More
specifically, 18/24 (75%) parallel/pre-post control designs reported random group
allocation, and only 18/61 (30%) crossover studies counterbalanced/randomised
presentation order, with control procedures typically occurring first. As this could
potentially result in bias from habituation or sensitisation to repeated pain
stimulation, the impact of randomisation vs. non-randomisation on effect size was
examined in moderation analysis. Only a few studies screened participants for pre-
existing pain (18%) or gave details on use of pain medication (25%), although these
would seem less likely to present serious threats to overall conclusions given the
primary use of crossover designs.
3.7 Rater agreement
For study selection, good rater agreement was shown at the full-text review stage
(95% agreement, kappa=.80), with initial discrepancies primarily due to uncertainty
over control group eligibility. For ratings of validity criteria, acceptable agreement
was demonstrated for the majority of the individual items (agreement=77-99%;
kappa=0.45-0.92) with agreement lowest for adequacy of control group description
(77%) and recruitment procedures (83%). In all cases of disagreement, 100%
consensus was reached after discussion with a third reviewer (TT).
3.8 Outliers
Studentized residuals>3.3 from initial meta-analysis (Viechtbauer and Cheung, 2010)
suggested one potential outlier for tolerance (Casiglia et al., 2007), one for pain
affect (Price and Barber, 1987) and two for pain intensity (Faymonville et al., 2003;
Crawford et al., 1993). Although no obvious reason for these outlying values could

HYPNOSIS AND PAIN
13
be identified from further scrutiny of these papers, these cases were conservatively
removed to prevent potential distortion of results (as these were all high positive
values, removal resulted in marginally reduced, rather than inflated, effect sizes).
3.9 Meta-analysis
Pain ratings: Intensity
Meta-analysis of 64 studies (205 effect sizes) of pain intensity across 3,039
participants (hypnosis n=2,366, control n=2,168), found hypnosis to result in lower
overall pain intensity, SMD=0.74, CI95[0.63, 0.84], p<.001 (Figure 2), classifiable as a
large effect (Cohen, 1988). Positive effect sizes were found in all but one study, but
with high inconsistency in magnitude (I2=75%).
Analysis of 52 studies which provided raw, unstandardized 0-10 ratings were
consistent with these results (Mean Difference=1.49, CI95[1.21, 1.78], p<.001). A
decrease from 5.5 to 4.0 points was observed with hypnosis, a reduction of around
27% or 1.5 points.
Pain ratings: Affect
Meta-analysis of 23 studies (103 effect sizes) of 751 participants (hypnosis n=665,
control n=587) revealed similarly lower affective pain ratings for hypnosis,
SMD=0.76, CI95[0.53, 0.99], p<.001. High inconsistency in effect size was observed
(I2=78%), although positive effect sizes were observed for all 23 studies. Analysis of
unstandardized 0-10 pain affect ratings from 18 studies indicated a mean reduction
of 1.53 points, CI95[1.14, 1.93], p<.001, for hypnosis.
Pain tolerance
Meta-analysis of 17 studies (33 effect sizes) of 696 participants (hypnosis n=536,
control n=470) indicated higher tolerance (i.e. reduced pain) for hypnosis,
SMD=0.54, CI95[0.38, 0.70], p<.001. Positive effects were indicated in all studies, but
with moderate inconsistency in effect size (I2=56%).

HYPNOSIS AND PAIN
14
Pain threshold
Meta-analysis of 16 studies (64 effect sizes) of 415 participants (hypnosis n=382,
control n=380) found higher pain threshold (i.e. reduced pain) for hypnosis,
SMD=0.66, CI95[0.38, 0.70], p<.001. Positive effects were found for all studies, but
with high inconsistency (I2=78%).
3.10 Publication bias
Funnel plots and Egger’s test suggested asymmetry in pain intensity (z=2.39, p=.017),
tolerance (z=2.30, p=.022) and threshold (z=2.06, p=.039), that was consistent with
possible publication bias. Trim and fill estimates produced slight reductions in effect
sizes for intensity (ΔSMD=-.06; Figure 3), tolerance (ΔSMD=- .06) and threshold
(ΔSMD=-.04).
3.11 Meta-regression
Meta-regression was performed for pain intensity only as study numbers (k=64)
were considerably higher than other pain outcomes (ks=16-23) and thus provide
more reliable parameter estimates.
Primary moderators
Analgesic suggestion (yes, no) and hypnotic suggestibility (low, medium, high) were
entered simultaneously as dummy-coded moderators, with no analgesic suggestion
and low suggestibility coded as reference levels. Both variables were well
represented by studies across their different levels (hypnotic suggestibility: low=31,
medium=15, and high=43 studies; analgesic suggestion: yes=48, no=24 studies).
Meta-regression parameter estimates are shown in Table 2 for unstandardized (0-
10) ratings and indicate greater pain relief for increasing suggestibility (+0.64 for
medium, +1.34 points for high) and inclusion of a direct analgesic suggestion (+0.94
points). Solving the regression equation at different predictor values revealed that
relative to control pain intensity ratings of 5.5, hypnosis with direct analgesic

HYPNOSIS AND PAIN
15
suggestion decreased pain by: 2.30 points (CI95[1.82, 2.80], p<.001) in high
suggestibles (42% reduction), 1.60 points (CI95[1.23, 1.99], p<.001) in medium
suggestibles (29% reduction), and 0.97 points (CI95[0.61, 1.32], p<.001) for low
suggestibles (17% reduction).
Hypnosis with no direct analgesic suggestion decreased pain ratings by: 1.36 points
(CI95 [0.48, 2.28], p=.004) in high suggestibles (25% reduction), 0.67 points (CI95[0.10,
1.23], p=.025) in medium suggestibles (12% reduction), and 0.03 points (CI95[-0.65,
0.59], p=.931) in low suggestibles (0.5% reduction), with the latter result not
significant.
Secondary moderators
Separate meta-regression was performed for the following moderators after
removing levels of any variable with low (<5) study numbers: delivery format (audio
recording, live), hypnotic induction method (standard procedure, standardized
induction), comparison (control, placebo), pain induction (heat, electric, pressure,
cold), age and study gender composition. We also examined whether randomisation
vs. non-randomisation influenced effect size (Section 3.6). Results indicated hypnotic
analgesia was marginally lower (ΔSMD=-.01) for studies reporting randomization
(primarily of presentation order) relative to those that did not, but this was not
significant (p=.90). No secondary moderators were significant (ps=.22-.85).
3.12 Sensitivity analysis
We re-ran analyses using alternative correlations of effect sizes (section 2.9), using
more stringent hypnotic suggestibility classifications (section 2.7), and with
extraction decisions specified in Section 2.6, but found no substantive changes in
parameter estimates.

HYPNOSIS AND PAIN
16
4 DISCUSSION
The effectiveness of hypnosis for reducing pain was supported by meta-analysis of
85 controlled experimental trials totalling 3,632 participants. Key findings were: (1)
hypnosis produced moderate to large overall analgesia for all pain outcomes; (2)
hypnotic suggestibility and the inclusion of a direct analgesic suggestion are
important determinants of intervention effectiveness; and (3) possible publication
bias was identified, but had minimal impact on effect sizes.
4.1 Magnitude of pain relief
Hypnosis with analgesic suggestion produced a 42% reduction in pain intensity for
those with high hypnotic suggestibility and a 29% reduction for those with medium
hypnotic suggestibility. This is broadly supportive of a meaningful level of analgesia
based on established guidelines for clinically important change, where a ≥30%
reduction in pain typically represents ‘much improved’ (although ≥50% reductions
are needed for ‘very much improved’)(Dworkin et al., 2008).
Importantly, pain relief approaching or exceeding 30% was dependent upon (1) the
inclusion of direct suggestion of pain relief, and (2) a target population of individuals
high or medium in hypnotic suggestibility. Insofar as the majority of the general
population (85-90%) fall into the medium to high hypnotic suggestibility range
(McConkey, 2012), these findings suggest that most individuals are able to
experience meaningful analgesia from hypnosis provided direct analgesic
suggestions are included. Hypnotic suggestibility has also been shown to influence
efficacy of hypnosis in clinical care settings, although a meta-analysis of 10 studies by
Montgomery et al. (2011) found relatively small moderating effects and questioned
the usefulness of pre-assessing hypnotic suggestibility. However, Montgomery et al.
(2011) examined a broad range of medical, dental and mental health conditions that
included only 3 available pain studies, and thus further data is needed before
conclusions on generalisability to clinical pain contexts can be made.

