1 s2.0 S0149763422003463 Main

Neuroscience and Biobehavioral Reviews 142 (2022) 104857
Contents lists available at ScienceDirect
Neuroscience and Biobehavioral Reviews

journal homepage: www.elsevier.com/locate/neubiorev
Treatment of eating disorders: A systematic meta-review of meta-analyses

and network meta-analyses
Alessio Maria Monteleone a, *, Francesca Pellegrino a, Giovanni Croatto b, Marco Carfagno a,
Anja Hilbert c, Janet Treasure d, Tracey Wade e, Cynthia M. Bulik f, g, h, Stephan Zipfel i, j,
Phillipa Hay k, Ulrike Schmidt d, Giovanni Castellini l, Angela Favaro b,
Fernando Fernandez-Aranda m, Jae Il Shin n, Ulrich Voderholzer o, p, q, Valdo Ricca l,
Davide Moretti l, Daniele Busatta l, Giovanni Abbate-Daga r, Filippo Ciullini s,
Giammarco Cascino t, Francesco Monaco u, Christoph U. Correll v, w, x, y, Marco Solmi z, aa, ab, ac
a
Department of Psychiatry, University of Campania L. Vanvitelli, Naples, Italy
b
Neurosciences Department, University of Padua, Padua, Italy
c
Integrated Research and Treatment Center AdiposityDiseases, Behavioral Medicine Research Unit, Department of Psychosomatic Medicine and Psychotherapy,
University of Leipzig Medical Center, Leipzig, Germany
d
King’s College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, London, UK
e
Flinders Institute for Mental Health and Well-Being, the Blackbird Initiative, Flinders University, South Australia, Australia
f
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, USA
g
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
h
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, USA
i
Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, Tuebingen, Germany
j
Centre of Excellence for Eating Disorders Tuebingen (KOMET), Germany
k
Translational Health Research Institute, School of Medicine, Western Sydney University, Australia
l
Psychiatry Unit, Department of Health Sciences, University of Florence, Florence, Italy
m
Department of Psychiatry, Bellvitge University Hospital-IDIBELL and CIBERobn, ISCIII, Barcelona, Spain
n
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
o
Schoen Clinic Roseneck, Prien am Chiemsee, Germany
p
Clinic for Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany
q
Clinic for Psychiatry and Psychotherapy, University Hospital of Munich, Munich, Germany
r
Eating Disorders Center for Treatment and Research, Department of Neuroscience, University of Turin, Turin, Italy
s
Department of General Psychology, University of Padova, Padova, Italy
t
Department of Medicine, Surgery and Dentistry ’Scuola Medica Salernitana’, Section of Neurosciences, University of Salerno, Salerno, Italy
u
Department of Mental Health, Asl Salerno, Salerno, Italy
v
Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA
w
Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
x
Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA
y
Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
z
Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada
aa
Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada
ab
Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
ac
Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
A R T I C L E I N F O A B S T R A C T
MONTELEONE, A.M., F. Pellegrino, G. Croatto, M. Carfagno, A. Hilbert, J. Treasure, T. Wade, C. Bulik, S. Zipfel,
P. Hay, U. Schmidt, G. Castellini, A. Favaro, F. Fernandez-Aranda, J. Il Shin, U. Voderholzer, V. Ricca, D. Moretti,
Keywords: D. Busatta, G. Abbate-Daga, F. Ciullini, G. Cascino, F. Monaco, C.U. Correll and M. Solmi. Treatment of Eating
Eating disorders
Disorders: a systematic meta-review of meta-analyses and network meta-analyses. NEUROSCI BIOBEHAV REV 21
Umbrella review
Treatment
(1) XXX-XXX, 2022.- Treatment efficacy for eating disorders (EDs) is modest and guidelines differ. We sum
Randomized controlled trials marized findings/quality of (network) meta-analyses (N)MA of randomized controlled trials (RCTs) in EDs.
* Correspondence to: Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie, 80138 Naples, Italy.
E-mail address: alessiomaria.monteleone@unicampania.it (A.M. Monteleone).
https://doi.org/10.1016/j.neubiorev.2022.104857
Received 14 May 2022; Received in revised form 27 August 2022; Accepted 2 September 2022
Available online 6 September 2022
0149-7634/© 2022 Elsevier Ltd. All rights reserved.
A.M. Monteleone et al. Neuroscience and Biobehavioral Reviews 142 (2022) 104857
Psychotherapy Systematic meta-review ((N)MA of RCTs, ED, active/inactive control), using (anorexia or bulimia or eating
Psychopharmacology disorder) AND (meta-analy*) in PubMed/PsycINFO/Cochrane database up to December 15th, 2020. Standard
ized mean difference, odds/risk ratio vs control were summarized at end of treatment and follow-up. In
terventions involving family (family-based therapy, FBT) outperformed active control in adults/adolescents with
anorexia nervosa (AN), and in adolescents with bulimia nervosa (BN). In adults with BN, individual cognitive
behavioural therapy (CBT)-ED had the broadest efficacy versus active control; also, antidepressants out
performed active. In mixed age groups with binge-eating disorder (BED), psychotherapy, and lisdexamfetamine
outperformed active control. Antidepressants, stimulants outperformed placebo, despite lower acceptability, as
did CBT-ED versus waitlist/no treatment. Family-based therapy is effective in AN and BN (adolescents). CBT-ED
has the largest efficacy in BN (adults), followed by antidepressants, as well as psychotherapy in BED (mixed).
Medications have short-term efficacy in BED (adults).
1. Introduction physical and psychological outcomes, and found that specialized psy
chological treatments outperformed control interventions on weight
Eating Disorders (EDs) have a peak age at onset during key devel outcomes, but not on psychological outcomes, and no differences
opmental adolescent years (Solmi et al., 2021), and have severe mental emerged between adolescents and adults with AN. Finally, a recent NMA
and physical health impacts (Voderholzer et al., 2020). The treatment of (Solmi et al., 2021) only based on standalone outpatient treatment of
EDs is complex and typically involves several health care disciplines adults with AN concluded that no reliable evidence supports the clear
(Monteleone et al., 2019). However, the efficacy of treatment is modest superiority or inferiority of any treatment recommended by the NICE
(Treasure et al., 2020), with remission ranging from 40% to 60% in guidelines.
anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder A previous umbrella review summarized meta-analytic evidence on
(BED) (Eddy et al., 2017; Linardon, 2018a; Slade et al., 2018; Stein the efficacy and acceptability of interventions for any mental disorders
hausen, 2002; Steinhausen and Weber, 2009; Zipfel et al., 2015). The including EDs (Correll et al., 2021). However, that umbrella review only
variability of remission also reflects the heterogeneous definition of focused on children and adolescents, and only considered a pre-selected
remission (Bardone-Cone et al., 2018), which should ideally encompass range of outcomes. A comprehensive umbrella review is needed to
psychological, cognitive, physical (i.e., body mass index, BMI) and summarize the findings and to grade the quality of previous
behavioural (i.e., binge eating or purging behaviours) criteria (Lil meta-analyses of RCTs in EDs, without restricting studies to specific age
ienfeld, 2019). Relapse frequently occurs in EDs, especially after groups or specific outcomes, and providing a synopsis of efficacy, safety,
discharge from inpatient treatment (Gregertsen et al., 2019; Marzola acceptability and tolerability of treatments for ED. Also, currently there
et al., 2021b). is no umbrella review accounting for effect modifiers and confounding
International guidelines (e.g., the National Institute for Health and factors, and conducting analyses by age group, type of intervention,
Care Excellence, NICE, National Guideline Alliance, 2017) recommend setting, control condition, ED diagnosis (i.e. AN, BN, BED, EDNOS), and
psychological interventions as first-line treatment for individuals with mode of treatment delivery. The present work aims to fill this gap,
AN. Across psychotherapies, manualised family-based therapy (FBT) is distilling clinically relevant information from a vast body of data to
suggested for adolescents with AN, while individual psychotherapies (i. inform clinical care, clinical guidelines, and research directions.
e., cognitive-behavioural therapy for eating disorders (CBT-ED), focal
psychodynamic psychotherapy (FPT), Maudsley Model of Anorexia 2. Methods
Nervosa Treatment for Adults (MANTRA), or Specialist Supportive
Clinical Management (SSCM)) are recommended for adults with AN. 2.1. Search, inclusion and exclusion criteria
With the exception of FPT among these therapies, some have been su
perior to ‘treatment as usual’ conditions, but none has been found to be This umbrella review followed an a priori PRISMA 2020-compliant
superior to another manualised specialist therapy (Byrne et al., 2017; (Page et al., 2021) protocol (https://osf.io/wg5de/?view_only=177
Schmidt et al., 2016; van den Berg et al., 2019; Zeeck et al., 2018; Zipfel c444c41514fadb386ef1d57dee99d) (Fig. 1, supplementary
et al., 2014). International guidelines concur that medications should Tables 1–2). We conducted a systematic search in PubMed, PsycINFO,
not be used as the sole or primary treatment for those with AN (Hilbert and Cochrane database up to December 15th, 2020, using the search key
et al., 2017). For BN, NICE (2017) guidelines recommend individual “(anorexia or bulimia or eating disorder) AND (meta-analy*)”. We also
psychological interventions as first-line treatment, namely FBT for ad manually searched references of included MAs and other relevant re
olescents or CBT-ED (in both the guided self-care and views. Two independent (FP, MC) authors conducted title/abstract
therapist-delivered forms) for adults. This latter intervention is also screening, full-text assessment, and data extraction into a pre-defined
considered the treatment of choice for BED in adults, yet no Excel spreadsheet. A third author (MS) resolved any conflicts.
evidence-based recommendation is available for adolescents. Antide Included were: a) MAs or NMAs, b) of RCTs testing any intervention
pressants, and selective serotonin reuptake inhibitors (SSRI) in partic in comparison to an active or inactive control condition, c) in any age
ular, have been proposed as an adjunctive treatment to psychotherapy group and setting, d) in participants with a DSM/ICD diagnosis of an
for people within binge-eating spectrum disorders although only lis eating disorder (AN, BN, BED, eating disorder not otherwise specified or
dexamfetamine has been approved in the US for BED (Hilbert et al., unspecified feeding or eating disorder (EDNOS or OS/UFED), e)
2019; Slade et al., 2018; Treasure et al., 2020). There is currently no reporting on comparative estimates of efficacy, and discontinuation due
approved medication for EDs in Europe except the fluoxetine for bulimia to any cause (acceptability) or due to adverse events (tolerability).
nervosa (Tortorella et al., 2014). Exclusion criteria were: a) systematic reviews without MA, b) pooling
However, notable differences exist among the current guidelines studies other than RCTs, c) including participants without an ED diag
(Hilbert et al., 2017). These inconsistent recommendations reflect nosis, d) MA reporting on pre-post changes of a given set of
methodological limitations. For instance, a network meta-analysis interventions.
(NMA) by Zeeck et al. (2018) only considered body weight as the pri Whenever two NMAs/MAs reported on the same combination of
mary outcome and found more rapid weight gain in adolescents than in disorders, interventions, comparisons and/or outcomes, we prioritized
adults and no superiority of a specific psychological approach for adults NMA over MA, or MA with more RCTs. NMAs have been prioritized over
with AN. A meta-analysis (MA) by Murray et al. (2019) considered both pairwise MAs previously, as they are deemed the highest level of
2
evidence in treatment guidelines (Leucht et al., 2016). To avoid relying from purging/all outcomes); weight or body mass index (WEIGHT/
on completely indirect estimates, we only extracted effect sizes from BODY). Whenever possible, we extracted outcomes both at end of
