World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders

Figures & data

Table 1. Depicts the results of the literature review of pharmacological studies in AN.

Author	Year	Mean age (age range)	N	Agent	Treatment setting	Study design	Randomisation	Placebo- controlled	Double- blind	Treatment duration	Weight gain	Favourable outcomes/ superiority to placebo	Unfavourable or non-significant outcomes	Psychotherapy
Antidepressants
Tricyclic antidepressants
Biederman et al.	1985	16.9 (11–27)	43	Amitriptyline up to 175 mg/day, mean 115 mg/day	Mixed	RCT	Yes	Yes	Yes	5 weeks	No	NR	No significant weight change, SADS-C, HSCL, EAT, GSS, GIS	Yes, mix of individualised, CBT and FBT
Halmi et al.*	1986	20.6 (13–36)	72	Amitriptyline max 160 mg/ placebo/ cyproheptadine max 32 mg	Inpatients	RCT	Yes	Yes	Yes	Up to 90 days	No	Cyproheptadine increased treatment efficiency (time to target weight) in AN-R and decreased treatment efficiency in AN-B/P	No significant weight change, BDI, HDRS, HSCL, AAS, ABS	No
Crisp et al.	1987	21.2 (NR)	16	Clomipramine 50 mg/day	Inpatients	RCT	Yes	Yes	NR	11 weeks	No	Initially, higher hunger and appetite	No significant weight change, sensation and emotions VASs	Yes, intensive individualised and FBT
Selective serotonin reuptake inhibitors (SSRIs)
Attia et al.	1998	26.2 (16–45)	33	Fluoxetine up to 60 mg/day if tolerated	Inpatients	RCT	Yes	Yes	Yes	Until goal weight maintained for 1 week or total of 7 weeks	No	NR	No significant weight change, HSCL-90, CGI, ABS, BDI, BSQ, EAT, YBC-EDS	Yes, individual psychotherapy including CBT
Kaye et al.	2001	22.5 (NR)	39	Fluoxetine 10-60 mg/day	Inpatients	RCT	Yes	Yes	Yes	Up to 12 months	Yes, for drug completers	Adherence to medication, at 1 year only; drug completers showed increases weight and reduced symptoms (HDRS, HARS, YBOCS, YBC-EDS)	NR	Yes, for inpatient phase and some of outpatient phase
Walsh et al.	2006	23.3 (16–45)	93	Fluoxetine up to 80 mg/day, usually 60 mg/day	Mixed	RCT	Yes	Yes	Yes	Up to 12 months	No	BAI	No significant weight change, time to relapse, EDI, BDI, RSE, YBC-EDS, QlesQ	Yes, manualized CBT for AN
Fassino et al.	2002	24.8 (16–35)	52	Citalopram 20 mg/day	Outpatients	RCT	Yes	No	No	12 weeks	No	BDI, HSCL-90 depression, obsessive-compulsive and somatisation subscales, EDI-2 ineffectiveness and impulsiveness subscales, STAXI tenemental anger	No significant weight change.	No
Luzier et al.	2019	13.5 (13–14)	2	Sertraline	Outpatients	Case report	No	No	No	NR	NA	Halt of relapse and reinduced remission	NR	No
Santonastaso et al.	2001	19.3 (14–34)	22	Sertraline 50–100 mg/day	Outpatients	Open trial	No	No	No	14 weeks	No	HSCL-58 depression, EDI interoceptive awareness, EDI ineffectiveness, EDI perfectionism	No significant weight change, other EDI subscales, HSCL-58 obsessive compulsive and anxiety symptoms	Yes, CBT
Other antidepressants
Naguy and Al-Mutairi	2018	16	1	Mirtazapine 30 mg/day	Outpatients	Case report	No	No	No	16 weeks	Yes	Weight gain, social and academic functioning	NR	Yes, CBT
Safer et al.	2011	50	1	Mirtazapine 30 mg/day	Outpatients	Case report	No	No	No	11 months	Yes	Weight gain and depression	NR	Yes, manualized CBT for AN and CBT for depression
Antipsychotics
Typical antipsychotics
Cassano et al.	2003	22.8 (NR)	13	Haloperidol 0.5–2 mg/day	Day program	Open trial	No	No	No	6 months	Yes	Weight gain, EDI (drive for thinness, bulimia and interoceptive awareness), EAT, CGI	NR	No
Mauri et al.	2013	25.8 (18–51)	9	Haloperidol 0.5–3.5 mg/day	Inpatients	Case series	No	No	No	During hospitalisation, up to 4 months	Yes	Weight gain, subjective clinical improvement in body image disturbance and drive for thinness	NR	No
Vandereycken	1984	23.5 (NR)	18	Sulpiride 300/400 mg/day	Inpatients	Double blind cross-over trial	Yes	Yes	Yes	3 weeks	No	NR	No significant weight change, EAT, BAT, ABSIO	Unclear, therapy given in later stage of admission
Vandereycken and Pierloot	1982	21.5 (15–36)	20	Pimozide 4–6 mg/day	Inpatients	Double blind cross-over trial	Yes	Yes	Yes	3 weeks	No	NR	Weight gain (trend only), ABSIO	Unclear, therapy given in later stage of admission
Atypical antipsychotics: olanzapine
Attia et al.	2011	27.7, >16	23	Olanzapine 2.5–10 mg/day	Outpatients	RCT	Yes	Yes	Yes	8 weeks	Yes	Weight gain	BAI, BDI, BSQ, EDI, YBC-EDS, PANSS	No
Attia et al.	2019	28 (18–65)	152	Olanzapine 2.5–10 mg/day	Outpatients	RCT	Yes	Yes	Yes	16 weeks	Yes	Weight gain	YBOCS, EDE, CES-D, Zung Anxiety Inventory, CGI	Possible, some patients may have been engaged and continued non-specific outpatient psychotherapy if they had not gained weight 4 weeks prior to recruitment
Ayyilduz et al.	2016	17	1	Olanzapine 5 mg/day	Inpatients	Case report	No	No	No	2 days	NA	NR	NMS developed after 2 days of treatment	Unclear
Bissada et al.	2008	26.8	34	Olanzapine 2.5–10 mg/day	Day program	RCT	Yes	Yes	Yes	10 weeks	Yes	Weight gain rate, target BMI reached, YBOCS obsessions	YBOCS compulsions, PAI	Unclear if psychotherapy is part of day program
Brambilla et al.	2007	25, >18	35	Olanzapine 2.5–5 mg/day	Outpatients	RCT	Yes	Yes	Yes	3 months	Yes, for AN-B/P	Weight gain for AN-B/P, YBC-EDS rituals, direct aggressiveness in BDRS and greater in AN-B/P, TCI persistence and greater in AN-R	EDI, YBC-EDS, HVA, HDRS, BDRS	Yes—CBT for AN
Haruta et al.	2014	36	1	Olanzapine 2.5 mg/day	Inpatients	Case report	No	No	No	22 days	NA	NR	Hypoglycaemia developed and was detected on day 22, blood glucose level 23	Yes, Unspecified
Kafantaris et al.	2011	17.1 (12.3–21.8)	20	Olanzapine 2.5–10 mg/day	Mixed	RCT	Yes	Yes	Yes	10 weeks	No	NR	No significant weight change, REE, RQ, EDE, YBC-EDS, HDRS, BPRS	Yes, individualised, FBT and multifamily group therapy
Leggero et al.	2010	13.7 (9.6-16.3)	13	Olanzapine 1.25–12.5 mg/day	NR	Open trial	No	No	No	6 months	Yes	Weight gain, CGAS, EAT-26, CGI-S, EDI interceptive awareness and impulsivity, CBCL, SIAB hyperactivity	EDI subscales	Yes, Unspecified
Marzola et al.*	2015	25.43 (NR)	75	Olanzapine and SSRI/aripiprazole and SSRI/SSRI	Inpatients	Retrospective case-control	No	No	No	NR	No	Greater reduction in YBC-EDS total and subscales in aripiprazole group compared to olanzapine and SSRI only. Decrease in purging in aripiprazole group vs. olanzapine group. Pre- and post-improvement in weight, HAM-A, HDRS	No significant weight change, No group effect for HAM-A, HDRS.	Yes, daily individual motivational and psychotherapy sessions, and weekly psycho-educational groups
Pruccoli et al.	2022	15.4	118	Olanzapine 3.4–4.4 mg/day	Inpatient and day care	Case control	No	No	No	NR	No	Low-dose olanzapine well tolerated. Improvement of BUT-GSI, BDI-II, and SAFA-D for all groups.	Full-dose olanzapine treated group experienced lower improvement in depressive measures: BDI-II and SAFA-D, than groups.	No
Spettigue et al.	2018	15.48 (11–17)	38	Olanzapine 2.5–15 mg/day	Mixed	Open trial	No	No	No	12 weeks trial, drug given until TGW achieved	Yes	Weight gain	Depression (CDI), Anxiety (MASC), EDI-3, EDEQ-A	Yes, individualised and FBT
Atypical antipsychotics: others
Frank	2016	13.25 (12–17)	4	Aripiprazole 1–5 mg/day	Mixed	Case series	No	No	No	1 month − 1 year	Yes	Weight gain, weight and shape concern, anxiety	NR	Yes, individualised, FBT and multifamily groups
Frank et al.	2017	14.52 (NR)	22	Aripiprazole 1–5 mg/day	Mixed	Retrospective case-control	No	Yes	No	NR	Yes	Weight gain	NR	No
Marzola et al.*	2015	25.43 (NR)	75	Aripiprazole and SSRI/SSRI/Olanzapine and SSRI	Inpatients	Retrospective case-control	No	No	No	NR	No	Greater reduction in YBC-EDS total and subscales in aripiprazole group compared to olanzapine and SSRI only. Decrease in purging in aripiprazole group vs. olanzapine group. Pre- and post-improvement in weight, HAM-A, HDRS	No significant weight change, No group effect for HAM-A, HDRS.	Yes, daily individual motivational and psychotherapy sessions, and weekly psycho-educational groups
Tahıllıoğlu et al.	2020	14.3 (11–17)	11	Aripiprazole 2.5–15 mg/day	Outpatients	Case series	No	No	No	18-28 months	Yes	weight, ED behaviours, BDI, CGI. Intervention effective: weight, ED behaviours, BDI, CGI.	One patient reported elevated appetite, one patient reported sedation	Yes, unspecified
Trunko et al.	2011	32 (15–55)	5	Aripiprazole 5–10 mg/day	NR	Case series	No	No	No	3 months and up	Yes	Weight gain, mood, anxiety, ED symptoms and rigidity	NR	Yes, Unspecified
Hagman et al.	2011	15.98 (12–21)	41	Risperidone 0.5–4 mg/day	Mixed	RCT	Yes	Yes	Yes	9 weeks	No	EDI interpersonal distrust subscale	No significant weight change, REE, EDI-2, MASC, BIS, CAPT, ADJ	No
Umehara et al.	2014	10	1	Risperidone 1mg/day, 12.5/2 weeks	Inpatients	Case report	No	No	No	1 month for oral admission, then 5 months for LA	Yes	Meal agitation and body image distortion decrease	NR	No
Powers et al.	2012	36 (18–65)	15	Quetiapine 177.7 mg/day (mean dose)	Outpatients	RCT	Yes	Yes	Yes	8 weeks	No	NR	No significant weight change, EDI, YBC-EDS, STAI, HDRS, PANSS	No
Ruggiero et al.	2001	24.11, >17	35	Amisulpride/ clomipramine/ fluoxetine	Inpatients	Head-to-head	Yes	No	No, single- blind	3 months	Yes, for amisulpride and fluoxetine, no between group difference		EDI	No
Antiepileptics and mood stabilisers
Gross et al.	1981	19.8 (12–32)	16	Lithium titrated to blood level of 0.9 mmol/liter	Inpatients	RCT	Yes	Yes	Yes	4 weeks	Only for week 3 and 4	Weight in weeks 3 and 4, denial score on GAAQ, selective appetite on PRS	Weight in weeks 1 and 2, GAAQ, HSCL, PRS	Yes, including behaviour modification treatment
Pruccoli and Parmeggiani	2022	15.9 (14–19)	14	Valproate 100–1000 mg/day	Inpatients	Case series	No	No	No	9 weeks	Yes	Weight gain	Somnolence	Yes, unspecified
Appetite modulators
Appetite stimulants