HYPNOSIS AND PAIN
17
4.2 Previous findings
Analgesic effects of hypnosis in experimental pain trials are consistent with a
previous meta-analysis published almost 20 years ago (Montgomery et al., 2000).
Due to a vastly increased number of experimental pain trials in the current (85
studies) compared to the original meta-analysis (12 studies), current findings were
also able to provide precise estimates of analgesia on a more meaningful (0-10)
metric. We were also able to identify hypnotic suggestibility and use of analgesic
suggestion as important determinants of treatment efficacy, as has long been
suspected (Patterson and Jensen, 2003). Beneficial effects of hypnosis on pain have
also been supported in reviews of labour pain (Madden et al., 2016), fibromyalgia
(Bernardy et al., 2011) and other pain conditions (Adachi et al., 2014), although
these reviews acknowledge the low quality of methodological evidence.
4.3 Implications
The present analysis has several important implications. Hypnosis may be an
effective intervention for pain that could be offered as a safe alternative to
medication, especially where concerns exist for an individual over the effectiveness,
addictive potential or side effects of drug treatment. If hypnosis could be
administered as effectively at home (e.g., in the form of pre-recorded audio) as
during live sessions with a practitioner, then this could also provide an inexpensive
treatment option for pain. This would be of considerable potential benefit given that
the costs of prescription opioid addiction alone are estimated at over $78 billion
annually in the US (Seth et al., 2018). However, while moderation analysis found no
differences in analgesia between recorded audio and live hypnosis, suggesting the
former may be similarly effective, we examined delivery format only as a secondary
moderator. Furthermore, we did not perform an economic analysis, and so no claims
of improved cost-effectiveness relative to opioids can therefore be made from the
current study.
Hypnotic interventions should also include direct suggestions of analgesia and
delivered to a high/medium hypnotic suggestibility target population to be most

HYPNOSIS AND PAIN
18
effective. As high/medium hypnotic suggestibility represents the majority of the
population, this suggests treatment may be widely effective. Although the extent to
which hypnotic suggestibility moderates treatment efficacy for clinical outcomes has
yet to be firmly established (Montgomery et al., 2011), brief suggestibility screening
(e.g., Morgan and Hilgard, 1978) may help identify therapeutic targets likely to
demonstrate optimal benefits from hypnosis. In addition, some evidence indicates
hypnotic suggestibility can be increased through training and practice (Patterson and
Jensen, 2003), non-invasive brain stimulation (Dienes and Hutton, 2013; Coltheart et
al., 2018), and pharmacological agents (Whalley and Brooks, 2009), and general
engagement improved with the use of virtual reality formats (Thompson et al.,
2011), which may help increase efficacy in those with low suggestibility.
4.4 Mechanisms
Although the precise analgesic mechanisms underpinning hypnosis have yet to be
established, several explanations have been considered. Imaging studies reliably
show hypnoanalgesic suggestion to alter activity in the anterior cingulate cortex,
insular and prefrontal areas (Del Casale et al., 2015), possibly reflecting the role of
these brain regions in mental relaxation, absorption and stimuli-awareness. As these
areas also form a critical part of the pain neuromatrix, which plays an important part
in pain modulation (Jensen and Patterson, 2014), this could provide a neural basis
for hypnotic analgesia. The anterior cingulate and frontal regions may also differ
across low and high suggestibles in both their structural properties and their
activation in response to hypnotic induction (Jensen et al., 2017), which could
account for the differential effectiveness of hypnosis across these groups.
Psychological models suggest that hypnotic induction produces an attentional shift
away from external perceptual information which decreases monitoring of sensory
cues and thus reduces pain (Jensen and Patterson, 2014). The fact that analgesia
appears to be far more pronounced in those with high suggestibility is perhaps
unsurprising, given that a greater responsivity to or willingness to engage with the

HYPNOSIS AND PAIN
19
psychological components of an intervention would seem likely to enhance any
therapeutic effects.
4.5 Limitations
The current findings have several important limitations. First, although evoked-pain
models allow precise experimental control, chronic pain is often more sustained,
diffuse and distressing, and this may threaten generalisability of the current findings
to clinical pain (Arendt-Nielsen and Hoeck, 2011). Nevertheless, evidence from the
current findings of meaningful pain reduction suggest a promising foundation for
hypnosis as a clinical pain management technique. Second, relatively brief, one-off
pain inductions were typically used, and the efficacy of hypnosis may decrease (or
increase) over longer time periods. Third, reduced self-reported pain ratings might
be partly attributable to undetected biases such as demand characteristics and
response expectancies (Lynn et al., 2008). This concern may be partly mitigated by
the analgesic effects of hypnosis for behavioural (threshold/tolerance) measures
found here, and on ‘objective’ biomarkers such as altered brain activity in the pain
matrix (Del Casale et al., 2015) and reduced medication requests in clinical settings
(Lang et al., 2000; Montgomery et al., 2007) in previous studies. Fourth, the low
mean study age (M=24.5, SD=4.4) questions applicability of findings to older
populations where non-pharmacological interventions have the potential to be most
useful due to increased sensitivity to the adverse effects of medication (Thompson
et al., 2017c). Finally, we are unable to comment on the relative efficacy of hypnosis
compared to analgesic medication, and there appear to be few, if any, primary
studies that have directly compared the two.
4.6 Future studies
Additional well-controlled research establishing whether the current findings
generalise to clinical pain is critical for establishing the viability of hypnosis as an
effective pain intervention. Although the role of hypnotic intervention in clinical pain
settings is well researched, limited high quality data with numerous design biases
prohibits reliable conclusions (Bernardy et al., 2011; Birnie et al., 2014; Landolt and

HYPNOSIS AND PAIN
20
Milling, 2011) and further well-controlled clinical studies are needed. In addition, the
use of experimental models that produce hyperalgesic states (e.g. through capsaicin
inflammation) and that mimic key pathological features of central sensitization in
chronic pain but with strict experimental control (Chizh, 2007) are also likely to
provide valuable insights.
4.7 Conclusions
This is the largest meta-analysis to date investigating the effectiveness of hypnosis as
a technique for pain reduction. Evidence from 85 controlled studies provides
convincing evidence that hypnosis produces substantive analgesia, with optimal pain
relief delivered when direct analgesic suggestions are used in a target population of
individuals high in suggestibility. Overall, the findings that hypnotic induction
resulted in a reliable decrease in experimentally-induced pain suggest that hypnosis
may represent a potentially effective and safe alternative or adjunct to
pharmacological intervention for acute pain. Well-controlled studies of non-
laboratory pain are, however, essential to establish the efficacy of hypnosis for the
treatment and management of clinical pain.
5 ACKNOWLEDGEMENTS
We are very grateful to Drs Casiglia, Croft, Facco, Milling, Santarcangelo and Sandrini
for their helpful responses to data requests.
6 FUNDING
This research did not receive any specific grant from funding agencies in the public,
commercial, or not-for-profit sectors.

HYPNOSIS AND PAIN
21
LIST OF FIGURE CAPTIONS
Figure 1. PRISMA flowchart of study selection process.
Figure 2. Forest plot of Standardised Mean Differences (with 95% confidence intervals) and
study weights for 64 pain intensity studies.
Figure 3. Funnel plot of standardized mean differences (SMDs) from 64 pain intensity studies
(filled circles) and 7 SMDs potentially missing due to publication bias imputed using the trim
and fill method (empty circles).
LIST OF TABLE CAPTIONS
Table 1. Summary characteristics of included studies.
Table 2. Meta-regression estimates of unstandardized (0-10) pain intensity ratings and 95%
confidence intervals (CI).

HYPNOSIS AND PAIN
22
REFERENCES
Adachi, T., Fujino, H., Nakae, A., Mashimo, T., & Sasaki, J., 2014. A meta-analysis of
hypnosis for chronic pain problems: A comparison between hypnosis, standard
care, and other psychological interventions. Int J Clin Exp Hypn. 62(1), 1-28.
Arendt-Nielsen, L., & Hoeck, H.C., 2011. Optimizing the early phase development of
new analgesics by human pain biomarkers. Expert Rev Neurother. 11, 1631-1651.
Benhaiem, J.M., Attal, N., Chauvin, M., Brasseur, L., & Bouhassira, D., 2001. Local and
remote effects of hypnotic suggestions of analgesia. Pain. 89(2-3), 167-173.
Bernardy, K., Füber, N., Klose, P., & Häuser, W., 2011. Efficacy of hypnosis/guided
imagery in fibromyalgia syndrome--a systematic review and meta-analysis of
controlled trials. BMC Musculoskelet Disord. 12, 1-11.
Bhatt, R.R. et al., 2017. The effect of hypnosis on pain and peripheral blood flow in
sickle-cell disease: a pilot study. J Pain Res. 10, 1635-1644.
Birnie, K.A. et al., 2014. Systematic review and meta-analysis of distraction and
hypnosis for needle-related pain and distress in children and adolescents. J Pediatr
Psychol. 39(8), 783-808.
Braboszcz, C., Brandao-Farinelli, E., & Vuilleumier, P., 2017. Hypnotic analgesia
reduces brain responses to pain seen in others. Sci Rep. 7(1), 9778.
Casiglia, E. et al., 2017. Hypnotic Focused Analgesia Obtained Through Body
Dysmorphism Prevents Both Pain and Its Cardiovascular Effects. Sleep & Hypnosis.
19(4), 89-95.
Casiglia, E. et al., 2007. Hypnosis prevents the cardiovascular response to cold
pressor test. Am J Clin Hypn. 49(4), 255-266.
Chizh, B.A., 2007. Low dose ketamine: a therapeutic and research tool to explore N-
methyl-D-aspartate (NMDA) receptor-mediated plasticity in pain pathways. J.
Psychopharmacol. 21(3), 259-271.
Cohen, J., 1988. Statistical power analysis for the behavioral sciences. Lawrence
Earlbaum Associates, Hillsdale, NJ
Coltheart, M. et al., 2018. Belief, delusion, hypnosis, and the right dorsolateral
prefrontal cortex: A transcranial magnetic stimulation study. Cortex. 101, 234-248.
Cooper, H., Hedges, L., & Valentine, J., 2009. Handbook of research synthesis and
meta-analysis. Russell Sage Foundation, NY
Crawford, H.J., Gur, R.C., Skolnick, B., Gur, R.E., & Benson, D.M., 1993. Effects of
hypnosis on regional cerebral blood flow during ischemic pain with and without
suggested hypnotic analgesia. Int J Psychophysiol. 15(3), 181-195.
Croft, R.J., Williams, J.D., Haenschel, C., & Gruzelier, J.H., 2002. Pain perception,
hypnosis and 40 Hz oscillations. Int J Psychophysiol. 46(2), 101-108.
Dahlgren, L.A., Kurtz, R.M., Strube, M.J., & Malone, M.D., 1995. Differential effects of
hypnotic suggestion on multiple dimensions of pain. J Pain Symptom Manage.
10(6), 464-470.
Danziger, N. et al., 1998. Different strategies of modulation can be operative during
hypnotic analgesia: a neurophysiological study. Pain. 75(1), 85-92.
De Pascalis, V., Bellusci, A., Gallo, C., Magurano, M.R., & Chen, A.C., 2004a. Pain-
reduction strategies in hypnotic context and hypnosis: ERPs and SCRs during a
secondary auditory task. Int J Clin Exp Hypn. 52(4), 343-363.
De Pascalis, V., Cacace, I., & Massicolle, F., 2004b. Perception and modulation of pain