NMAs that were based on at least one direct comparison for the outcome treatment and at follow up (any time point). Acceptability (inferred from
of interest. drop out due to any cause) and safety (adverse effects of medications)
were also extracted.
2.2. Participants, interventions, comparison, outcomes, setting The setting in which the intervention was delivered was inpatient
operationalization only, outpatient only, or mixed.
Participants were diagnosed with AN, BN, BED, EDNOS/OSFED, or 2.3. Quality of evidence
combined ED. Their age group could be adolescents (<18 years only),
adults (> 18 years old only) or mixed. The quality of MAs and NMAs was measured using A Measurement
We categorized interventions as follows: behavioural therapy Tool for the Assessment of Multiple Systematic Reviews (AMSTAR-
(including behavioral weight loss therapy) (BT), CBT-ED, family therapy PLUS) (Correll et al., 2017) to quantify the methodological quality of
(FAM) (separating specific family-based therapy, FBT), interpersonal both MAs and NMAs with the first 11 items (AMSTAR) (Shea et al.,
psychotherapy (IPT), Maudsley Model of Anorexia Nervosa Treatment 2007), and of included RCTs with six additional items (AMSTAR-Con
for Adults, mixed or unspecified psychotherapy (PT), multidisciplinary tent (Correll et al., 2017), for each MA/NMA primary outcome).
care (including SSCM) (MULTI), psychodynamic-oriented (PSD-O), Methodological quality was categorized as low (<4), medium (4− 7),
psychoeducation (EDU), physical exercise, and pharmacological treat and high (>7). Content quality was categorized as low (<4), medium
ments. Pharmacological treatments were subdivided by class (antide (4− 6), and high (>6), as done previously (Correll et al., 2021; Solmi
pressants, anticonvulsants, antipsychotics, stimulants, anti-obesity). et al., 2020). Quality assessment was done by two independent re
Treatment format was individual (-i), group (-g), self-help (-s), or their viewers. Full details on the quality assessment are available elsewhere
combinations. (Correll et al., 2021; Solmi et al., 2020).
Comparators were specific drug or psychological intervention
(active), treatment as usual (TAU), placebo (PBO), waiting list or no 2.4. Statistical analysis
treatment (WL/NT), mixed TAU and WL/NT, mixed active and WL/NT.
Outcomes were ED-specific behaviours (BEHAVIOURAL, i.e. binge- We did not recalculate all NMAs or MAs, and just reported what the
eating and/or purging episodes remission or frequency, compensatory original authors had done. However, in order to provide results on the
behaviours), neuropsychological functioning (COGNITION, i.e. central same scale in Fig. 2, where possible, we standardized and harmonized
coherence, emotion recognition), eating disorder-specific psychopa effect sizes. For instance, where mean difference was reported, we
thology (EDP, i.e. body dissatisfaction, drive for thinness, shape/weight transformed it into standardized mean difference (SMD). Also, we
concern); functioning and quality of life (F-QOL); general psychiatric harmonized outcome reporting, so that SMD> 0 and odds ratio/risk
symptoms (GENERAL, i.e. depressive/anxiety/obsessive-compulsive); ratio (OR/RR) > 1 favor intervention for all outcomes. For example, if a
global course of the disease (GLOBAL, i.e. response/remission/ MA reported ED psychopathology improvement as SMD< 0, we inverted
relapse/clinical improvement/abstinence from binge eating/abstinence the mathematical sign and 95% confidence interval. For AN, weight gain
Fig. 1. PRISMA 2020 study selection flow diagram.
3
Fig. 2. Forest plot of interventions with evidence of efficacy in eating disorders. Results are presented as SMD (ES; CI), ordered by control condition, and by magnitude
within the control condition. In forest plot, in black comparisons against Active control, in grey against TAU. Legend: 3WPT, third wave psychotherapies; A, Active control; AC,
anticonvulsants; AD, mixed antidepressants; ADU, adults; BEHAV, eating disorder behaviours; BT, behavioural therapy; CBT-ED, cognitive behavioural therapy for eating
disorders; CI, confidence interval; EDP, eating disorder psychopathology; ES, effect size; FAM, family therapy; FBT, family-based treatment; g, group therapy; GENSX, general
psychiatric symptoms; GLOBAL, response/remission/relapse; HOR, hormones; i, individual therapy; LDX, lisdexamfetamine; MIX, mixed age group; ORL, orlistat; P, placebo;
SGAD, second generation antidepressants; SMD, standardized mean difference; SSRI, selective serotonin reuptake inhibitors; T, treatment as usual; TCA, tricyclic antide
pressants; TOP, topiramate; WEIGHT/BODY, change in weight or body composition.
was reported as SMD> 0, whilst for BED weight loss was reported with 65%/35%/0%; BN: 60%/20%/20%; BED: 47.4%/26.3%/26.3%; com
SMD> 0, so that the statistical direction matched the clinical direction bined EDs: 94.1%/0%/5.9%). Overall, 33 different
of the finding. non-pharmacological interventions and 19 different (combinations of)
medications have been identified. Regarding age groups, 19 (57.6%) (N)
3. Results MAs reported on adults, five (15.2%) on adolescents, and the remaining
nine (27.3%) reported on mixed or unspecified age. Only one MA (1.7%)
The search flow is reported in Fig. 1. Out of 884 articles, 55 MAs and reported on inpatients, and in AN only; eight (13.6%) reported on out
4 NMAs were included (Albano et al., 2019; Bacaltchuk et al., 1999; patients; and the others on any or unspecified settings.
Josue Josué Bacaltchuk et al., 2000; Josue Bacaltchuk et al., 2000; Josué The number of trials for a specific outcome ranged from 2 to 35
Josue Bacaltchuk et al., 2000; Josué Bacaltchuk et al., 2000; Bacaltchuk (median=4, interquartile range=2–7).
and Hay, 2003; Barakat et al., 2019; Berkman et al., 2015; Brownley Quality of included studies is reported in supplementary table 4.
et al., 2016; Cassioli et al., 2020; Claudino et al., 2006; Couturier et al., Overall AMSTAR/AMSTAR-Content mean scores were 7.9 ± 1.7 and
2013; Cuijpers et al., 2016; de Vos et al., 2014; Dold et al., 2015; Fisher 2.7 ± 1.5. Thirty-five (59.3%) (N)MAs had an AMSTAR > 7, one (1.7%)
et al., 2018, 2010; Fornaro et al., 2016; Ghaderi et al., 2018; Ghaderi and had the maximum score (11), whilst none had an AMSTAR-Content
Andersson, 1999; Grenon et al., 2018a; Hagan et al., 2020; Hasselbalch score > 6. The main reasons for lower quality rating had to do with
et al., 2020; Hay et al., 2019, 2015, 2004, 2001, 2009; Hilbert et al., the quality of the meta-analyzed RCTs included in (N)MAs, and namely
2019; Kishi et al., 2012; Lebow et al., 2013; Linardon, 2018b; Linardon no “double-blind” design in most of the studies (81%), primary outcome
et al., 2020, 2019, 2017a, 2017b, 2017c; Loucas et al., 2014; Low et al., result not confirmed in at least one large study with approximately 100
2021; Machado and Ferreira, 2014; Murray et al., 2019; Naka patients per arm (74%), and the presence of publication bias regarding
sh-Eisikovits et al., 2002; Ng et al., 2013; Nourredine et al., 2020; Pal the primary outcome result (78%).
avras et al., 2017; Peat et al., 2017; Perkins et al., 2006; Polnay et al., Below, effect sizes versus WL/NT, PBO, TAU and Active are reported
2014; Reas and Grilo, 2008; Eric Slade et al., 2018; Solmi et al., 2021; by disorder (see Tables 2–3). We left results from MAs mixing TAU with
Stefano et al., 2008, 2006; Svaldi et al., 2019; Swift et al., 2017; active or inactive controls in supplementary tables only, as those com
Thompson-Brenner et al., 2003; Traviss-Turner et al., 2017; van den parisons inappropriately mixed different control groups (see supple
Berg et al., 2019; Vocks et al., 2010; Zeeck et al., 2018). Publications mentary tables 5–6). In the paragraphs below, results are reported with
excluded after full-text assessment, with reason for exclusion are avail number of RCTs (k), number of subjects (n), effect size with 95% con
able in supplementary table 3. MAs and NMAs included in the umbrella fidence interval, quality score, and quality category (L/low, M/medium,
review are reported in Table 1. Among included (N)MAs, 33 (55.9%) H/high).
assessed non-pharmacological interventions only, 16 (27.1%) pharma
cological interventions only, while 10 (17%) assessed both (AN:
4
Table 1
Meta-analyses and network meta-analyses of randomized controlled trials of pharmacological and psychological interventions in patients with eating disorders
included in the umbrella review.
Author, year Age group Setting Intervention Controls Outcomes A C
Anorexia Nervosa
Albano, 2019(31) MIX MIX EDU-S MIXED, TAU/ ACCEPT, F-QOL, GENSX, WEIGHT/ 8 4
WL BODY
Cassioli, 2020(32) MIX MIX PHARMA PBO GENSX, WEIGHT/BODY 8 4
Claudino, 2006(33) MIX MIX PHARMA PBO ACCEPT, GENSX 9 1
Couturier, 2013(34) ADO OUT FAM-I ACTIVE GLOBAL 9 3
de Vos, 2014(35) MIX MIX PHARMA PBO WEIGHT/BODY 9 2
Dold, 2015(36) ADU, MIX MIX PHARMA PBO/NT ACCEPT, EDP, WEIGHT/BODY 10 4
Fisher, 2010(37) MIX MIX FAM-I ACTIVE, TAU EDP, GLOBAL, WEIGHT/BODY 9 2
Fisher, 2018(38) ADO, ADU, MIX FAM-I ACTIVE, TAU ACCEPT, EDP, GLOBAL, WEIGHT/ 9 3
MIX BODY
Hagan, 2020(39) ADU MIX MULTI MIXED COG, EDP, GENSX, WEIGHT/BODY 8 4
Hasselbalch, 2020 ADU MIX PHARMA PBO COG 9 1
(40)
Hay, 2015(41) MIX OUT CBT-ED-I, PDO-I ACTIVE, ACCEPT, EDP, GLOBAL, WEIGHT/ 9 3
MIXED, TAU BODY
Hay, 2019(42) MIX IN MULTI ACTIVE ACCEPT, GENSX, GLOBAL, WEIGHT/ 9 2
BODY
Kishi, 2012(43) MIX MIX PHARMA PBO ACCEPT, EDP, SAFETY, WEIGHT/BODY 6 4
Lebow, 2013(44) MIX MIX PHARMA MIXED, PBO EDP, GENSX 6 2
Linardon, 2017c(45) MIX MIX CBT-ED-I ACTIVE EDP 6 3
Murray, 2019(23) MIX MIX MULTI MIXED GLOBAL, WEIGHT/BODY 10 3
Ng, 2013(46) MIX MIX EXE-I PBO WEIGHT/BODY 7 1
Solmi, 2021(24) ADU OUT CBT-ED-I, FAM-I, MANTRA-I, PDO-I ACTIVE, TAU ACCEPT, BEHAV, WEIGHT/BODY 10 2
van den Berg, 2019 ADO, ADU, MIX, CBT-ED-I, FAM-I, PDO-I, PT-G, PT-I ACTIVE, EDP, F-QOL, WEIGHT/BODY 10 4
(16) MIX OUT MIXED, PBO
Zeeck, 2018(17) ADO, ADU MIX CBT-ED-I, FAM-I, IPT-I, MANTRA-I, MULTI, PDO- ACTIVE WEIGHT/BODY 6 2
I, SUP-I
Bulimia Nervosa
Bacaltchuk, 1999(47) MIX OUT PHARMA ACTIVE ACCEPT, BEHAV, GENSX, GLOBAL 7 1
Bacaltchuck, 2000a MIX MIX PHARMA PBO GLOBAL 7 6
(48)
Bacaltchuk, 2000b ADU MIX PHARMA, PT-I ACTIVE ACCEPT, BEHAV, GENSX, GLOBAL 8 2
(49)
Bacaltchuk, 2003(50) MIX MIX PHARMA PBO ACCEPT, BEHAV, GENSX, GLOBAL 10 3
Ghaderi, 1999(51) ADU MIX CBT-ED-I ACTIVE BEHAV 5 1
Hay, 2001(52) MIX MIX PHARMA, PT-I ACTIVE ACCEPT, BEHAV, GENSX, GLOBAL 10 1
Hay, 2004(53) ADU MIX CBT-ED-I, EDU-I, PT-I ACTIVE, WL ACCEPT, BEHAV, F-QOL, GENSX, 5 2
GLOBAL, WEIGHT/BODY
Hay, 2009(54) MIX MIX CBT-ED-I, EDU-S, PT-I ACTIVE, WL, ACCEPT, BEHAV, F-QOL, GENSX, 7 1
WL/NT GLOBAL, WEIGHT/BODY
Linardon, 2017b(55) MIX MIX CBT-ED-I, CBT-ED-I+S, EDU-S, MULTI, PT-I, PT- ACTIVE, TAU/ BEHAV, GENSX 6 3
I+S WL
Linardon, 2017c(45) ADO, ADU, MIX CBT-ED-G, CBT-ED-I, CBT-ED-S ACTIVE, TAU/ BEHAV, EDP, GLOBAL 6 3
MIX WL
Linardon, 2018(56) MIX MIX CBT-ED-I ACTIVE, TAU/ EDP 8 2
WL
Linardon, 2019(57) MIX MIX CBT-ED-I, EDU-S, PT-I ACTIVE, TAU/ GENSX 8 3
WL
Linardon, 2020(58) MIX MIX e-PT MIXED BEHAV, EDP 7 2
Loucas, 2014(59) MIX MIX CBT-ED-S NT, WL BEHAV, EDP 10 4
Nakash-Eisikovits, MIX MIX PHARMA PBO BEHAV 5 3
2002(60)
Polnay, 2014(61) ADU OUT CBT-ED-G NT BEHAV, GENSX, GLOBAL 9 3
Slade, 2018(62) ADU MIX BT-G, BT-I, CBT-ED-G, CBT-ED-I, CBT-ED-S, EXE- ACTIVE, WL GLOBAL 8 3
I, IPT-I, MULTI, PHARMA, PT-I
Svaldi, 2019(63) MIX MIX CBT-ED-I, EDU-S, MULTI, PHARMA, PT-I TAU/WL ACCEPT, BEHAV, EDP, GENSX, 9 3
GLOBAL
Thompson-Brenner, MIX MIX BT, BT-G, BT-I, CBT-ED, CBT-ED-G, CBT-ED-I, PT- MIXED BEHAV 4 1
2003(64) G, PT-I
Binge-Eating Disorder
Berkman, 2015(65) ADU, MIX MIX CBT-ED-I, PHARMA PBO, WL BEHAV, GENSX, GLOBAL, SAFETY, 11 3
WEIGHT/BODY
Brownley, 2016(66) ADU MIX CBT-ED-I, PHARMA PBO, WL BEHAV, EDP, GENSX, GLOBAL, 8 4
WEIGHT/BODY
Fornaro, 2016(67) ADU MIX PHARMA PBO ACCEPT, BEHAV, GLOBAL, WEIGHT/ 9 4
BODY
Ghaderi, 2018(68) MIX MIX BT-G, BT-I, CBT-ED-I, CBT-ED-S, IPT-I, PHARMA ACTIVE, PBO, BEHAV, EDP, GENSX, GLOBAL, 9 2
WL WEIGHT/BODY
Hay, 2009(54) MIX MIX CBT-ED-I ACTIVE, TAU/ ACCEPT, BEHAV, GLOBAL, WEIGHT/ 7 1
NT BODY
Hilbert, 2019(22) MIX MIX BT-I, EDU-S, MULTI, PHARMA, PT, PT-I 9 5
(continued on next page)
5
Table 1 (continued )
Author, year Age group Setting Intervention Controls Outcomes A C
ACTIVE, TAU/ ACCEPT, BEHAV, EDP, GENSX,

