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. 2022 Dec 7;10(12):3167. doi: 10.3390/biomedicines10123167

Table 1.

Summary of the results of the included studies.

Study Population Intervention Comparison Outcome
Olanzapine
Spettigue et al., 2018 [20] N: 32; sex: 29 females, 3 males; mean age: 15.48; age range: 11–17. Olanzapine

  • Min. dose: 1.25 mg/day (range: 1.25–5 mg/day);

  • Max dose: mean 5.28 mg/day (range: 2.5–15 mg/day);

Duration: mean 55.18 days; range 16–86 days.		 Eligible to switch into the medication group up until the end of week 8 in the study Side effects/tolerability: patients tended to experience headaches and constipation more than the comparison group. They reported more muscle dizziness, stiffness, somnolence, and dry mouth;
Psychopathology: decrease in depression and anxiety; decrease in self-reported ED behavior;
Weight: more weight per week than those in the comparison group;
Duration of hospitalization: na
Norris et al., 2011 [21] N: 43; sex: females; mean age: 14.4; age range: 10–17. Olanzapine

  • Min. dose: 3.5 mg/day;

  • Max. dose: 7.5 mg/day;

  • Mean dose: 5.0 mg/day;

Duration: 252 days;		 Patients chosen by age and diagnosis at assessment, and then treatment intensity level was undertaken after assessment (i.e., outpatient care, entry into our day program, or admission to the inpatient unit). Side effects/tolerability: sedation (more common); abnormalities in blood work (elevations in the fasting lipid profile; one had elevated liver function test);
Psychopathology: no significative differences were found;
Weight: no significant gain;
Duration of hospitalization: na
Leggero et al., 2010 [22] N: 13; sex: females; mean age: 13.7; age range: 9.6–16.3. Olanzapine

  • Min. dose: 1.25 mg/day (range: 1.25–2.5 mg/day);

  • Max dose: mean 4 ± 3.40 mg/day (range: 3.75–12.5 mg/day);

  • Mean dose: 4.1 ± 2.9 mg/day

Duration: n.a.		 / Side effects/tolerability: An increase in liver enzymes occurred in two patients;
Psychopathology: CGAS and CGI-S improved significantly. Both the CBCL Total Score and Internalizing Scale improved significantly. The EAT-26 total scores markedly improved, including Dieting, Bulimic, and Oral Control. The EDI-2 showed significant improvement only in two areas, Interoceptive Awareness, and Impulsivity; hyperactivity (according to SIAB-EX) resulted in significant improvement;
Weight: BMI score improved significantly;
Duration of hospitalization: na
Dennis et al., 2006 [23] N: 5; sex: females; mean age: 15.6; age range: 12–18. Olanzapine

  • Min. dose: 1.25 mg/day;

  • Max dose: 7.5 mg/day;

Duration: n.a.		 / Side effects/tolerability: pt 1: mild sedation; pt 4: excessive sedation; patient 5: itching (stop assumption after 2 months);
Psychopathology: pt 1: anxiety around mealtimes subsided and agitation with family decreased markedly; pt 2: improved sleep and decreased anxiety; decreased irritability and combativeness at mealtimes; pt 3: decreased worry about eating and decreased body image concern. She reported less rumination about food, fewer depressive symptoms, and decreased anxiety; pt 4: decreased anxiety. She felt calmer before meals; pt 5: no improvement was recorded;
Weight: improved markedly only for two patients;
Duration of hospitalization: n.a.
Pruccoli et al., 2022 [24] N: 66; sex: 63 females, 3 males; mean age: 15.4; age range: 13–18. Olanzapine Group 1, (low-dose)

  • N: 37

  • Min. dose: mean 3.4 mg/day;

  • Max dose: mean 4.4 mg/day;

Duration: mean 132 days;
Group 2 (full-dose)

  • N: 29

  • Min. dose: mean 6 mg/day;

  • Max. dose: mean 9 mg/day;