HYPNOSIS AND PAIN
23
in waking and hypnosis: functional significance of phase-ordered gamma
oscillations. Pain. 112(1-2), 27-36.
De Pascalis, V., & Carboni, G., 1997. P300 event-related-potential amplitudes and
evoked cardiac responses during hypnotic alteration of somatosensory perception.
Int J Neurosci. 92(3-4), 187-207.
De Pascalis, V., Magurano, M.R., & Bellusci, A., 1999. Pain perception,
somatosensory event-related potentials and skin conductance responses to painful
stimuli in high, mid, and low hypnotizable subjects: effects of differential pain
reduction strategies. Pain. 83(3), 499-508.
De Pascalis, V., Magurano, M.R., Bellusci, A., & Chen, A.C., 2001. Somatosensory
event-related potential and autonomic activity to varying pain reduction cognitive
strategies in hypnosis. Clin Neurophysiol. 112(8), 1475-1485.
De Pascalis, V., & Perrone, M., 1996. EEG asymmetry and heart rate during
experience of hypnotic analgesia in high and low hypnotizables. Int J Psychophysiol.
21(2-3), 163-175.
De Pascalis, V., & Scacchia, P., 2016. Hypnotizability and Placebo Analgesia in Waking
and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An
ERP Study. PLoS ONE. 11(8), e0159135.
De Pascalis, V., Varriale, V., & Cacace, I., 2015. Pain modulation in waking and
hypnosis in women: event-related potentials and sources of cortical activity. PLoS
ONE. 10(6), e0128474.
De Pascalis, V., Cacace, I., & Massicolle, F., 2008. Focused analgesia in waking and
hypnosis: Effects on pain, memory, and somatosensory event-related potentials.
Pain. 134(1-2), 197-208.
DeBenedittis, G., Panerai, A.A., & Villamira, M.A., 1989. Effects of hypnotic analgesia
and hypnotizability on experimental ischemic pain. Int J Clin Exp Hypn. 37(1), 55-69.
Del Casale, A. et al., 2015. Hypnosis and pain perception: An Activation Likelihood
Estimation (ALE) meta-analysis of functional neuroimaging studies. J Physiol Paris.
109(4-6), 165-172.
Derbyshire, S.W.G., Whalley, M.G., Seah, S.T.H., & Oakley, D.A., 2017. Suggestions to
Reduce Clinical Fibromyalgia Pain and Experimentally Induced Pain Produce Parallel
Effects on Perceived Pain but Divergent Functional MRI-Based Brain Activity.
Psychosom. Med. 79(2), 189-200.
Dienes, Z., & Hutton, S., 2013. Understanding hypnosis metacognitively: rTMS
applied to left DLPFC increases hypnotic suggestibility. Cortex. 49(2), 386-392.
Duval, S., & Tweedie, R., 2000. Trim and fill: A simple funnel-plot-based method of
testing and adjusting for publication bias in meta-analysis. Biometrics. 56(2), 455-
463.
Dworkin, R.H. et al., 2008. Interpreting the clinical importance of treatment
outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 9(2),
105-121.
Egger, M., Davey Smith, G., Schneider, M., & Minder, C., 1997. Bias in meta-analysis
detected by a simple, graphical test. BMJ. 315(7109), 629-634.
Enea, V., Dafinoiu, I., Opriş, D., & David, D., 2014. Effects of hypnotic analgesia and
virtual reality on the reduction of experimental pain among high and low
hypnotizables. Int J Clin Exp Hypn. 62(3), 360-377.
Evans, M.B., & Paul, G.L., 1970. Effects of hypnotically suggested analgesia on

HYPNOSIS AND PAIN
24
physiological and subjective responses to cold stress. J Consult Clin Psychol. 35(3),
362-371.
Facco, E. et al., 2011. Effects of hypnotic focused analgesia on dental pain threshold.
Int J Clin Exp Hypn. 59(4), 454-468.
Faymonville, M.E. et al., 2000. Neural mechanisms of antinociceptive effects of
hypnosis. Anesthesiology. 92(5), 1257-1267.
Faymonville, M.E. et al., 2003. Increased cerebral functional connectivity underlying
the antinociceptive effects of hypnosis. Cogn Brain Res. 17(2), 255-262.
Fidanza, F., Varanini, M., Ciaramella, A., Carli, G., & Santarcangelo, E.L., 2017. Pain
modulation as a function of hypnotizability: Diffuse noxious inhibitory control
induced by cold pressor test vs explicit suggestions of analgesia. Physiology &
Behavior. 171, 135-141.
Fisher, Z., & Tipton, E., 2014. robumeta: Robust variance meta-regression. R package
version 1.3.
Fricton, J.R., & Roth, P., 1985. The effects of direct and indirect hypnotic suggestions
for analgesia in high and low susceptible subjects. Am J Clin Hypn. 27(4), 226-231.
Friederich, M. et al., 2001. Laser-evoked potentials to noxious stimulation during
hypnotic analgesia and distraction of attention suggest different brain mechanisms
of pain control. Psychophysiology. 38(5), 768-776.
Gaskin, D.J., & Richard, P., 2012. The economic costs of pain in the United States. J
Pain. 13(8), 715-724.
Collaborators, G.B.D.C.O.D., 2017. Global, regional, and national age-sex specific
mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global
Burden of Disease Study 2016. Lancet. 390(10100), 1151-1210.
Goodin, B.R. et al., 2012. Experimental pain ratings and reactivity of cortisol and
soluble tumor necrosis factor-α receptor II following a trial of hypnosis: results of a
randomized controlled pilot study. Pain Med. 13(1), 29-44.
Gracely, R.H., 2005. Studies of pain in human subjects, in: R. Melzack & P. Wall
(Eds.), Textbook of pain (5th ed., pp. 267-289). London: Elsevier.
Green, S.A., 2010. Experimental pain in hypnosis research: Ischemic vs
transcutaneous electrical nerve stimulation (TENS). Dissertation Abstracts
International: Section B: The Sciences and Engineering. 71(4-B), 2685.
Greene, R.J., & Reyher, J., 1972. Pain tolerance in hypnotic analgesic and imagination
states. J. Abnorm. Psychol. 79(1), 29-38.
Hargadon, R., Bowers, K.S., & Woody, E.Z., 1995. Does counterpain imagery mediate
hypnotic analgesia? J. Abnorm. Psychol. 104(3), 508-516.
Hedges, L.V., Tipton, E., & Johnson, M.C., 2010. Robust variance estimation in meta-
regression with dependent effect size estimates. Res Synth Methods. 1, 39-65.
Higgins, J.P., Thompson, S.G., Deeks, J.J., & Altman, D.G., 2003. Measuring
inconsistency in meta-analyses. BMJ. 327(7414), 557-560.
Hilgard, E.R., Crawford, H.J., & Wert, A., 1979. The Stanford Hypnotic Arm Levitation
Induction and Test (SHALIT): a six-minute hypnotic induction and measurement
scale. Int J Clin Exp Hypn. 27(2), 111-124.
Hofbauer, R.K., Rainville, P., Duncan, G.H., & Bushnell, M.C., 2001. Cortical
representation of the sensory dimension of pain. J. Neurophysiol. 86(1), 402-411.
Jacobs, A.L., Kurtz, R.M., & Strube, M.J., 1995. Hypnotic analgesia, expectancy
effects, and choice of design: a reexamination. Int J Clin Exp Hypn. 43(1), 55-69.

