Virtual Reality Exposure Therapy For Social Anxiety Disorder: A Systematic Review and Meta-Analysis

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Psychological Medicine Virtual reality exposure therapy for social

cambridge.org/psm
anxiety disorder: a systematic review and
meta-analysis
Toshiro Horigome1, Shunya Kurokawa1, Kyosuke Sawada2, Shun Kudo3,
Review Article
Kiko Shiga1, Masaru Mimura1 and Taishiro Kishimoto1,4
Cite this article: Horigome T, Kurokawa S,
Sawada K, Kudo S, Shiga K, Mimura M, 1
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 2Asaka Hospital, Fukushima,
Kishimoto T (2020). Virtual reality exposure
Japan; 3Department of Neuropsychiatry, Japanese Red Cross Ashikaga Hospital, Tochigi, Japan and 4Psychiatry at
therapy for social anxiety disorder: a
systematic review and meta-analysis. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, New York, USA
Psychological Medicine 1–11. https://doi.org/
10.1017/S0033291720003785 Abstract
Received: 20 July 2020 Background. Virtual reality exposure therapy (VRET) is currently being used to treat social
Revised: 17 September 2020 anxiety disorder (SAD); however, VRET’s magnitude of efficacy, duration of efficacy, and
Accepted: 22 September 2020 impact on treatment discontinuation are still unclear.
Key words:
Methods. We conducted a meta-analysis of studies that investigated the efficacy of VRET for
Dropout rate; in vivo exposure; long-term SAD. The search strategy and analysis method are registered at PROSPERO
efficacy; social anxiety disorder; virtual reality (#CRD42019121097). Inclusion criteria were: (1) studies that targeted patients with SAD or
exposure related phobias; (2) studies where VRET was conducted for at least three sessions; (3) studies
Author for correspondence:
that included at least 10 participants. The primary outcome was social anxiety evaluation score
Taishiro Kishimoto, change. Hedges’ g and its 95% confidence intervals were calculated using random-effect mod-
E-mail: taishiro-k@mti.biglobe.ne.jp els. The secondary outcome was the risk ratio for treatment discontinuation.
Results. Twenty-two studies (n = 703) met the inclusion criteria and were analyzed. The effi-
cacy of VRET for SAD was significant and continued over a long-term follow-up period:
Hedges’ g for effect size at post-intervention, −0.86 (−1.04 to −0.68); three months post-inter-
vention, −1.03 (−1.35 to −0.72); 6 months post-intervention, −1.14 (−1.39 to −0.89); and 12
months post-intervention, −0.74 (−1.05 to −0.43). When compared to in vivo exposure, the
efficacy of VRET was similar at post-intervention but became inferior at later follow-up
points. Participant dropout rates showed no significant difference compared to in vivo
exposure.
Conclusion. VRET is an acceptable treatment for SAD patients that has significant, long-last-
ing efficacy, although it is possible that during long-term follow-up, VRET efficacy lessens as
compared to in vivo exposure.

Introduction
Social anxiety disorder (SAD) is one of the most common psychiatric disorders (Kessler et al.,
2005) and many patients with SAD are refractory to pharmacotherapy (Keller, 2006; Yonkers,
Dyck, & Keller, 2001). Among other treatment methods, exposure therapy has been identified
as effective (Heimberg, Becker, Goldfinger, & Vermilyea, 1985; Ponniah & Hollon, 2008).
However, when performing exposure therapy for SAD patients, it takes a great deal of effort
and time to accurately recreate interpersonal situations that will provoke the appropriate level
of fear response in patients (e.g. in order to conduct exposure therapy for a patient with a fear
of public speaking, one would need to gather an audience and regulate their reactions). Virtual
reality (VR) has made large advances and has allowed for experimenting with the use of VR in
exposure therapy (Virtual reality exposure therapy: VRET) to treat phobias and anxiety disor-
ders (Mishkind, Norr, Katz, & Reger, 2017). There is currently research being done on the effi-
cacy of VRET for treating SAD, public speaking anxiety (PSA), fear of public speaking (FPS),
and similar conditions, and several meta-analyses of such studies already exist. In all these
meta-analyses, the effectiveness shown in pre-post and waiting list comparisons was the
same. When comparing in vivo exposure, Wechsler, Mühlberger, and Kümpers (2019)
reported that in vivo exposure had greater efficacy than VRET, but meta-analyses that included
larger numbers of studies, such as those by Chesham, Malouff, and Schutte (2018) and Carl
et al. (2019) reported that evidence suggests VRET may have the similar efficacy as in vivo
© The Author(s) 2020. Published by Cambridge exposure. However, because other types of studies, such as single-arm studies and randomized
University Press controlled trials (RCTs) that had control groups other than in vivo exposure, were not included
in these previous meta-analyses, there are many more studies on the efficacy of VRET for SAD
that should be considered. Therefore, these should also be examined to confirm whether
results so far may change with more information. Also, only Kampmann, Emmelkamp, and
Morina (2016b) conducted meta-analyses of follow-up studies and the number of studies

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2 Toshiro Horigome et al.