Duration: mean 132 days;		 Same characteristics of the cases, but not treated with antipsychotic Side effects/tolerability: Group 1: two patients (5.4%) developed a mild elevation of total cholesterol levels; one patient (2.7%) showed elevated transaminase. Group 2: 3 patients (10.5%) presented a mild elevation of total cholesterol levels, 1 patient (3.5%) developed somnolence, 1 patient (3.5%) showed a reduction of blood pressure;
Psychopathology: improvement of BUT-GSI (p < 0.001), BDI-II (p < 0.001), and SAFA-D (p < 0.001) for the entire sample, but group 2 experienced a significantly lower improvement in depressive measures than the other groups;
Weight: significant gain.
Duration of hospitalization: group 1: mean 121 days; group 2: mean 116 days.
Boachie et al., 2002 [25] N: 4; sex: females; mean age: 11; age range: 10–12. Olanzapine

  • Min dose: 2.5 mg/day;

  • Max dose: 2.5 mg/day;

Duration: pt 1: n.a.; pt 2: 155 days; pt 3: 84 days; pt 4: n.a.		 / Side effects/tolerability: no ADR reported;
Psychopathology: pt 1: better in sleeping, less anxious, fewer compulsive rituals, and fewer food preoccupations; pt 2: at discharge, she was not agitated, was sleeping well, was an improved relationship with others; pt 3: clinical improvement in her general and premeal anxiety levels, as well as a reduction in agitation; pt 4: improvement in her general anxiety level and agitation’s reduction;
Weight: significant gain;
Duration of hospitalization: pt 1, 49 days; pt 2, 70 days; pt 3, 77 days, pt 4, 120 days.
Mehler et al., 2001 [26] N: 5; sex: females; mean age: 15.4; age range: 12–17. Olanzapine

  • Min. dose: 2.5 mg/day (range 2.5–10 mg/day);

  • Max dose: 12.5 mg/day (range 5–12.5 mg/day);

Duration: pt 1, 42 days; pt 2, 112 days; pt 3, 56 days; pt 4, 48 days; pt 5: na		 / Side effects/tolerability: no ADR reported. Pt 3 increased appetite with the first episode of binge eating;
Psychopathology: improvement of the delusional quality of thinking, and fears about weight;
Weight: significant gain;
Duration of hospitalization: pt 1: 77 days, pt 2: 56 days; pt 3: 70 days; pt 4 n.a.; pt 5 n.a.
Ercan et al., 2003 [27] N: 1; sex: female; age: 15. Olanzapine:

  • Min. dose: 2.5 mg/day;

  • Max dose: 10 mg/day;

Duration: 196 days;		 / Side effects/tolerability: no ADR reported;
Psychopathology: remission of psychiatric symptoms (irritability, compulsive thoughts about body weight, food, and physical activity)
Weight: significant gain;
Duration of hospitalization: 133 days.
Dadic-Hero et al., 2009 [28] N: 1; sex: female; age: 15. Olanzapine

  • Min. dose: 2.5 mg/day;

  • Max dose: 5 mg/day;

Duration: 720 days;		 / Side effects/tolerability: no ADR reported
Psychopathology: na
Weight: significant gain;
Duration of hospitalization: 112 days.
La Via et al., 2000 [29] N: 1; sex: female; age: 15. Olanzapine

  • Min. dose: 2.5 mg/day;

  • Max dose: 15 mg/day;

Duration: 180 days;		 / Side effects/tolerability: mild sedation;
Psychopathology: reduction in agitation and anxiety;
Weight: significant gain;
Duration of hospitalization: 98 days
Duvvuri et al., 2012 [30] N: 1; sex: female; age: 12. Olanzapine

  • Min. dose: 2.5 mg/day;

  • Max dose: 3.75 mg/day;

Duration: 270 days;		 Identical twin, with the same diagnosis, treated with fluoxetine Side effects/tolerability: no ADR reported
Psychopathology: reduced ED preoccupations or rituals, obsessions, and compulsions;
Weight: IBW restored;
Duration of hospitalization: outpatient treatment.
Ayyildiz et al., 2015 [31] N: 1; sex: male; age: 17. Olanzapine

  • Min dose: 5 mg/day;

Duration: 2 days		 / Side effects/tolerability: NMS occurred 48 h after the first administration;
Psychopathology: no improvement;
Weight: no improvement;
Duration of hospitalization: na.
Tateno et al., 2008 [32] N: 1; sex: female; age: 17 Olanzapine

  • Min. dose: 2.5 mg/day;