NT GLOBAL, WEIGHT/BODY
Linardon, 2017a(69) MIX MIX PT-I ACTIVE, WL BEHAV, EDP, GENSX, GLOBAL 7 0
Linardon, 2017c(45) MIX MIX CBT-ED-G, CBT-ED-I, CBT-ED-S, PT-I ACTIVE, TAU/ BEHAV, EDP, GLOBAL 6 3
WL
Linardon, 2018(56) MIX MIX CBT-ED-I ACTIVE, TAU/ EDP 8 2
WL
Linardon, 2019(57) MIX MIX CBT-ED-I, EDU-S, PT-I ACTIVE, TAU/ GENSX 8 3
WL
Linardon, 2020(58) MIX MIX e-PT MIXED BEHAV, EDP 7 2
Loucas, 2014(59) MIX MIX CBT-ED-S WL BEHAV, GLOBAL 10 4
Nourredine, 2020(70) ADU MIX PHARMA PBO ACCEPT, BEHAV, GENSX, WEIGHT/ na na
BODY
Palavras, 2017(71) ADU OUT BT-I ACTIVE ACCEPT, BEHAV, WEIGHT/BODY 9 2
Peat, 2017(72) MIX MIX PHARMA ACTIVE, PBO BEHAV, EDP, GLOBAL 6 4
Stefano, 2008(73) MIX MIX PHARMA PBO BEHAV, GENSX, GLOBAL 6 2
Swift, 2017(74) ADU MIX MULTI, PT-I ACTIVE, MIXED ACCEPT 5 0
Reas, 2008(75) MIX MIX PHARMA PBO ACCEPT, GLOBAL, WEIGHT/BODY 8 6
Vocks, 2010(76) MIX MIX EDU-S, PHARMA, PT-I PBO/WL BEHAV, EDP, WEIGHT/BODY 7 3
Mixed Eating Disorders
Barakat, 2019(77) MIX MIX EDU-S MIXED BEHAV, EDP, F-QOL, GENSX, WEIGHT/ 7 5
BODY
Cuijpers, 2016(78) MIX MIX IPT-I ACTIVE, MIXED BEHAV, EDP, GLOBAL, WEIGHT/BODY 10 6
Grenon, 2019(79) MIX MIX CBT-ED-G, CBT-ED-I, PT-G, PT-I ACTIVE, WL BEHAV, EDP, F-QOL, GENSX 9 4
Hay, 2003(50) ADU MIX CBT-ED-I, CBT-ED-S, EDU-S ACTIVE, WL ACCEPT, BEHAV, F-QOL, GENSX, 5 2
GLOBAL, WEIGHT/BODY
Hay, 2009(54) MIX MIX CBT-ED-I, CBT-ED-S, EDU-S, PT-I ACTIVE, WL, ACCEPT, BEHAV, EDP, F-QOL, GENSX, 7 1
WL/NT GLOBAL, WEIGHT/BODY
Linardon, 2017a(69) MIX MIX PT-I ACTIVE, WL BEHAV, EDP, GENSX, GLOBAL 7 0
Linardon, 2017c(45) MIX MIX CBT-ED-I ACTIVE BEHAV, EDP, GLOBAL 6 3
Linardon, 2018(56) MIX MIX CBT-ED-I, CBT-ED-S ACTIVE, TAU/ BEHAV, EDP 8 2
WL
Linardon, 2020(58) MIX MIX e-PT ACTIVE, MIXED BEHAV, EDP 7 2
Loucas, 2014(59) MIX MIX CBT-ED-S WL GLOBAL 10 4
Low, 2021(80) MIX MIX, VR-CBT-ED ACTIVE BEHAV, EDP, WEIGHT/BODY 7 0
OUT
Machado, 2014(81) MIX MIX EXE-I TAU/WL BEHAV, F-QOL, WEIGHT/BODY 7 2
Perkins, 2006(82) MIX MIX EDU-S, MULTI ACTIVE, WL ACCEPT, BEHAV, EDP, F-QOL, GENSX, 9 2
WEIGHT/BODY
Stefano, 2006(83) MIX MIX EDU-S ACTIVE, WL ACCEPT, BEHAV 5 0
Swift, 2017(74) ADU MIX MULTI, PHARMA, PT-I ACTIVE, MIXED ACCEPT 5 0
Traviss-Turner, 2017 MIX MIX EDU-S MIXED, WL BEHAV, EDP 9 3
(84)
Legend. A, AMSTAR score; ACCEPT, acceptability, ADO, adolescents; ADU, adults; BEHAV, behavioural symptoms; BT-G, group behavioural therapy; BT-I, individual
behavioural therapy; C, AMSTAR-Content score; CBT-ED-G, group cognitive behavioural therapy; CBT-ED-I, individual cognitive behavioural therapy; CBT-ED-S, self-
help cognitive behavioural therapy; EDP, eating disorder psychopathology; EDU-I, individual psychoeducation; EDU-S, self-help psychoeducation; EXE-I, individual
guided physical exercise; F-QOL, functioning/quality of life; FAM-I, individual family therapy; GENSX, psychiatric general symptoms; GLOBAL, improvement/
response/remission/relapse; IN, inpatient; IPT-I, individual interpersonal psychotherapy; MANTRA-I, individual Maudsley Anorexia Treatment for Adults; MIX, mixed
or not specified age group or setting; MIXED, active+inactive control; MULTI, mixed active interventions/multiprofessional treatment; PBO. Placebo; PHARMA,
pharmacological intervention; PDO-I, individual psychodynamic-oriented psychotherapy; e-PT, digital psychotherapy; PT-I, individual psychotherapy; PT-G, group
psychotherapy; OUT, outpatient; VR-CBT-ED, CBT-ED plus virtual reality.
3.1. Anorexia nervosa 3.1.1. Bulimia nervosa efficacy