HYPNOSIS AND PAIN
25
Jensen, M.P. et al., 2015. Mechanisms of hypnosis: toward the development of a
biopsychosocial model. Int J Clin Exp Hypn. 63(1), 34-75.
Jensen, M.P. et al., 2017. New directions in hypnosis research: strategies for
advancing the cognitive and clinical neuroscience of hypnosis. Neurosci Conscious.
3(1), 1-14.
Jensen, M.P., & Patterson, D.R., 2014. Hypnotic approaches for chronic pain
management: clinical implications of recent research findings. Am Psychol. 69(2),
167-177.
Karlin, R.A., Morgan, D., & Goldstein, L., 1980. Hypnotic analgesia: A preliminary
investigation of quantitated hemispheric electroencephalographic and attentional
correlates. J. Abnorm. Psychol. 89(4), 591-594.
Kiernan, B.D., Dane, J.R., Phillips, L.H., & Price, D.D., 1995. Hypnotic analgesia
reduces R-III nociceptive reflex: Further evidence concerning the multifactorial
nature of hypnotic analgesia. Pain. 60(1), 39-47.
Kramer, S., Zims, R., Simang, M., Rüger, L., & Irnich, D., 2014. Hypnotic relaxation
results in elevated thresholds of sensory detection but not of pain detection. BMC
Complement Altern Med. 14(1), 600-615.
Landolt, A.S., & Milling, L.S., 2011. The efficacy of hypnosis as an intervention for
labor and delivery pain: a comprehensive methodological review. Clin Psychol Rev.
31(6), 1022-1031.
Lang, E.V. et al., 2000. Adjunctive non-pharmacological analgesia for invasive
medical procedures: a randomised trial. Lancet. 355(9214), 1486-1490.
Langlade, A., Jussiau, C., Lamonerie, L., Marret, E., & Bonnet, F., 2002. Hypnosis
increases heat detection and heat pain thresholds in healthy volunteers. Reg
Anesth Pain Med. 27(1), 43-46.
Larkin, M., 1999. Hypnosis makes headway in the clinic. Lancet. 353(9150), 386.
Li, C.L. et al., 1975. Acupuncture and hypnosis: Effects on induced pain. Exp Neurol.
49(1, Pt 1), 272-280.
Lynn, S.J., Kirsch, I., & Hallquist, M.N., 2008. Social cognitive theories of hypnosis, in:
M. R. Nash & A. J. Barnier (Eds.), The Oxford handbook of hypnosis: Theory,
research and practice (pp. 111-140). Oxford: Oxford University Press.
Madden, K., Middleton, P., Cyna, A.M., Matthewson, M., & Jones, L., 2016. Hypnosis
for pain management during labour and childbirth. Cochrane Database Syst Rev. 5,
CD009356.
Malone, M.D., Kurtz, R.M., & Strube, M.J., 1989. The effects of hypnotic suggestion
on pain report. Am J Clin Hypn. 31(4), 221-230.
Maurer, C., Santangelo, M., & Claiborn, C.D., 1993. The effects of direct versus
indirect hypnotic suggestion on pain in a cold pressor task. Int J Clin Exp Hypn.
41(4), 305-316.
McConkey, K.M., 2012. Generations and landscapes of hypnosis: Questions we’ve
asked, questions we should ask, in: M. R. Nash & A. J. Barnier (Eds.), The Oxford
Handbook of Hypnosis (pp. 53-77). Oxford, UK: Oxford University Press.
Milling, L.S., 2009. Response expectancies: A psychological mechanism of suggested
and placebo analgesia. Contemporary Hypnosis. 26(2), 93-110.
Milling, L.S., & Breen, A., 2003. Mediation and moderation of hypnotic and cognitive-
behavioural pain reduction. Contemporary Hypnosis. 20(2), 81-97.
Milling, L.S., Coursen, E.L., Shores, J.S., & Waszkiewicz, J.A., 2010a. Imaginative

HYPNOSIS AND PAIN
26
suggestibility and hypnotizability: Deconstructing hypnotic suggestibility.
Contemporary Hypnosis. 27(4), 233-256.
Milling, L.S., Coursen, E.L., Shores, J.S., & Waszkiewicz, J.A., 2010b. The predictive
utility of hypnotizability: The change in suggestibility produced by hypnosis. J
Consult Clin Psychol. 78(1), 126-130.
Milling, L.S., Kirsch, I., Allen, G.J., & Reutenauer, E.L., 2005. The Effects of Hypnotic
and Nonhypnotic Imaginative Suggestion on Pain. Ann Behav Med. 29(2), 116-127.
Milling, L.S., Kirsch, I., Meunier, S.A., & Levine, M.R., 2002. Hypnotic analgesia and
stress inoculation training: Individual and combined effects in analog treatment of
experimental pain. Cog. Ther. Res. 26(3), 355-371.
Milling, L.S., Shores, J.S., Coursen, E.L., Menario, D.J., & Farris, C.D., 2007. Response
expectancies, treatment credibility, and hypnotic suggestibility: Mediator and
moderator effects in hypnotic and cognitive-behavioral pain interventions. Ann
Behav Med. 33(2), 167-178.
Milling, L.S., Kirsch, I., & Burgess, C.A., 1999. Brief modification of suggestibility and
hypnotic analgesia: too good to be true. Int J Clin Exp Hypn. 47(2), 91-103.
Milling, L.S., Levine, M.R., & Meunier, S.A., 2003. Hypnotic enhancement of
cognitive-behavioral interventions for pain: an analogue treatment study. Health
Psychol. 22(4), 406-413.
Moher, D. et al., 2015. Preferred reporting items for systematic review and meta-
analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 4(1), 1-9.
Montgomery, G.H. et al., 2007. A randomized clinical trial of a brief hypnosis
intervention to control side effects in breast surgery patients. J. Natl. Cancer Inst.
99(17), 1304-1312.
Montgomery, G.H., Schnur, J.B., & David, D., 2011. The impact of hypnotic
suggestibility in clinical care settings. Int J Clin Exp Hypn. 59(3), 294-309.
Montgomery, G.H., DuHamel, K.N., & Redd, W.H., 2000. A meta-analysis of
hypnotically induced analgesia: How effective is hypnosis. Int J Clin Exp Hypn. 48(2),
138-153.
Morgan, A.H., & Hilgard, J.R., 1978. The Stanford hypnotic clinical scale for adults.
Am J Clin Hypn. 21, 134-147.
Morgan, A.H., Lezard, F., Prytulak, S., & Hilgard, E.R., 1970. Augmenters, reducers,
and their reaction to cold pressor pain in waking and suggested hypnotic analgesia.
J Pers Soc Psychol. 16(1), 5-11.
Morris, S.B., & DeShon, R.P., 2002. Combining effect size estimates in meta-analysis
with repeated measures and independent-groups designs. Psychol Methods. 7(1),
105.
Patterson, D.R., Hoffman, H.G., Palacios, A.G., & Jensen, M.J., 2006. Analgesic effects
of posthypnotic suggestions and virtual reality distraction on thermal pain. J.
Abnorm. Psychol. 115(4), 834-841.
Patterson, D.R., & Jensen, M.P., 2003. Hypnosis and clinical pain. Psychol Bull.
129(4), 495-521.
Price, D.D., & Barber, J., 1987. An analysis of factors that contribute to the efficacy of
hypnotic analgesia. J. Abnorm. Psychol. 96(1), 46-51.
R Core Team., 2017. R: A language and environment for statistical computing. R
Foundation for Statistical Computing, Vienna, Austria
Rainville, P., Bao, Q.V., & Chrétien, P., 2005. Pain-related emotions modulate

HYPNOSIS AND PAIN
27
experimental pain perception and autonomic responses. Pain. 118(3), 306-318.
Rainville, P., Carrier, B., Hofbauer, R.K., Bushnell, M.C., & Duncan, G.H., 1999.
Dissociation of sensory and affective dimensions of pain using hypnotic
modulation. Pain. 82(2), 159-171.
Rainville, P., Duncan, G.H., Price, D.D., Carrier, B., & Bushnell, M.C., 1997. Pain affect
encoded in human anterior cingulate but not somatosensory cortex. Science.
277(5328), 968-971.
Ray, W.J., Keil, A., Mikuteit, A., Bongartz, W., & Elbert, T., 2002. High resolution EEG
indicators of pain responses in relation to hypnotic susceptibility and suggestion.
Bio. Psychol. 60(1), 17-36.
Röder, C.H., Michal, M., Overbeck, G., van de Ven, V.G., & Linden, D.E., 2007. Pain
response in depersonalization: a functional imaging study using hypnosis in healthy
subjects. Psychother Psychosom. 76(2), 115-121.
Sandrini, G. et al., 2000. Effects of hypnosis on diffuse noxious inhibitory controls.
Physiology & Behavior. 69(3), 295-300.
Santarcangelo, E.L. et al., 2013. Cognitive modulation of psychophysical, respiratory
and autonomic responses to cold pressor test. PLoS ONE. 8(10), e75023.
Seth, P., Scholl, L., Rudd, R.A., & Bacon, S., 2018. Overdose Deaths Involving Opioids,
Cocaine, and Psychostimulants - United States, 2015-2016. MMWR. 67(12), 349-
358.
Sharav, Y., & Tal, M., 2004. Focused analgesia and generalized relaxation produce
differential hypnotic analgesia in response to ascending stimulus intensity. Int J
Psychophysiol. 52(2), 187-196.
Sharav, Y., & Tal, M., 2006. Focused hypnotic analgesia: Local and remote effects.
Pain. 124(3), 280-286.
Shor, R.E., & Orne, E.C., 1963. Norms on the Harvard group scale of hypnotic
susceptibility, form A. Int J Clin Exp Hypn. 11, 39-47.
Spanos, N.P., Gwynn, M.I., & Stam, H.J., 1983a. Instructional demands and ratings of
overt and hidden pain during hypnotic analgesia. J. Abnorm. Psychol. 92(4), 479-
488.
Spanos, N.P., & Hewitt, E.C., 1980. The hidden observer in hypnotic analgesia:
Discovery or experimental creation. J Pers Soc Psychol. 39(6), 1201-1214.
Spanos, N.P., & Katsanis, J., 1989. Effects of instructional set on attributions of
nonvolition during hypnotic and nonhypnotic analgesia. J Pers Soc Psychol. 56(2),
182-188.
Spanos, N.P., Kennedy, S.K., & Gwynn, M.I., 1984. Moderating effects of contextual
variables on the relationship between hypnotic susceptibility and suggested
analgesia. J. Abnorm. Psychol. 93(3), 285-294.
Spanos, N.P., MacDonald, D.K., & Gwynn, M.I., 1988. Instructional set and the
relative efficacy of hypnotic and waking analgesia. Canadian Journal of Behavioural
Science. 20(1), 64-72.
Spanos, N.P., Ollerhead, V.G., & Gwynn, M.I., 1985. The effects of three instructional
treatments on pain magnitude and pain tolerance: Implications for theories of
hypnotic analgesia. Imagination, Cognition and Personality. 5(4), 321-337.
Spanos, N.P., Perlini, A.H., Patrick, L., Bell, S., & Gwynn, M.I., 1990. The role of
compliance in hypnotic and nonhypnotic analgesia. J Res Pers. 24(4), 433-453.
Spanos, N.P., Voorneveld, P.W., & Gwynn, M.I., 1986. The mediating effects of