Andries et al.	2014	33 (>18)	25	Dronabinol (delta-9-tetrahydrocannabinol) 5 mg/day	Mixed	Double blind cross-over trial	Yes	Yes	Yes	4 weeks each	Yes	Weight gain, 20% increase in intensity of physical activity	EDI, duration of physical activity	Yes, unspecified
Gross et al.	1983	23.6 (NK)	11	Dronabinol (delta-9-tetrahydrocannabinol) 7.5–30 mg/day/diazepam 3–15 mg/day	Inpatients	Double blind cross-over trial	Yes	No—diazepam	Yes	4 weeks total, 2 weeks each drug	No	HSCL—somatisation, sleep disturbance and interpersonal sensitivity	No significant weight change, calorie intake	Yes, including individualised, group and CBT
Golberg et al.	1979	NR	81	Cyproheptadine 12–32 mg/day	Inpatients	RCT	Yes	Yes	Yes	NR	Only for severe AN: history of birth complications, significant weight loss or previous treatment failure		NR	Yes, drug given with or without CBT
Halmi et al.*	1986	20.6 (13–36)	72	Cyproheptadine max 32 mg/amitriptyline max 160 mg/placebo	Inpatients	RCT	Yes	Yes	Yes	Up to 90 days	No	Cyproheptadine increased treatment efficiency (time to target weight) in AN-R and decreased treatment efficiency in AN-B/P	No significant weight change, BDI, HDRS, HSCL, AAS, ABS	No
Opioid antagonists
Marrazzi et al.	1995	25.5 (20–36)	6	Naltrexone 200 mg/day	Outpatients	Double blind cross-over trial	Yes	Yes	Yes	6 weeks	No	Reduction in B/P symptoms	No significant weight change	Yes, unspecified
Hormonal and endocrine treatments
Gradl-Dietsch et al.	2022	15	1	Metreleptin 3–5.8 mg/d subcutaneously	4 days inpatients, then 5 days outpatients	Case report	No	No	No	9 days	Yes	Self-reported increments of appetite and hunger, improvement of eating disorder cognitions and depression	NR	No
Antel et al.	2022	16	1	Metreleptin 3–9 mg/d subcutaneously	Inpatients	Case report	No	No	No	10 days	Yes, after treatment period	Improvement of mood, eating disorder-related cognitions and hyperactivity	NR	No
Milos et al.	2022	17, 19, and 26	3	Metreleptin 2–11.3 mg/d	Inpatients	Case series	No	No	No	6–14 days	Yes, in 2 of 3 patients	Improvement of overactivity, repetitive thoughts of food, inner restlessness, weight phobia and depression	NR	No
Hill et al.	2000	14.8 (12–18)	15	rhGH 0.05 mg/kg/day	Inpatients	RCT	Yes	Yes	Yes	4 weeks or until discharge	No	Time to medical stability	No weight change, duration of hospitalisation	No
Fazeli et al.	2010	28 (18–45)	21	rhGH 15–36.6 μg/kg/day titrated by IGF-I level	Outpatients	RCT	Yes	Yes	Yes	12 weeks	No	NR	No significant weight change	No
Fazeli et al.	2018	28.9 (NR)	22	Relamorelin 100 μg/day	Outpatients	RCT	Yes	Yes	Yes	4 weeks	No (trend)	Decreased gastric emptying time	Weight change (trend only), VAS hunger scores, BDI-2	No
Haruta et al.	2015	38	1	GHRP-2	Inpatients	Case report	No	No	No	1 year	Yes	Weight, appetite, muscle strength, fatigue, GI functions, hypoglycaemia.	NR	Yes—CBT
Russell at al.	2018	23.2 (16–57)	41	Oxytocin 36 IU	Inpatients	RCT	Yes	Yes	Yes	4–6 weeks (2 studies)	No	Lower EDE eating concern for OT, lower perseverative errors in WCST for OT, lower salivary response in wait for afternoon snack	No significant weight change, EDE-global, AQ, Leibowitz, REMT	No
Kim et al.	2015	22.5, >17	115 (AN, BN, healthy)	Oxytocin 35.2 mg	Mixed	Double-blind crossover study single session	Yes	Yes	Yes	24 h		EDE-Q, BDI, STAI, Wechsler Adult Intelligence Scale	No effect on food consumption in AN group	No
Kimball et al.	2019	(18–45)	90	Transdermal testosterone, 300 μg daily	Research centre	RCT	Yes	Yes	Yes	24 weeks	No	Week 4 trend towards a greater decrease in HAM-D score. Testosterone is safe and well tolerated.	Mean BMI increased by 0.0 ±  1.0 kg/m^2. No significant differences in eating disorder scores.	No
Léger et al.	2021	13.7	14	GH injection 0.050 mg/kg/day	Outpatients	RCT	Yes	Yes	Yes	12 months	No	A median (25th–75th percentile) HV increase of 1.0 cm/year. The effect of GH treatment increase after 6 months with height gain of 9.65 cm after 12 months.	Treatment adverse effects including increased fasting insulinemia and HOMA-IR, increase in IGF-1 SDS in one patient and glucose intolerance at 12 months in one patient and one suicidal attempt.	No
Gastroprokinetic agents
Stacher et al.	1987	23.7 (18–35)	12	Cisapride 8 mg IV once	Inpatients	Double blind cross-over trial	Yes	Yes	Yes	Once	NR	Decreased gastric emptying time, increased antral contractile amplitude and decreased contraction frequency.	NR	No
Stacher et al.	1993 (19–34)	22.5 (NR)	12	Cisapride 30 mg/day	Outpatients	Double blind cross-over trial	Yes	Yes	Yes	6 weeks	No	Decreased gastric emptying time	No significant weight change, EDI, BDI, STAI	yes, individualised and group psychotherapy
Szmukler et al.	1995	21.9 (18–40)	29	Cisapride 30 mg/day	Inpatients	RCT	Yes	Yes	Yes	8 weeks	No	Subjective hunger and general improvement	Gastric emptying, weight, BDI	Yes, unspecified
Saleh and Lebwohl	1980	28.7 (18–49)	7	Metoclopramide 40 mg/day	NR	Open trial	No	No	No	1 month	No	Pre and post weight gain, decreased GI symptoms, increased gastric emptying, and decreased gastric retention	NR	NK
McCallum et al.	1985	20 (14–40)	16	Metoclopramide	Inpatients	Single session	No	No	No	Once	NA	Accelerated gastric emptying	NR	Yes, including behavioural modification
Russel at al.	1983	17	1	Domperidone 30 mg/day	Inpatients	Case report	No	No	No	14 days	No	Improved subjective satiety and accelerated gastric emptying	No significant weight change,	No
Nutritional supplements
Katz et al.	1987	16.42 (14–18)	15	Elemental zinc 50 mg/day	Mixed	RCT	Yes	Yes	Yes	6 months	No	STAI state anxiety, Zung depression scale	Weight, taste function, sexual maturation, skin abnormalities resolution	yes, including behavioural modification
Birmingham et al.	1994	22.3 (12–25)	35	Elemental zinc 14 mg/day	Inpatients	RCT	Yes	Yes	Yes	Until target weights reached (10% above baseline weight)	Yes	Increased weight gain	NR	Yes, including individualised and group psychotherapy and behavioural modification
Manos et al.	2018	14.7, <21	24	Omega-3 polyunsaturated fatty acid (PUFA)	Day program	RCT	Yes	Yes	Yes	12 weeks	No	NR	No significant weight change, EAT-26, CES-D, higher anxiety (BAIT) in PUFA group	No
Hart et al.	2021	13.5 (12–15)	2	Tyrosine (Amino Acid) 5 gr/day	Inpatients	Case report	No	No	No	12 weeks	Yes for 1 of the 2 participants	NA	No	No
Other medications
Steinglass et al.	2014	25.6 (18–60)	20	Alprazolam 0.75 mg pre-meal	Inpatients	Double blind cross-over trial	Yes	Yes	Yes	NR	NA	NR	Caloric intake, anxiety	No
Casper et al.	1987	NR (19–28)	4	Clonidine 150–500–700/micrograms/day	Inpatients	Cross-over study	Yes	Yes	NR	4 weeks each intervention	No	NR	No significant weight change, hunger or satiety sensations, MHPG levels, depression or anxiety	Yes, unspecified
Steinglass et al.	2007	27 (18–45)	14	d-cycloserin 50 mg before meal	Inpatients	RCT	Yes	Yes	Yes	4 sessions over 2 weeks, baseline assessment on admission, and FU 1 week after last training meal	No	NR	Caloric intake, BAI, sensations VASs, BDI (trend)	Yes, exposure therapy
Levinson et al.	2015	25.4 (14–49)	36	d-cycloserin 250 mg/day	Day program	RCT	Yes	Yes	Yes	4 sessions over 2 weeks, and another 1-month FU	Yes	Weight	Mealtime anxiety	Yes, exposure therapy
Okita et al.	2013	22.5 (NR)	2	Tandospirone 60 mg/day	Outpatients	Case series	No	No	No	6 months	Yes	Weight, EDE-Q	NR	No
Solmi et al.	2013	26	1	Adalimumab	Outpatient	Case report	No	No	No	9 months	Yes	Weight gain, resumption of menses at 9 months, decrease in weight and shape concern	NR	No
Scolnick et al.	2020	29	1	Ketamine 4 ketamine infusions over 4 days	Outpatient	Case report	No	No placebo controlled	No double blind, no multicentre	14 days	Yes	weight, mood, ED obsessions and behaviours	NR	No
Dechant et al.	2020	29	1	Ketamine 0.5 mg/kg IV	Outpatient	Case report	NA	NA	NA	5 weeks	NK	Suicidality and symptoms improvement. Treatment is more effective after weight restoration phase.	NR	No
Schwartz et al.	2021	49 and 30	4 (2 AN)	Ketamine 0.4 mg/kg IM, 0.5 mg/kg IM	Outpatients	Case series	NA	NA	NA	NR	Yes	Depression, ED symptoms, mood, energy, general wellbeing, BDI, anxiety, suicidality, BMI, hopelessness, food variety, anxiety related to eating certain foods, motivation and drive, STAI, regular menstrual periods	NR	Clinical management only
Mills et al.	1998	23–42	15	Ketamine, 20 mg/h for 10 h until patients appeared sedated	NK	Case series	NA	NA	NA	NK	Yes	Compulsion scores, sustained clinical response seen in improved eating behaviour and acceptance of increased weight.	Hallucinations in two patients In 80% of patients, treatment caused initially headache 30% had nausea but not severe	NK
Meta-analyses
Dold et al.	2015	24.1	201	Olanzapine (4) Quetiapine (2) Risperidone (1)	NR	Random effect model meta-analysis of 7 RCTs for SGAs and individual agents	NA	NA	NA	NA	No	NR	No significant between group difference when pooling the all SGAs or for individual SGAs—for BMI change or secondary outcomes	NA
Lebow et al.	2013	24.5	200	Olanzapine (5), Amisulpride (1), Risperidone (1)	NR	Random effect model meta-analysis of 7 RCTs	NA	NA	NA	NA	No	Beneficial effect for drugs over placebo for depression (2 studies included)	Nonsignificant increase in BMI with minimal inconsistency across studies and no effect of ED symptoms and cognitions.	NA
Kishi et al.	2012	NR	221	Olanzapine (4), quetiapine (1), risperidone (1), pimozide (1), sulpiride (1)	NR	Random effect model meta-analysis	NA	NA	NA	NA	No	Quetiapine better for eating attitudes and anxiety.	No significant difference in weight or questionnaire for depression, AN, body shape	NA
de Vos et al.	2014	>12	869	Antidepressants, Antipsychotics	In- and/or out-patients and/or others not reported	Meta-analysis	Yes	NA	NA	NR	Yes	Pharmacotherapy better than placebo pooled together ES 0.33 hormonal ES 0.42 significant but high heterogeneity	Antidepressant ES 0.26 non-significant, antipsychotic 0.25 non-significant	NA