  • Max. dose: 5 mg/day;

Duration: na		 / Side effects/tolerability: no ADR reported;
Psychopathology: abnormal eating habits gradually remitted;
Weight: reached the standard;
Duration of hospitalization: na.
Risperidone
Kracke et al., 2014 [33] N: 1; sex: female; age: 17. Risperidone

  • Min. dose: 0.25 mg/day;

  • Max: dose: 0.5 mg/day;

Duration: 670 days;		 / Side effects/tolerability: no ADR reported
Psychopathology: improvement in rigidity during meal timing;
Weight: significant gain;
Duration of hospitalization: no hospitalization.
Umehara et al., 2014 [34] N: 1; sex: male; age: 10 Risperidone

  • Min. dose: 1 mg/day;

Duration: 84 days;
Risperidone long-acting injection (RLAI)

  • Dose: 12.5 mg/2 weeks;

Duration: 365 days.		 / Side effects/tolerability: he refused oral risperidone because he believed it was making him fat
Psychopathology: reduction of agitation during enteral feeding; reduction of his complaints based on body distortion
Weight: significant gain;
Duration of hospitalization: 448 days.
Newman-Toker, 2000 [35] N: 1; sex: female; age: 12. Risperidone:

  • Min. dose: 0.5 mg/day;

  • Max dose: 1.5 mg/day;

Duration: n.a.		 / Side effects/tolerability: no ADR reported;
Psychopathology: cheerful, energetic, insight about anorexia, lowered anxiety
Weight: BMI improvement;
Duration of hospitalization: na
Fisman et al., 1996 [36] N: 1; sex: female; age: 13. Risperidone

  • Min. dose: 0.5 mg/day;

Duration: na		 / Side effects/tolerability: no ADR reported;
Psychopathology: striking decrease in agitation and aggression, loss of paranoid ideation, more focused attention, and generally more settled and malleable behavior.
Weight: significant gain;
Duration of hospitalization: na.
Clotiapine
Pruccoli et al., 2021 [37] N: 2; sex: females; mean age: 17.5; age range: 17–18. Clotiapine

  • Min. dose: mean 15 mg/day (range 10–20);

  • Max dose: 70 mg/day;

Duration: 270 days;		 / Side effects/tolerability: fatigue (pt 1) which caused withdrawal in 3 days;
Psychopathology: decrease of delusional symptoms, restored proper hygiene habits;
Weight: n.a.
Duration of hospitalization: 330 days.
Aripiprazole
Frank et al., 2016 [38] N: 4; sex: females; mean age: n.a.; age range: 12–17 Aripiprazole

  • Min. dose: mean 1.25 mg/day (range: 1–2 mg/day);

  • Max. dose: mean 2.5 mg/day (range: 1–5 mg/day);

Duration: n.a.		 / Side effects/tolerability: Patient 1: neutropenia;
Psychopathology: improvement in psychopathology from subjective reports;
Weight: Improvement in IBW
Duration of hospitalization: na
Frank et al., 2017 [39] N: 22; sex: na; mean age: 15; age range: na Aripiprazole

  • Min. dose: 1 mg/day;

  • Max dose: 5 mg/day;

Duration: na		 Comparison groups took part in the same specialized eating disorder inpatient or partial hospital program and were matched for age and had a similar number of inpatient days. Side effects/tolerability: no ADR reported;
Psychopathology: no data were collected
Weight: greater improvement in the aripiprazole group;
Duration of hospitalization: mean 18.9 days (inpatient); mean 40.4 days (partial hospital treatment).
Tahilioglu et al., 2020 [40] N: 11; sex: females; mean age: 14; age range: 11–17. Aripiprazole

  • Min. dose: 0.5 mg/day;

  • Max dose: 15 mg/day;

Duration: 540–840 days		 / Side effects/tolerability: no ADR reported;
Psychopathology: improvements in obsessive eating attitudes and behaviors in all patients. Increased appetite; change in the CGI-S scores
Weight: significant gain;
Duration of hospitalization: na
Pimozide
Plantey, 1977 [41] N: 1; sex: male; age: 17. Pimozide

  • Min. dose: 12 mg/day;