HYPNOSIS AND PAIN
28
expectation on hypnotic and nonhypnotic pain reduction. Imagination, Cognition
and Personality. 6(3), 231-245.
Spanos, N.P., Perlini, A.H., & Robertson, L.A., 1989. Hypnosis, suggestion, and
placebo in the reduction of experimental pain. J. Abnorm. Psychol. 98(3), 285-293.
Spanos, N.P. et al., 1983b. The Carleton University Responsiveness to Suggestion
Scale: relationship with other measures of hypnotic susceptibility, expectancies,
and absorption. Psychol Rep. 53(3 Pt 1), 723-734.
Stam, H.J., 1984. Hypnotic analgesia and the placebo effect: Controlling ischemic
pain. PhD. Carleton University, Ottawa, Canada.
Stam, H.J., & Spanos, N.P., 1980. Experimental designs, expectancy effects, and
hypnotic analgesia. J. Abnorm. Psychol. 89(6), 751-762.
Stam, H.J., & Spanos, N.P., 1987. Hypnotic analgesia, placebo analgesia, and ischemic
pain: the effects of contextual variables. J. Abnorm. Psychol. 96(4), 313-320.
Swain, N.R., & Trevena, J., 2014. A comparison of therapist-present or therapist-free
delivery of very brief mindfulness and hypnosis for acute experimental pain. New
Zealand Journal of Psychology. 43(3), 22-28.
Tanner-Smith, E.E., & Tipton, E., 2014. Robust variance estimation with dependent
effect sizes: practical considerations including a software tutorial in Stata and SPSS.
Res Synth Methods. 5(1), 13-30.
Tenenbaum, S.J., Kurtz, R.M., & Bienias, J.L., 1990. Hypnotic susceptibility and
experimental pain reduction. Am J Clin Hypn. 33(1), 40-49.
Terhune, D.B., & Cardeña, E., 2016. Nuances and Uncertainties Regarding Hypnotic
Inductions: Toward a Theoretically Informed Praxis. Am J Clin Hypn. 59(2), 155-174.
Thompson, T., Oram, C., Correll, C.U., Tsermentseli, S., & Stubbs, B., 2017a. Analgesic
Effects of Alcohol: A Systematic Review and Meta-Analysis of Controlled
Experimental Studies in Healthy Participants. J Pain. 18(5), 499-510.
Thompson, T., Steffert, T., Steed, A., & Gruzelier, J., 2011. A randomized controlled
trial of the effects of hypnosis with 3-D virtual reality animation on tiredness,
mood, and salivary cortisol. Int J Clin Exp Hypn. 59(1), 122-142.
Thompson, T. et al., 2017b. Pain perception in Parkinson’s disease: A systematic
review and meta-analysis of experimental studies. Ageing Res Rev. 35, 74-86.
Thompson, T., Mendoza, M.E., & Docking, R., 2017c. Pain Management and
Assessment, in: R. E. Docking & J. Stock (Eds.), International Handbook of Positive
Aging (pp. 115-131). London, UK: Routledge.
Valentini, E., Betti, V., Hu, L., & Aglioti, S.M., 2013. Hypnotic modulation of pain
perception and of brain activity triggered by nociceptive laser stimuli. Cortex. 49(2),
446-462.
Van Gorp, W.G., Meyer, R.G., & Dunbar, K.D., 1985. The efficacy of direct versus
indirect hypnotic induction techniques on reduction of experimental pain. Int J Clin
Exp Hypn. 33(4), 319-328.
Vanhaudenhuyse, A. et al., 2009. Pain and non-pain processing during hypnosis: a
thulium-YAG event-related fMRI study. Neuroimage. 47(3), 1047-1054.
Viechtbauer, W., & Cheung, M.W., 2010. Outlier and influence diagnostics for meta-
analysis. Res Synth Methods. 1(2), 112-125.
Viechtbauer, W., 2010. Metafor: meta-analysis package for R. R package version.
2010, 1-0.
Weitzenhoffer, A.M., & Hilgard, E.R., 1962. Stanford hypnotic susceptibility scale,

HYPNOSIS AND PAIN
29
form C. Consulting Psychologists Press, Palo Alto, US
Whalley, M.G., & Brooks, G.B., 2009. Enhancement of suggestibility and imaginative
ability with nitrous oxide. Psychopharmacology (Berl). 203(4), 745-752.
Williams, J.D., Croft, R.J., Ferdinand, J., & Gruzelier, J.H., 2010. Hypnotic analgesia
affects the processing of painful stimuli. Australian Journal of Clinical &
Experimental Hypnosis. 38(2), 77-90.
Wolf, T.G. et al., 2016. Effectiveness of Self-Hypnosis on the Relief of Experimental
Dental Pain: A Randomized Trial. Int J Clin Exp Hypn. 64(2), 187-199.
Wood, D.R., 1976. The differential effects of hypnosis, rationale, and self-talk in
coping with pain on the cold pressor test. PhD. Doctoral dissertation, University of
Ottawa, Canada.
Wright, B.R., & Drummond, P.D., 2001. The effect of rapid induction analgesia on
subjective pain ratings and pain tolerance. Int J Clin Exp Hypn. 49(2), 109-122.
Yaqub, F., 2015. Pain in the USA: states of suffering. Lancet. 386(9996), 839.
Zachariae, R., Andersen, O.K., Bjerring, P., Jørgensen, M.M., & Arendt-Nielsen, L.,
1998. Effects of an opioid antagonist on pain intensity and withdrawal reflexes
during induction of hypnotic analgesia in high- and low-hypnotizable volunteers.
European Journal of Pain. 2(1), 25-34.
Zachariae, R., & Bjerring, P., 1994. Laser-induced pain-related brain potentials and
sensory pain ratings in high and low hypnotizable subjects during hypnotic
suggestions of relaxation, dissociated imagery, focused analgesia, and placebo. Int J
Clin Exp Hypn. 42(1), 56-80.

HYPNOSIS AND PAIN
30
Table 1. Summary characteristics of included studies.
Study
Study
Design
N
Hyp
N
Control
Hypnotic Induction Procedure
Delivery
Analgesic
Suggestion
Control Procedure
Pain
Induction
Pain
Measure
Derbyshire et al, 2017
RM
15
15
Standard hypnotic instructions with relaxation
and imagery including suggestions to alter pain
(e.g. to imagine pain on a dial with instructions
to turn the dial down)
Live
Yes, No
Nothing
Heat
Intensity
Bhatt et al, 2017
RM
14
14
Standard hypnotic procedure lasting 30 mins
with relaxation and positive imagery with
analgesic suggestion (e.g. ‘imagine the arm
being completely filled with sensation of relief’)
Live
Yes
Nothing
Heat
Intensity
Threshold
Tolerance
Fidanza et al, 2017
RM
51
51
Standard hypnotic instructions with and without
glove analgesia
NS
Yes, No
Nothing
Electric
Intensity
Casiglia et al, 2017
RM
8
8
Standard hypnotic induction with disassociation
(e.g. ‘the hand no longer belongs to the body’)
Live
No
Nothing
Cold
Intensity
Tolerance
Braboszcz et al, 2017
RM
11
11
Standard hypnotic induction with relaxation and
pleasant imagery plus analgesic suggestion (e.g.
‘your arm cannot feel anything’)
Live through
headphones
Yes
Nothing
Heat
Threshold
Wolf et al, 2016
RM
37
37
Standard hypnotic induction
Live
No
Nothing
Pressure
Intensity
Threshold
De Pascalis et al, 2016
RM
51
51
Stanford Hypnotic Clinical Scale
Live
No
Nothing, but told
may receive
analgesic or sham
cream
Cold
Affect
De Pascalis et al, 2015
RM
20
20
Stanford Hypnotic Clinical Scale
Live
Yes, No
Relaxation
Electric
Intensity
Affect
Kramer et al, 2014
RM
23
23
Fixation method + recall feelings of wellbeing
Live
No
Nothing
Cold + Heat
+ Pressure
Threshold
Swain et al, 2014
RM
120
120
*Standard hypnotic induction
Live / DVD
No
Nothing
Cold
Intensity
Tolerance
Enea et al, 2014
PPC
60
30
Stanford SHSS:C
Live
Yes
Nothing
Pressure
Intensity
Affect
Valentini et al, 2013
RM
24
24
Stanford SHSS:A
Live
Yes
Nothing
Heat
Intensity
Affect