NA: not applicable; NR: not reported; NK: not known; AAS: Anorectic Attitude Scale; ABS: Anorectic Behaviour Scale; ABSIO: Anorectic Behaviour Scale for Inpatient Observation; ADJ: adjustment; AN-B/P: anorexia nervosa binge-eating/purging type; AN-R: anorexia nervosa-restricting type; BAI: Beck Anxiety Inventory; BAT: burnout assessment tool; BDI: Beck’s Depression Inventory; BDI-II: Beck’s Depression Inventory-II; BDRS: Bipolar Depression Rating Scale; BIS: Barratt Impulsiveness Scale; BMI: Body Mass Index; BPRS: Brief Psychiatric Rating Scale; BSQ: Body Shape Questionnaire; BUT-GSI: Body Uneasiness Test, Global Severity Index; CAPT: Color-A-Person Test; CBCL: Child Behaviour Checklist; CDI: Children’s Depression Inventory; CES-D: Centre for Epidemiologic Studies Depression Scale; CGAS: Children Global Assessment Scale; CGI: Clinical Global Impression; CGI-S: Clinical Global Impressions-Severity of Illness Scale; EAT: Eating Attitude Test; EAT-26: Eating Attitude Test 26 items; EDE: Eating Disorder Examination; EDE-Q: Eating Disorder Examination-Questionnaire; EDEQ-A: Eating Disorders Examination Questionnaire-Adolescents; EDI: Eating Disorder Inventory; EDI-2: Eating Disorder Inventory version 2; EDI-3: Eating Disorder Inventory version 3; GIS: Global Improvement Scale; GSS: Gudjonosson Suggestibility Scale; HARS: Hamilton Anxiety Rating Scale; HDRS: Hamilton Depression Rating Scale; HSCL: Hopkins Symptom CheckList; HSCL-90: Hopkins Symptom Checklist 90 items; HSCL-58: Hopkins Symptom Checklist 58 items; HVA: Hazard and Vulnerability Assessment; LA: Long-Acting; MASC: Multidimensional Anxiety Scale for Children; NMS: Neuroleptic Malignant Syndrome; PAI: Personality Assessment Inventory; PANSS: Positive and Negative Syndrome Scale; QlesQ: Quality of Life, Enjoyment, and Satisfaction Questionnaire; RCT: Randomised Controlled Trial; REE: Resting Energy Expenditure; RQ: Respiratory Quotient; RSE: Rosenberg Self-Esteem scale; SADS-C: Schedule of Affective Disorders and Schizophrenia-Change in symptomology; SAFA-D: Self-Administered Psychiatric Scales for Children and Adolescents, Depression subtest; SIAB: Structure Interview for Anorexic and Bulimic disorders; STAXI: State-Trait Anger eXpression Inventory; TGW: Treatment Goal Weight; VAS: Visual Analogue Scale; YBC-EDS: Yale-Brown-Cornell Eating Disorder Scale; YBOCS: Yale-Brown Obsessive Compulsive Scale; CBT: cognitive behavioural therapy; FBT: family-based therapy.

Lightly shaded rows indicate the inclusion of children and adolescents. Mean and range of age were reported where available.

*Study mentioned twice in the table.

Table 3. Depicts the results of the literature review of pharmacological studies in BN.