BN was investigated in one NMA and 19 MAs; two (10.0%) reported
AN was investigated in two NMAs and 18 MAs; four (20.0%) re data on adolescents, six (30.0%) on adults.
ported data on adolescents, seven (35.0%) on adult patients. For adolescents, compared to active control, in outpatients individ
In adolescent outpatients, individual family-based therapy proved ual family-based therapy improved global course of the disease at
efficacious versus active control for global course of the disease at follow follow-up (k = 2, n = 37, OR=2.22, 95%CI=1.02–4.82, AMSTAR/
up (k = 3, n = 183, OR=2.08, 95%CI=1.07–4.03, AMSTAR/Quality=9/ Quality=9/H), whereas in Mixed settings cognitive behavioural therapy
H), and individual family therapy in mixed settings for change in weight for eating disorders did not differ from active control.
or body composition (k = 4, n = 178, SMD=0.44, 95%CI=0.14–0.74, In adults, 42.9% of the interventions proved beneficial and 7.1% had
AMSTAR/Quality 9/ H) (40.0% of interventions). both beneficial and detrimental effects. In outpatients, only group
In adults, overall, 25.0% of the interventions had evidence of effi cognitive behavioural therapy for eating disorders was covered,
cacy, but none in the outpatient setting, 33.3% in mixed settings, and compared to wait list-no treatment, with efficacy regarding eating dis
only compared to TAU; specifically, individual family therapy proved order behaviours (k = 4, n = 51, SMD=0.56, 95%CI=0.15–0.96,
beneficial for global course of the disease (k = 2, n = 81, RR=3.50, 95% AMSTAR/Quality=9/H) and global course of the disease (k = 2, n = 31,
CI=1.49–8.23, AMSTAR/Quality=9/H). RR=1.29, 95%CI=1.04–1.61, AMSTAR/Quality=9/H). In mixed set
Results on mixed age groups are reported in eResults section. tings, compared to wait list-no treatment, individual cognitive behav
ioural therapy for eating disorders and individual psychotherapy were
both beneficial for eating disorder behaviours (k = 9, n = 323,
6
Table 2
Efficacy of interventions against Placebo/Wait-list/No treatment control.
Age Setting Outcome Intervention I/ Control N of % significance ES type ES (95% CI) min-max Source A/Q
group G/S estimates
Anorexia Nervosa
ADU MIX COG PHARMA I PBO 1 100% NS SMD 0.06 (− 0.34 to 0.46) MA 9/H
(HOR)
MIX MIX ACCEPT PHARMA I PBO 2 100% NS RR ns MA 9/H
(AD)
PHARMA I PBO 2 100% NS RR ns MA 6/M
(SGA)
EDP PHARMA I PBO 4 100% NS SMD ns MA 6/M
(SGA)
GENSX PHARMA I PBO 2 100% NS SMD ns MA 8.5 /
(AD) H
PHARMA I PBO 2 100% NS SMD ns MA 8/H
(SGA)
SAFETY PHARMA I PBO 2 100% DETR RR 0.27 (0.10 – 0.75) to 0.09 MA 6/M
(SGA) (0.02 – 0.34)
WEIGHT/ PHARMA I PBO 1 100% EFF d 0.42 (0.11 – 0.73) MA 9/H
BODY (HOR)
PHARMA I PBO 1 100% EFF d 0.33 (0.14 – 0.52) MA 9/H
(MIX)
PHARMA I PBO 1 100% NS d ns MA 9/H
(AD)
(SGA)
Bulimia Nervosa
ADU OUT BEHAV CBT-ED G WL/ 1 100% EFF SMD 0.56 (0.15–0.96) MA 9/H
NT
GENSX CBT-ED G WL/NT 1 100% NS SMD ns MA 9/H
GLOBAL CBT-ED G WL/ 1 100% EFF RR 1.29 (1.04 – 1.61) MA 9/H
NT
MIX ACCEPT CBT-ED I WL/NT 1 100% NS RR ns MA 5/M
PT I WL/NT 1 100% NS RR ns MA 5/M
BEHAV PT I WL/ 1 100% EFF SMD 1.22 (0.92 – 1.52) MA 5/M
NT
CBT-ED I WL/ 1 100% EFF SMD 1.01 (0.68 – 1.33) MA 5/M
NT
GENSX CBT-ED I WL/ 1 100% EFF SMD 0.8 (0.37 – 1.22) MA 5/M
NT
PT I WL/ 1 100% EFF SMD 0.58 (0.18 – 0.98) MA 5/M
NT
GLOBAL BT G WL/ 1 100% EFF OR 28.7 (3.11–455) NMA 8/H
NT
CBT-ED G WL/ 1 100% EFF OR 7.67 (1.51 – 55.7) NMA 8/H
NT
CBT-ED S WL/ 2 100% EFF OR 3.49 (1.20 – 11.2) to 3.81 NMA 8/H
NT (1.51 – 10.9)
CBT-ED I WL/ 2 100% EFF OR 1.49 (1.28 – 1.72) to 3.89 MA; 6.5 /
NT (1.19 – 14.0) NMA M
PT I WL/ 2 50% EFF; 50% NS OR ns to 1.54 (1.30 – 1.82) NMA; 6.5 /
NT MA M
BT I WL/NT 1 100% NS OR ns NMA 8/H
EDU I WL/NT 1 100% NS OR ns NMA 8/H
IPT I WL/NT 1 100% NS OR ns NMA 8/H
MULTI I WL/NT 1 100% NS OR ns NMA 8/H
PHARMA I PBO 1 100% NS OR ns NMA 8/H
(AD)
MIX MIX ACCEPT PHARMA I PBO 10 10% EFF; 70% NS; RR 0.52 (0.30 – 0.87) to 1.22 MA 10 /
(AD) 20% DETR (1.01 – 1.47) H
CBT-ED I WL/NT 1 100% NS RR ns MA 7/M
BEHAV PT I WL/ 1 100% EFF SMD 1.22 (0.92 – 1.52) MA 7/M
NT
NT
PHARMA I PBO 9 77.8% EFF; 22.2% SMD ns to 0.75 (0.38 – 1.12) MA 4/M
(AD) NS
CBT-ED S WL/ 4 75% EFF; 25% NS SMD ns to 0.44 (0.11 – 0.77) MA 10 /
NT H
BEHAV FU CBT-ED S WL/NT 1 100% NS RR ns MA 10 /
H
EDP CBT-ED S WL/NT 4 100% NS SMD ns MA 10 /
H
EDP FU CBT-ED S WL/NT 1 100% NS SMD ns MA 10 /
H
7
group G/S estimates
F-QOL EDU S WL/NT 1 100% NS SMD ns MA 7/M

GENSX CBT-ED I WL/ 1 100% EFF SMD 0.80 (0.37 – 1.22) MA 7/M
NT
PT I WL/ 1 100% EFF SMD 0.58 (0.18 – 0.98) MA 7/M
NT
EDU S WL/NT 1 100% NS SMD ns MA 7/M
PHARMA I PBO 3 100% NS SMD ns MA 10 /
(AD) H
GLOBAL PT I WL/ 1 100% EFF RR 1.54 (1.30 – 1.82) MA 7/M
NT
CBT-ED I WL/ 1 100% EFF RR 1.49 (1.28 – 1.72) MA 7/M
NT
PHARMA I PBO 10 80% EFF; 20% NS RR ns to 3.45 (1.59 – 7.69) MA 10 /
(AD) H
Binge-Eating Disorder
ADU MIX ACCEPT PHARMA I PBO 1 100% DETR RR 0.46 (0.21 – 0.97) MA 9/H
(STIM)
PHARMA I PBO 2 50% NS; 50% RR 0.52 (0.31 – 0.88) to ns MA 5/M
(MS) DETR
BEHAV PHARMA I PBO 1 100% EFF SMD 0.56 (0.28 – 0.84) MA 9/H
(STIM)
CBT-ED I WL/ 1 100% EFF MD 2.32 (0.09 – 4.56) MA 11 /
NT H
PHARMA I PBO 2 100% EFF MD 0.98 (0.15 – 1.80) to 1.31 MA 5/M
(MS) (0.03–2.58)
PHARMA I PBO 1 100% EFF MD 0.67 (0.09 – 1.26) MA 8/H
(AD)
EDP PHARMA I PBO 1 100% EFF MD 6.50 (4.18 – 8.82) MA 8/H
(STIM)
PHARMA I PBO 1 100% EFF MD 3.84 (1.13 – 6.55) MA 8/H
(AD)
GENSX PHARMA I PBO 1 100% EFF MD 1.97 (0.28 – 3.67) MA 8/H
(AD)
PHARMA I PBO 1 100% NS SMD ns MA 5/M
(MS)
GLOBAL CBT-ED I WL/ 1 100% EFF RR 4.95 (3.06 – 8.00) MA 8/H
NT
PHARMA I PBO 2 100% EFF RR 1.58 (1.35 – 1.84) to 2.43 MA 9/H
(STIM) (1.95 – 3.01)
PHARMA I PBO 1 100% EFF RR 1.67 (1.24 – 2.26) MA 8/H
(AD)
PHARMA I PBO 1 100% NS MD ns MA 11 /
(MS) H
SAFETY PHARMA I PBO 2 100% DETR RR 0.61 (0.42 – 0.88) to 0.38 MA 11 /
(STIM) (0.23 – 0.61) H
WEIGHT/ PHARMA I PBO 1 100% EFF MD 4.91 (3.41 – 6.42) MA 5/M
BODY (MS)
PHARMA I PBO 1 100% EFF SMD 1.28 (1.06 – 1.51) MA 9/H
(STIM)
PHARMA I PBO 2 100% NS MD ns MA 8/H
(AD)
MIX MIX ACCEPT PHARMA I PBO 1 100% NS RR ns MA 8/H
(AD)
PHARMA I PBO 1 100% NS RR ns MA 8/H
(ORL)
(MIX)
(MS)
BEHAV PT I WL/ 1 100% EFF g 0.89 (0.59 – 1.19) MA 7/M
NT
CBT-ED I WL/ 1 100% EFF SMD 0.83 (0.55 – 1.11) MA 9/H
NT
PHARMA I PBO 1 100% EFF MD 1.39 (1.12 – 1.66) NMA 6/M
(STIM)
PHARMA I PBO 3 66.7% EFF; 33.3% MD ns to 0.91 (0.28 – 1.54) NMA, 6/M
(AD) NS MA
CBT-ED S PBO 2 50% EFF; 50% NS SMD ns to 0.51 (0.17 – 0.84) MA 9.5 /
H
(MS)
EDP PT I WL/ 4 100% EFF g 0.77 (0.36 – 1.18) to 1.03 MA 7/M
NT (0.38 – 1.69)
(STIM)
8
group G/S estimates

