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Appetite measures as correlates of clinical response in mood disorders treated with ketamine: systematic review

Jakub Słupski, Agnieszka Mechlińska, Adam Włodarczyk, Aleksander Kwaśny, Joanna Szarmach, Anita Słupska, Wiesław Jerzy Cubała

Frontiers in Nutrition August 21, 2025 Peer reviewed DOI: 10.3389/fnut.2025.1616859 via OpenAlex

Summary

Ketamine treatment may improve depressive symptoms related to appetite in patients with treatment-resistant mood disorders, although the effects can vary. Out of five studies reviewed involving 678 participants, two reported significant improvements in appetite, one showed no change, another indicated a worsening of appetite, and one noted minimal effects on increased appetite. This suggests that appetite could be an important factor in assessing the antidepressant effects of treatments.

Study at a glance

Design systematic review
Sample size 678
Population patients with treatment-resistant mood disorders
Key finding Ketamine treatment may contribute to the improvement of depressive symptoms related to appetite or exhibit neutral effects on food consumption desire.

Abstract

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BP), significantly impact global health, with MDD affecting over 300 million people and BP affecting approximately 2% of the world's population. Ketamine, originally an anesthetic, has emerged as a promising treatment for patients with treatment-resistant depression (TRD), due to its unique pharmacological properties, such as N-methyl-D-aspartate (NMDA) receptor antagonism and anti-inflammatory effects. The potential of ketamine in treating depression has sparked debate regarding its effects on appetite. This paper aims to conduct a systematic review focusing on the complex interplay between ketamine treatment and appetite. A total of 78 references were identified from electronic databases: PubMed, Web of Science, APA PsycINFO, and EBSCOhost, with 5 meeting the inclusion criteria for this review, encompassing 678 participants. Appetite was assessed using both clinician-rated and self-reported scales. Two studies reported significant improvement in reduced appetite following ketamine or esketamine treatment; one reported no significant change; one found a paradoxical worsening of reduced appetite; and one noted minimal effect on increased appetite and atypical symptoms. The data presented suggest that in patients with treatment-resistant mood disorders, ketamine may contribute to the improvement of depressive symptoms, including those related to appetite, or may exhibit neutral effects on food consumption desire. Appetite measurement may be a valuable indicator of the antidepressant effect, facilitating signal detection for substances beyond traditional monoaminergic antidepressants. Despite limited data, establishing a confirmed link between appetite and antidepressants could aid in treatment planning, particularly for patients with metabolic disorders or those at risk of malnutrition, potentially improving adherence and outcomes in treatment-resistant mood disorders. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024510640, identifier CRD42024588790.

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