Author	Year	Age (mean, range)	N	Agent	Treatment setting	Study design	Rando misation	Placebo- controlled	Double- blind	Treatment duration	Favourable outcome/superiority to placebo	Unfavourable or non-significant outcomes	Psychotherapy
Antidepressants
Tri- and tetracyclic antidepressants
Agras et al.	1987	30.9 (21–48)	22	Imipramine 300 mg/day	Mixed	RCT	Yes	Yes	Yes	16 weeks	Reduction in purging at 6 weeks and 16 weeks. BDI reduction at 6 weeks only	BDI: no significant difference at 16 weeks	No
Alger et al.*	1991	32.5 (NR)	69 (33 obese bingers, 22 BN)	Imipramine 200 mg/day, Naltrexone 100–150 mg/day	Mixed	RCT	Yes	Yes	Yes	8 weeks	Naltrexone reduced binge duration in BN; imipramine significantly reduced binge duration in obese bingers	No significant difference between treatment groups and placebo.	No
Mitchell et al.	1990	23.9 (18–40)	171	Imipramine 300 mg/day	Outpatients	RCT	Yes	Yes	Yes	12 weeks	Imipramine alone, imipramine with group therapy and placebo with group therapy all led to improvements in eating behaviours, HAM-D, HAM-A and global severity/improvement. Greater effects in all measures observed in group therapy alone compared to drug alone. Imipramine added to group therapy increased improvement of HAM-D, HAM-A and global severity/improvement.	NR	Yes, Intensive group treatment program, CBT, given with drug or placebo
Pope et al.	1983	27.7 (17–43)	22	Imipramine 200 mg/day	Outpatients	RCT	Yes	Yes	Yes	6 weeks	Binge frequency, binge intensity, preoccupation with food), subjective global improvement HAM-D	Self-control with food	No
Rothschild et al.	1994	32.8 (NR)	24	Imipramine 275 mg/day, Phenelzine 75 mg/day	Mixed	RCT	Yes	Yes	Yes	6 weeks	Phenelzine superior to imipramine and placebo in HAM-D and SCL-90-R overeating item. Phenelzine superior to imipramine and placebo (trend only) in binge/purge frequency		No
Agras et al.	1992	29.6 (18–65)	71	Desipramine 300-350 mg/day	Outpatients	Open trial	Yes	No	No	32 weeks	At 32 weeks, the combined (medication and CBT) 24-week treatment was superior to medication only given for 16 weeks, in reducing binges and purges. The combined treatment was superior to medication in reducing dietary preoccupation (16 weeks) and hunger inhibition (24 weeks).	No significant weight change	Yes, drug given with or without CBT
Agras et al.	1994	NR	61	Desipramine	NR	Open trial	Yes	No	No	24 weeks	At 16 weeks CBT or CBT with medication were superior to medication in binge frequency and purging.		Yes, CBT
Barlow et al.	1988	27.2 (NR)	47	Desipramine 150 mg/day	Outpatients	Double-blind crossover study	Yes	Yes	Yes	6 weeks	Binge frequency, vomiting frequency fatigue scale of the POMS	EDI, SCL-90	No
Blouin et al.*	1988	25.5 (20–30)	36	Desipramine 150 mg/day, Fenfluramine 60 mg/day	Volunteers	Double-blind crossover study	Yes	Yes	Yes	15 weeks	Both fenfluramine and desipramine were effective for binge frequency, vomiting frequency and psychological symptoms. Greater response rate to fenfluramine	NR	No
Hughes et al.	1986	25.4 (18–40)	22	Desipramine 200 mg/day	Outpatients	RCT	Yes	Yes	Yes	6 weeks	Binge frequency, Global clinical status, ZSRDS, BSS		No
Walsh et al.	1991	25.2 (18–45)	80	Desipramine 200–300 mg/day	Volunteers	RCT	Yes	Yes	Yes	8 weeks (acute treatment), 34 weeks (maintenance), 14 months (discontinuation)	Reduced binge frequency, improved EAT, BSQ, SCL-90 and trait STRAI at 8 weeks. Binge frequency	29% of participants in 16-week maintenance phase relapsed. Not enough participants in 6-month discontinuation phase.	No
Brambilla et al.*	1995	22 (17–29)	15	Amineptine 300 mg/day, Fluvoxamine 300 mg/day	Outpatients	Open trial	Yes	No	No	4 months	BITE symptoms, BITE gravity for both drugs	Global EDI scores, HAM-D, HAM-A, BMI	Yes, CBT
Mitchell and Groat	1984	25 (20–37)	32	Amitriptyline 150 mg	Outpatients	RCT	Yes	Yes	Yes	4 weeks	Depressive symptoms	Eating behaviour	YES, Minimal behavioural treatment program
Sabine et al.	1983	23.7 (16–65)	50	Mianserin 60 mg/day	Outpatients	RCT	Yes	Yes	Yes	8 weeks	NR	No significant differences between groups in HAM-D, HAM-A, EAT, BRS, weight	No
Selective serotonin reuptake inhibitors
Brambilla et al.*	1995	22 (17–29)	15	Fluvoxamine 300 mg/day, Amineptine 300 mg/day	Outpatients	Open trial	Yes	No	No	4 months	BITE symptoms, BITE gravity for both drugs	Global EDI scores, HAM-D, HAM-A, BMI	Yes, CBT
Fichter et al.	1996	Fluvoxamine: 25.3, placebo: 23.7 (18–50)	72	Fluvoxamine	NR	RCT	Yes	Yes	Yes	15 weeks	Binges in previous week, urges to binge, EDI-bulimia, SIAB total, fasting and vomiting subscales. scores.	EDI-total and SIAB bulimia subscale significant only in completer analysis and not in intention-to-treat	No
Schmidt et al.	2004	NR 18–50	267	Fluvoxamine 300 mg/day	Outpatients	RCT	Yes	Yes	Yes	8 weeks, 1 year	After 1 year, greater proportion of remission without additional psychotherapy for drug group.	No effects in bulimic or other symptoms at 8 or 1 year	Yes, CBT
Fichter et al.	1991	25.5 (NR)	40	Fluoxetine 60 mg/day	Inpatients	RCT	Yes	Yes	Yes	5 weeks	Weight reduction	No differences in eating behaviour and general psychopathology	Yes, intensive broad-spectrum behavioural treatment program
Fluoxetine Bulimia Nervosa Collaborative Study Group	1992	27.1 (>18)	270	Fluoxetine 60/20 mg/d	Outpatients	RCT	Yes	Yes	Yes	8 weeks	Binge frequency and vomiting frequency reduced with 60mg dose. Depression, carbohydrate craving, and pathologic eating attitudes and behaviours also improved with dose effect.	More adverse effects with fluoxetine: insomnia, nausea, asthenia, and tremor, without discontinuation	No
Goldbloom et al.	1997	25.8 (18–45)	76	Fluoxetine 60 mg/day	Outpatients	Open trial	Yes	No	No	14 weeks	Binge episodes, vomiting episodes and combined fluoxetine and CBT was superior to fluoxetine alone.	Binge-eating, vomiting, dietary restraint, mood and self-esteem similar among groups. No superiority for combined treatment over CBT.	Yes, CBT with or without medication
Goldstein et al.	1995	26.5 (>18)	398	Fluoxetine 60 mg/day	Outpatients	RCT	Yes	Yes	Yes	16 weeks	Binge-eating, vomiting, EDI, CGI, PGI	HAM-D	No
Jacobi et al.	2002	26 (18–65)	53	Fluoxetine 60 mg/day	Outpatients	Open trial	Yes	No	No	4 months	Binge-eating and vomiting improved in all groups. Similar improvement in psychopathology.		Yes, CBT with or without medication
Kotler et al.	2003	16.2 (12–18)	10	Fluoxetine 60 mg/day	Outpatients	Open trial	No	No	No	8 weeks	Weekly binge-eating episodes, weekly purge episodes, CGI-I scale.	NR	Yes, Supportive psychosocial treatment
Mitchell et al.	2001	26.6 (18–46)	91	Fluoxetine 60 mg/day	Outpatients	Open trial	Yes	Yes	No	4 weeks, 16 weeks	Both drug effect and self-manual effective in reducing binge-eating episodes at vomiting at 4 and 16 weeks. Additive effect for combined treatment. CGI and PGI improved only with fluoxetine, not with manual.	EDI, HAM-D, laxative abuse, diuretic abuse, and days fasting	Self-help manual with or without drug/placebo
Romano et al.	2002	29.7 (>18)	232	Fluoxetine 60 mg/day	Outpatients	RCT	Yes	Yes	Yes	8 + 52 weeks	Longer time to relapse with drug than placebo. Binging and vomiting episodes, CGI, YBC-ED	NR	No
Sysko et al.	2010	26.9 (17–63)	785	Fluoxetine 20/60 mg/day	Outpatients	Open trial	Yes	Yes	No	8 weeks	NR	Patients with BN who did not report a ≥60% decrease in the frequency of binge-eating or vomiting at week 3 were unlikely to respond to fluoxetine	No
Walsh et al.	2000	29.9 (NR)	22	Fluoxetine 60 mg/day	Mixed	RCT	Yes	Yes	Yes	8 weeks	Frequency of objective binge-eating episodes, frequency of purging, global EDE, TFEQ disinhibition score.		No
Leombruni, Amianto, et al.	2006	27.5 (NR)	37	Fluoxetine 20–60 mg/day vs. Citalopram 20–40 mg/day	Outpatients	Open trial	Yes	No	No	12 weeks	Vomiting, CGI and BSQ improved in both groups. BDI improved only with citalopram and anger introjection improved only with fluoxetine.	NR	No
Sundblad et al.	2005	27 (21–45)	46	Citalopram 40 mg/day, Flutamide 500 mg/day	Volunteers	RCT	Yes	Yes	Yes	12 weeks	Reduction in binge-eating with flutamide alone or combined flutamide and citalopram	No binge reduction with citalopram only or placebo	No
Milano et al.	2004	NR 24–36	20	Sertraline 100 mg/day	Outpatients	Open trial	Yes	Yes	No	12 weeks	Decrease in binge-eating episodes and purging episodes		No
Other selective monoamine reuptake inhibitors
Christensen and Averbuch	2009	35	1	Duloxetine 60 mg/day (12 weeks), then 30 mg/day (4 months)	Outpatient	Case report	No	No	No	12 weeks + 4 months	Single reported binge/purge episode over an entire month. No symptoms over 3 months period.		Yes, CBT
Hazen and Fava.	2006	33	1	Duloxetine 120 mg/day	Outpatient	Case report	No	No	No	16 weeks	Complete remission of the patient’s binge/purge symptoms and improvement in mood		No
El-Giamal et al.	2000	27.9 (19–53)	7	Reboxetine 8 mg/day	Outpatients	Case series	No	No	No	12 weeks	Binge-eating frequency, vomiting frequency, HAM-	Significant constipation in 2 patients leading to laxative use and dropout	No
Fassino et al.	2004	27.1 (NR)	28	Reboxetine 4 mg/day	Outpatients	Open trial	Yes	No	No	3 months	EDI-2 subscales, BSQ total, HAM-D, GAF	NR	No
Horne et al.	1988	NK	81	Bupropion	NR	RCT	Yes	Yes	Yes	8 weeks	Reduced binge-eating and purging episodes	Four subjects experienced grand mal seizures	No
Monoamine oxidase inhibitors
Carruba et al.	2001	25.4 (18–40)	78	Moclobemide 600 mg/day	Outpatients	RCT	Yes	Yes	Yes	6 weeks	NR	Binge-eating and vomiting episodes, HAM-D, BITE Symptoms, BITE Severity Scale.	No
Kennedy et al.	1988	26.4 (18–40)	18	Isocarboxazid 60 mg/day	Outpatients	Double-blind crossover study	Yes	Yes	Yes	13 weeks	Binge-eating and vomiting	Over 50% of patients decided to discontinue isocarboxazid 1 year after the study	No
Kennedy et al.	1993	26.7 (18–40)	36	Brofaromine 200 mg/day	Outpatients	RCT	Yes	Yes	Yes	8 weeks	Vomiting episodes, weight	binge-eating episodes, eating and shape attitudes, depression and anxiety	Yes, CBT
Rothschild et al.*	1994	32.8 (NR)	24	Phenelzine 75 mg/day, Imipramine 275 mg/day	Volunteers	RCT	Yes	Yes	Yes	6 weeks	Phenelzine superior to imipramine and placebo in HAM-D and SCL-90-R overeating item Phenelzine superior to imipramine and placebo (trend only) in binge/purge frequency		No
Walsh et al.	1984	26.5 (21–36)	35	Phenelzine 60–90 mg/day	Volunteers	RCT	Yes	Yes	Yes	10 weeks	Binge-eating episodes	NR	No
Walsh et al.	1988	27 (18–45)	62	Phenelzine 60–90 mg/day	Volunteers	RCT	Yes	Yes	Yes	8 weeks	Binge-eating frequency, EAT	HAM-D, BDI, SCL-90,	No
Other serotonergic antidepressants
Pope et al.	1989	26 (19–38)	46	Trazodone 400 mg/day	Volunteers	RCT	Yes	Yes	Yes	6 weeks	Frequency of binge-eating and vomiting patients’ subjective assessments of improvement	NR	No
Antipsychotics
Atypical antipsychotics
Trunko et al.	2011	33.6 (15–55)	8 (5 AN, 3 BN)	Aripiprazole 5–15 mg/day	Outpatients	Case series	No	No	No	>4 months	Improved eating disordered, behaviour, depression, anxiety, and cognitive flexibility	NR	No
Antiepileptics and mood stabilisers
Guerdjikova, Blom, Martens, et al.	2013	32.6 (21–39)	12	Zonisamide 100–600 mg/day	Volunteers	Open trial	No	No	No	12 weeks	Frequency of binge/purge episodes. CGI-S, YBOCS-BE (total, obsession, and compulsion), TFEQ (disinhibition and hunger), HAM-D.	Weight was unchanged	No
Hedges et al.	2003	29.0 (16–50)	69	Topiramate	NR	RCT	Yes	Yes	Yes	10 weeks	EDI, EAT, HAM-A, PGI	HAM-D	No
Hoopes et al.	2003	29.0 (16–50)	35	Topiramate	NR	RCT	Yes	Yes	Yes	10 weeks	Binge and purge frequency	NR	No
Nickel et al.	2005	21.3, >18	60	Topiramate 250 mg/day	Volunteers	RCT	Yes	Yes	Yes	10 weeks	Binge/purge episodes, weight, SF-36	NR	No
Hsu et al.	1991	25.4 (NR)	68	Lithium carbonate 600–1200 mg/day	Outpatients	RCT	Yes	Yes	Yes	8 weeks	NR	No significant effect on BN compared to placebo	No
Kaplan et al.	1983	24.7 (20–34)	6	Carbamazepine serum levels 6–10 mg/ml	Outpatients	Double-blind crossover trial	No	Yes	Yes	6 weeks	Only one patient with comorbid bipolar disorder improved	Five patients had either no response or an equivocal response	No
Trunko et al.	2014	17.8 (15–21)	2	Lamotrigine 75–400 mg/day	Mixed	Case series	No	No	No	5-48 months	Reduced binge/purge frequency, improved mood and functioning	NR	No
Trunko et al.	2017	30.1 (18–42)	14 (AN, BN)	Lamotrigine 100–300 mg/day	Mixed	Open trial	No	No	No	60 or more days	BEST, ZAN-BPD	EDE-Q, STAI, BDI-II	Yes, DBT
Anti-ADHD medication and stimulants
Guerdjikova and McElroy	2013	32 (NK)	1 BN	Methylphenidate 54–72 mg/day	Inpatient	Case report	No	No	No	1 year	Remission in binge/purge symptoms and improvement in ADHD after bipolar, substance use, and panic disorders were successfully treated with hospitalisation, intensive psychotherapy, quetiapine, and lamotrigine	NR	Yes, Psychosocial
Sokol et al.	1999	29 (20–38)	2	Methylphenidate 15/20 mg/day	Outpatients	Case report	No	No	No	4 days + 10 months	Decreased binging and purging	NR	No
Keshen et al.	2021	(18–55)	18	Lisdexamfetamine	Volunteers and outpatients	Open trial	No	No	No	8 weeks	Weight reduction, reduction in objective binge episodes and compensatory behaviours.	Increase in heart rate. 1 participant withdrawn for clinically significant weight loss.	NK
Appetite modulators
Appetite suppressants
Blouin et al.*	1988	25.4 (18–41)	36	Fenfluramine 60 mg/day, Desipramine 150 mg/day	Volunteers	Double-blind crossover study	Yes	Yes	Yes	15 weeks	Both fenfluramine and desipramine were also effective for binge frequency, vomiting frequency and psychological symptoms. Greater response rate to fenfluramine	NR	No
Fahy et al.	1993	24 (18–45)	43	d- Fenfluramine 45 mg/day	Outpatients	RCT	Yes	Yes	Yes	8 weeks	Binges, BITE symptom	'Weight, vomiting,, MADRAS, EAT, BITE severity	Yes, CBT
Ferreira et al.	2018	51	1	Sibutramine 180 mg/day	Outpatient	Case report	No	No	No	NR	NR	Recurrent psychotic symptoms following misuse of high dose sibutramine	No
Opioid antagonists
Alger et al.*	1991	32.5 (NR)	69 (33 obese bingers, 22 BN)	Naltrexone 100–150 mg/day, Imipramine 200 mg/day	Mixed	RCT	Yes	Yes	Yes	8 weeks	Naltrexone reduced binge duration in BNs	Binge frequency in BN and obese bingers	No
Huseman et al.	1990	NK	8	Naltrexone	NK	RCT	Yes	Yes	Yes	10 weeks	NR	No effect on frequency of binge/vomiting	No
Jonas and Gold	1988	NR	16	Naltrexone 100–300 mg/day	Outpatients	Open trial	Yes	No	No	6 weeks	Reduction of binge-eating and purging frequency in high-dose group only	HAM-D	No
Mitchell et al.	1989	23.7	19	Naltrexone 50 mg/day	Mixed	Double-blind crossover study	Yes	Yes	Yes	6 weeks	NR	No reduction in binge-eating and vomiting episodes	No
Hormonal and endocrine treatments
Kim et al.	2015	22.5, >17	115 (AN, BN, healthy)	Oxytocin 35.2 mg	Mixed	Double-blind crossover study single session	Yes	Yes	Yes	24 h	Decrease in calorie consumption over 24 h in patients with BN.	No effect on food consumption in AN group	No
Other serotonergic agents
Faris et al.	2000	29.1 (21–46)	26	Ondansetron 24 mg/day	Volunteers	RCT	Yes	Yes	Yes	6 weeks	Decreased binge and vomiting frequency, decreased time engaged in BN symptoms, increased normal meals and snacks consumption.	NR	No
Other medications
Broft et al.	2007	34.6 (25–43)	7 (4 BED, 3 BN)	Baclofen 60 mg/day	Outpatients	Open trial	No	No	No	10 weeks	Reduction in binge-eating frequency in patients with BED and BN	BDI	No
Guerdjikova, Blom, Mori, et al.	2013	32 (20–58)	8	N-acetylcysteine 600–2400 mg/day	Outpatients	Open trial	No	No	No	12 weeks	NR	Binge-purge episodes frequency, eating pathology, mood or clinical impression	No
Combinations
Sundblad et al.	2005	27 (21–45)	46	Citalopram 40 mg/day, Flutamide 500 mg/day	Volunteers	RCT	Yes	Yes	Yes	12 weeks	Reduction in binge-eating with flutamide alone or combined flutamide and citalopram	No changes in the groups given binge reduction with citalopram only or placebo	No
Meta-analyses
Bacaltchuk and Hay	2003	>18	NA	TCA’s, SSRIs, MAOI, and other ADs	NA	Systematic review and meta-analysis	NA	NA	NA	NA	Pooled relative risk for binge remission with drugs 0.87 similar efficacy among drug groups, fluoxetine had better patient acceptability	Ads (TCAs) treated patients has higher drop rate, more adverse drug effects in treated arm (antidepressants) causing treatment discontinuation.	No