HYPNOSIS AND PAIN
31
Santarcangelo et al,
2013
RM
40
40
Standard hypnotic induction with relaxation and
pleasant imagery, plus glove analgesic
suggestion (e.g. ‘you cannot feel pain because
the glove you are wearing prevents you from
feeling it’)
Live
Yes
Nothing
Cold
Intensity
Threshold
Goodin et al, 2012
PPC
12
12
Modified verbal, movement and eye fixation
method + glove analgesia
Live
Yes
Nothing
Cold
Intensity
Affect
Tolerance
Facco et al, 2011
RM
31
31
Hypnosis with relaxation and well-being
suggestions
Live
Yes
Nothing
Electric
Threshold
Milling et al, 2010b
RM
173
173
Hypnosis as per Spanos (1977)
Live
Yes
Nothing
Pressure
Intensity
Milling et al, 2010a
(2 experiments)
PPC
52
143
52
143
Standard hypnotic induction + glove analgesic
suggestion + relaxation
Live
Yes
Nothing
Pressure
Intensity
Green et al, 2010
BG
26
24
Stanford Hypnotic Clinical Scale + glove
analgesic suggestion
Live
Yes
Nothing
Ischemic
Intensity
Williams et al, 2010
RM
33
33
Standard hypnotic induction
Live
Yes, No
Not reported
Electric
Intensity
Milling et al, 2009
PPC
46
83
CURSS hypnotic induction with & without 45-sec
glove analgesic suggestion
Live
Yes, No
Placebo- sham oil
labelled Trivaricaine
Nothing
Pressure
Intensity
Vanhaudenhuyse et
al, 2009
RM
13
13
Relaxation, fixation + memory recall
Live
No
Nothing
Laser
Intensity
De Pascalis, 2008
RM
36
36
Stanford SHSS:C
Live
Yes, No
Nothing
Electric
Intensity
Affect
Roder et al, 2007
RM
7
7
Hypnosis + Fixation + relaxation
Hypnosis +Fixation + depersonalization
Live
No
Nothing
Electric
Intensity
Casgalia et al, 2007
RM
20
20
Hypnosis with suggestion of relaxation and
analgesia
Live
Yes
Nothing
Cold
Intensity
Tolerance
Milling et al, 2007
PPC
42
41
CURSS
Live
Yes
Placebo- sham oil
labelled Trivaricaine
Nothing
Pressure
Intensity
Sharav et al, 2006
RM
25
25
Hypnotic induction with generalized relaxation,
guided imagery and focused analgesia
Live
Yes
Nothing
Electric
Intensity
Patterson et al, 2006
PPC
51
26
Stanford Hypnotic Clinical Scale with relaxation
+ analgesic/no analgesic suggestion
Audio
recording
Yes, No
Nothing
Heat
Intensity
Affect
Milling et al, 2005
RM
40
40
CURSS + glove analgesic suggestion
Live
Yes
Placebo topical oil
Nothing
Pressure
Intensity

HYPNOSIS AND PAIN
32
Rainville et al, 2005
RM
69
69
Standard hypnotic induction
Live
No
Nothing
Heat
Intensity
Affect
De Pascalis, Cacace et
al, 2004
RM
38
38
Stanford SHSS:C
Live
Yes, No
Nothing
Electric
Intensity
Affect
De Pascalis, Bellusci
et al, 2004
RM
30
30
Stanford SHSS:C with relaxation + dissociation
Live
Yes, No
Placebo
Cold
Intensity
Sharav et al, 2004
RM
15
15
Hypnotic relaxation induction with/without
focused analgesic suggestion
Live
Yes, No
Nothing
Electric
Intensity
Milling and Breen,
2003
PPC
55
55
CURSS with pain control or glove analgesic
suggestion
Audio
recording
Yes, No
Placebo- sham oil
labelled Trivaricaine
Nothing
Pressure
Intensity
Milling, Levine et al,
2003
PPC
95
47
CURSS
Live
Yes, No
Nothing
Pressure
Intensity
Faymonville et al,
2003
RM
19
19
Hypnosis with eye fixation and muscle
relaxation
Live
Yes
Nothing
Heat
Intensity
Croft et al, 2002
BG
11
9
Hypnosis with relaxation, fixation and imagery
Live
Yes, No
Oddball task
Electric
Intensity
Milling et al, 2002
PPC
22
18
CURSS + glove analgesia
Live
Yes
Nothing
Pressure
Intensity
Langlade et al, 2002
RM
15
15
Hypnosis with fixation, relaxation and analgesic
suggestion
Live
Yes
Nothing
Heat
Threshold
Tolerance
Ray et al, 2002
RM
12
12
Stanford SHSS:C
Audio
recording
Yes
Nothing
Electric
Intensity
Friederich et al, 2001
RM
20
20
Stanford Hypnotic Clinical Scale
glove analgesic suggestion + relaxation imagery
Live
Yes
Nothing
Heat
Intensity
Affect
Wright et al, 2001
PPC
30
28
Rapid induction Analgesia
Live
Yes
Reading
Chemical
Pressure
Intensity
Affect
Threshold
Tolerance
De Pascalis et al, 2001
RM
29
29
Stanford SHSS:C with relaxation, dissociation
and analgesic suggestion
Live
Yes, No
Nothing
Placebo topical
anaesthetic
Electric
Intensity
Affect
Benhaiem et al, 2001
RM
32
32
Hypnosis with deep relaxation and focused
analgesia
Live
Yes, No
Nothing
Heat
Threshold

HYPNOSIS AND PAIN
33
Hofbauer et al, 2001
RM
10
10
Stanford SHSS:A
Live
Yes, No
Nothing
Heat
Intensity
Affect
Faymonville et al,
2000
RM
11
11
Stanford SHSS:C with muscle relaxation and
pleasant memory recall
Live
No
Nothing
Heat
Intensity
Affect
Sandrini et al, 2000
RM
20
20
Standard hypnotic induction
Live
Yes
Nothing
Cold
Tolerance
De Pascalis et al, 1999
RM
29
29
Stanford SHSS:C with relaxation, dissociative
imagery and analgesic suggestion
Live
Yes, No
Nothing
Placebo topical gel
Electric
Intensity
Affect
Threshold
Rainville et al, 1999
PPC
11
6
Stanford SHSS:A
Live
Yes
Nothing
Heat
Intensity
Affect
Milling et al, 1999
PPC
50
48
Stanford SHSS:C
Audio
recording
Yes
Nothing
Pressure
Intensity
Danziger et al, 1998
RM
18
18
Hypnosis with deep relaxation, fixation and
Analgesic suggestion
Live
Yes
Nothing
Electric
Threshold
Zachariae et al, 1998
RM
20
20
Standard hypnotic induction
Live
Yes, No
Nothing
Electric
Intensity
Rainville et al, 1997
RM
8
8
Stanford SHSS:A
Live
Yes, No
Nothing
Heat
Intensity
Affect
De Pascalis et al, 1997
RM
20
20
Stanford SHSS:C with subjective sensitivity to
somatosensory stimuli emphasised
Audio
recording
Yes, No
‘normal attention’
control
(recognition task)
Electric
Intensity
Threshold
De Pascalis et al, 1996
RM
16
16
Stanford SHSS:C
Live
Yes, No
Nothing
Electric
Intensity
Affect
Jacobs et al, 1995
RM
24
24
Stanford SHSS:C
Audio
recording
Yes
Nothing
Cold
Intensity
Kiernan et al, 1995
RM
15
15
Hypnosis with suggestion of relaxation, comfort,
and wellbeing
Live
Yes
Nothing
Electric
Intensity
Affect
Hargadon et al, 1995
RM
66
66
Standard hypnotic induction with glove
analgesic suggestion
Live
Yes
Nothing
Pressure
Intensity
Dahlgren et al, 1995
RM
16
16
Stanford hypnotic clinical scale with deep
relaxation
Live
Yes
Nothing
Cold
Intensity
Affect
Zachariae et al, 1994
RM
20
20
Hypnosis using eye fixation technique and
standardised countdown deepening procedure
with deep relaxation/ dissociative imagery/
focused analgesia
Live
Yes, No
Placebo
anaesthetic spray
Laser
Intensity

HYPNOSIS AND PAIN
34
Crawford et al, 1993
RM
11
11
Stanford SHSS:C with mention of sleep and
drowsiness
NG
Yes, No
Nothing
Ischemic
Intensity
Affect
Maurer et al, 1993
RM
42
42
Direct hypnosis induction with focused attention
and repetitive direct suggestion
Indirect hypnosis with ‘Rapid Induction
Analgesia’
Live
Yes
Nothing
Cold
Intensity
Spanos et al, 1990
(2 experiments)
PPC
(RM)
15
28
15
28
Hypnosis (Barber, 1969)
Audio
recording
Yes
Nothing
Pressure
Intensity
Tenenbaum et al,
1990
RM
48
48
Stanford Hypnotic Clinical Scale
Audio
recording
Yes
Nothing
Cold
Tolerance
Malone et al, 1989
RM
45
45
Hypnosis (Barber, 1969) with relaxation and
analgesic suggestion
Live
Yes, No
Nothing
Electric
Intensity
Affect
Spanos, Perlini et al,
1989
2 experiments
PPC
64
60
32
30
Hypnosis (Barber, 1969)
Live
Yes
Nothing
Pressure
Intensity
Spanos and Katsanis,
1989
PPC
20
10
Hypnosis modified from Barber (1969) as
passively (analgesia without voluntary effort) or
actively (analgesia due to mental control)
worded instructions
Live
Yes
Nothing
Pressure
Intensity
De Benedettis et al,
1989
RM
21
21
Standard hypnotic induction
Live
Yes`
Nothing
Ischemic
Affect
Tolerance
Spanos et al, 1988
PPC
45
15
Hypnosis (Barber, 1969)
Live
Yes
Nothing
Pressure
Tolerance
Price et al, 1987
RM
16
16
Standard hypnotic induction
Live
Yes
Nothing
Heat
Intensity
Affect
Stam et al, 1987
RM
32
32
Standard hypnotic Induction
Live
Yes
Nothing
Ischemic
Threshold
Tolerance
Spanos et al, 1986
PPC
64
32
Hypnosis (Barber, 1969)
Audio
recording
Yes
Nothing
Pressure
Intensity
Tolerance
Van Gorp et al, 1985
PPC
20
20
Rapid induction analgesia which includes
suggestion of relaxation and altering memory
Standard hypnotic induction
Audio
recording
Yes, No
Nothing
Cold
Intensity
Spanos et al, 1985
PPC
21
19
Hypnosis (Barber, 1969)
Audio
recording
Yes
Nothing
Cold
Tolerance