included was small. It is important to look at the long-term effects majority of RCTs for VR intervention have small case sizes.
of a large number of studies. This is because evaluations done dir- This means that, in order to conduct a meta-analysis of all the
ectly following the intervention period will reflect a decrease in research and participants, we considered it is best to also include
the fear targeted by the VRET experience, and there is a possibil- single-arm studies. However, case reports with small numbers of
ity that anxiety felt in real-life social situations is not reflected; or cases are more likely to be influenced by reporting bias, and in
that after VR intervention has finished, once the subject is placed order to avoid this, we established the inclusion criteria of 10 or
in real-life social situations, it may be easier for symptoms to more participants. For both the primary and secondary screenings
reoccur as compared to conventional therapy. Furthermore, as of the articles, two of the five investigators looked at each article,
far as we know, there have been no meta-analyses done for drop- and in cases where investigators disagreed on the status of an art-
out rates for SAD patients. Also, methods for treating SAD are icle, a third investigator was asked to assist in the decision-making
becoming more diverse, which means that VRET need not consist process.
purely of VR exposure; in fact, there are multiple studies that
combine VRET with additional treatment methods such as cogni-
tive behavioral therapy (CBT) and other psychotherapy practices. Data extraction
This diversification of methodology makes it more difficult to Studies that met all the eligibility criteria outlined above were each
fully understand which methods are effective. reviewed by two investigators who extracted the data from each
In this study, our aim was to conduct a meta-analysis of study. The primary outcome was the change in social anxiety
research that has used VRET as an intervention for SAD, and score from the baseline point. In cases where social anxiety was
to comprehensively evaluate the efficacy of VRET. To accomplish measured with more than one method, we used the Liebowitz
this, we investigated the following three points of inquiry in our Social Anxiety Scale (LSAS) score (Liebowitz, 1987). For missing
analysis: (1) How do symptoms change with the use of VRET, data (e.g. missing standard deviations), we asked for data and
and especially, how do they change over a long-term period? clarification by sending an email directly to the relevant study
(2) When VRET is compared with waiting lists or authors. If the standard deviation value of the outcome was not
treatment-as-usual (TAU), what are the effect size and dropout available, we estimated the value based on other research that
rates? (3) When VRET is compared with in vivo exposure, are used the same outcome (Furukawa, Barbui, Cipriani, Brambilla,
there differences in efficacy (over both short and long terms) or & Watanabe, 2006). The secondary outcome was the dropout rate.
in dropout rates?

Comparisons
Methods
Improvement of symptoms and duration thereof following VRET
Search strategy In order to investigate how effective VRET is, and how long the
This systematic review and meta-analysis followed the standards effects will continue, we first compared symptom severity at baseline
set forth in the Preferred Reporting Items for Systematic v. the following five-time points, respectively: post-intervention, 3
Reviews and Meta-Analyses (PRISMA) guidelines (Moher, months post-intervention, 6 months post-intervention, 12 months
Liberati, Tetzlaff, & Altman, 2009). The search strategy and ana- post-intervention, and 6 years post-intervention.
lysis method are registered at PROSPERO (#CRD42019121097).
The systematic literature search was done by five investigators Comparison with waiting list or treatment-as-usual groups
using PubMed, PsycINFO, and Scopus databases. The search In order to examine the effect size of VRET as compared to
terms used were [SAD OR ‘social anxiety’ OR ‘social fear’ OR untreated controls and standard treatments, the change in symp-
‘social phobia’ OR ((speak* OR speech) AND (anxiety OR toms from baseline to post-intervention was compared between
fear))] AND [(virtual OR augmented OR artificial OR mixed) the VRET group and waiting list/TAU group. The dropout rate
AND (environment OR reality OR audience)]. The last search for the VRET and waiting list/TAU groups was also compared.
was conducted in May 2020. There was no lower publication
date limit to the searches. Comparison with in vivo exposure
To investigate the differences in efficacy between VRET and in
vivo exposure therapy, the change in symptoms from baseline
Study selection to post-intervention was compared between the VRET group
A primary screening of the studies identified in the literature and in vivo exposure group. The long-term effect was also com-
search was done by reviewing the titles and abstracts for those pared based on symptom differences between the baseline and
items that appeared to focus on intervention methods using follow-up time points. Additionally, the dropout rate for VRET
VR. For studies that were selected via this screening method, as and in vivo exposure was compared.
well as studies that had been used in the previous meta-analyses
on this topic, we obtained full versions of the articles, and, in a
Sensitivity analysis and moderator analysis
secondary screening process, determined if the articles met the
following eligibility criteria: (1) study participants were diagnosed We conducted a sensitivity analysis and moderator analysis on the
with one of the following: SAD, FPS, or PSA; (2) VRET was con- results from baseline and post-intervention comparisons. To
ducted for three or more sessions; (3) study participants num- investigate whether or not the treatment efficacy changed depend-
bered 10 or more people. This meta-analysis included not only ing on differences in intervention methods, study protocol, and
RCTs, but also single-arm studies where all subjects were given subjects’ diagnoses, we conducted sensitivity analyses for the fol-
VR intervention. Research using VR has so far been experimental lowing: (1) whether VRET was used with or without structured
and focused mainly on smaller numbers of cases, so even the psychotherapy; (2) whether the study protocol was an RCT or