NR: not reported; NA: not applicable; NK: not known; TCAs: tricyclic antidepressants; SSRIs: selective serotonin reuptake inhibitors; BDI: Beck Depression Inventory; BEST: Borderline Evaluation of Severity over Time; BITE: BN Investigation Test; BMI: Body Mass Index; BSQ: Body Shape Questionnaire; BSS: Bulimia Symptom Scale; BULIT: Bulimia Test; CGI: Clinical Global Impression Scale; CGI-I: Clinical Global Impressions-Improvement; EAT: Eating Attitudes Test; EDE: Eating Disorder Examination; EDI: Eating Disorder Inventory; EDI-2: Eating Disorder Inventory-2; FCI-II: Food Craving Inventory-II; GAF: Goldman’s Global Assessment of Functioning Scale; HAM-A: Hamilton Rating Scale for Anxiety; HAM-D: Hamilton Rating Scale for Depression; MADRS: Montgomery-Åsberg Depression Rating Scale; PGI: Patient’s Global Impression; POMS: Profile of Mood States; SCL-90: Symptom Checklist-90; SCL-90-R: Revised Form of the Hopkins Symptom Check List; SF-36: The Short Form Health Survey; SIAB: Structured Interview for Anorexia and Bulimia Nervosa; STAI: State-Trait Anxiety Inventory; STAXI: State-Trait Anger Expression Inventory; TFEQ: Three Factor Eating Questionnaire; VAS: Visual Analogue Scale; YBCEDS: Yale-Brown-Cornell Eating Disorder Scale; YBOCS: Young-Brown Obsessive-Compulsive Symptoms; YMRS: Young Mania Rating Scale; ZAN-BPD: Zanarini Rating Scale for Borderline Personality Disorder; ZSRDS: Zung Self-rated Depression Scale; CBT: cognitive behavioural therapy; DBT: dialectical behavioural therapy.

Lightly shaded rows indicate the inclusion of children and adolescent. Mean and range of age were reported where available.

*Study mentioned twice in the table.

Table 5. Depicts the results of the literature review of pharmacological studies in BED.

