Impact of Antipsychotic Medications on Weight Gain and Eating Disorder-Related Psychopathology in Adult Inpatients with Anorexia Nervosa

Abstract

Introduction The impact of antipsychotic use on weight gain and eating disorder-related psychopathology in adult inpatients with anorexia nervosa (AN) is unclear.

Methods Consecutively hospitalized adults with AN were retrospectively analyzed. Co-primary outcomes were body mass index (BMI) and weekly weight change. Secondary outcomes were Eating Disorder Inventory-2 (EDI-2) subscale scores ‘drive for thinness’ and ‘body dissatisfaction’. Admission-to-discharge changes were compared in patients continuing pre-admission antipsychotics (APcont), starting antipsychotics (APnew) and patients without psychopharmacotherapy (noMed) using linear mixed models. Sensitivity analyses were conducted in subgroups matched for age, length of stay, baseline BMI and baseline EDI-2 scores. Subgroups were also compared regarding BMI trajectories, using non-linear growth curve models. Within-group analyses compared weight gain before vs. after the median antipsychotic onset week.

Results Of 775 adult inpatients (mean length of stay =103.5±48.0 days), 21.7% received antipsychotics (APcont =7.7%; APnew=13.9%), i. e., olanzapine (n=127, dose =5.5±3.1 mg/day) or quetiapine (n=41, dose=100.0±97.7 mg/day), while 78.3% did not receive any medication. Comparing all three groups, a significant time×group interaction was found for noMed and APnew vs. APcont (p=0.011), but this effect disappeared when comparing matched subgroups. However, in matched subgroups (n=54 each) APnew showed steeper weight gain vs. APcont both overall (p=0.011) and after median antipsychotic initiation (5.8±5.0 weeks) (p≤0.001). No significant group differences emerged in EDI-2 subscale scores.

Discussion In this naturalistic study, 22% of adult inpatients received antipsychotics. However, neither weight gain nor AN-related psychopathology changed differently in patients treated with vs. without antipsychotics. Newly initiated antipsychotic treatment vs. continuation from pre-admission had better weight gain outcomes.