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Psychological Medicine 3

not; (3) whether participants were diagnosed with SAD or other psychotherapy, CBT was the most-used psychotherapy method,
disorders (i.e. PSA and FPS). appearing in eight studies (Table 1).
Next, with the goal of determining which factors are important The number of participants included in the meta-analysis was
for VRET to be effective, we conducted a meta-regression analysis 586 [VRET 325 (VRET + psychotherapy 163, VRET-only 162), in
of the following continuous moderator variables: (1) number of vivo exposure therapy 138, waiting list/TAU 123], and the average
VR sessions; (2) number of total sessions; (3) ratio of VR sessions age was 33.5 years.
to total sessions; (4) time of total VR sessions; (5) time of total
sessions; (6) ratio of VR sessions’ time to total sessions’ time;
Improvement of symptoms and duration thereof following
(7) baseline LSAS-total score; (8) publication year. However, we
VRET
did not conduct multiple meta-regression analyses because we
considered there were too few studies to do so. There was a significant decrease in symptom evaluation scores
from baseline to post-intervention [studies = 20, n = 299,
Hedges’ g = −0.86 (−1.04 to −0.68), p < 0.001; heterogeneity I 2
Meta-analytic procedures = 77.6%, Q = 84.9, p < 0.001; prediction interval = −0.80 (−1.54
Hedges’ g ± 95% confidence intervals (CIs) were calculated for to −0.06)] (Fig. 1). Each follow-up time points also displayed a
continuous outcomes (i.e. social anxiety score) using significant decrease in symptom scores from baseline (Fig. 1).
random-effect models. For dichotomous outcome, the risk ratio Effect sizes at each follow-up time points are as follows: 3 months
was calculated using random-effect models. To evaluate hetero- post-intervention [studies = 5, n = 80, Hedges’ g = −1.03 (−1.35 to
geneity, I 2, Q, and p values were reported. When there were −0.72), p < 0.001; heterogeneity I 2 = 70.0%, Q = 13.3, p = 0.01;
three or more studies, we also calculated the prediction interval. prediction interval = −0.96 (−1.94 to 0.03)], 6 months post-
Comprehensive Meta-analysis Version 3 was used for the analysis. intervention [studies = 2, n = 38, Hedges’ g = −1.14 (−1.39 to
−0.89), p < 0.001; heterogeneity I 2 = 0%, Q < 0.01, p = 0.94)], 12
months post-intervention [studies = 2, n = 55, Hedges’ g = −0.74
Risk of bias assessment (−1.05 to −0.43), p < 0.001; heterogeneity I 2 = 64.5%, Q = 2.8, p
For all studies that met the eligibility criteria, two investigators = 0.09], and 6 years post-intervention [studies = 1, n = 13,
evaluated each study for risk of bias. These assessments were Hedges’ g = −0.43 (−0.77 to −0.09), p = 0.01; heterogeneity
done in accordance with the Cochrane Collaboration’s tool for I 2 = 0%, Q < 0.01, p < 0.001].
assessing the risk of bias in RCTs (Higgins et al., 2011).
Publication bias was assessed via visual inspection of funnel VRET v. waiting list or treatment-as-usual
plots using Egger’s intercept test (Egger, Smith, Schneider, &
Minder, 1997) and trim and fill procedure (Duval & Tweedie, VRET was significantly more effective compared with waiting list/
2000). TAU [studies = 7, n = 273, Hedges’ g = −1.23 (−1.70 to −0.76),
p < 0.001; heterogeneity I 2 = 67.6%, Q = 18.5, p = 0.005; prediction
interval = −1.23 (−2.71 to 0.25)] (Fig. 2).
Results There was no difference in dropout rates between VRET
Search results groups and waiting list/TAU groups [studies = 6, n = 118,
Risk ratio = 1.25 (0.66 to 2.37), p = 0.49; heterogeneity I 2 = 0%,
Out of 478 articles that were screened in the primary and second- Q = 4.70, p = 0.45; prediction interval = 1.25 (−0.33 to 2.84)]
ary processes, 22 articles met the eligibility criteria for this (online Supplementary Fig. S2).
meta-analysis (online Supplementary Fig. S1). The 78 articles
that were excluded during the secondary screening were rejected
for the following reasons: 14 studies had less than three interven- VRET v. in vivo exposure
tion sessions; four studies had too few participants; 32 studies did There was no significant difference between the effect size of
not measure efficacy; six studies did not actually utilize VR in VRET and in vivo exposure at post-intervention [studies = 10, n
their intervention methods; two studies did not investigate SAD, = 355, Hedges’ g = 0.07 (−0.41 to 0.55), p = 0.78; heterogeneity
PSA, and/or FPS; six were review articles; 13 studies examined I 2 = 78.6%, Q = 42.0, p < 0.001; prediction interval = 0.07 (−1.57
the exact same cohort; and lastly, one study looked at the efficacy to 1.71)] (Fig. 3).
of virtual space in a social game as an intervention method (Yuen However, at 3 months post-intervention, in vivo exposure
et al., 2013), and it was felt that the heterogeneity of this study was showed greater efficacy [studies = 3, n = 129, Hedges’ g = 0.81
too high compared to the others, so it was excluded. (0.01 to 1.61), p = 0.047; heterogeneity I 2 = 76.8%, Q = 8.6, p =
0.01; prediction interval = 0.81 (−8.57 to 10.19)], whereas at 6
months post-intervention, VRET showed greater efficacy [studies
Study characteristics
= 1, n = 39, Hedges’ g = −0.86 (−1.51 to −0.21), p = 0.10]. Then at
Of the 22 studies selected for our meta-analysis, 14 of those stud- 12 months post-intervention [studies = 2, n = 118, Hedges’
ies investigated patients with SAD, and eight studies investigated g = 0.46 (0.09–0.82), p = 0.01; heterogeneity I 2 = 0%, Q = 0.32,
FPS or PSA. Eleven studies were RCTs. Seven studies reported p = 0.57] and 6 years post-intervention [studies = 1, n = 28,
data for waiting list/TAU groups as control groups. Ten studies Hedges’ g = 1.12 (0.34–1.90), p = 0.005], in vivo exposure, again,
had in vivo exposure (including group exposure, imaginary expos- showed greater efficacy compared to VRET (Fig. 3).
ure, etc.) comparison groups. Twelve studies used a combination There was no significant difference in dropout rates between
of VRET and psychotherapy, nine studies used only VRET, and VRET and in vivo exposure [studies = 4, n = 126, risk ratio =
one study used both VRET and psychotherapy separately. 0.63 (0.37–1.06), p = 0.08; heterogeneity I 2 = 0%, Q = 2.79,
Within the studies that used a combination of VRET and p = 0.43; prediction interval = −0.33 (−1.17 to 0.51)] (Fig. 4).