(AD)
CBT-ED S WL/ 1 100% EFF MD 0.58 (0.17 – 0.98) MA 9/H
NT
CBT-ED I WL/ 1 100% EFF MD 0.50 (0.12 – 0.88) MA 9/H
NT
EDP FU PT I WL/ 1 100% EFF g 1.34 (0.87 – 1.82) MA 7/M
NT
GENSX CBT-ED I WL/ 1 100% EFF SMD 0.42 (0.18 – 0.67) MA 9/H
NT
CBT-ED S WL/ 1 100% EFF SMD 0.35 (0.07 – 0.63) MA 9/H
NT
PHARMA I PBO 6 83.3% EFF; 16.7% MD/ ns to MD 3.84 (1.12 – 6.55) / MA 11 /
(AD) NS SMD SMD 0.38 (0.03 – 0.74) H
PT I PBO 2 100% NS g ns MA 7/M
GLOBAL CBT-ED S WL/ 2 100% EFF RD/ RD 0.25 (0.12 – 0.38) / RR MA 9/H
NT RR 4.58 (1.54 – 13.6)
PHARMA I PBO 1 100% EFF RR 2.61 (2.04 – 3.33) NMA 6/M
(STIM)
PHARMA I PBO 3 100% EFF RR 1.23 (1.06 – 1.43) to 1.67 NMA, 6/M
(AD) (1.24 – 2.26) MA
(MIX)
(ORL)
CBT-ED I WL/ 1 100% EFF RD 0.4 (0.3 – 0.5) MA 9.5 /
NT H
PHARMA I PBO 2 50% EFF; 50% NS RR ns to 1.59 (1.28 – 1.96) MA 8.5 /
(MS) H
WEIGHT/ PHARMA I PBO 1 100% EFF MD 5.23 (3.94 – 6.52) MA 9/H
BODY (STIM)
PHARMA I PBO 1 100% EFF WMD 4.58 (3.79 – 5.36) MA 8/H
(MS)
(ORL)
(MIX)
PHARMA I PBO 4 25% EFF; 75% NS WMD ns to 1.72 (0.37 – 3.06) MA 9/H
(AD)
CBT-ED I WL/NT 1 100% NS SMD ns MA 9/H
CBT-ED S WL/NT 1 100% NS SMD ns MA 9/H
ADU MIX ACCEPT CBT-ED I WL/NT 1 100% NS RR ns MA 5/M
EDU S WL/NT 1 100% NS RR ns MA 5/M
BEHAV CBT-ED I WL/ 1 100% EFF SMD 0.95 (0.68 – 1.22) MA 5/M
NT
GLOBAL CBT-ED I WL/ 1 100% EFF RR 1.45 (1.25 – 1.69) MA 5/M
NT
WEIGHT/ CBT-ED I WL/ 1 100% EFF SMD 0.33 (0.001 – 0.66) MA 5/M
BODY NT
MIX MIX ACCEPT CBT-ED I WL/NT 1 100% NS RR ns MA 7/M
BEHAV PT I WL/ 4 100% EFF SMD 0.81 (0.58 – 1.04) to 1.14 MA 8/H
NT (0.89 – 1.39)
NT
EDU S WL/ 11 54.5% EFF; 45.5% SMD ns to 0.98 (0.69 – 1.27) MA 7/M
NT NS
EDP EDU S WL/ 2 100% EFF SMD 0.58 (0.37 – 0.79) to 0.71 MA 9/H
NT (0.41 – 1.01)
PT I WL/ 4 75% EFF; 25% NS SMD ns to 1.13 (0.61 – 1.66) MA 8/H
NT
F-QOL EDU S WL/ 2 50% EFF; 50% NS SMD ns to 0.34 (0.02 – 0.67) MA 8/H
NT
CBT-ED I WL/NT 1 100% NS SMD ns MA 7/M
PT I WL/NT 1 100% NS g ns MA 9/H
GENSX PT I WL/ 5 100% EFF SMD 0.30 (0.13 – 0.47) to 0.71 MA 7/M
NT (0.29 – 1.14)
NT
EDU S WL/ 3 33.3% EFF; 66.7% WMD ns to 0.32 (0.13 – 0.51) MA 9/H
NT NS
GLOBAL PT I 1 100% EFF RR 1.59 (1.20 – 2.08) MA 7/M
9
group G/S estimates
WL/
NT
CBT-ED I WL/ 1 100% EFF RR 1.45 (1.27 – 1.64) MA 7/M
NT
CBT-ED S WL/NT 1 100% NS RR ns MA 10 /
H
WEIGHT/ CBT-ED I WL/NT 1 100% NS SMD ns MA 7/M
BODY EDU S WL/NT 2 100% NS SMD ns MA 8/H
PT I WL/NT 1 100% NS SMD ns MA 7/M
Legend. A, quality as per AMSTAR 0–11 score (median if >1 comparison); ACCEPT, acceptability; AD, antidepressants; ADU, adults; BEHAV, behavioural symptoms;
BT, behavioural therapy; CBT-ED, cognitive behavioural therapy for eating disorders; CI, confidence interval; EDP, eating disorder psychopathology; EDU, psycho
education; EFF, statistically significant difference that favours intervention; ES, effect size; F-QOL, functioning/quality of life; FU, at follow up; G, group intervention;
g, Hedges’ g; GENSX, psychiatric general symptoms; GLOBAL, improvement/response/remission/relapse; I, individual intervention; IPT, interpersonal psychotherapy;
MD, mean difference; MIX, mixed or not specified age group/setting/medications; MULTI, mixed active interventions; NS/ns, no statistically significant difference; OR,
odds ratio; OUT, outpatient; PBO, placebo; PHARMA, pharmacological intervention; PT, psychotherapy; Q, quality level (L=low-AMSTAR <4, M=medium-AMSTAR
4–7, H=high-AMSTAR >7); RD, risk difference; RR, risk ratio; S, self-help intervention; SMD, standardized mean difference; WEIGHT/BODY, changes in weight/BMI/
body composition; WL/NT, wait-list/no treatment; WMD, weighted mean difference.
Significant results are presented in bold. Results are ordered as significant ones first, ordered by ES magnitude and % significant comparisons, and then non-significant
ones in alphabetical order.
SMD=1.01, 95%CI=0.68–1.33, AMSTAR/Quality=5/M; k = 5, Compared to wait list-no treatment, individual cognitive behavioural
n = 206, SMD=1.22, 95%CI=0.92–1.52, AMSTAR/Quality=5/M), therapy for eating disorders proved beneficial for eating disorder be
general psychiatric symptoms (k = 6, n = 223, SMD=0.80, 95% haviours (k = 3, n = 208, MD=2.32, 95%CI=0.09–4.56, AMSTAR/
CI=0.37–1.22, AMSTAR/Quality=5/M; k = 3, n = 101, SMD=0.58, Quality=11/H) and global course of the disease (k = 4, n = 401,
95%CI=0.18–0.98, AMSTAR/Quality=5/M) and global course of the RR=4.95, 95%CI=3.06–8.00, AMSTAR/Quality=8/H). Compared to
disease (k = 5, n = 204, OR=1.49, 95%CI=1.28–1.72, AMSTAR/Qual placebo, antidepressants were superior for eating disorder behaviours
ity=6.5/M; k = na, n = 554, OR=3.89, 95%CI=1.19–14.0, AMSTAR/ (k = 7, n = na, MD=0.67, 95%CI=0.09–1.26, AMSTAR/Quality=8/H),
Quality=6.5/M; k = 4, n = 162, OR=1.54, 95%CI=1.30–1.82, eating disorder psychopathology (k = 3, n = na, MD=3.84, 95%
AMSTAR/Quality=6.5/M). Global course of the disease was amelio CI=1.13–6.55, AMSTAR/Quality=8/H), general psychiatric symptoms
rated also by group behavioural therapy (k = na, n = 207, OR=28.7, (k = 3, n = na, MD=1.97, 95%CI=0.28–3.67, AMSTAR/Quality=8/H)
95%CI=3.11–455, AMSTAR/Quality=8/H), group cognitive behav and global course of the disease (k = 8, n = 548, RR=1.67, 95%
ioural therapy for eating disorders (k = na, n = 245, OR=7.67, 95% CI=1.24–2.26, AMSTAR/Quality=8/H). Also, stimulants improved
CI=1.51–55.7, AMSTAR/Quality=8/H) and self-help cognitive behav eating disorder behaviours (k = 3, n = 1033, SMD=0.56, 95%
ioural therapy for eating disorders (k = na, n = 302, OR=3.49, 95% CI=0.28–0.84, AMSTAR/Quality=9/H), eating disorder psychopathol
CI=1.20–11.2, AMSTAR/Quality=8/H; k = na, n = 392, OR=3.81, ogy (k = 3, n = na, MD=6.50, 95%CI=4.18–8.82, AMSTAR/Qual
95%CI=1.51–10.9, AMSTAR/Quality=8/H). Compared to Active con ity=8/H), global course of the disease (k = 3, n = 1033, RR=1.58, 95%
trol, individual cognitive behavioural therapy for eating disorders had CI=1.35–1.84, AMSTAR/Quality=9/H; k = 3, n = 1033, RR=2.43, 95%
the broadest efficacy, namely for eating disorder behaviours (k = 25, CI=1.95–3.01, AMSTAR/Quality=9/H) and change in weight or body
n = na, g=0.23, 95%CI=0.06–0.37, AMSTAR/Quality=5/M), EDP composition (k = 3, n = 1033, SMD=1.28, 95%CI=1.06–1.51,
(k = 16, n = na, g=0.27, 95%CI=0.08–0.45, AMSTAR/Quality=6/M), AMSTAR/Quality=9/H). Anticonvulsants improved eating disorder
and global course of the disease (k = 7, n = 484, OR=1.20, 95% behaviours (k = na, n = na, MD=0.98, 95%CI 0.15–1.80, AMSTAR/
CI=1.03–1.41, AMSTAR/Quality=5/M; k = 14, n = na, OR=1.70, 95% Quality=5/M; k = 3, n = 528, MD=1.31, 95%CI=0.03–2.58, AMSTAR/
CI=1.21–2.38, AMSTAR/Quality=6/M). Individual psychotherapy was Quality=5/M) and change in weight or body composition (k = 3,
worse than control for global course of the disease (k = 6, n = 257, n = 528, MD=4.91, 95%CI=3.41–6.42, AMSTAR/Quality=5/M). No
RR=0.83, 95%CI=0.69–0.98, AMSTAR/Quality=8/H). Antidepressants intervention outperformed active control.
were beneficial for eating disorder behaviours (k = 3, n = 89, RR=2.08, Results on mixed age groups are reported in eResults section.
95%CI=1.09–25.0, AMSTAR/Quality=8/H) and general psychiatric
symptoms (k = 3, n = 117, RR=2.13, 95%CI=1.09–100, AMSTAR/ 3.1.4. Binge-eating disorder acceptability
Quality=8/H). Antidepressants induced more adverse events (k = 3, n = 938,
Results on mixed age groups are reported in eResults section. RR=0.61, 95%CI=0.42–0.88, AMSTAR/Quality=11/H; k = 3, n = 938,
RR=0.38, 95%CI=0.23–0.61, AMSTAR/Quality=11/H) and had lower
3.1.2. Bulimia nervosa acceptability acceptability (k = 3, n = 1032, RR=0.46, 95%CI=0.21–0.97, AMSTAR/
Individual psychotherapy was more acceptable than active control Quality=9/H) than placebo.
(k = 6, n = 295, RR=1.75, 95%CI=1.14–2.63, AMSTAR/Quality=8/H). Anticonvulsivants had lower acceptability (k = 3, n = 528,
RR=0.52, 95%CI=0.31–0.88, AMSTAR/Quality=5/M) than placebo.
3.1.3. Binge-eating disorder Efficacy
Data for BED were extracted from one NMA and 18 MAs; none 4. Discussion
provided information on adolescents, six (31.6%) specifically on adults.
In adult outpatients, individual cognitive behavioural therapy for To our knowledge this is the first umbrella review to systematically
eating disorders outperformed active control improving eating disorder assess efficacy and acceptability of interventions specifically for EDs
behaviours (k = 4, n = 323, MD=2.04, 95%CI=0.35–3.73, AMSTAR/ from (N)MAs of RCTs, and both the quality of the (N)MAs and of the
Quality=9/H). In mixed settings, 57.1% of the interventions proved meta-analysed RCTs. This umbrella review also follows recent recom
beneficial, and 28.6% had both favourable and unfavourable outcomes. mendations regarding the need to consider a wide range of outcomes in
10
Table 3
Efficacy of interventions against Treatment As Usual/Active control.
Age Setting Outcome Intervention I/G/ Control N of % significance ES ES (95% CI) Source A/Q
group S estimates type
Anorexia Nervosa
ADO OUT GLOBAL FU FBT I ACTIVE 1 100% EFF OR 2.08 (1.07 – 4.03) MA 9/H
MIX ACCEPT FAM I TAU 1 100% NS RR ns MA 9/H
FAM I ACTIVE 1 100% NS RR ns MA 9/H
EDP PT I TAU 1 100% NS g ns MA 10 /
H
FAM I ACTIVE 1 100% NS SMD ns MA 9/H
EDP FU FAM I ACTIVE 1 100% NS SMD ns MA 9/H
GLOBAL FAM I ACTIVE 1 100% NS RR ns MA 9/H
GLOBAL FU FAM I ACTIVE 1 100% NS RR ns MA 9/H
WEIGHT/ FAM I ACTIVE 3 33.3% EFF; 66.7% SMD ns to 0.44 (0.14 – 0.74) NMA, 6/M
BODY NS MA
FBT I ACTIVE 2 100% NS SMD ns NMA 6/M
PT I TAU 1 100% NS g ns MA 10 /
H
MULTI I ACTIVE 4 100% NS SMD ns NMA 6/M
PDO I ACTIVE 1 100% NS SMD ns NMA 6/M
WEIGHT/ FAM I ACTIVE 1 100% NS SMD ns MA 9/H
BODY FU
ADU OUT ACCEPT CBT-ED I TAU 1 100% NS RR ns NMA 10 /
H
FBT I TAU 1 100% NS RR ns NMA 10 /
H
MANTRA I TAU 1 100% NS RR ns NMA 10 /
H
PDO I TAU 1 100% NS RR ns NMA 10 /
H
CBT-ED I ACTIVE 1 100% NS RR ns NMA 10 /
H
FBT I ACTIVE 1 100% NS RR ns NMA 10 /
H
BEHAV CBT-ED I TAU 1 100% NS SMD ns NMA 10 /
H
FBT I TAU 1 100% NS SMD ns NMA 10 /
H
MANTRA I TAU 1 100% NS SMD ns NMA 10 /
H
PDO I TAU 1 100% NS SMD ns NMA 10 /
H
CBT-ED I ACTIVE 1 100% NS SMD ns NMA 10 /
H
FBT I ACTIVE 1 100% NS SMD ns NMA 10 /
H
BEHAV FU CBT-ED I TAU 1 100% NS SMD ns NMA 10 /
H
H
H
H
H
H
WEIGHT/ CBT-ED I TAU 1 100% NS SMD ns NMA 10 /
BODY H
H
H
H
H
H
WEIGHT/ CBT-ED I TAU 1 100% NS SMD ns NMA 10 /
BODY FU H
H
H
11