Author	Year	Age	N	Agent	Treatment setting	Study design	Rando misation	Placebo controlled	Double blind	Treatment duration	Positive outcomes/superior to placebo	Unfavourable or non-significant outcomes	Psychotherapy
Antidepressants
Tricyclic antidepressants
Alger et al.*	1991	32.5 (NR)	69 (33 obese bingers, 22 BN)	Imipramine 250 mg/day; Naltrexone 100–150 mg/day	Mixed	RCT	Yes	Yes	Yes	8 weeks	Imipramine significantly reduced binge duration in obese bingers. Naltrexone significantly reduced binge duration in BNs	Binge frequency in BN and obese bingers	No
Laederach- Hofmann et al.	1999	38.2 (20–60)	31 obese-BE	Imipramine 75 mg/day	Outpatients	RCT	Yes	Yes	Yes	8-week, 6 months (open phase)	Imipramine was superior to placebo in weight loss (8 weeks, 6 months). Imipramine was superior to placebo in reducing depression at follow-up (6 months)	depression (8 weeks) and frequency of BE	Yes, behavioural-oriented psychological support including individualised and group therapy
McCann and Agras	1990	NR	23 non-purging BN	Desipramine 100–300 mg/day	Volunteers	RCT	Yes	Yes	Yes	12 weeks	BE frequency, disinhibition, hunger, and restraint scores on TFEQ,	BDI, weight, BMI, BTS	No
Selective serotonin reuptake inhibitors
Arnold et al.	2002	41.9 (18–60)	60	Fluoxetine 20–80 mg/day	Outpatients	RCT	Yes	Yes	Yes	6-week	Frequency of BE, BMI, weight, CGI-S, HAM-D	NR	No
Devlin et al.	2005	43 (18–70)	116 Obese and overweight patients with BED	Fluoxetine 20–60 mg/day	Volunteers	RCT	Yes	Yes	Yes	20-week	Fluoxetine was effective in reducing depressive symptoms	CBT effective in reducing BE remission/frequency	Yes, fluoxetine/placebo with or without CBT
Devlin et al. (same study as Devlin et al. 2005)	2007	43 (18–70)	116	Fluoxetine 20–60 mg/day	Volunteers	RCT	Yes	Yes	Yes	5-month initial phase of treatment and 2-year maintenance phase	Fluoxetine effective in reducing depressive symptoms in follow‐up period	CBT effective in reducing BE remission/frequency in follow‐up period	Yes, fluoxetine/placebo with or without CBT
Grilo et al.	2006	44.0 (18–60)	108	Fluoxetine 60 mg/day	Outpatients	RCT	Yes	Yes	Yes	16-week	Rapid response related to better treatment outcome, CBT > fluoxetine	CBT superior to fluoxetine and placebo in BE remission/frequency No between group difference in rapid response	Yes, fluoxetine/placebo with or without CBT,
Grilo, Crosby, et al.	2012	44.2 (18–60)	81 overweight patients with BED	Fluoxetine 60 mg/day	Outpatients	RCT	Yes	Yes	Yes	12-month	NR	CBT with placebo or with fluoxetine superior to fluoxetine-only in BE remission/frequency, EDE-Q subscales and BDI. No added benefit to fluoxetine with CBT. No group difference in weight/BMI	Yes, fluoxetine with or without CBT, placebo with CBT
Grilo, Masheb, et al. (same study as Grilo et al. 2006)	2012	44.0 (18–60)	108	Fluoxetine 60 mg/day	Outpatients	RCT	Yes	Yes	Yes	16-week	Younger participants had greater binge-eating reduction with fluoxetine	Lower self-esteem, negative-affect, and overvaluation of shape/weight indicated better improvements with CBT	Yes, fluoxetine/placebo given with or without CBT
Grilo, Masheb, Wilson (same study as Grilo et al. 2006 and Grilo, Masheb, et al. 2012)	2005	44 (21–59)	108	Fluoxetine 60 mg/day	Outpatients	RCT	Yes	Yes	Yes	16-week	NR	CBT with placebo or with fluoxetine superior to fluoxetine-only/placebo	Yes, CBT
Leombruni et al.*	2008	NR (21–57)	42 obese-BED	Fluoxetine 40–80 mg/day; sertraline 100–200 mg/day	Outpatients	Randomised trial, but no placebo arm.	NR	NR	NR	24 weeks	Significant improvement in binge-eating and weight loss during treatment with both, sertraline and fluoxetine.	No difference between sertraline and fluoxetine groups.	NR
Marcus et al.	1990	39.0 (18–50)	45 obese (22 BE, 23 No—BE)	Fluoxetine 60 mg/day	Volunteers	RCT	Yes	Yes	Yes	52-week	Fluoxetine superior to placebo regarding weight loss	No drug effect on frequency of BE, BDI or EDI	Behaviour modification program with placebo/fluoxetine
Ricca et al.*	2001	25.9 (18–45)	108	Fluoxetine 60 mg/day; Fluvoxamine 300 mg/day	Outpatients	Open trial	Yes	No	No	24-week, 1 year	CBT + fluvoxamine superior to CBT + fluoxetine and fluvoxamine alone in EDE total scores. CBT, fluvoxamine, and CBT + fluvoxamine superior to fluoxetine and CBT + fluoxetine in STAI scores.	At 24 weeks all CBT groups superior to medications alone in binge-eating frequency, weight and EDE scores. BDI reduced in all groups. At 1 year FU EDE scores remained unchanged. BMI higher than at 24 weeks.	Yes, CBT with or without fluoxetine or fluvoxamine
de Zwaan et al.	1992	39 (19–54)	64 obese (22 with BE episodes	Fluvoxamine 100 mg	Outpatients	Open trial	No	Yes	No	NR	Greater improvement in HAM-D with fluvoxamine	Weight loss, BDI, BDQ,	Yes, CBT
Hudson et al.	1998	42 (18–60)	85	Fluvoxamine 50–300 mg/day	Outpatients	RCT	Yes	Yes	Yes	9 weeks	Reduction rate in frequency of binge-eating episodes, CGI improvement rate, BMI reduction rate	Rate of decrease in HAM-D	No
Pearlstein et al.	2003	41 (NR)	25	Fluvoxamine 239 mg/day	Volunteers	RCT	Yes	Yes	Yes	12 weeks	NR	No drug effect in any of the variables.	No
Grant et al.	2019	40 (18–65)	80	Vortioxetine 10–20 mg/day	Outpatients	RCT	Yes	Yes	Yes	12 weeks	Not superior to placebo	Most common adverse events includes nausea, dry mouth, headache and dizziness	No
Guerdjikova et al.	2008	38.9 (18–60)	44 BED and obesity	Escitalopram 10–30 mg/day	Outpatients	RCT	Yes	Yes	Yes	12-week	Weight reduction, BMI, frequency of BE, binge days and severity of BED	Obsessive-compulsive symptoms	No
McElroy et al.	2000	42.0 (18–60)	34	Sertraline 50–200 mg/day	Outpatients	RCT	Yes	Yes	Yes	6 weeks	Greater rates of decrease in frequency of BE episodes, decrease in severity of illness, increase in global improvement, and BMI reduction	NR	No
Leombruni et al.*	2008	NR (21–57)	42 obese-BED	Sertraline 100–200 mg/day; Fluoxetine 40–80 mg/day	Outpatients	Randomised trial, but no placebo arm.	NR	NR	NR	24 weeks	Improvement in binge-eating, weight loss, BES and BDI during treatment with both, sertraline and fluoxetine.	No difference between sertraline and fluoxetine group.	NR
Leombruni, Pierò, et al.	2006	41.3 (18–65)	32 obese (14 BED)	Sertraline 100 or 200 mg/day	Outpatients	Open trial	No	No	No	24 weeks	Improvement over time of binge frequency, weight loss, BES, BDI, CGI	NR	No
McElroy, Hudson, et al.	2003	NK	38	Citalopram 20–60 mg/day	Outpatients	RCT	Yes	Yes	Yes	6 weeks	Frequency of BE, binge days, BMI CGI-S, YBOCS-BE, HAM-D	NR	No
Other selective monoamine reuptake inhibitors
Malhotra et al.	2002	45.9 (28–68)	35 BED, overweight or obesity	Venlafaxine 75–300 mg/day	Outpatients	Case series	No	No	No	120 days	BE frequency, CGI-S, weight, BMI, waist circumference, and diastolic blood pressure	Dry mouth, sexual dysfunction, insomnia, and nausea	No
Silveira et al.	2005	33.3 (NR)	9 BED and obesity	Reboxetine 8 mg/day	Outpatients	Open trial	No	No	No	12 weeks	BE frequency, weight, BMI, BES, BES, CGI-S , WHOQOL-BREF improved in overall quality of life, general health, and psychological domain	NR	No
Antiepileptics and mood stabilisers
Appolinario et al.	2002	32.6 (NR)	8	Topiramate 150 mg/day	Outpatients	Open trial	No	No	No	16 weeks	BE frequency, BES, weight loss	Paraesthesia, fatigue, and somnolence	No
Claudino et al.	2007	NK (18–60)	73	Topiramate 200 mg/day	Outpatients	RCT	Yes	Yes	Yes	21 weeks	Weight loss, BE remission	BE frequency, BES scores, and BDI scores. Paraesthesia and taste disturbance	Yes, CBT with topiramate or placebo
Guerdjikova et al.	2005	47.3 (43–55)	3	Topiramate (after bariatric surgery) 25–1000 mg/day	Outpatients	Case report	No	No	No	10 months	Amelioration of BE symptoms and weight loss	NR	No
Kalaria et al. (article based on data from McElroy, Arnold, et al. 2003)	2020	40.8 (NR)	61 obese-BED	Topiramate 50-600 mg/day	Outpatients	RCT	Yes	Yes	Yes	14 weeks	The identified dose-response relationship demonstrated a daily dose of 125 mg needed to exhibit a marked reduction in BE frequency	NR	No
McElroy, Arnold, et al.	2003	40.8 (18–60)	61	Topiramate 25–600 mg/day	Outpatients	RCT	Yes	Yes	Yes	14 weeks	BE frequency (BMI, weight, CGI, Y-BOCS-BE	Headache (N = 3) and paraesthesia’s (N = 2)	No
McElroy, Hudson, et al.	2007	44.5 (18–65)	394	Topiramate 25–400 mg/day	Outpatients	RCT	Yes	Yes	Yes	16 weeks	BE frequency, BE remission, weight loss, BMI	Paraesthesia, upper respiratory tract infection, somnolence, and nausea	No
McElroy, Shapira, et al.	2004	40.9 (18–60)	43	Topiramate 25–600 mg/day	Volunteers	RCT	Yes	Yes	Yes	42 weeks	BE frequency	Nonadherence (N = 17) Adverse events (N = 14)	No
Guerdjikova et al.	2009	(18–65)	51	Lamotrigine	Outpatients	RCT	Yes	Yes	Yes	16 weeks	BE frequency, CGI-S, YBOCS-BE, MADRS, EDE-Q, BIS, TFEQ	Significant reduction in fasting levels of glucose, insulin, and triglycerides	No
Guerdjikova, Blom, Martens, et al.	2013	32.6 (21–40)	12 BN	Zonisamide 420 mg/day	Volunteers	Open trial	No	No	No	NR	BE frequency, weight loss, BMI, Y-BOCS-BE, TFEQ	Weight loss, high discontinuation rate. Panic attacks (N = 1)	No
McElroy et al.	2006	NK	60 BED	Zonisamide 100–600 mg/day	Outpatients	RCT	Yes	Yes	Yes	16 weeks	BE frequency, weight loss, BMI, CGI-S, Y-BOCS-BE, TFEQ	Bone fracture (N = 2), psychological complaints (N = 2), and cognitive complaints (N = 2)	No
McElroy, Kotwal, et al.	2004	36.8 (18–60)	15	Zonisamide 100–600 mg/day	Outpatients	Open trial	No	No	No	12 weeks	BE frequency, BMI, weight, CGI-S, YBOCS-BE total scores, and TFEQ hunger and disinhibition scores.	NR	No
Ricca et al.	2009	35.4 (18–60)	28 BED (subthreshold too)	Zonisamide	NR	Open trial	No	No	No	24 weeks, 1 year	24 weeks: BES, BMI, EDE-Q total, BDI 1 year: BMI, BE frequency, BES, EDE-Q restraint, STAI	NR	Yes, CBT groups with or without zonisamide
Anti-ADHD medication and stimulants
Guerdjikova et al.	2016	37.7 (18–55)	50	Lisdexamfetamine 20–70 mg/day	Outpatients	RCT	Yes	Yes	Yes	12-week	Longitudinal analysis: BMI, fasting triglycerides Endpoint: BE frequency, BMI	Longitudinal analysis: BE frequency, CGI-S, YBOCS-BE Endpoint analysis: CGI, YBOCS-BE. Serious cardiovascular event.	No
Hudson et al.	2017	38.7 (18–55)	275 Lisdexamfetamine responders	Lisdexamfetamine 50–70 mg/day	Volunteers	RCT	Yes	Yes	Yes	26-week	Lisdexamfetamine superior to placebo regarding time to relapse	NR	No
McElroy et al.	2016	37.9 (18–55)	745	Lisdexamfetamine 50–70 mg/day	Volunteers	RCT	Yes	Yes	Yes	11-week	Change in BE, BE cessation, weight, CGI-I, YBOCS-BE, blood triglycerides	TEAEs 1% placebo, 0.6–1.6% LDX	No
McElroy et al.	2015	38.7 (18–55)	255	Lisdexamfetamine 30–70 mg	Volunteers	RCT	Yes	Yes	Yes	11-week	BE frequency (50 mg, 70 mg), BE cessation (50 mg, 70 mg), weight, CGI-I, TFEQ, BES, YBOCS-BE	BE frequency (30 mg) BE cessation (30 mg) HAM-A, MADRS. TEAEs: 59% placebo, 81–86% LDX	No
McElroy, Guerdjikova, et al.	2007	43.1 (18–65)	40	Atomoxetine 40–120 mg/day	Outpatients	RCT	Yes	Yes	Yes	10 weeks	BE frequency, weight, BMI, CGI-S, YBOCS-BE TFEQ hunger subscale	Increased depressive symptoms (N = 1), constipation (N = 1), and nervousness (N = 1)	No
Grilo et al.	2021	37.6	491	Dasotraline 4 or 6 mg/d.	Outpatients	RCT	Yes	Yes	Yes	12 weeks	Endpoint: Treatment associated with significant improvement in the number of binge-eating days/week on the dose of 6 but not 4 mg/d. Improvement observed for 6 and 4 mg/d, respectively on several measures of BED psychopathology	The most common adverse events were insomnia, dry mouth, headache, decreased appetite, nausea, and anxiety	No
McElroy et al.	2020	38.3 (18–55)	315	Dasotraline 4, 6, or 8 mg/d	Outpatients	RCT	Yes	Yes	Yes	12 weeks	Treatment with dasotraline was associated with a significantly greater reduction in binge-eating days/week and led to 4 weeks cessation of binge-eating	The most common adverse events were insomnia, dry mouth, decreased appetite, and anxiety. Discontinuation was due to adverse events occurred in 11.3% of treated patients.	No
Quilty et al.	2019	(18–50)	49	Methylphenidate	Outpatients	Randomised trial	Yes	No	No	12 weeks	Greater BMI decrease with methylphenidate	Similar results with CBT and methylphenidate in objective and subjective BE, BES, QOLI	Yes, as a comparison group
Appetite modulators
Appetite suppressants
Appolinario et al.	2003	35.9 (18–60)	60	Sibutramine 15 mg/day	Outpatients	RCT	Yes	Yes	Yes	12 weeks	BE frequency, weight loss, BES, BDI	Dry mouth and constipation	No
Bauer et al.	2006	41.9 (18–75)	73 obese (29 subclinical BED)	Sibutramine 10–15 mg/day	Volunteers	RCT	Yes	Yes	Yes	16 weeks	BWL programs + Sibutramine superior to BWL in weight loss	Binge frequency	Yes, cognitive-behavioural weight loss, BWL
Grilo et al.	2014, 2015	43.9 (18–65)	104 obese-BED	Sibutramine 15 mg/day	Volunteers	RCT	Yes	Yes	Yes	16 weeks	Weight loss	BE remission an frequency, EDE, BDI	Yes, self-help, CBT, shCBT with and without sibutramine/placebo
Milano et al.	2005	NR (24–36)	20	Sibutramine 10 mg/day	Outpatients	RCT	Yes	Yes	Yes	12 weeks	BE frequency, weight loss	Dry mouth and constipation	No
Wilfley et al.	2008	41.9 (18–65)	304	Sibutramine 15 mg/day	Volunteers	RCT	Yes	Yes	Yes	24 weeks	BE frequency, weight loss, BMI, BE frequency, weight, TFEQ disinhibition and hunger subscales abstinence from BE	TFEQ cognitive restraint subscale, quality-of-life. Sibutramine was associated with significantly higher incidence of headache, dry mouth, constipation, insomnia, and dizziness	No
Stunkard et al.	1996	NR	28	d-Fenfluramine 15 mg/day	Volunteers	RCT	Yes	Yes	Yes	8 weeks	Patients on d-fenfluramine three times more rapidly in remission of BE than those on placebo	Increase of binge frequency at 4-mounth follow-up	No
Opioid Antagonists
Alger et al.*	1991	32.5 (NR)	69 (33 obese bingers, 22 BN)	Naltrexone 100–150 mg/day; Imipramine 250 mg/day	Mixed	RCT	Yes	Yes	Yes	8 weeks	Imipramine significantly reduced binge duration in obese bingers Naltrexone significantly reduced binge duration in BNs	Binge frequency in BN and obese bingers	No
GLP-1 agonists
Robert et al.	2015	34 (NR)	44 obese-BE	Liraglutide 1.8 mg	Volunteers	Open trial	Yes	No	No	12 weeks	Liraglutide group showed improvement in BES, weight, BMI, waist circumference, systolic blood pressure, fasting glucose and total cholesterol. Ghrelin levels were significantly increased	BES improved with placebo	No
GABAergic medications
Broft et al.	2007	31.7 (18–45)	7 (4 BED, 3 BN)	Baclofen 60 mg/day	Volunteers	Open trial	No	No	No	10 weeks	Baclofen reduced BE frequency, food craving	Weight, BDI	No
Corwin et al.	2012	NR	12	Baclofen 60 mg/day	Volunteers	Crossover	No	Yes	Yes	48 days	BE frequency	Increase in depression symptoms (HADS), FMDF, BES, FC-II, weight Tiredness, fatigue and upset stomach	No
de Beaurepaire et al.	2015	50.2 (42–60)	5	Baclofen 50–180 mg/day	Outpatients	Case series	No	No	No	NR	All the patients reported that baclofen suppressed their craving for food. All patients lost weight	Hypomania (n = 1)	No
Ricoux et al.	2019	60	1	Baclofen 70–300 mg/day	Outpatient	Case report	No	No	No	NR	BE frequency, weight loss	Distorted perception of time, cognitive disorders, intermittent short-term memory loss, and irritability, delusions, aggressiveness	No
McElroy et al.	2011	45.1 (21–65)	10	Sodium Oxybate 7.1 g/day	Volunteers	Open trial	No	No	No	22 weeks	BE frequency, binge days, weight, BMI, CGI-S, CGI-I, YBOCS-BE, TFEQ, FCI	MADRS Insomnia and racing thoughts, chest pain (N = 1), headache and paraesthesia (N = 1)	9 received psychotherapy
Intestinal enzyme blockers
Grilo and White	2013	46.32 (21–65)	79 (40 obese-BED, 39 obese no-BED)	Orlistat 360 mg/day	Inpatients	RCT	Yes	Yes	Yes	4 months	Orlistat-plus-BWL produced significantly greater weight-loss in non-BED group and a moderate weight loss in BED group	The addition of orlistat to BWL was not associated with greater improvements in BED group. No drug effect for EDE, BDI	No (but addition of behavioural weight loss, BWL)
Grilo, Masheb, Salant	2005	47.0 (35–60)	50	Orlistat 360 mg/day	Volunteers	RCT	Yes	Yes	Yes	12 weeks	BE remission rates higher for orlistat + CBTgsh than placebo + CBTgsh at posttreatment but not at 3-month follow-up 5% weight loss higher for orlistat + CBTgsh than placebo + CBTgsh at posttreatment and 3-month follow-up	NR	Yes, CBT delivered as guided self-help, CBTgsh
Golay et al.	2005	40.9 (18–65)	89	Orlistat 360 mg/day	Outpatients	RCT	Yes	Yes	Yes	24 weeks	Weight loss, EDI-2	NR	No
Combinations
Grilo, Lydecker, et al.	2021	50.4 (18–65)	22	Naltrexone 50 mg and bupropion 300 mg	Outpatients	RCT	Yes	Yes	Yes	12 weeks	The percentage of patients who attained 3% weight loss was significantly greater in patients treated with naltrexone/bupropion than with placebo (45.5 vs. 0%).	most outcomes (binge-eating, eating-disorder psychopathology, depression) were not statistically different from placebo.	No
Guerdjikova et al.	2018	45.3 (28–57)	10 BED, obese or overweight	Phentermine 3.75–7.5mg/day; Topiramate 23–46mg/day	Volunteers	Open trial	No	No	No	12 weeks	BE frequency, CGI-S, weight, EDE-Q, YBOCS-BE	Dysgeusia	No
Safer et al.	2020	42.9 (18–60)	22 (18 BED, 4 BN)	Topiramate 23–92 mg/day, Phentermine 3.75–15 mg/day	Outpatients	Double-blind crossover study	Yes	Yes	Yes	34 weeks	BE days, weight, EDE-Q global, eating and shape concern subscales, TFEQ hunger subscale, PHQ-9,	EDE-Q dietary restraint and weight concern subscales, TFEQ cognitive restraint and disinhibition subscale	No