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4
Table 1. Characteristics of studies and patients

No. of No. of Long-term


Mean total exposure follow-up
Study Diagnosis Design VR intervention method Comparison N age sessions sessions (months)

Anderson, Zimand, SAD (DSM-IV) Single-arm study Psychoeducation and cognitive – 11 44.6 8 4 3
Schmertz, and Ferrer therapy + VRET
(2007) First four sessions:
psychoeducation and cognitive
therapy; second four sessions:
patient manipulates exposure
software and proceeds through
session. Questions for therapist
possible.
Anderson et al. (2013) SAD (DSM-IV) RCT Original protocol using CBT + EGT/waiting list 58 39 8 4 3/12
VRET
VRET conducted 4 times.
Therapist controls the reactions
of the virtual humans.
Homework given at each session.
Anderson, Edwards, SAD (DSM-IV) RCT Original protocol using CBT + EGT 28 42 8 4 72
and Goodnight (2017) VRET
Follow-up study of Anderson et
al. (2013).
Bouchard et al. (2017) SAD (DSM-5) RCT CBT + VRET CBT + in vivo 59 34.5 14 8 6
Incorporated VR into existing CBT exposure/waiting list
protocol (Clark & Wells, 1995).
Denizci Nazligul et al. PSA (LSAS RCT VRET Psychoeducationa 14 21.4 4 3 –
(2019) fear and Session 1: assessment by
avoidance therapist and focus on
each ⩾20) psychoeducation. Sessions 2–4:
VRET wherein therapist controls
the reactions of the virtual
humans; after VRET, discussion
with therapist about cognition.
Gebara, Barros-Neto, SAD (DSM-IV) Single-arm study VRET – 25 39 12 7 6
Gertsenchtein, and Six types of VR exposure
Lotufo-Neto (2016) scenarios that are repeated until
anxiety is reduced. Therapist
with CBT training controls the
reactions of the virtual humans.
Geraets et al. (2019) SAD Single-arm study CBT + VRET – 15 34.9 16 14 3
Incorporated VR into existing CBT

Toshiro Horigome et al.


protocol (Pot-Kolder et al., 2018).
Therapist controls the number of
audience members and their eye
lines.
Grillon, Riquier, SAD (DSM-IV) Single-arm study VRET – 10 – 11 8 –
Herbelin, and Protocol based on Hofmann’s
Thalmann (2006) model with added use of VR.
Homework given at each session.
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Harris, Kemmerling, & FPS (PRCS RCT VRET Waiting list 17 – 4 4 –

Psychological Medicine
North (2002) ⩾16) VR exposure for public speaking
scenarios. Therapist controls
number of audience members
and their behavior; also uses
audience applause to encourage
the patient and draw patient’s
line of sight to the audience.
Kampmann et al. SAD (DSM-IV) RCT VRET In vivo exposure / 60 36.9 10 7 3
(2016a) Protocol using only behavioral waiting list
exposure elements (Hofmann &
Otto, 2008; Scholing&
Emmelkamp, 1993) in
conjunction with VR. Therapist
communicated with patient
before and after treatment.
Kim et al. (2017) SAD (DSM-IV) Controlled clinical VRET Normal controla 48 23 8 8 –
trial (demographic Treatment was VRET-only.
data used for
matching)
Klinger et al. (2005) SAD (DSM-IV) Controlled clinical Original psychotherapy + VRET CBGT 36 31.6 12 12 –
trial (demographic While using VRET, therapist
data used for supports patient in learning
matching) about adapted cognition and
behavior to help them lessen
anxiety in real-life settings.
Kovar (2018) SAD Non-randomized Psychotherapy + VRET Psychotherapya 10 34.6 10 8 –
parallel comparison Intervention combining
trial psychotherapy and VRET.
Lister et al. (2010) FPS (PRCS RCT VRET Waiting listb 20 – 4 4 –
⩾21) VRET consisting of a scenario
where patient reads a children’s
book to a virtual audience.
North, North, and FPS (DSM-IV) Controlled clinical VRET Placebo (exposed to 16 – 5 5 –
Coble (1998) trial (demographic VR exposure for public speaking trivial VR scenes)a
data used for scenarios. Therapist controls
matching) number of audience members
and their behavior.
Robillard, Bouchard, SAD (DSM-IV) RCT CBT + VRET CBT + in vivo 45 34.9 – 16 –
Dumoulin, Guitard, Intervention combining CBT and exposure/waiting list
and Klinger (2010) VRET.
Roy et al. (2003) SAD (DSM-IV) No information on Original psychotherapy + VRET CBGT 10 36.1 12 12 –
randomization While using VRET, therapist
supports patient in learning
about adapted cognition and
behavior to help them lessen
anxiety in real-life settings.
Safir, Wallach, and PSA RCT CBT + VRET CBT + imaginary 49 27 12 – 12
Bar-Zvi (2012) Follow-up study of Wallach, Safir, exposure
and Bar-Zvi (2009).
(Continued )