HYPNOSIS AND PAIN
35
Fricton et al, 1985
RM
10
10
Indirect hypnosis induction uses language that is
individualised – implies control rests with the
subject
Direct hypnosis induction uses focused attention
and repetitive direct suggestion
Live
No
Nothing
Electric
Threshold
Spanos et al, 1984
RM
75
75
Hypnosis (Barber, 1969)
Live
Yes
Nothing
Cold
Intensity
Stam et al, 1984
(2 experiments)
RM
(PPC)
16
10
16
10
Standard hypnotic induction
Audio
recording
Yes
Nothing
Ischemic
Threshold
Tolerance
Spanos et al, 1983
RM
16
16
Hypnosis (Barber, 1969) with suggestions of
more or less aware of pain from overt and
hidden part of body
Audio
recording
Yes
Nothing
Cold
Intensity
Karlin et al, 1980
RM
11
11
Standard hypnotic induction
Audio
recording
Yes
Nothing
Cold
Intensity
Spanos et al, 1980
RM
8
8
Hypnotic induction with hidden observer cues
Audio
recording
Yes
Nothing
Cold
Intensity
Stam et al, 1980
PPC
20
10
Standard hypnotic procedure
Live
Yes
Nothing
Cold
Intensity
Wood et al, 1976
PPC
10
10
Standard hypnotic induction
Audio
recording
No
Nothing
Cold
Tolerance
Lli et al, 1975
RM
14
14
Standard hypnotic induction with relaxation
Live
Yes
Nothing
Electric
Tolerance
Threshold
Greene et al, 1972
RM
36
36
Standard hypnotic induction with pleasant
imager with/without analgesic suggestion
Live
Yes, No
Nothing
Electric
Tolerance
Morgan et al, 1970
RM
12
12
Standard hypnotic induction
NG
Yes
Nothing
Cold
Intensity
Evans et al, 1970
PPC
32
16
Hypnotic induction with eye fixation &
relaxation
Live
Yes, No
Nothing
Cold
Affect
Key. RM=repeated-measures; BG=between-groups; PPC=pre-post control; CURSS=Carlton University Responsiveness to Suggestion Scale; SHSS=Stanford Hypnotic Suggestibility
Scale (Forms A and C).

HYPNOSIS AND PAIN
36
Table 2. Meta-regression estimates of unstandardized (0-10) pain intensity ratings and 95%
confidence intervals (CI).
Estimate
95% CI
p
Intercept
0.03
-0.59, 0.64
.931
Hypnotisability (Medium)
0.64
0.26, 1.03
.003
Hypnotisability (High)
1.34
0.75, 1.93
<.001
Analgesic suggestion (Yes)
0.94
0.25, 1.63
.009

Figure 1. PRISMA flow diagram
Records identified through
database searching
(n = 6,413)
Screening
Included
Eligibility
Identification
Additional records identified
through other sources
(n = 14)
Records after duplicates removed
(n = 4,801)
Records screened
(n = 4,801)
Records excluded
(n = 4572)
Full-text articles assessed
for eligibility
(n =229)
Full-text articles excluded
(n = 144)
Review/editorial/book (n = 28)
No hypnotic induction (n = 22)
Unsuitable pain assessment / induction
(n = 19)
Published articles not retrievable (typically
>25 years old) (n = 15)
Insufficient data (n = 14)
Dissertations not retrievable (n=12)
Article not in English (n = 11)
Unsuitable/absent control (n = 9)
Did not use healthy participants (n = 6)
Hypnosis part of multi-treatment (n=4)
Duplicate data (n=2)
Data available for combined groups only
(n = 2)
Studies included in
qualitative synthesis
(n = 85)
Studies included in
quantitative synthesis
(meta-analysis)
(n = 85)

1.3%
0.8%
1.5%
1.8%
1.6%
2.2%
1.8%
1.4%
2.0%
2.0%
2.0%
1.8%
1.8%
1.8%
1.7%
1.1%
2.0%
0.9%
1.2%
1.4%
1.4%
1.7%
2.0%
1.9%
1.5%
1.8%
1.6%
1.7%
1.2%
1.7%
1.6%
1.6%
1.6%
1.8%
1.6%
1.7%
1.6%
1.9%
1.4%
1.6%
1.5%
1.6%
1.6%
1.7%
1.3%
2.1%
1.8%
2.3%
1.2%
1.4%
2.1%
1.4%
2.2%
1.2%
1.5%
1.1%
1.1%
1.1%
1.5%
0.6%
1.0%
1.2%
1.5%
1.1%
WeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeightWeight
Summary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMDSummary SMD
Faymonville et al 2000
Casiglia et al 2007
Jacobs et al 1995
Stam et al 1980
Roder et al 2007
Price et al 1987
Spanos & Katsanis 1989
Spanos et al 1980
DePascalis et al 2001
Vanhaudenhuyse et al 2009
Zachariae at al 1994
Hargadon et al 1995
Casiglia 2017
Milling et al 2010b
Hofbauer et al 2001
Goodin et al 2012
Milling et al 2010a
Fidanza et al 2017
Wolf et al 2016
Sharav et al 2004
Williams et al 2010
Spanos et al 1985
Maurer et al 1993
DePascalis et al 1999
Milling et al 2002
Spanos et al 1983
Milling et al 2009
Milling, Levine et al 2003
Milling et al 2005
DePascalis et al 2015
Kiernan et al 1995
Spanos et al 1990
Zachariae et al 1998
Spanos et al 1986
Green et al 2010
DePascalis et al 1996
Milling, Breen et al 2003
DePascalis et al 2008
Bhatt et al 2017
Spanos, Perlini et al 1989
Dahlgren et al 1995
Spanos et al 1984
Karlin et al 1980
Ray et al 2002
Wright et al 2001
VanGorp et al 1985
Patterson et al 2006
Friederich et al 2001
Rainville et al 1999
De Pascalis, Bellusci et al 2004
Sharav et al 2006
De Pascalis, Cacace et al 2004
Morgan et al 1970
Milling et al 2007
Santarcangelo et al 2013
Rainville et al 2005
Enea et al 2014
Malone et al 1989
Swain et al 2014
Rainville et al 1997
Valentini et al 2013
Milling et al 1999
Croft et al 2002
Derbyshire et al 2017
-1 012
Favours Control -- Favours Hypnosis
Figure 2. Forest plot of pain intensity

SMD
(Pain Intensity Ratings)
Standard Error
0.831 0.623 0.416 0.208 0
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
−1 0 1 2

Appendix S1. Search terms for PubMed
(hypno* OR trance) AND (pain OR nocicept* OR analge*) AND (threshold OR
tolerance OR cold OR heat OR thermal OR ischemi* OR ischaemi* OR chemical OR
pressure OR mechanical OR electric* OR chemical OR capsaicin OR reflex OR
experimental OR acute)

Appendix S2. Endorsement of validity criteria (1= criteria met, 0= criteria not met)
Study
q1
q2
q3
q4
q5
q6
q7
q8
q9
q10
q11
q12
q13
q14
q15
Derbyshire et al (2017)
1
1
1
0
0
0
1
1
1
0
1
1
1
1
1
Bhatt et al (2017)
1
1
0
1
1
0
1
1
1
1
0
1
1
1
0
Fidanza et al (2017)
1
1
0
1
0
1
1
1
0
0
1
1
1
1
0
Casiglia et al (2017)
1
0
0
0
0
0
1
1
0
0
0
1
0
1
0
Braboszcz et al (2017)
1
1
1
0
0
0
0
1
1
1
1
1
1
1
1
Wolf et al (2016)
1
1
1
1
0
1
0
1
1
0
0
1
0
1
1
DePascalis et al (2016)
1
1
1
1
1
1
1
1
0
1
1
1
1
1
0
DePascalis et al (2015)
1
1
1
1
0
1
1
1
1
1
1
0
1
1
1
Kramer et al (2014)
1
0
1
1
0
0
1
1
1
0
1
1
1
1
0
Swain et al (2014)
1
1
1
1
1
0
1
1
0
1
0
0
1
1
0
Enea et al (2014)
1
1
1
0
0
0
1
1
1
1
1
1
0
1
1
Valentini et al (2013)
1
0
0
1
1
1
1
1
1
0
1
1
1
1
1
Santarcangelo et al (2013)
1
1
1
1
1
0
1
1
0
1
1
1
1
1
0
Goodin et al (2012)
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
Facco et al (2011)
1
1
0
1
1
1
1
1
1
0
1
1
1
1
0
Williams et al (2012)
1
0
0
0
0
0
1
1
0
0
1
1
1
1
1
Milling et al (2010)
1
1
1
0
0
0
1
0
0
1
1
1
1
1
0
Green et al (2010)
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
Milling et al (2010)
1
1
1
1
1
0
1
1
0
1
0
0
1
1
0
Milling et al (2009)
1
1
1
0
1
0
1
1
1
1
1
0
1
1
1
Vanhaudenhuyse et al (2009)
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
DePascalis et al (2008)
1
1
0
1
1
1
1
1
0
1
1
1
1
1
1
Roder et al (2007)
1
0
0
0
0
0
1
1
1
0
1
0
1
1
0
Casiglia et al (2007)
1
0
0
0
0
1
1
1
1
0
0
1
1
1
0
Milling et al (2007)
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
Sharav et al (2006)
1
1
1
0
0
0
1
1
1
0
1
1
1
1
0
Patterson et al (2006)
1
1
0
0
0
0
1
1
1
0
1
0
1
1
1

