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Cited by 99Schizophrenia research and treatmentPharmacology and Obesity TreatmentObesity, Physical Activity, Diet

The Burden of Antipsychotic-Induced Weight Gain and Metabolic Syndrome in Children

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Libowitz, Mark R., Nurmi, Erika L.·2021·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2021.623681PMC PMC7994286
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Abstract

Antipsychotic medications are critical to child and adolescent psychiatry, from the stabilization of psychotic disorders like schizophrenia, bipolar disorder, and psychotic depression to behavioral treatment of autism spectrum disorder, tic disorders, and pediatric aggression. While effective, these medications carry serious risk of adverse events—most commonly, weight gain and cardiometabolic abnormalities. Negative metabolic consequences affect up to 60% of patients and present a major obstacle to long-term treatment. Since antipsychotics are often chronically prescribed beginning in childhood, cardiometabolic risk accumulates. An increased susceptibility to antipsychotic-induced weight gain (AIWG) has been repeatedly documented in children, particularly rapid weight gain. Associated cardiometabolic abnormalities include central obesity, insulin resistance, dyslipidemia, and systemic inflammation. Lifestyle interventions and medications such as metformin have been proposed to reduce risk but remain limited in efficacy. Furthermore, antipsychotic medications touted to be weight-neutral in adults can cause substantial weight gain in children. A better understanding of the biological underpinnings of AIWG could inform targeted and potentially more fruitful treatments; however, little is known about the underlying mechanism. As yet, modest genetic studies have nominated a few risk genes that explain only a small percentage of the risk. Recent investigations have begun to explore novel potential mechanisms of AIWG, including a role for gut microbiota and microbial metabolites. This article reviews the problem of AIWG and AP metabolic side effects in pediatric populations, proposed mechanisms underlying this serious side effect, and strategies to mitigate adverse impact. We suggest future directions for research efforts that may advance the field and lead to improved clinical interventions.

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  • The effect of reducing or discontinuing antipsychotic medication on weight is likely mediated via neurotransmitter signaling involving histamine and serotonin.

    “The effect is likely mediated via neurotransmitter signaling involving histamine and serotonin (16), and some suggest that thyroid function is associated with antipsychotic medication (17).”

    From Reversibility of Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis (2021) · cites this paper as [16]

    The Histamine Signaling and Serotonin Signaling sections (page not provided) describe both pathways as possible mechanisms of antipsychotic-induced weight gain. The Risk for Antipsychotic-Related Metabolic Effects section reports some weight loss after discontinuation, but does not link that loss to histamine or serotonin signaling. The claimed mechanism for weight change after reducing or stopping medication is therefore an extension beyond what the source says. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Sorted by citations

Authors
Libowitz, M. R., & Nurmi, E. L.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Nurmi, Erika L.
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2021-03-12
Volume
12
Pages
623681-623681
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2021.623681
PMC
PMC7994286
OpenAlex
W3137919242
Cited by
99
References
17
Citations by year
2026: 22 · 2025: 20 · 2024: 16 · 2023: 22 · 2022: 14 · 2021: 5
FWCI
2.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD095548)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
Keywords
antipsychotic-induced weight gain, metabolic syndrome, abdominal obesity, insulin resistance, dyslipidemia, systemic inflammation, metformin, lifestyle intervention, gut microbiota, microbial metabolites, risk genes, rapid weight gain, children and adolescents

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