Keywords

anorexia nervosa - adults - inpatients - weight gain - antipsychotics

Publication History

Received: 23 May 2024

Accepted after revision: 29 August 2024

Article published online:
19 November 2024

• References

• 1 Solmi M, Radua J, Olivola M. et al. Age at onset of mental disorders worldwide: Large-scale meta-analysis of 192 epidemiological studies. Mol Psychiatry 2022; 27: 281-295
• 2 Treasure J, Zipfel S, Micali N. et al. Anorexia nervosa. Nat Rev Dis Primers 2015; 1: 15074
• 3 Grosser J, Hofmann T, Stengel A. et al. Psychological and nutritional correlates of objectively assessed physical activity in patients with anorexia nervosa. Eur Eat Disord Rev 2020; 28: 559-570
• 4 Lehmann CS, Hofmann T, Elbelt U. et al. The role of objectively measured, altered physical activity patterns for body mass index change during inpatient treatment in female patients with anorexia nervosa. J Clin Med 2018; 7: 289
• 5 Solmi M, Monaco F, Højlund M. et al. Outcomes in people with eating disorders: A transdiagnostic and disorder-specific systematic review, meta-analysis and multivariable meta-regression analysis. World Psychiatry 2024; 23: 124-138
• 6 Chan JKN, Correll CU, Wong CSM. et al. Life expectancy and years of potential life lost in people with mental disorders: A systematic review and meta-analysis. eClinicalMedicine 2023; 65: 102294
• 7 Koerner T, Haas V, Heese J. et al. Outcomes of an accelerated inpatient refeeding protocol in 103 extremely underweight adults with anorexia nervosa at a specialized clinic in Prien, Germany. J Clin Med 2020; 9: 1535
• 8 Haas V, Kohn M, Körner T. et al. Practice-based evidence and clinical guidance to support accelerated re-nutrition of patients with anorexia nervosa. J Am Acad Child Adolesc Psychiatry 2021; 60: 555-561
• 9 Monteleone AM, Pellegrino F, Croatto G. et al. Treatment of eating disorders: A systematic meta-review of meta-analyzes and network meta-analyzes. Neurosci Biobehav Rev 2022; 142: 104857
• 10 Herpertz S, Fichter M, Herpertz-Dahlmann B. et al. Gemeinsame S3-Leitlinie ”Diagnostik und therapie der essstörungen” [Joint German Guideline “Diagnosis and treatment of eating disorders”]. Berlin: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. (AWMF); 2018
• 11 National Guideline Alliance (UK). Eating disorders: Recognition and treatment. London: National Institute for Health and Care Excellence (NICE); 2017. updated 2020
• 12 Crone C, Fochtmann LJ, Attia E. et al. The American Psychiatric Association Practice Guideline for the treatment of patients with eating disorders. Am J Psychiatry 2023; 180: 167-171
• 13 Himmerich H, Lewis YD, Conti C. et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders. World J Biol Psychiatry 2023; 24: 1-64
• 14 Bak M, Fransen A, Janssen J. et al. Almost all antipsychotics result in weight gain: A meta-analysis. PLoS One 2014; 9: e94112
• 15 Bissada H, Tasca GA, Barber AM. et al. Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: A randomized, double-blind, placebo-controlled trial. Am J Psychiatry 2008; 165: 1281-1288
• 16 Attia E, Kaplan AS, Walsh BT. et al. Olanzapine versus placebo for out-patients with anorexia nervosa. Psychol Med 2011; 41: 2177-2182
• 17 Brambilla F, Garcia CS, Fassino S. et al. Olanzapine therapy in anorexia nervosa: Psychobiological effects. Int Clin Psychopharmacol 2007; 22: 197-204
• 18 Kafantaris V, Leigh E, Hertz S. et al. A placebo-controlled pilot study of adjunctive olanzapine for adolescents with anorexia nervosa. J Child Adolesc Psychopharmacol 2011; 21: 207-212
• 19 Powers PS, Klabunde M, Kaye W. Double-blind placebo-controlled trial of quetiapine in anorexia nervosa. Eur Eat Disord Rev 2012; 20: 331-334
• 20 Attia E, Steinglass JE, Walsh BT. et al. Olanzapine versus placebo in adult outpatients with anorexia nervosa: A randomized clinical trial. Am J Psychiatry 2019; 176: 449-456
• 21 Kishi T, Kafantaris V, Sunday S. et al. Are antipsychotics effective for the treatment of anorexia nervosa? Results from a systematic review and meta-analysis. J Clin Psychiatry 2012; 73: e757-e766
• 22 Lebow J, Sim LA, Erwin PJ. et al. The effect of atypical antipsychotic medications in individuals with anorexia nervosa: A systematic review and meta-analysis. Int J Eat Disord 2013; 46: 332-339
• 23 de Vos J, Houtzager L, Katsaragaki G. et al. Meta-analysis on the efficacy of pharmacotherapy versus placebo on anorexia nervosa. J Eat Disord 2014; 2: 27
• 24 Dold M, Aigner M, Klabunde M. et al. Second-generation antipsychotic drugs in anorexia nervosa: A meta-analysis of randomized controlled trials. Psychother Psychosom 2015; 84: 110-116
• 25 Han R, Bian Q, Chen H. Effectiveness of olanzapine in the treatment of anorexia nervosa: A systematic review and meta-analysis. Brain Behav 2022; 12: e2498
• 26 Barbarich NC, McConaha CW, Gaskill J. et al. An open trial of olanzapine in anorexia nervosa. J Clin Psychiatry 2004; 65: 1480-1482
• 27 Bosanac P, Kurlender S, Norman T. et al. An open-label study of quetiapine in anorexia nervosa. Hum Psychopharmacol 2007; 22: 223-230
• 28 Resmark G, Herpertz S, Herpertz-Dahlmann B. et al. Treatment of anorexia nervosa-new evidence-based guidelines. J Clin Med 2019; 8: 153
• 29 Watanabe N, Omori IM, Nakagawa A. et al. Safety reporting and adverse-event profile of mirtazapine described in randomized controlled trials in comparison with other classes of antidepressants in the acute-phase treatment of adults with depression: Systematic review and meta-analysis. CNS Drugs 2010; 24: 35-53
• 30 Pillinger T, Howes OD, Correll CU. et al. Antidepressant and antipsychotic side-effects and personalised prescribing: A systematic review and digital tool development. Lancet Psychiatry 2023; 10: 860-876
• 31 Garner DM. Eating Disorder Inventory-2: Professional Manual. Psychological Assessment Resources. 1991
• 32 Paul T, Thiel A. Eating Disorder Inventory-2: Deutsche Version. Hogrefe Verlag; 2005
• 33 R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. 2021
• 34 Pinheiro J, Bates D, DebRoy S. et al. nlme: Linear and Nonlinear Mixed Effects Models. R package version 3.1–153
• 35 Ho D, Imai K, King G. et al. MatchIt: Nonparametric preprocessing for parametric causal inference. J Stat Softw 2011; 42: 1-28
• 36 Mirman D. Growth Curve Analysis and Visualization Using R. Chapman and Hall; 2014
• 37 Bates D, Mächler M, Bolker B. et al. Fitting linear mixed-effects models using lme4. J Stat Softw 2015; 67: 1-48
• 38 Frank B, Arnold S, Jaite C. et al. Antipsychotic effects on anthropometric outcomes in anorexia nervosa: A retrospective chart review of hospitalized children and adolescents. J Eat Disord 2023; 11: 151
• 39 Solmi M, Murru A, Pacchiarotti I. et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: A state-of-the-art clinical review. Ther Clin Risk Manag 2017; 13: 757-777
• 40 Correll CU, Lencz T, Malhotra AK. Antipsychotic drugs and obesity. Trends Mol Med 2011; 17: 97-107
• 41 De Young K, Bottera A, Kambanis E. et al. Delusional intensity as a prognostic indicator among individuals with severe to extreme anorexia nervosa hospitalized at an acute medical stabilization program. Int J Eat Disord 2022; 55: 215-222
• 42 Pruccoli J, Bergonzini L, Pettenuzzo I. et al. The role of risperidone in the treatment of children and adolescents with anorexia nervosa. J Psychopharmacol 2023; 37: 545-553
• 43 Hagman J, Gralla J, Sigel E. et al. A double-blind, placebo-controlled study of risperidone for the treatment of adolescents and young adults with anorexia nervosa: A pilot study. J Am Acad Child Adolesc Psychiatry 2011; 50: 915-924
• 44 Tahıllıoğlu A, Özcan T, Yüksel G. et al. Is aripiprazole a key to unlock anorexia nervosa?: A case series. Clin Case Rep 2020; 8: 2827-2834
• 45 Frank GK, Shott ME, Hagman JO. et al. The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa. Int J Eat Disord 2017; 50: 447-450