5
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Table 1. (Continued.)

6
No. of No. of Long-term
Mean total exposure follow-up
Study Diagnosis Design VR intervention method Comparison N age sessions sessions (months)

Stupar-Rutenfrans PSA Single-arm study VRET – 38 – 8 8 –


et al. (2017) (PRCA ⩾ 55) VRET with public speaking
scenarios only. Number of virtual
audience members was
controlled.
Wallach et al. (2009) PSA RCT CBT + VRET CBT + imaginary 112 27 12 8 –
Original CBT protocol combined exposure/waiting list
with VRET.
Wallach, Safir, and PSA RCT VRET / CBT + VRETc CTa/waiting listc 78 27 12 – –
Bar-Zvi (2011) VRET group was given exposure
therapy based on the behavioral
aspects of a treatment outlined
by Heimberg and Becker (2002).
Cognitive aspects were not
touched on. CBT + VRET group
referenced data from Wallach
et al. (2009).
Yuen et al. (2019) SAD (DSM-IV) Non-randomized ACT + VRET ACT + 26 43.5 6 4 3
parallel comparison ACT program members using a videoconferencing
trial video conferencing system were exposure
given additional homework to
participate in 4 sessions of VRET.
ACT, acceptance and commitment therapy; CBT, cognitive behavioral therapy; CBGT, cognitive behavioral group therapy; CT, cognitive therapy; DSM, Diagnostic and Statistical Manual of Mental Disorders; EGT, exposure group therapy; FPS, fear of
public speaking; LSAS, Liebowitz Social Anxiety Scale; PRCA, Personal Report of Communication Apprehension; PRCS, Personal Report of Confidence as a Speaker; PSA, public speaking anxiety; SAD, social anxiety disorder; VRET, virtual reality exposure
therapy.
a
This comparison is different from that of in vivo exposure and waiting list groups, and was not included in our analysis.
b
Due to inadequacies in the data, we did not include them in our analysis.
c
These data are duplicated from other studies, and so were not used in our analysis.

Toshiro Horigome et al.


Psychological Medicine 7

Fig. 1. Symptom reduction compared to baseline score at each time point. Negative scores indicate treatment efficacy.

Fig. 2. Comparison of treatment efficacy for VRET and waiting list/treatment-as-usual groups at treatment end-point.

Sensitivity analysis and moderator analysis I 2 = 71.3%, Q = 41.8, p < 0.001; prediction interval = −0.96
(−1.65 to −0.28)]; FPS or PSA [studies = 7, n = 103, Hedges’
Regardless of whether VRET was combined with psychotherapy
g = −0.58 (−0.82 to −0.33), p < 0.001; heterogeneity I 2 = 69.0%,
or not, there was significant improvement after intervention for
Q = 19.3, p = 0.004; prediction interval = −0.55 (−1.26 to 0.15)]
combination VRET and psychotherapy [studies = 10, n = 163,
(online Supplementary Fig. S5).
Hedges’ g = −1.05 (−1.25 to −0.84), p < 0.001; heterogeneity
A meta-regression analysis showed that none of the individual
I 2 = 64.1%, Q = 25.0, p = 0.003; prediction interval = −1.01
moderators had a statistically significant effect on the effect size of
(−1.63 to −0.39)), and for VRET only (studies = 10, n = 162,
VR (online Supplementary Table S1). Although there were no signifi-
Hedges’ g = −0.67 (−0.90 to −0.44), p < 0.001; heterogeneity
cant effects, we found that there was a trend for effect size to increase
I 2 = 75.7%, Q = 37.0, p < 0.001; prediction interval = −0.62
as the number of total sessions increased (β = −0.05, p = 0.06).
(−1.36 to 0.13)] (online Supplementary Fig. S3).
Similarly, both RCT and non-RCT studies showed significant
treatment effect: RCTs [studies = 9, n = 142, Hedges’ g = −0.73
Study quality and publication bias
(−0.93 to −0.52), p < 0.001; heterogeneity I 2 = 66.6%, Q = 23.9, p
= 0.002; prediction interval = −0.75 (−1.36 to −0.15)]; non-RCTs For many studies, there was an inadequate amount of detail
[studies = 11, n = 157, Hedges’ g = −1.00 (−1.30 to −0.71), p < necessary to determine whether they contained information that
0.001; heterogeneity I 2 = 83.3%, Q = 60.0, p < 0.001; prediction should be considered for bias risk (online Supplementary
interval = −0.84 (−1.85 to 0.18)] (online Supplementary Fig. S4). Fig. S6). Only three studies mentioned random sequence gener-
Likewise, patients with SAD as well as those with FPS or PSA ation, and two studies mentioned allocation concealment
responded to VRET treatment: SAD [studies = 13, n = 196, (Anderson et al., 2013; Kampmann et al., 2016a), but one study
Hedges’ g = −1.01 (−1.21 to −0.81), p < 0.001; heterogeneity did not have enough information about concealment (Bouchard