H
H
H
MIX ACCEPT FAM I ACTIVE 1 100% NS RR ns MA 9/H
EDP FAM I ACTIVE 1 100% NS SMD ns MA 9/H
H
EDP FU FAM I ACTIVE 1 100% NS SMD ns MA 9/H
GLOBAL FAM I TAU 1 100% EFF RR 3.50 (1.49 – 8.23) MA 9/H
GLOBAL FU FAM I ACTIVE 1 100% NS RR ns MA 9/H
WEIGHT/ MULTI I TAU 1 100% NS SMD ns NMA 6/M
BODY CBT-ED I ACTIVE 3 100% NS SMD ns NMA 6/M
FBT I ACTIVE 1 100% NS SMD ns NMA 6/M
IPT I ACTIVE 1 100% NS SMD ns NMA 6/M
MANTRA I ACTIVE 1 100% NS SMD ns NMA 6/M
PDO I ACTIVE 2 100% NS SMD ns NMA 6/M
WEIGHT/ FAM I ACTIVE 1 100% NS SMD ns MA 9/H
BODY FU
MIX IN ACCEPT MULTI NA ACTIVE 1 100% DETR RR 0.75 (0.64 – 0.88) MA 9/H
GENSX MULTI NA ACTIVE 2 100% NS SMD ns MA 9/H
GLOBAL MULTI NA ACTIVE 1 100% NS RR ns MA 9/H
WEIGHT/ MULTI NA ACTIVE 1 100% NS SMD ns MA 9/H
BODY
OUT ACCEPT CBT-ED I ACTIVE 1 100% NS RR ns MA 9/H
PDO I TAU 1 100% NS RR ns MA 9/H
EDP CBT-ED I ACTIVE 1 100% NS SMD ns MA 9/H
H
EDP FU CBT-ED I ACTIVE 1 100% NS SMD ns MA 9/H
F-QOL PT I TAU 1 100% NS g ns MA 10 /
H
GLOBAL CBT-ED I ACTIVE 1 100% NS RR ns MA 9/H
PDO I TAU 1 100% NS RR ns MA 9/H
WEIGHT/ CBT-ED I ACTIVE 1 100% NS MD ns MA 9/H
BODY PT I TAU 1 100% NS g ns MA 10 /
H
WEIGHT/ CBT-ED I ACTIVE 1 100% NS MD ns MA 9/H
BODY FU
MIX ACCEPT FBT I ACTIVE 1 100% NS RR ns MA 9/H
FAM I TAU 1 100% NS RR ns MA 9/H
EDP CBT-ED I TAU 1 100% NS g ns MA 10 /
H
FAM I TAU 2 100% NS SMD ns MA 9.5 /
H
PDO I TAU 1 100% NS g ns MA 10 /
H
H
PT G TAU 1 100% NS g ns MA 10 /
H
CBT-ED I ACTIVE 1 100% NS g ns MA 6/M
FBT G ACTIVE 1 100% NS MD ns MA 9/H
EDP FU CBT-ED I ACTIVE 1 100% NS g ns MA 6/M
FBT I ACTIVE 2 100% NS SMD ns MA 9/H
F-QOL CBT-ED I TAU 1 100% NS g ns MA 10 /
H
H
H
PT I ACTIVE 1 100% NS g ns MA 10 /
H
GLOBAL FBT G ACTIVE 1 100% EFF RR 1.79 (1.20 – 2.63) MA 9/H
FAM I TAU 2 50% EFF; 50% NS RR ns to 3.83 (1.60 – 9.13) MA 9/H
GLOBAL FU FBT I ACTIVE 3 100% NS RR ns MA 9/H
WEIGHT/ FBT I ACTIVE 5 33.3% EFF; 66.7% SMD ns to 0.32 (0.01 – 0.63) MA 9/H
BODY NS
CBT-ED I TAU 1 100% NS g ns MA
12
10 /
H
EXE I TAU 1 100% NS g ns MA 7/M
FAM I TAU 1 100% NS g ns MA 10 /
H
H
H
PT G TAU 1 100% NS g ns MA 10 /
H
PT I ACTIVE 1 100% NS g ns MA 10 /
H
WEIGHT/ FBT I ACTIVE 2 100% NS SMD ns MA 9/H
BODY FU
Bulimia Nervosa
ADO OUT GLOBAL FU FBT I ACTIVE 1 100% EFF OR 2.22 (1.02 – 4.82) MA 9/H
MIX BEHAV CBT-ED I ACTIVE 1 100% NS g ns MA 6/M
EDP CBT-ED I ACTIVE 1 100% NS g ns MA 6/M
ADU MIX ACCEPT PT I ACTIVE 2 50% EFF; 50% NS RR ns to 1.75 (1.14 – 2.63) MA 8/H
CBT-ED I ACTIVE 2 100% NS RR ns MA 5/M
EDU I ACTIVE 1 100% NS RR ns MA 5/M
PHARMA (AD) I ACTIVE 1 100% NS RR ns MA 8/H
BEHAV PHARMA I ACTIVE 1 100% EFF RR 2.08 (1.09 – 25.0) MA 8/H
(AD)
CBT-ED I ACTIVE 4 25% EFF; 25% NS; g ns to 0.23 (0.06 – 0.37) MA 5/M
50% NA*
EDU I ACTIVE 1 100% NS SMD ns MA 5/M
PT I ACTIVE 2 100% NS SMD ns MA 6.5 /
M
EDP CBT-ED I ACTIVE 1 100% EFF g 0.27 (0.08 – 0.45) MA 6/M
F-QOL CBT-ED I TAU 1 100% NS SMD ns MA 5/M
GENSX PHARMA I ACTIVE 1 100% EFF RR 2.13 (1.09 – 100) MA 8/H
(AD)
CBT-ED I ACTIVE 2 100% NS SMD ns MA 5/M
EDU I ACTIVE 1 100% NS SMD ns MA 5/M
PT I ACTIVE 1 100% NS SMD ns MA 8/H
GENSX FU EDU I ACTIVE 1 100% NS SMD ns MA 5/M
GLOBAL CBT-ED I ACTIVE 2 100% EFF OR 1.20 (1.03 – 1.41) to MA 5.5 /
1.70 (1.21 – 2.38) M
PT I ACTIVE 3 66.7% NS; 33.3% RR 0.83 (0.69 – 0.98) to ns NMA, 8/H
DETR MA
BT I ACTIVE 1 100% NS OR ns NMA 8/ H
BT G ACTIVE 1 100% NS OR ns NMA 8/ H
CBT-ED G ACTIVE 1 100% NS OR ns NMA 8/ H
CBT-ED S ACTIVE 2 100% NS OR ns NMA 8/ H
EXE I ACTIVE 1 100% NS OR ns NMA 8/ H
IPT I ACTIVE 1 100% NS OR ns NMA 8/ H
MULTI I ACTIVE 1 100% NS OR ns NMA 8/ H
PHARMA (AD) I ACTIVE 2 100% NS OR ns NMA, 8/ H
MA
WEIGHT/ CBT-ED I ACTIVE 1 100% NS SMD ns MA 5/M
BODY
MIX OUT ACCEPT PHARMA I ACTIVE 1 100% DETR RR 0.46 (0.23 – 0.92) MA 7/M
(AD)
BEHAV PHARMA (AD) I ACTIVE 1 100% NS SMD ns MA 7/M
GENSX PHARMA (AD) I ACTIVE 1 100% NS RR ns MA 7/M
GLOBAL PHARMA (AD) I ACTIVE 1 100% NS RR ns MA 7/M
MIX ACCEPT PT I ACTIVE 3 66.7% EFF; 33.3% RR ns to 1.82 (1.11 – 3.03) MA 10 /
NS H
EDU I ACTIVE 1 100% NS RR ns MA 7/M
PHARMA (AD) I ACTIVE 1 100% NS RR ns MA 10 /
H
BEHAV CBT-ED I ACTIVE 12 41.7% EFF; 58.3% g ns to 0.42 (0.16 – 0.67) MA 6/M
NS
CBT-ED IþS ACTIVE 2 50% EFF; 50% NS g ns to 0.30 (0.07 – 0.53) MA 6/M
CBT-ED G ACTIVE 1 100% NS g ns MA 6/M
EDU S ACTIVE 1 100% NS SMD ns MA 7/M
PHARMA (AD) I ACTIVE 1 100% NS SMD ns MA 10 /
H
PT I ACTIVE 2 100% NS SMD ns MA 8.5 /
H
PT I+S ACTIVE 2 100% NS g ns MA 6/M
BEHAV FU CBT-ED I ACTIVE 1 100% EFF g 0.31 (0.10 – 0.52) MA 6/M
13
EDP CBT-ED I ACTIVE 9 87.8% EFF; 22.2% g ns to 0.53 (0.31 – 0.74) MA 6/M
NS
EDP FU CBT-ED I ACTIVE 1 100% NS g ns MA 6/M
F-QOL CBT-ED I ACTIVE 1 100% NS SMD ns MA 7/M
GENSX CBT-ED I ACTIVE 4 25% EFF; 75% NS g ns to 0.25 (0.03 – 0.46) MA 6.5 /
M
CBT-ED I+S ACTIVE 1 100% NS g ns MA 6/M
PHARMA (AD) I ACTIVE 1 100% NS SMD ns MA 10 /
H
PT I+S ACTIVE 1 100% NS g ns MA 6/M
GENSX FU CBT-ED I+S ACTIVE 1 100% NS g ns MA 6/M
GLOBAL CBT-ED I ACTIVE 7 42.9% EFF; 57.1% OR ns to 2.08 (1.23 – 3.53) MA 6/M
NS
PT I ACTIVE 4 75% NS; 25% DETR RR 0.82 (0.69 – 0.98) to ns MA 10 /
H
PHARMA (AD) I ACTIVE 1 100% NS RR ns MA 10 /
H
GLOBAL FU CBT-ED I ACTIVE 1 100% NS OR ns MA 6/M
BODY
Binge Eating Disorder
ADU OUT ACCEPT BT I ACTIVE 1 100% NS RR ns MA 9/H
ACCEPT FU BT I ACTIVE 1 100% NS RR ns MA 9/H
BEHAV CBT-ED I ACTIVE 1 100% EFF MD 2.04 (0.35 – 3.73) MA 9/H
BEHAV FU BT I ACTIVE 1 100% NS MD ns MA 9/H
WEIGHT/ BT I ACTIVE 1 100% NS MD ns MA 9/H
BODY
WEIGHT/ BT I ACTIVE 1 100% NS MD ns MA 9/H
BODY FU
MIX ACCEPT PT I ACTIVE 1 100% NS OR ns MA 5/M
MIX MIX ACCEPT PT I ACTIVE 1 100% EFF OR 5.00 (2.50 – 10.0) MA 9/H
BEHAV BT I ACTIVE 1 100% EFF SMD 0.27 (0.05 – 0.48) MA 9/H
CBT-ED I ACTIVE 4 50% EFF; 50% NS SMD ns to 0.31 (0.02 – 0.61) MA 6/M
CBT-ED S ACTIVE 1 100% NS g ns MA 6/M
IPT I ACTIVE 1 100% NS SMD ns MA 9/H
PHARMA I ACTIVE 1 100% NS SMD ns NMA 6/M
(STIM)
PT I ACTIVE 3 100% NS g ns MA 7/M
BEHAV FU BT I ACTIVE 1 100% DETR SMD -0.24 (¡0.46 to ¡0.01) MA 9/H
IPT I ACTIVE 1 100% NS SMD ns MA 9/H
PT I ACTIVE 1 100% NS SMD ns MA 9/H
EDP PT I ACTIVE 3 66.7% EFF; 33.3% g ns to 0.49 (0.21 – 0.78) MA 7/M
NS
CBT-ED I ACTIVE 6 16.7% EFF; 83.3% g ns to 0.17 (0.01 – 0.33) MA 7/M
NS
CBT-ED S ACTIVE 1 100% NS g ns MA 6/M
PHARMA I ACTIVE 1 100% NS SMD ns NMA 6/M
(STIM)
EDP FU PT I ACTIVE 2 50% EFF; 50% NS g ns to 0.51 (0.19 – 0.83) MA 8/H
GENSX BT I ACTIVE 1 100% NS MD ns MA 9/H
CBT-ED I ACTIVE 1 100% NS g ns MA 8/H
GENSX FU BT I ACTIVE 1 100% NS MD ns MA 9/H
GLOBAL PHARMA I ACTIVE 1 100% EFF RR 1.56 (1.06 – 2.29) NMA 6/M
(STIM)
BT G ACTIVE 1 100% NS RD ns MA 9/H
CBT-ED I ACTIVE 3 100% NS OR ns MA 6/M
CBT-ED G ACTIVE 1 100% NS OR ns MA 6/M
CBT-ED S ACTIVE 1 100% NS OR ns MA 6/M
IPT I ACTIVE 1 100% NS RD ns MA 9/H
PT I ACTIVE 3 100% NS OR ns MA 7/M
GLOBAL FU BT G ACTIVE 1 100% DETR RD -0.13 (¡0.25 to ¡0.02) MA 9/H
CBT-ED I ACTIVE 1 100% NS OR ns MA 6/M
IPT I ACTIVE 1 100% NS RD ns MA 9/H
PT I ACTIVE 1 100% NS OR ns MA 9/H
WEIGHT/ PT I ACTIVE 2 50% NS; 50% DETR MD -0.46 (¡0.94 to ¡0.07) MA 9/H
BODY to ns
BT I ACTIVE 1 100% NS SMD ns MA 9/H
CBT-ED I ACTIVE 1 100% NS SMD ns MA 7/M
14
IPT I ACTIVE 1 100% NS MD ns MA 9/ H

