Psychopharmacology of eating disorders: Systematic review and meta-analysis of randomized controlled trials

Background: The concurrent assessment of weight and affective psychopathology outcomes relevant to the psychopharmacology of major eating disorders (EDs), namely anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), warrants systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: PubMed, Scopus, and ClinicalTrials.gov were inquired from inception through August 31st, 2022, for RCTs documenting any psychopharmacological intervention for EDs diagnosed according to validated criteria and reporting weight and psychopathology changes. Adopted keywords were: "anorexia nervosa," "bulimia nervosa," "binge eating disorder," "antidepressant," "antipsychotic," and "mood stabilizer." No language restriction applied. Results: 5122 records were identified, and 203 full-texts were reviewed. Sixty-two studies entered the qualitative synthesis (AN = 22, BN = 23, BED = 17), of which 22 entered the meta-analysis (AN = 9, BN = 10, BED = 3). Concerning BMI increase in AN, olanzapine outperformed placebo (Hedges'g = 0.283, 95%C center dot I. = 0.051-0.515, I-2 = 0 %; p =.017), whereas fluoxetine failed (Hedges'g = 0.351, 95%C.I. = 0.248 to 0.95, I-2 = 63.37 %; p =.251). Fluoxetine not significantly changed weight (Hedges'g = 0.147, 95%C.I. = 0.157-0.451, I2 = 0 %; p =.343), reducing binging (Hedges'g = 0.203, 95%C.I. = 0.007-0.399, I2 = 0 %; p =.042), and purging episodes (Hedges'g = 0.328, 95%C.I. = 0.061-0.717, I-2 = 58.97 %; p =.099) in BN. Lisdexamfetamine reduced weight (Hedges'g = 0.259, 95%C.I. = 0.071-0.446, I-2 = 0 %; p =.007) and binging (Hedges'g = 0.571, 95%C.I. = 0.282-0.860, I-2 = 53.84 %; p <.001) in BED. Limitations: Small sample size, short duration, and lack of reliable operational definitions affect most of the included sponsored RCTs. Conclusions: The efficacy of different drugs varies across different EDs, warranting additional primary studies recording broad psychopathological and cardiometabolic outcomes besides weight, especially against established psychotherapy interventions.