Duration: 30 days.		 / Side effects/tolerability: no ADR reported;
Psychopathology: implacable obsession with weight disappeared; reduction of hyperactivity;
Weight: significant gain;
Duration of hospitalization: na
Chlorpromazine
Foster and Kupfer, 1975 [42] N: 1; sex: female; age: 17. Chlorpromazine

  • Min. dose: 200 mg/day;

  • Max. dose: 800 mg/day;

Duration: 98 days		 / Side effects/tolerability: no ADR reported;
Psychopathology: reduction in nocturnal activity;
Weight: regained her body weight;
Duration of hospitalization: na
Roberts et al., 1986 [43] N: 1; sex: female; age: 16. Chlorpromazine

  • Min. dose 25 mg/day;

  • Max dose: 75 mg/day;

Duration: na		 / Side effects/tolerability: “grand mal” seizure (direct association unclear potentially mediated by variations in plasma electrolytes).
Psychopathology: not directly reported: commented as “reduction of anxiety [...] and fear of eating” in the case report section, in light of the previous literature
Weight: significant gain;
Duration of hospitalization: na
Roussonis, 1971 [44] N:1; sex: male; age: 11. Chlorpromazine

  • Min. dose na;

  • Max dose: na;

Duration: na		 / Side effects/tolerability: no ADR reported.
Psychopathology: not mentioned;
Weight: significant gain;
Duration of hospitalization: na
Studies including Multiple Drugs
Rossi et al., 2007 [45] N: 19; sex: 17 females, 2 males; mean age: n.a.; age range: 12–18 Haloperidol (n: 4); olanzapine (n: 3); risperidone (n: 1):

  • Min. dose: na *;

  • Max. dose: na *;

Duration: mean 150 days;
*”low and medium range according to international pharmacological guidelines”		 The comparison group has the same characteristics but was treated with SSRIs. Side effects/tolerability: none 75%, severe drowsiness (12.5%), worsening eating disorder (12.5%);
Psychopathology: based on the CGI-S assessment, 75% of the patients showed an improvement in their eating behavior and their psychological status;
Weight: BMI increased in all the patients except one (clinical worsening due to haloperidol administration).
Duration of hospitalization: n.a.
Ritchie et al., 2009 [46] N: 1; sex: female; age: 15. Olanzapine

  • Min. dose: 2.5 mg/die;

  • Max dose: 5 mg/day;

Duration: n.a.
Risperidone

  • Min. dose: 0.25 mg/day;

  • Max dose 0.75 mg/day;

Duration: n.a.
Quetiapine

  • Min. dose: 25 mg/day;

  • Max. dose: 50 mg/day;

Duration: na;		 / Side effects/tolerability: prolonged QTc (olanzapine and risperidone);
Psychopathology: Patient’s anxiety and mood stability improved (quetiapine);
Weight: Reestablishment of a healthy weight;
Duration of hospitalization: >71 days
Dodig-Ćurković et al., 2010 [47] N: 1; sex: female; age: 15. Sulpiride

  • Min. dose 200 mg/day;

Duration: na.
Olanzapine

  • Min. dose 5 mg/day;

  • Max. dose 15 mg/day

Duration: na.		 / Side effects/tolerability: no ADR reported;
Psychopathology: decreased delusions of her appearance and body weight; decreased the irrational food selection and caloric values of certain foods;
Weight: BMI improvement;
Duration of hospitalization: na.

Abbreviations: ADR: Adverse Drug Reactions; N: number; Min: minimum; Max: maximum; n.a.: not available; pt: patient; BMI: Body Mass Index; ED: Eating Disorder; IBW: Ideal Body Weight; RLAI: Risperidone long-acting injection; CGAS: Global Measures of Functioning; CGI-S: Clinical Global Impression scale (Severity of Illness); SSRI: Selective Serotonin Reuptake Inhibitors; CBCL: Child Behavior Checklist; EAT-26: Eating Attitude Test—26 Item; EDI-2: Eating Disorder Inventory-2; SIAB-EX: structured Inventory for Anorexic and Bulimic Eating Disorders; BUT-GSI: Body Uneasiness Test Global Severity Index; BDI-II: Beck Depression Inventory; SAFA-D: Self Administered Psychiatric Scales for Children and Adolescents-Depression; NMS: Neuroleptic Malignant Syndrome.