WEIGHT/ BT I ACTIVE 1 100% NS SMD ns MA 9/ H
BODY FU IPT I ACTIVE 1 100% NS MD ns MA 9/ H
PT I ACTIVE 1 100% NS SMD ns MA 9/ H
ADO OUT GLOBAL FBT I ACTIVE 3 33.3% EFF; 66.7% OR ns to 2.14 (1.29 – 3.53) MA 9/H
NS
GLOBAL FU FBT I ACTIVE 1 100% EFF OR 2.35 (1.33 – 4.14) MA 9/H
ADU MIX ACCEPT CBT-ED I ACTIVE 1 100% NS RR ns MA 5/M
CBT-ED S ACTIVE 1 100% NS RR ns MA 5/M
PHARMA I ACTIVE 1 100% NS OR ns MA 5/M
(MIX)
PT I ACTIVE 1 100% NS OR ns MA 5/M
BEHAV CBT-ED S ACTIVE 1 100% EFF SMD 0.42 (0.09 – 0.76) MA 5/M
CBT-ED I ACTIVE 2 50% EFF; 50% NS SMD ns to 0.19 (0.05 – 0.33) MA 5/M
F-QOL CBT-ED I ACTIVE 1 100% NS SMD ns MA 5/M
GENSX CBT-ED I ACTIVE 2 50% EFF; 50% NS SMD ns to 0.49 (0.01 – 0.97) MA 5/M
CBT-ED S ACTIVE 2 100% NS SMD ns MA 5/M
GLOBAL CBT-ED I ACTIVE 1 100% EFF RR 1.23 (1.09 – 1.39) MA 5/M
BODY CBT-ED S ACTIVE 1 100% NS SMD ns MA 5/M
MIX OUT BEHAV VR-CBT-ED I ACTIVE 2 50% EFF; 50% NS MD ns to 0.29 (0.01 – 0.57) MA 7/M
MIX ACCEPT CBT-ED I ACTIVE 1 100% NS RR ns MA 7/M
EDU S ACTIVE 5 100% NS RR ns MA 9/H
MULTI S ACTIVE 2 100% NS RR ns MA 9/H
BEHAV CBT-ED S ACTIVE 1 100% EFF SMD 0.42 (0.09 – 0.76) MA 7/M
e-PT I ACTIVE 1 100% EFF g 0.28 (0.07 – 0.51) MA 7/M
CBT-ED I ACTIVE 4 50% EFF; 50% NS g ns to 0.29 (0.09 – 0.49) MA 8.5 /
H
PT I ACTIVE 5 20% EFF; 80% NS SMD ns to 0.19 (0.05 – 0.33) MA 9/H
IPT I ACTIVE 1 100% DETR g -0.22 (¡0.39 to ¡0.05) MA 10 /
H
PT G ACTIVE 2 100% NS g ns MA 9/H
BEHAV FU CBT-ED I ACTIVE 3 100% NS RR ns MA 9/H
CBT-ED G ACTIVE 1 100% NS RR ns MA 9/H
PT I ACTIVE 3 100% NS RR ns MA 9/H
EDP CBT-ED I ACTIVE 9 100% EFF g 0.18 (0.01 – 0.35) to MA 8/H
0.37 (0.18 – 0.56)
MULTI I ACTIVE 2 50% EFF; 50% NS SMD ns to 0.72 (0.25 – 1.20) MA 7/M
IPT I ACTIVE 4 50% EFF; 50% NS g ns to 0.56 (0.27 – 0.85) MA 10 /
H
CBT-ED S ACTIVE 3 66.7% EFF; 33.3% g ns to 0.39 (0.14 – 0.65) MA 8/H
NS
PT I ACTIVE 11 9.1% EFF; 91.9% g ns to 0.17 (0.03 – 0.32) MA 7/M
NS
CBT-ED G ACTIVE 1 100% NS g ns MA 9/H
EDU S ACTIVE 2 100% NS SMD ns MA 9/H
PT G ACTIVE 1 100% NS g ns MA 9/H
EDP FU PT I ACTIVE 6 16.7% EFF; 83.3% g ns to 0.92 (0.71 – 1.21) MA 7/M
NS
CBT-ED I ACTIVE 3 66.7% EFF; 33.3% g ns to 0.33 (0.05 – 0.62) MA 9/H
NS
CBT-ED G ACTIVE 1 100% NS g ns MA 9/H
EDU S ACTIVE 1 100% NS MD ns MA 9/H
F-QOL CBT-ED I ACTIVE 2 100% NS SMD ns MA 8/H
F-QOL FU CBT-ED I ACTIVE 1 100% NS g ns MA 9/H
GENSX CBT-ED I ACTIVE 4 100% NS SMD ns MA 8/H
CBT-ED S ACTIVE 2 100% NS SMD ns MA 7/M
PT I ACTIVE 4 100% NS g ns MA 8/H
GENSX FU CBT-ED I ACTIVE 2 100% NS g ns MA 9/H
GLOBAL CBT-ED I ACTIVE 1 100% NS RR ns MA 7/M
IPT I ACTIVE 1 100% NS g ns MA 10 /
H
PT I ACTIVE 1 100% NS RR ns MA 7/M
GLOBAL FU CBT-ED I ACTIVE 1 100% NS OR ns MA 6/M
PT I ACTIVE 1 100% NS RR ns MA 6/M
CBT-ED I ACTIVE 1 100% EFF SMD 0.18 (0.01 – 0.34) MA 7/M
15
WEIGHT/ CBT-ED S ACTIVE 1 100% NS SMD ns MA 7/M