Milling et al (2005)
1
1
1
0
0
0
1
1
1
1
1
0
0
1
1
Rainville et al (2005)
1
1
0
0
0
0
1
1
0
1
1
1
1
1
0
DePascalis, Cacace et al (2004)
1
1
0
0
0
0
1
1
0
1
1
1
1
1
1
DePascalis, Bellusci et al (2004)
1
1
1
1
0
0
1
1
1
0
1
1
1
1
0
Sharav et al (2004)
1
1
1
1
0
1
1
1
1
1
1
1
1
1
0
Milling, Breen et al (2003)
1
1
1
0
0
0
1
1
1
1
1
0
0
1
1
Faymonville et al (2003)
1
0
0
0
0
0
1
1
1
1
1
1
1
1
0
Milling, Levine et al (2003)
1
1
1
0
0
0
1
1
1
0
1
0
0
1
1
Croft et al (2002)
1
1
1
0
0
0
1
1
1
0
1
0
1
1
1
Milling et al (2002)
1
1
1
0
0
0
1
1
1
1
1
1
0
1
1
Langlade et al (2002)
0
1
1
0
0
0
1
1
0
0
0
1
1
1
1
Ray et al (2002)
1
1
0
0
0
0
0
1
0
1
0
1
1
1
0
Wright et al (2001)
1
1
1
0
0
0
1
1
1
0
0
1
1
1
0
DePascalis et al (2001)
1
1
0
1
0
0
1
1
1
1
1
1
1
1
0
Benhiem et al (2001)
1
0
1
1
0
1
1
1
1
0
1
1
1
1
0
Hofbauer et al (2001)
1
0
0
0
0
0
1
1
1
1
1
1
1
1
0
Freiderich et al (2001)
1
1
1
0
0
0
1
1
1
1
1
0
0
1
1
Faymonville et al (2000)
1
0
0
0
0
1
1
1
0
0
1
1
1
1
0
Sandrini et al (2000)
1
1
0
0
0
1
1
1
1
0
1
1
1
1
1
DePascalis et al (1999)
1
0
0
0
0
0
1
1
1
1
1
1
1
1
0
Rainville et al (1999)
1
1
0
0
0
0
1
1
1
1
0
1
1
1
0
Milling et al (1999)
1
1
1
0
0
0
1
1
0
0
1
1
0
1
1
Danzinger et al (1998)
1
1
0
1
0
1
0
1
1
0
1
1
0
1
0
Zachariae et al (1998)
1
0
1
0
0
0
1
1
1
1
1
0
1
1
0
Rainville et al (1997)
1
0
0
0
0
0
0
1
0
1
1
1
0
1
0
DePascalis et al (1997)
1
1
1
0
0
0
1
1
0
0
1
1
0
1
0
DePascalis et al (1996)
1
1
0
0
0
0
1
1
0
1
1
1
1
1
0
Jacobs et al (1995)
1
1
1
0
0
0
1
1
0
0
1
1
0
1
0
Kiernan et al (1995)
1
1
1
1
0
1
1
0
1
0
0
1
1
1
0

Hargadon et al (1995)
1
0
0
0
0
0
1
1
1
1
1
1
0
1
0
Dahlgren et al (1995)
1
1
0
1
0
1
0
0
0
1
1
1
0
1
0
Zachariae et al (1994)
1
1
1
0
0
0
1
1
1
1
1
1
1
1
1
Maurer et al (1993)
1
1
0
0
0
0
1
1
1
1
1
1
1
1
0
Crawford et al (1993)
1
1
1
1
1
1
1
1
0
1
1
1
1
1
1
Spanos et al (1990)
1
1
1
0
0
0
1
1
1
1
1
0
0
1
1
Tenenbaum et al (1990)
1
0
1
1
0
1
1
1
0
0
1
0
0
1
0
Malone et al (1989)
0
1
1
0
0
0
1
1
1
0
1
0
0
1
1
Spanos, Perlini et al (1989)
1
1
1
0
0
0
1
1
1
1
1
1
1
1
1
Spanos and Katsanis et al (1989)
1
1
1
0
0
0
1
1
1
1
1
0
0
1
1
Debenedittis et al (1989)
1
1
1
0
0
0
1
1
1
0
1
1
1
1
0
Spanos et al (1988)
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
Stam et al (1987)
1
1
1
1
0
1
1
1
0
1
0
1
1
1
0
Price et al (1987)
1
1
1
0
0
0
1
1
1
0
0
1
1
1
0
Spanos et al (1986)
1
1
1
0
0
0
1
1
1
1
1
1
0
1
1
VanGorp et al (1985)
1
1
0
0
0
0
1
1
1
1
1
1
0
1
1
Spanos et al (1985)
1
1
1
0
0
0
1
1
1
1
0
1
0
1
1
Fricton et al (1985)
1
0
0
0
0
0
1
1
1
0
1
1
0
1
0
Spanos et al (1984)
1
1
1
0
0
0
1
1
1
0
1
1
1
1
1
Stam et al (1984)
1
1
1
1
1
0
1
1
1
1
1
0
1
1
0
Spanos et al (1983)
1
1
1
1
0
0
1
1
1
0
1
1
0
1
0
Karlin et al (1980)
0
1
1
1
0
0
1
1
0
0
1
1
1
1
0
Stam et al (1980)
1
1
1
0
0
0
1
1
1
1
1
1
1
1
1
Spanos et al (1980)
1
1
1
0
0
0
1
1
1
1
1
1
0
1
0
Wood et al (1976)
1
1
0
0
0
0
1
1
1
1
1
0
0
1
0
Li et al (1975)
0
1
0
1
1
0
0
1
1
1
0
0
1
1
0
Greene et al (1972)
1
1
1
0
0
0
1
1
1
1
1
1
0
1
1
Morgan et al (1970)
1
0
0
0
0
0
1
1
0
0
1
1
0
1
0
Evans et al (1970)
1
1
1
0
0
0
1
1
1
0
1
0
1
1
0

Mean Item Endorsement
0.95
0.79
0.64
0.34
0.18
0.25
0.92
0.96
0.71
0.59
0.82
0.73
0.67
1.00
0.42
Key: 1-Was there a clear specification of study objectives; 2-Was it clearly described where particpants were drawn from (e.g. University etc); 3-Was it clearly described how participants were
recruited (e.g. advertisement, course credits, volunteers etc etc); 4-Was there a clear description of the inclusion and exclusion criteria; 5-Were participants assessed to see if they had pre-
existing pain; 6-Were participants asked to report (or abstain from using) any medication that might affect their experience of pain (e.g. painkilllers); 7-Pain Assessment: Was the method of
pain assessment clearly described; 8-Pain Induction: Was the method of pain induction clearly reported; 9-Hypnosis: Was the hypnotic intervention described in adequate detail; 10-Control:
Was the control condition described in adequate detail; 11-Was hypnotisability assessed; 12-Comparability of cases and controls; 13-Were relevant participant characteristics adequately
described (age, sex etc); 14-Were complete outcome data (i.e., Ms and SDs) available (e.g. reported in article or given via response to data request); 15-Were paticipants randomly allocated
to groups (independent-sample designs) or presentation order (repeated-measures designs)?

PRISMA 2009 Checklist
`Section/topic
#
Checklist item
Reported
on page #
TITLE
Title
1
Identify the report as a systematic review, meta-analysis, or both.
1
ABSTRACT
Structured summary
2
Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria,
participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and
implications of key findings; systematic review registration number.
2
INTRODUCTION
Rationale
3
Describe the rationale for the review in the context of what is already known.
3
Objectives
4
Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons,
outcomes, and study design (PICOS).
4
METHODS
Protocol and registration
5
Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide
registration information including registration number.
5
Eligibility criteria
6
Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered,
language, publication status) used as criteria for eligibility, giving rationale.
5
Information sources
7
Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify
additional studies) in the search and date last searched.
5
Search
8
Present full electronic search strategy for at least one database, including any limits used, such that it could be
repeated.
Appendix
S1
Study selection
9
State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable,
included in the meta-analysis).
6
Data collection process
10
Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes
for obtaining and confirming data from investigators.
7
Data items
11
List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and
simplifications made.
7
Risk of bias in individual
studies
12
Describe methods used for assessing risk of bias of individual studies (including specification of whether this was
done at the study or outcome level), and how this information is to be used in any data synthesis.
Table S1
Summary measures
13
State the principal summary measures (e.g., risk ratio, difference in means).
8
Synthesis of results
14
Describe the methods of handling data and combining results of studies, if done, including measures of consistency
(e.g., I2) for each meta-analysis.
9

PRISMA 2009 Checklist
Page 1 of 2
Section/topic
#
Checklist item
Reported
on page #
Risk of bias across studies
15
Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective
reporting within studies).
10
Additional analyses
16
Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating
which were pre-specified.
9
RESULTS
Study selection
17
Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at
each stage, ideally with a flow diagram.
10,
Fgiure 1
Study characteristics
18
For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and
provide the citations.
11, Table
1
Risk of bias within studies
19
Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).
12, Table
S1
Results of individual studies
20
For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each
intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.
Figure 2
Synthesis of results
21
Present results of each meta-analysis done, including confidence intervals and measures of consistency.
13-14
Risk of bias across studies
22
Present results of any assessment of risk of bias across studies (see Item 15).
14
Additional analysis
23
Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).
14-15
DISCUSSION
Summary of evidence
24
Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to
key groups (e.g., healthcare providers, users, and policy makers).
16
Limitations
25
Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of
identified research, reporting bias).
19
Conclusions
26
Provide a general interpretation of the results in the context of other evidence, and implications for future research.
17, 19
FUNDING
Funding
27
Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the
systematic review.
20
From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097.
doi:10.1371/journal.pmed1000097
For more information, visit: www.prisma-statement.org.
Page 2 of 2