NR: not reported; NA: not applicable; BDI: Beck Depression Inventory; BDQ: Body Distortion Questionnaire; BE: Binge-eating; BES: Binge-eating Scale; BMI: Body Mass Index; BTS: BN Thoughts Scale; BWL: behavioural weight loss treatment; CBT: cognitive behavioural therapy; CGI: Clinical Global Impression Scale; CGI-S: Clinical Global Impressions-Severity of Illness Scale; EDE: Eating Disorder Examination; EDE-Q: Eating Disorder Examination-Questionnaire; EDI: Eating Disorder Inventory; EDI-2: Eating Disorder Inventory-2; FCI: Food Craving Inventory; gsh-CBT: guided self-help CBT; HAM-D: Hamilton Rating Scale for Depression; STAI: State-Trait Anxiety Inventory; TEAEs: treatment-emergent adverse events; TFEQ: Three‐Factor Eating Questionnaire; WHOQOL-BREF: World Health Organisation Quality of Life Assessment Scale; YBOCS-BE: Yale-Brown Obsessive Compulsive Scale Modified for BE.

Mean and range of age were reported where available.

*Study mentioned twice in the table.

Table 7. Depicts the results of the literature review of pharmacological studies in ARFID.

Author	Year	Mean age (age range)	N	Agent	Treatment setting	Study design	Rando misation	Placebo- controlled	Double- blind	Treatment duration	Weight gain	Favourable outcomes/superiority to placebo	Unfavourable or non-significant outcomes	Psychotherapy
Antidepressants
Mirtazapine
Gray et al.	2018	15.2 ± 5.5 (7–23)	14	Mirtazapine 25.5 ± 17.9 mg	Outpatients	Retrospective chart review Case series	NA	NA	NA	13.7 ± 5.2 weeks	Yes	Average change in BMI after starting olanzapine significantly higher than pre-treatment BMI change	Drowsiness, Sedation and anxiety	No
Naviaux	2019	12	1	Mirtazapine 7.5 mg	Inpatient	Case report	NA	NA	NA	NR	No	Fluctuating weight gain and loss	NR	Family-based therapy
Naguy A. et al.	2021	15	1	Mirtazapine 7.5 mg	Outpatient	Case report	NA	NA	NA	NR	Yes	Improvement in eating patterns, weight, mood, phobic avoidance, glycemic control, and socialisation	NR	Dialectical behavioural therapy
Selective serotonin reuptake inhibitors (SSRIs)
Mahr et al.	2022	NK	53	SSRIs	NK	Retrospective chart review	NA	NA	NA	NR	Yes	Improvement in weight, eating behaviours, mood, anxiety and fear of food	NK	NK
Spettigue W. et al.	2018	12.9 ± 1.13	6	Fluoxetine 10–40 mg, Olanzapine 2.5–7.5 mg cyproheptadine 2–4 mg and fluvoxamine 25 mg.	Inpatients	Case report	NA	NA	NA	NA	Yes	Improvement in weight and anxiety	NR	Family therapy and cognitive behavioural therapy
Dolman et al.	2021	11	1	Sertraline 25–75 mg, olanzapine 0.625–5 mg	Inpatient	Case report	Na	NA	NA	7 weeks	Yes	Improvement in weight and dietary patterns,	NR	Cognitive behavioural therapy and family-based therapy
Antipsychotics
Atypical antipsychotics
Brewerton and D’Agostino	2017	14.4 ± 4.1 (9–19)	9	Olanzapine	Inpatients	Case series	NA	NA	NA	53.4 ± 22.4 days	Yes	Improvement in weight, anxiety, depressive symptoms and cognitive functioning.	NR	Structured behavioural therapy
Spettigue W. et al.	2018	12.9 ± 1.13	6	Olanzapine 2.5–7,5 mg/day, fluoxetine 10–40 mg/day, cyproheptadine 2–4 mg and fluvoxamine 25 mg/day.	Inpatients	Case report	NA	NA	NA	NA	Yes	Improvement in weight and anxiety	NR	Family therapy and cognitive behavioural therapy
Dolman et al.	2021	11	1	Olanzapine 0.625–5 mg/day and sertraline 25–75 mg/day	Inpatient	Case report	Na	NA	NA	7 weeks	Yes	Improvement in weight and dietary patterns	NR	Cognitive behavioural therapy and family-based therapy
Appetite modulators
Appetite stimulants
Spettigue W. et al.	2018	12.9 ± 1.13	6	Cyproheptadine 2–4 mg/day, olanzapine 2.5–7.5 mg/day, fluoxetine 10–40 mg/day and fluvoxamine 25 mg/day.	Inpatients	Case report	NA	NA	NA	NA	Yes	Improvement in weight and anxiety	NR	Family therapy and cognitive behavioural therapy

NR: not reported; NA: not applicable; NK: not known.

Lightly shaded rows indicate the inclusion of children and adolescent. Mean and range of age were reported where available.

Table 9. Depicts the results of the literature review of pharmacological studies in Pica.

Author	Year	Mean age (age range)	N	Agent	Treatment setting	Study design	Rando misation	Placebo- controlled	Double- blind	Treatment duration	Weight gain	Favourable outcomes/superiority to placebo	Unfavourable or non-significant outcomes	Psychotherapy
Antidepressants
SSRIs
Fekih-Romdhane and Cheour	2022	17	1	Paroxetine 20 mg/day	Outpatient	Case report	NA	NA	NA	6 months	NR	Pica was resolved, depression and anxiety symptoms improved	Remained at risk for psychosis	CBT
Choure et al.	2006	13	1	Fluoxetine 10 mg/day.	Outpatient	Case report	NA	NA	NA	4 weeks	NR	Complete remission of pica and depression	NR	Psychodynamic psychotherapy
Bhatia and Gupta	2009	35	1	Escitalopram 5 mg/day and clonazepam 0.25 mg/day	Outpatient	Case report	NA	NA	NA	3 weeks	NR	Improvement in mood and pica symptoms	NR	No
Upadhyaya and Sharma	2012	26	1	Fluoxetine 40 mg/day	Outpatient	Case report	NA	NA	NA	3 months	NR	Improvement after treatment targeted for OCD, and not pica.	NR	No
Kanamori et al.	2021	80	1	Fluvoxamine 75 mg and trazodone 50 mg/day	Inpatient	Case report	NA	NA	NA	NR	NR	complete remission from pica symptoms	NR	No
Antipsychotics
Atypical antipsychotics
You et al.	2021	34	1	Paliperidone 234 mg IM and olanzapine 10–20 mg/day	Inpatient	Case report	NA	NA	NA	NR	NR	Improvement of psychotic symptoms as well as resolution of pica.	NR	No
Peña-Salazar and Kazah	2020	27	1	Lithium 1200 mg/day, olanzapine 25 mg/day and topiramate 450 mg/day	NR	Case report	NA	NA	NA	3 months	NR	Decreased severity and frequency of pica	Achypsychia, tachylalia, hyperthymia, inappropriate laughing, increased socialisation, and decreased need for sleep	No
Hergüner and Hergüner	2016	17	1	Risperidone 1 mg/day and afterwards aripiprazole 7.5 mg/day	Outpatient	Case report	NA	NA	NA	3 weeks	NR	Decrease in disruptive and compulsive behaviours, and complete resolution of pica symptoms	No side effects reported with aripiprazole	No
Antiepileptics and mood stabilisers
Peña-Salazar and Kazah	2020	27	1	Topiramate 450 mg/day, lithium 1200 mg/day and olanzapine 25 mg/day	NR	Case report	NA	NA	NA	3 months	NR	Decreased severity and frequency of pica	Disturbance of the perception of time, tachylalia, hyperthymia, inappropriate laughing, increased socialisation, and decreased need for sleep	No
Benzodiazepines
Bhatia and Gupta	2009	35	1	Clonazepam 0.25 mg/day and escitalopram 5 mg/day	Outpatient	Case report	NA	NA	NA	3 weeks	NR	Improvement in mood and pica symptoms	NR	No
Anti-ADHD medication and stimulants
Hergüner and Hergüner	2010	8	1	Methylphenidate	Outpatient	Case report	NA	NA	NA	3 weeks	NR	complete resolution of pica symptoms	NR	No

NR: not reported; NA: not applicable; CBT: cognitive behavioural therapy.

Mean and range of age were reported where available.

Lightly shaded rows indicate the inclusion of children and adolescents.

Table 11. Depicts the results of the literature review of pharmacological studies in rumination disorder.