BODY EDU S ACTIVE 1 100% NS WMD ns MA 9/H
IPT I ACTIVE 1 100% NS g ns MA 10 /
H
MULTI I ACTIVE 1 100% NS MD ns MA 10 /
H
Legend. * , unclear from the MA if the effect size was significant or not; A, quality as per AMSTAR 0–11 score (median if >1 comparison); ACCEPT, acceptability; AD,
antidepressants; ADU, adults; BEHAV, behavioural symptoms; BT, behavioural therapy; CBT-ED, cognitive behavioural therapy for eating disorders; eCBT-ED,
electronic/virtual CBT-ED; CI, confidence interval; DETR, statistically significant difference that favours control; EDP, eating disorder psychopathology; EDU, psy
choeducation; EFF, statistically significant difference that favours intervention; ES, effect size; EXE, guided physical exercise; F-QOL, functioning/quality of life; FAM,
mixed family interventions; FBT, family-based therapy; FU, at follow up; G, group intervention; g, Hedges’ g; GENSX, psychiatric general symptoms; GLOBAL,
improvement/response/remission/relapse; I, individual intervention; IPT, interpersonal psychotherapy; MANTRA, Maudsley Anorexia Treatment for Adults; MD,
mean difference; MIX, mixed or not specified age group/setting/medications; MULTI, mixed active interventions; NA, not assessed; NS/ns, no statistically significant
difference; Q, quality level (L=low-AMSTAR <4, M=medium-AMSTAR 4–7, H=high-AMSTAR >7); OR, odds ratio; OUT, outpatient; PDO, psychodynamic-oriented
psychotherapy; PHARMA, pharmacological intervention; PT, psychotherapy; RD, risk difference; RR, risk ratio; S, self-help intervention; SMD, standardized mean
difference; STIM, psychostimulants; VR-CBT-ED, CBT-ED plus virtual reality; TAU, treatment as usual; WEIGHT/BODY, changes in weight/BMI/body composition;
WMD, weighted mean difference.
Significant results are presented in bold. Results are ordered as significant ones first, ordered by ES magnitude and % significant comparisons, and then non- significant
ones in alphabetical order.
EDs (Murray et al., 2018) including treatment acceptability (Grenon seems to have been neglected by guidelines, which recommend indi
et al., 2018b). Pooling data from 55 MAs and 4 NMAs, this work ad vidual psychotherapy for adults with AN, especially cognitive behav
vances the field by filtering the enormous body of meta-analytic evi ioural therapy for ED (Hilbert et al., 2017). A recent NMA (Solmi et al.,
dence on interventions in EDs (1154 effect sizes), rating quality, and 2021) found no superiority of the most recommended individual psy
providing clinicians, guideline developers and researchers with an chotherapies (e.g. CBT-ED, MANTRA, SSCM, psychodynamic therapies)
informative synopsis of what works better than treatment as usual versus treatment as usual in adult outpatients with AN. However, that
and/or active control, for which symptoms, at which time-points, and work focused on symptoms, and not global remission as the outcome.
based on what quality of evidence. Thus, the current findings suggest that interventions involving family
For AN, family-based treatment was the only intervention supported might be considered in young adults with AN, although research should
by some evidence against other active treatments for both remission and aim to develop good alternatives, which does not essentially shift the
weight gain. In BN, individual cognitive behavioural therapy for ED treatment responsibility to families, as not all adults with AN have
outperformed other active treatments for ED psychopathology and be families involved in their care. No medication was found to be effective
haviours, as well as remission. Among pharmacological interventions, in reducing ED behaviours/psychopathology or general symptoms or in
tricyclic antidepressants (TCAs) and SSRIs were the most efficacious for improving weight outcome, supporting previous evidence that the use of
ED behaviours and remission. In BED, general psychotherapy (i.e., any medications cannot be recommended to improve body weight or
manualised psychological therapy) was more efficacious versus active ED-specific psychopathology in AN (Treasure et al., 2020; Zipfel et al.,
controls for ED psychopathology and drop-out, but less effective for 2015), unless psychiatric comorbidity is present.
weight reduction; while behavioural treatments (including behavioural In BN, the most robust evidence exists for individual cognitive
weight loss treatment) and cognitive behavioural therapy for ED were behavioural therapy for ED, which was more effective in reducing spe
more efficacious than active treatments for ED psychopathology and cific and, possibly, general symptoms compared with active treatments
behaviours, respectively. Lisdexamfetamine and antidepressants were at the end of treatment. The positive effect on ED behaviours persisted at
more efficacious than placebo for ED psychopathology, ED behaviours, follow-up. Compared to wait list-no treatment, not only cognitive
and remission. Antidepressants were also more effective than placebo behavioural therapy for ED but also general psychotherapy (i.e., any
for general psychiatric symptoms, while lisdexamfetamine as well as manualised psychological therapy) was more efficacious. The evidence
anticonvulsants and sibutramine were more effective than placebo for for adolescents was different, here family-based therapy outperformed
weight reduction. All these findings refer to status at the end of other active interventions on remission at follow-up. These findings
treatment. support international clinical guidelines (Hilbert et al., 2017) which
Regarding data on follow-up, a smaller body of evidence was avail recommend individual cognitive behavioural therapy for ED as the first
able. In adolescent outpatients with AN and with BN, family-based line treatment for adults with BN and family-based therapies for younger
therapy was more effective than active control on remission. In BN, patients. The NICE guidelines (2017) suggest the use of guided self-help
cognitive behavioural therapy for ED outperformed other active treat cognitive behavioural therapy for ED as the first choice: however, this
ments regarding ED behaviours. In BED, behavioural treatment was less recommendation is not corroborated by our findings that confirm the
effective than active control for ED behaviours and remission, whereas efficacy of self-help as well as group-delivered cognitive behavioural
psychotherapy was more effective for ED psychopathology. therapy for ED only in comparison to wait list-no treatment, where
This distilled evidence calls for a critical analysis of current treat expectation effects are not controlled for. NICE includes a
ment guidelines for EDs. For AN, this umbrella review supports the cost-effectiveness outcome that was not considered in the present work,
practice guidelines that recommend family-based therapy for younger which might contribute to the highlighted discrepancy. Furthermore,
patients (Hilbert et al., 2017), although a recent Cochrane review antidepressants (both SSRIs and TCAs) outperformed active treatments
(Fisher et al., 2019) commented that there is a limited amount of for ED behaviours and general symptoms and were more effective than
low-quality evidence to suggest that family therapy approaches may be placebo for ED behaviours and remission. However, antidepressants
more effective compared to treatment as usual. In young adults (mean were less acceptable than placebo, when contrasted with psychotherapy.
age: 15.2–26.2) with AN, family therapy (not family-based treatment) These findings are in line with the recommendations from most guide
was more effective than treatment as usual regarding global remission at lines (Hilbert et al., 2017), suggesting antidepressants (i.e., the SSRIs)
the end of treatment (medium-large effect). This finding is novel and and psychotherapy for people with BN, although there was no evidence
16
relating to the combination of these two treatments over monotherapy. limitation of treatment literature. Fifth, apart from few MAs (M Solmi
In BED, the largest evidence existed for lisdexamfetamine and anti et al., 2021), many MAs, and most of those with significant findings
depressants. Across psychotherapies, general psychotherapy (i.e., any considered mixed settings of care and did not yield specific recom
manualised psychological therapy) and behavioural treatment out mendations for the inpatient and outpatient levels of care. Sixth, feasi
performed active treatments for ED psychopathology as did cognitive bility and acceptability were poorly reported in the included (N)MAs.
behavioural therapy for ED for ED behaviours at the end of treatment. Seventh, the duration of follow-up data cannot be gleaned from the
Although general psychotherapy was less efficacious than active treat present findings. Finally, individual patient data meta/analyses are
ments for weight reduction, it was considered more acceptable and its needed to generate fine grained insight on specific clinical sub
effect on ED psychopathology persisted at follow-up in comparison to populations. Nevertheless, despite these limitations, to our knowledge,
both active treatments and wait list-no treatment. In contrast, behav this is the most comprehensive and inclusive umbrella review of in
ioural treatment was less efficacious than active treatments at follow-up. terventions for people with EDs that can inform clinicians, patients and
Our findings only partially concur with guidelines (Hilbert et al., 2017) their families, guideline developers and researchers.
that consistently recommend the use of cognitive behavioural therapy Based on these findings, many gaps remain in the literature. For
for ED as the specific psychological intervention for BED. Indeed, other example, long-term effects and the effectiveness of combined in
(non-CBT-ED) psychotherapies including third wave psychotherapies terventions (e.g., the combination of psychotherapy and pharmaco
were efficacious when pooled with cognitive behavioural therapy for therapy, which is an effective strategy in common mental disorders
ED. However, cognitive behavioural therapy remains the psychological (Cuijpers et al., 2020)), has been poorly studied or there are, in people
treatment of choice for BED with evidence for a broad set of efficacy with BED (Hilbert et al., 2019), many different combination treatment
outcomes, relatively low attrition and some evidence on low side effects, arms, which prevent detailed comparison. Similarly, second order
and cognitive behavioural therapy was evaluated in the largest number treatments for those individuals for whom first line treatments fail have
of RCTs in comparison with wait-list. Regarding pharmacological in been neglected. Moreover, no meta-analytic evidence was found for
terventions, antidepressants (SSRIs), anticonvulsants (namely top treatments in people with OSFED. Finally, the cost-effectiveness
iramate) and anti-obesity drugs (orlistat and sibutramine) are outcome, required by NICE, has not been largely addressed in ED
recommended in some but not all the guidelines. However, lisdex treatment studies and has thus not been reported in (N)MAs, but this
amfetamine is the only medication indicated for BED by the US Food and outcome needs to be considered in future studies.
Drug Administration (Fornaro et al., 2016). Nevertheless, for consider In conclusion, this umbrella review supports the recommendations
ation of a range of treatment options, the present findings suggest that from most guidelines relating to BN, and extends support of multidi
all guidelines may consider pharmacological treatments for BED, given mensional short-term treatment efficacy, especially for cognitive
the benefits on a wide range of outcomes at the end of treatment. behavioural therapy for ED. Our results also confirm the absence of a
However, there is no evidence regarding the effectiveness of medica differential effect across most specialized individual psychological in
tions at follow-up in people with BED, direct comparisons with psy terventions for AN, apart from family-based therapy in adolescents, and
chological interventions are lacking and, compared to placebo, interventions involving families show some efficacy in young adults.
lisdexamfetamine was associated with more adverse events, and top Importantly, such interventions outperformed active control on a
iramate was considered less acceptable. This lack of evidence on sus limited number of outcomes. Our findings are partially consistent with
tainability at follow-up may explain why the European Medications current guidelines for BED, supporting the efficacy of psychotherapy
Agency (EMA) has not approved any medication for BED, and medica (including cognitive behavioural therapy for ED). In addition, short-
tions can only be recommended off-label in clinical guidelines. term efficacy of medications (especially SSRIs and the lisdexamfet
Remarkably, three findings emerged as transdiagnostic features of amine) may be considered and long-term effects require further study.
treatments for people with EDs and are worth outlining. First, except for Despite the importance of the transdiagnostic perspective in EDs
long-term effects of family-based treatment, no treatment showed a (Fairburn et al., 2003) and in other mental disorders (Fusar-Poli et al.,
significant and positive impact for psychopathology and/or behaviours 2019), these findings highlight the importance of not viewing EDs as a
of adolescents with AN or with BN, while for those with BED studies of monolithic diagnostic entity. Differences across the main ED diagnoses
family-based treatment are missing. Future studies are encouraged to in terms of treatment response need to be considered by researchers and
assess treatment effectiveness in adolescents given that most of EDs, clinicians, while acknowledging some transdiagnostic general psycho
except BED, have onset during adolescence (Volpe et al., 2016). Second, pathology (Monteleone and Cascino, 2021; Solmi et al., 2018), and risk
long-term treatment effects were found only for psychotherapy in factors (Marzola et al., 2021a). Future meta-analyses should avoid
terventions, while medications displayed significant effects only at the clustering different populations (namely intervention studies should
end of treatment. This finding suggests that maintenance treatment have more descriptors related to the clinical presentation such as weight
studies with medications are needed. Third, some medications showed status or illness duration), interventions, controls, and outcomes, and
either less acceptability or safety than placebo. This finding suggests that novel treatments should be tested in particular for individuals with AN
clinicians and patients need to be aware of and monitor if/to what de of all ages and for adolescents with all specific EDs.
gree pharmacological or psychotherapeutic interventions potentially do
harm. Overall, these findings may help clinicians with decision making Funding
and suggest possible areas for future research.
Limitations of this umbrella review need to be acknowledged. First, This research did not receive any specific grant from funding
we selected network over pairwise meta-analyses, and chose the largest agencies in the public, commercial, or not-for-profit sectors.
(rather than the highest quality) of the meta-analyses regarding the
same population, intervention, control, and outcome. Individual RCTs CRediT authorship contribution statement
not pooled in previous MAs were not included. Second, we combined
different active control conditions, leading to a loss of granularity AM and MS designed the study. All authors contributed to the
regarding potential differences in the efficacy between different active interpretation of the findings. AM and MS drafted the first version of the
treatment conditions. However, we separated TAU from active control manuscript, all authors critically revised it for important intellectual
treatments. Third, the number of studies and participants varied across content. All authors approve the final version of the work. All authors
interventions, comparisons, and outcomes. However, for transparency, agree to be accountable for all aspects of the work in ensuring that
we also reported how large the body of evidence was for each result. questions related to the accuracy or integrity of any part of the work are
Fourth, fewer data were available for long-term outcomes, which is a appropriately investigated and resolved.
17
Conflicts of interest Appendix A. Supporting information
CMB reports: Shire (grant recipient, Scientific Advisory Board Supplementary data associated with this article can be found in the
member); Idorsia (consultant); Lundbeckfonden (grant recipient); online version at doi:10.1016/j.neubiorev.2022.104857.
Pearson (author, royalty recipient); Equip Health Inc. (clinical advisory
board). PH receives/has received sessional fees and lecture fees from the References
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Neuroscience and Biobehavioral Reviews 142 (2022) 104857

Contents lists available at ScienceDirect

Neuroscience and Biobehavioral Reviews

Treatment of eating disorders: A systematic meta-review of meta-analyses

Fig. 1. PRISMA 2020 study selection flow diagram.

ACTIVE, TAU/ ACCEPT, BEHAV, EDP, GENSX,

3.1. Anorexia nervosa 3.1.1. Bulimia nervosa efficacy

F-QOL EDU S WL/NT 1 100% NS SMD ns MA 7/M

PHARMA I PBO 1 100% EFF MD 3.83 (1.43 – 6.24) NMA 6/M

PDO I TAU 1 100% NS SMD ns NMA 10 /

IPT I ACTIVE 1 100% NS MD ns MA 9/ H

WEIGHT/ CBT-ED S ACTIVE 1 100% NS SMD ns MA 7/M

Conflicts of interest Appendix A. Supporting information

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