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8 Toshiro Horigome et al.

Fig. 3. Comparison of treatment efficacy for VRET and in vivo exposure groups at each post-treatment time point.

Fig. 4. Dropout comparison between VRET and in vivo exposure groups.

et al., 2017). There were no studies that mentioned blinding for However, although VRET was shown to be significantly more
data analysts. The analyses in three studies were considered to effective at 6 months post-intervention, in vivo exposure was
have attrition bias (Anderson et al., 2013; Bouchard et al., 2017; shown to be more effective at 3 months, 12 months, and 6
Kampmann et al., 2016a). For reporting bias, study protocols years post-intervention. There was no difference in dropout
were available for only two studies (Bouchard et al., 2017; rates between VRET and in vivo exposure.
Kampmann et al., 2016a) and all studies reported their predicted
outcomes. For other bias, one study used multiple recruiting
methods, which consequently made the randomization of those Efficacy of VRET at post-intervention
methods unequal (Harris, Kemmerling, & North, 2002). VRET intervention for SAD showed a large effect size for symp-
A funnel plot appeared to show asymmetry in the effect size of tom evaluation scores at post-intervention and also showed a
the standard error and Egger’s test showed significance ( p = 0.03) large effect size when compared with waiting list/TAU groups.
(online Supplementary Fig. S7). Applying Duval and Tweedie’s In prior meta-analyses, conclusions regarding the efficacy of
trim and fill procedure did not alter results. VRET when compared with in vivo exposure differed across stud-
ies (Carl et al., 2019; Chesham et al., 2018; Kampmann et al.,
2016b; Wechsler et al., 2019), but we found that VRET had the
Discussion similar efficacy as in vivo exposure. Even when we examined
the efficacy of VRET for FPS/PSA and SAD separately in our ana-
Summary of results lysis, we did not find a significant difference in efficacy.
We conducted a systematic review and meta-analysis targeting 22 Additionally, there was no significant difference in efficacy
studies that examined the efficacy of VRET for SAD, PSA, and between intervention methods that combined VRET with psycho-
FPS. Compared to previous meta-analyses on this topic, this therapy and VRET-only methods.
meta-analysis comprises the largest number of articles to date.
The results of our analysis showed that the efficacy of VRET inter-
Long-term efficacy of VRET
vention for SAD had a large effect size and that throughout the
follow-up time points of 3 months to 6 years, there was a long- When compared to baseline data, the efficacy of VRET interven-
lasting effect. Even when compared with waiting list/TAU groups, tion continued for a long-term period following treatment and
there was a large effect size and dropout rates were similar. had a large effect size at time points of 3 months and 6 months
Compared to in vivo exposure intervention, the efficacy of post-intervention. Based on these findings, we believe that the
VRET at the post-intervention time points was similar. changes caused by VRET intervention allowed for a decrease in