Author	Year	Mean age (age range)	N	Agent	Treatment setting	Study design	Rando misation	Placebo- controlled	Double- blind	Treatment duration	Weight gain	Favourable outcomes/ superiority to placebo	Unfavourable or non-significant outcomes	Psychotherapy
Antipsychotics
Typical antipsychotics
Lee et al. (2007)	2017	41.9 ± 2.6	21	Levosulpiride 25 mg three times a day	Outpatients	Open prospective study	NA	NA	NA	7.9 ± 0.9 months	NR	Improvement was reported by 38%	NR	Yes, psychotherapy
GABAergic medications
Pauwels et al. (2018)	2018	18–61	20	Baclofen 10 mg three times a day	Outpatients	RCT	Yes	Yes	Yes	2 weeks	NR	Reduction in postprandial manometry and symptoms improvement in 63%	NR	No

NR: not reported; NA: not applicable.

Mean and range of age were reported where available.

Table 2. Anorexia nervosa: level of evidence (LoE) and grade of recommendation (GoR).

	LoE			GoR
Medication	Evidence that the intervention is effective	No sufficient evidence	Evidence that the intervention is NOT effective	Recommendation for using the intervention	No recommendation possible	Recommendation AGAINST using the intervention
Antidepressants
Tricyclic antidepressants
Amitriptyline			−A			−1
Clomipramine			−B			−2
Selective serotonin reuptake inhibitors
Fluoxetine			−A			−1
Citalopram			−B			−2
Sertraline		D			4
Other antidepressants
Mirtazapine	C2			3
Antipsychotics
Typical antipsychotics
Haloperidol	C2			3
Sulpiride			−B			−2
Pimozide			−B			−2
Atypical antipsychotics
Olanzapine	A^a			2
Aripiprazole	C1			3
Risperidone			−B			−2
Quetiapine			−B			−2
Amisulpride		D			4
Antiepileptics and mood stabilisers
Lithium	B			3
Valproate	C2			3
Appetite modulators
Appetite stimulants
Delta-9-tetrahydrocannabinol/dronabinol	B			2
Cyproheptadine	B			3
Opioid antagonists
Naltrexone		D			4
Hormones and endocrine medication
Metreleptin	C1			3
rhGH			−A			−1
Relamorelin	C1				4	−2
GHRP-2	C2			3
Oxytocin		D			4	−2
Testosterone			−B			−2
Gastroprokinetic agents
Cisapride			−A			−1
Metoclopramide	C2^b			3^b
Domperidone	C2^b			3^b
Nutritional supplements
Zinc		D			4
Polyunsaturated fatty acids			−B			−2
Tyrosine	C2			3
Other medications
Alprazolam		D			4
Clonidine			−C2			−3
D-cycloserin		D			4
Tandospirone	C2			3
Adalimumab	C2^c			3^c
Ketamine	C2			3

The row for olanzapine is shaded green, because this is the best possible recommendation for AN. Olanzapine has the highest evidence for the treatment of AN among the tested medications. Due to its limited acceptability and adherence, the recommendation is, however, limited.

LoE: A: Strong evidence that the intervention is effective; B: Limited evidence that the intervention is effective; C(1–3): Low evidence that the intervention is effective; D: No evidence; −A: Strong evidence that the intervention is NOT effective; −B: Limited evidence that the intervention is NOT effective; −C(1–3): Low evidence that the intervention is NOT effective.

GoR: 1: Strong recommendation for using the intervention; 2: Limited recommendation for using the intervention; 3: Weak recommendation for using the intervention; 4: No recommendation possible; −1: Strong recommendation AGAINST using the intervention; −2: Limited recommendation AGAINST using the intervention; −3: Weak recommendation AGAINST using the intervention.

Please note: For details regarding the grading of LoE and GoR see text. The grading was performed according to Hasan et al. (2019).

^aEvidence is restricted to adult patients and refers to weight gain only, not to psychopathological improvement.

^bEvidence and recommendation refer to treatment of fullness and delayed gastric emptying in AN, not weight gain or other DSM-5 symptoms of AN.

^cEvidence and recommendation limited to patients with AN and Crohn’s disease. Green shading: Best possible recommendation for AN.

Table 4. Bulimia nervosa: level of evidence and grade of recommendation.

	LoE			GoR
Medication	Evidence that the intervention is effective	No sufficient evidence	Evidence that the intervention is NOT effective	Recommendation for using the intervention	No recommendation possible	Recommendation AGAINST using the intervention
Antidepressants
Tri- and tetracyclic antidepressants
Imipramine		D			4
Desipramine	A			3
Amineptine		D			4
Amitriptyline			−B			−2
Mianserin			−B			−2
Selective serotonin reuptake inhibitors
Fluvoxamine		D			4
Fluoxetine	A			1
Citalopram			−B			−2
Sertraline	C1			3
Other selective monoamine reuptake inhibitors
Duloxetine	C2			3
Reboxetine	C1			3
Bupropion	B					−2
Monoamine oxidase inhibitors
Moclobemide			−B			−2
Isocarboxazid	B			2
Brofaromine			−B			−2
Phenelzine	B			2
Other serotonergic antidepressants
Trazodone	B			2
Antipsychotics
Atypical antipsychotics
Aripiprazole	C2			3
Antiepileptics and mood stabilisers
Oxcarbazepine		D			4
Zonisamide	C2			3
Topiramate	A			1^a
Lithium			−B			−2
Carbamazepine			−C2			−3
Lamotrigine	C2			3
Anti-ADHD medication and stimulants
Methyl-Phenidate	C2			3
Lisdexamfetamine	C1				4
Appetite modulators
Appetite suppressants
Sibutramine			−C2			−1
Fenfluramine	B					−1
d-Fenfluramine			−B			−1
Opioid antagonists
Naltrexone			−B			−2
Hormones and endocrine treatments
Oxytocin			−B			−2
Other serotonergic agents
Ondansetron	B			2
GABAergic medications
Baclofen	C2			3
Other medications
N-acetylcysteine			−C2			−3
Combinations
Flutamide and citalopram	B			−2
Combination of pharmacotherapy with psychotherapy
Desipramine and CBT	C1			3

LoE: A: Strong evidence that the intervention is effective; B: Limited evidence that the intervention is effective; C(1–3): Low evidence that the intervention is effective; D: No evidence; −A: Strong evidence that the intervention is NOT effective; −B: Limited evidence that the intervention is NOT effective; −C(1–3): Low evidence that the intervention is NOT effective.

GoR: 1: Strong recommendation for using the intervention; 2: Limited recommendation for using the intervention; 3: Weak recommendation for using the intervention; 4: No recommendation possible; −1: Strong recommendation AGAINST using the intervention; −2: Limited recommendation AGAINST using the intervention; −3: Weak recommendation AGAINST using the intervention.

Please note: For details regarding the grading of the Level of Evidence (LoE) and the Grade of Recommendation (GoR) see text. The grading was performed according to Hasan et al. (2019).

^aTopiramate is contraindicated in pregnancy and in women of childbearing potential if not using a highly effective method of contraception. Green shading: Best possible recommendations for BN.

Table 6. Binge-eating disorder: level of evidence and grade of recommendation.

	LoE			GoR
Medication	Evidence that the intervention is effective	No sufficient evidence	Evidence that the intervention is NOT effective	Recommendation for using the Intervention	No recommendation possible	Recommendation AGAINST using the intervention
Antidepressants
Tricyclic antidepressants
Imipramine	B			3
Desipramine	B			3
Selective serotonin reuptake inhibitors
Escitalopram			−B			−2
Citalopram	B			2
Fluvoxamine	B			3
Fluoxetine			−B			−2
Sertraline	B			2
Vortioxetine			−B			−2
Other selective monoamine reuptake inhibitors
Venlafaxine	C1			3
Reboxetine	C2			3
Antiepileptics and mood stabilisers
Topiramate	A			1^a
Zonisamide	B			3
Lamotrigine		D			4
Anti-ADHD medication and stimulants
Lisdexamfetamine	A			1
Dasotraline	B				4
Atomoxetine	B			2
Methylphenidate	C1			3
Appetite modulators
Appetite suppressants
Sibutramine	A					−1
d-Fenfluramine	B			−1
Opioid antagonists
Naltrexone			−B			−2
GLP-1 Agonists
Liraglutide	C1			3
GABAergic medications
Baclofen	B					−3
Intestinal enzyme blocker
Orlistat	C1				4
Other medications
Sodium oxybate	C1			3		−3
Combinations
Naltrexone and bupropion		D			4
Phentermine and topiramate	B				4

The rows for lisdexamfetamine and topiramate are shaded green, because these are the best possible recommendations for BED.

LoE: A: Strong evidence that the intervention is effective; B: Limited evidence that the intervention is effective; C(1–3): Low evidence that the intervention is effective; D: No evidence; −A: Strong evidence that the intervention is NOT effective; −B: Limited evidence that the intervention is NOT effective; −C(1–3): Low evidence that the intervention is NOT effective.

GoR: 1: Strong recommendation for using the intervention; 2: Limited recommendation for using the intervention; 3: Weak recommendation for using the intervention; 4: No recommendation possible; −1: Strong recommendation AGAINST using the intervention; −2: Limited recommendation AGAINST using the intervention; −3: Weak recommendation AGAINST using the intervention.

Please note: For details regarding the grading of the Level of Evidence (LoE) and the Grade of Recommendation (GoR) see text. The grading was performed according to Hasan et al. (2019).

^aTopiramate is contraindicated in pregnancy and in women of childbearing potential if not using a highly effective method of contraception. Green shading: Best possible recommendations for BED.

Table 8. Avoidant restrictive food intake disorder: level of evidence and grade of recommendation.

	LoE			GoR
Medication	Evidence that the intervention is effective	No sufficient evidence	Evidence that the intervention is NOT effective	Recommendation for using the intervention	No recommendation possible	Recommendation AGAINST using the intervention
Antidepressants
Mirtazapine	C2			3
SSRIs
Fluoxetine	C2			3
Sertraline	C2			3
Antipsychotics
Atypical antipsychotics
Olanzapine	C2			3
Appetite modulators
Appetite stimulants
Cyproheptadine	C2			3

LoE: C2: Low evidence that the intervention is effective.

GoR: 3: Weak recommendation for using the intervention.

Table 10. Pica: level of evidence and grade of recommendation.

	LoE			GoR
Medication	Evidence that the intervention is effective	No sufficient evidence	Evidence that the intervention is NOT effective	Recommendation for using the intervention	No recommendation possible	Recommendation AGAINST using the intervention
Antipsychotics
Atypical antipsychotics
Olanzapine	C2			3
Paliperidone	C2			3
Risperidone	C2			3
Aripiprazole	C2			3
Antidepressant
SSRIs
Escitalopram	C2			3
Fluoxetine	C2			3
Fluvoxamine	C2			3
Paroxetine	C2			3
Antiepileptics and mood stabiliser
Lithium	C2			3
Topiramate	C2			3
Benzodiazepines
Clonazepam	C2			3
Stimulants
Methylphenidate	C2			3

LoE: C2: Low evidence that the intervention is effective.

GoR: 3: Weak recommendation for using the intervention.

Table 12. Rumination disorder: level of evidence and grade of recommendation.

	LoE			GoR
Medication	Evidence that the intervention is effective	No sufficient evidence	Evidence that the intervention is NOT effective	Recommendation for using the intervention	No recommendation possible	Recommendation AGAINST using the intervention
Antipsychotics
Typical antipsychotics
Levosulpiride	C1			3
GABAergic medications
Baclofen	B			3

LoE: B: Limited evidence that the intervention is effective; C1: Low evidence that the intervention is effective.

GoR: 3: Weak recommendation for using the intervention.

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