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Psychological Medicine 9

fear felt in real-life situations and prevented relapses following the The results of this meta-analysis show that: dropout rates are
intervention. However, the effect size was smaller at 12 months similar for VRET and in vivo exposure interventions; efficacy is
and 6 years post-intervention. VRET was more effective than in also similar for at least the post-intervention time point; and
vivo exposure at 6 months post-intervention, but for all other that the VR technology used in research is at a level that allows
follow-up time points, in vivo exposure showed more efficacy. It for practical clinical application.
was reported that methods such as traditional CBT and exposure It should be noted that it is still unclear what role feeling of
therapy using in vivo exposure had continued efficacy for more presence plays in using VRET to treat SAD and there are even
than 12 months (Ponniah & Hollon, 2008; van Dis et al., 2020). reports that feeling of presence in a VR environment does not
Compared to that, although it is difficult to make a definitive actually affect the anxiety levels of SAD patients (Ling, Nefs,
statement since only a few studies have compared the long-term Morina, Heynderickx, & Brinkman, 2014; Morina, Brinkman,
efficacy of in vivo exposure, the long-term effects of VRET inter- Hartanto, & Emmelkamp, 2014). However, Price, Mehta, Tone,
vention may be inferior. and Anderson (2011) analyzed the relationship between the treat-
ment effect of VRET for SAD and feeling of presence at each sub-
scale. As a result, they found that the realness subscale (the degree
Influence of VRET on dropout rates
to which the virtual stimulus matches the expected value of the
There were no significant differences in dropout rates between real stimulus) was connected to anxiety levels and that the
VRET and in vivo exposure or waiting list/TAU groups. While involvement subscale (the degree to which a subject stays focused
there may be a perception that dropout rates for VRET are on the virtual stimulus) was associated with symptom improve-
high, the truth may actually be counterintuitive, as it has been ment. Further investigation is needed to determine what virtual
pointed out that dropout rates for in vivo exposure are high due environment/stimulus is most appropriate for treating SAD.
to patients’ strong reluctance to undergo the treatment (Choy,
Fyer, & Lipsitz, 2007) and one of the merits of VRET is that
patients have a less psychological aversion to participating in it
Recommendations for future research
(Garcia-Palacios, Botella, Hoffman, & Fabregat, 2007). While
there is still room for research on why dropout rate for VRET There were significant differences regarding VRET content, num-
is low, if VRET treatment technology was to advance even further ber of VRET sessions, the proportion of VRET sessions to the
than it has now, VRET could provide a more gentle introduction total number of sessions, and use or non-use of psychotherapy
to exposure therapy than in vivo methods, possibly leading to a among the studies that were included in this meta-analysis.
lower dropout rate. Further research may uncover the ideal way to utilize VRET.
It is also important to note that the working alliance of a However, we also anticipate that there will be individual differences
patient and their healthcare provider is a major variable in psy- between subjects as to what situations cause the greatest anxiety,
chotherapy (Flückiger, Del Re, Wampold, & Horvath, 2018; their degree of symptom severity, etc. Therefore, the ideal treatment
Sharf, Primavera, & Diener, 2010) and the working alliance has would be one that can be optimized for each patient by providing
been shown to have an effect on the treatment efficacy and drop- the ability to access a diversity of content and adjust the
out rates for SAD patients when treated with CBT (Haug et al., anxiety-inducing stimuli. VRET is suitable for this purpose and
2016). While we do not yet know how the working alliance thus could be an important tool in exposure therapy.
may influence the outcome of VRET (Meyerbröker & There are already some approaches that can be used to adjust
Emmelkamp, 2010), two of the studies included in this VRET to create a tailor-made treatment for each SAD patient. To
meta-analysis evaluated the working alliance as part of their find the best exposure environment for each SAD patient, various
research. Anderson et al. (2013) stated that there was no differ- scenarios are used in VRET, such as speeches, meetings, meals,
ence in the working alliance between VRET and group exposure and ordering in shops. There are also a few methods to regulate
therapy. Bouchard et al. (2017) reported that there was no statis- anxiety. For example, patients with SAD are more likely to be anx-
tical difference in the working alliance between a CBT + VRET ious about the negative expressions of others (Phan, Fitzgerald,
group and CBT + in vivo exposure group and that the working Nathan, & Tancer, 2006; Stein, Goldin, Sareen, Zorrilla, &
alliance data were a predictor of symptom improvement for Brown, 2002; Straube, Mentzel, & Miltner, 2005), so patients’ anx-
both groups. In light of this, it would appear that the working alli- iety levels can be controlled by varying the facial expressions on
ance would be a major factor when utilizing VRET to treat SAD VR avatars used in VRET (Qu, Brinkman, Ling, Wiggers, &
and it is possible that the use of VR technology would not cause Heynderickx, 2014). Additionally, in public speaking settings,
dropout rates to increase by way of negatively impacting the work- there have been attempts to control patients’ anxiety levels by
ing alliance. adjusting the number of audience members they see
(Kampmann et al., 2016a; North, North, & Coble, 1998;
Stupar-Rutenfrans, Ketelaars, & van Gisbergen, 2017). In the
Quality of VR technology
future, creating these controlled stimuli using VR will become
In the case of VRET, the quality of the VR technology used can increasingly easier than preparing real-life situations. It is also
influence the efficacy of the treatment. When using VRET to possible to use VR technology to create even stronger trigger
treat anxiety disorder, the feeling of presence created by VR tech- situations that would be hard to produce in real-life situations,
nology is thought to influence subjects’ anxiety levels and this is such as creating an audience of 100 000 people in a stadium for
an important factor in making the treatment effective (Price & a public speaking situation. Furthermore, among SAD patients,
Anderson, 2007; Robillard, Bouchard, Fournier, & Renaud, there are those who have a strong fear of speaking to authority fig-
2003). Additionally, it was reported that when the levels of feeling ures, and with VR technology it is possible to put patients
of presence and anxiety produced via the VR technology are too face-to-face with great historical figures, like past presidents,
low, there is an increase in the dropout rate (Krijn et al., 2004). and have them converse or have a meal together.

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10 Toshiro Horigome et al.

The other method for diversifying treatment is to conduct Anderson, P., Zimand, E., Schmertz, S. K., & Ferrer, M. (2007). Usability and
exposure therapy while monitoring patients’ autonomic nervous utility of a computerized cognitive-behavioral self-help program for public
systems and adjusting exposure until the ideal anxiety level is speaking anxiety. Cognitive and Behavioral Practice, 14(2), 198–207.
Bouchard, S., Dumoulin, S., Robillard, G., Guitard, T., Klinger, E., Forget, H.,
achieved. It is thought that skin conductance response and
… Roucaut, F. X. (2017). Virtual reality compared with in vivo exposure in
heart rate fluctuate based on changes in anxiety levels are trig-
the treatment of social anxiety disorder: A three-arm randomised controlled
gered by VRET. Several studies included in our meta-analysis trial. The British Journal of Psychiatry, 210(4), 276–283.
monitored such biological signals during treatments but were Carl, E., Stein, A. T., Levihn-Coon, A., Pogue, J. R., Rothbaum, B.,
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Joordens, 2010; North et al., 1998). It would be advantageous to trials. Journal of Anxiety Disorders, 61, 27–36.
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stimulus based on such biological information. efficacy of virtual reality exposure therapy for social anxiety. Behaviour
Change, 35(3), 152–166.
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Limitations
Clark, D. M., & Wells, A. (1995). A cognitive model of social phobia. In
There were several limitations for this meta-analysis study. First, Heimberg, R. G., Liebowitz, M. R., Hope, D. A., & Schneier, F. R. (Eds.),
there were large differences in how VR technology was used in Social phobia: Diagnosis, assessment and treatment (pp. 69–93).
each study and there was also a broad range among the studies New York: Guilford Press.
Denizci Nazligul, M., Yilmaz, M., Gulec, U., Yilmaz, A. E., Isler, V., O’Connor,
of how much time was provided for VR exposure at each session
R. V., … Clarke, P. (2019). An interactive 3d virtual environment to reduce
and how many sessions were done in total. Second, it is likely that the public speaking anxiety levels of novice software engineers. IET
there were differences in the ‘reality’ created by the different VR Software, 13(2), 152–158.
software used among the studies. Third, few studies had sufficient Duval, S., & Tweedie, R. (2000). Trim and fill: A simple funnel-plot–based
study quality, which highlights the need for more high-quality, method of testing and adjusting for publication bias in meta-analysis.
large-scale RCTs. In particular, there were very few studies that Biometrics, 56(2), 455–463.
did long-term evaluations of efficacy and it is possible that con- Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997). Bias in
clusions put forth thus far may change based on the results of meta-analysis detected by a simple, graphical test. BMJ, 315(7109), 629–634.
future long-term research. Flückiger, C., Del Re, A. C., Wampold, B. E., & Horvath, A. O. (2018). The
alliance in adult psychotherapy: A meta-analytic synthesis. Psychotherapy,
55(4), 316.
Furukawa, T. A., Barbui, C., Cipriani, A., Brambilla, P., & Watanabe, N. (2006).
Conclusion Imputing missing standard deviations in meta-analyses can provide accur-
VRET is an acceptable treatment for SAD patients that has signifi- ate results. Journal of Clinical Epidemiology, 59(1), 7–10.
cant, long-lasting efficacy, although it is possible that during long Garcia-Palacios, A., Botella, C., Hoffman, H., & Fabregat, S. (2007). Comparing
acceptance and refusal rates of virtual reality exposure vs. in vivo exposure
term follow-up, VRET efficacy lessens as compared to in vivo
by patients with specific phobias. Cyberpsychology & Behavior, 10(5), 722–
exposure. While VRET offers flexibility in how it can be tailored 724.
to the individual situation of each patient with SAD, there is still Gebara, C. M., Barros-Neto, T. P. D., Gertsenchtein, L., & Lotufo-Neto, F.
much that is unclear about which intervention method is most (2016). Virtual reality exposure using three-dimensional images for the
appropriate. More high-quality RCTs that examine the long-term treatment of social phobia. Brazilian Journal of Psychiatry, 38(1), 24–29.
effects of VRET are needed. Geraets, C. N., Veling, W., Witlox, M., Staring, A. B., Matthijssen, S. J., & Cath,
D. (2019). Virtual reality-based cognitive behavioural therapy for patients
Supplementary material. The supplementary material for this article can with generalized social anxiety disorder: A pilot study. Behavioural and
be found at https://doi.org/10.1017/S0033291720003785. Cognitive Psychotherapy, 47(6), 745–750.
Grillon, H., Riquier, F., Herbelin, B., & Thalmann, D. (2006). Virtual reality as
Acknowledgements. We would like to thank Dr Hélène Wallach for provid-
therapeutic tool in the confines of social anxiety disorder treatment.
ing additional data and Dr Max North for his advice on our analysis. This
International Journal in Disability and Human Development, 5(3), 243–250.
research received no specific grant from any funding agency, commercial or
Harris, S. R., Kemmerling, R. L., & North, M. M. (2002). Brief virtual reality
not-for-profit sectors.
therapy for public speaking anxiety. Cyberpsychology & Behavior, 5(6),
Authors contributions. TH, TK, and MM contributed to designing the 543–550.
study, analyzing the data, and writing the manuscript. The systematic literature Haug, T., Nordgreen, T., Öst, L. G., Tangen, T., Kvale, G., Hovland, O. J., …
search and data extraction were done by TH, S Kurokawa, K Sawada, S Kudo, Havik, O. E. (2016). Working alliance and competence as predictors of out-
K Shiga, and TK. come in cognitive behavioral therapy for social anxiety and panic disorder
in adults. Behaviour Research and Therapy, 77, 40–51.
Conflict of interest. None. Heimberg, R. G., & Becker, R. E. (2002). Cognitive-Behavioral group therapy
for social phobia: Basic mechanisms and clinical strategies. New York:
Guilford Press.
Heimberg, R. G., Becker, R. E., Goldfinger, K., & Vermilyea, J. A. (1985).
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