Ketamine as a Novel Psychopharmacotherapy for Eating Disorders: Evidence and Future Directions

Ragnhildstveit, Anya; Slayton, Matthew; Jackson, Laura; Brendle, Madeline; Ahuja, Sachin; Holle, Willis; Moore, Claire E.; Sollars, Kellie; Seli, Paul; Robison, Reid

doi:10.3390/brainsci12030382

Cited by 21 publications

(14 citation statements)

References 166 publications

(184 reference statements)

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“…Therapeutic use of ketamine, a dissociative anesthetic the effects of which are mainly mediated by its NMDA receptor antagonism, can be also considered within the amino acidergic (glutamatergic) strategy [68] . Due to its rapid clinical effect in depression [69] , ketamine is extensively studied for other psychiatric indications, including EDs [70] . Preliminary clinical data on the efficacy and safety of ketamine in EDs suggest its therapeutic potential, but this should be confirmed in RCTs [70] .…”

Section: Resultsmentioning

confidence: 99%

Pharmacological strategies for appetite modulation in eating disorders: a narrative review

Popov,

Lepik,

Kozlovskii

et al. 2023

Consortium Psychiatricum

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BACKGROUND: Over the past decades, a substantial increase in the prevalence of eating disorders (ED) has been noticed. In the treatment of ED priority is justifiably given to psychosocial interventions. However, it is well known that centrally acting drugs can significantly affect appetite and food consumption. AIM: The aim of this review is to analyze and summarize the available neurobiological data on the mechanisms of central regulation of eating behavior as a rationale for pharmacological strategies for appetite modulation in ED. METHODS: The authors have carried out a narrative review of scientific papers published from 2013 to 2023. The studies presented in the PubMed and Web of Science electronic databases were analyzed. Relevant studies were included regardless of their design. Descriptive analysis was used to summarize the information obtained. RESULTS: Neurobiological mechanisms of central regulation of eating behavior are reviewed. Pharmacological strategies for appetite modulation in ED based on neurobiological and clinical data are discussed. The influence of age on efficacy and safety of pharmacotherapy is also discussed, with an emphasis on adolescence. CONCLUSIONS: The progress in neurobiological understanding of the mechanisms of central regulation of appetite reveals the opportunities for new pharmacotherapeutic approaches aimed at changing the patterns of eating behavior. Obviously, treatment of ED is a much broader problem and cannot be reduced to the correction of food consumption. Nevertheless, at certain stages of treatment, drug-induced modulation of appetite can play an important role among multi-targeted biological and psychosocial interventions. Translation of neurobiological data into clinical practice requires a large number of clinical studies to confirm the long-term efficacy and safety of pharmacotherapeutic approaches and to develop personalized algorithms for the treatment of various forms of ED in different age groups.

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Section: Resultsmentioning

confidence: 99%

Pharmacological strategies for appetite modulation in eating disorders: a narrative review

Popov,

Lepik,

Kozlovskii

et al. 2023

Consortium Psychiatricum

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“…Primarily, we saw the low doses (1 mM) of ketamine, escitalopram, and fluoxetine increased both feeding and locomotion (Figure 4 and 5). Although the effects of ketamine on feeding had not been characterized in Drosophila , several new clinical studies have shown that microdosing ketamine increases appetite and has positive effects for patients with co-morbid eating disorders and depression (Ragnhildstveit et al, 2022; Robison et al, 2022; Schwartz et al, 2021). Similar to our Drosophila studies, low doses of ketamine also cause hyperlocomotion in mammals (Can et al, 2016; Irifune et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Microdosing ketamine inDrosophiladoes not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors

Dunham,

Khaled,

Weizman

et al. 2023

Preprint

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Recently, the FDA approved microdosing ketamine for treatment resistant depression. Traditional antidepressants, like serotonin selective reuptake inhibitors (SSRIs), block serotonin reuptake, but it is not clear if ketamine blocks serotonin reuptake. Here, we tested the effects of feeding ketamine and SSRIs toDrosophila melanogasterlarvae, which has a similar serotonin system to mammals, and is a good model to track depression behaviors, such as locomotion and feeding. Fast-scan cyclic voltammetry (FSCV) was used to measure optogenetically-stimulated serotonin changes, and locomotion tracking software and blue dye feeding to monitor behavior. We fed larvae various doses (1-100 mM) of antidepressants for 24 hours and found that 1 mM ketamine did not affect serotonin, but increased locomotion and feeding. Low doses (≤ 10 mM) of escitalopram and fluoxetine inhibited dSERT and also increased feeding and locomotion behaviors. At 100 mM, ketamine inhibited dSERT and increased serotonin concentrations, but decreased locomotion and feeding due to its anesthetic properties. Since microdosing ketamine causes behavioral effects, we also investigated behavior changes with low doses of other NMDA receptor antagonists and 5-HT1Aand2agonists, which are other possible sites for ketamine action. NMDA receptor antagonism increased feeding, while serotonin receptor agonism increased locomotion, which could explain these effects with ketamine. Ultimately, this work shows thatDrosophilais a good model to discern antidepressant mechanisms, and that ketamine does not work on dSERT like SSRIs at microdoses, but affects behavior with other mechanisms.Graphical abstractMicrodosing ketamine is a novel depression treatment, but it is not clear how it changes serotonin in real-time.Drosophila melanogaster(fruit fly) is a good model to study depression behaviors. Here, we used fast-scan cyclic voltammetry, video tracking, and feeding assays to measure serotonin and behavior after feeding ketamine and SSRIs to larvae. At microdoses, ketamine did not affect serotonin, which was different from SSRIs. However, higher doses inhibited dSERT. Locomotion and feeding changes were also dose-dependent, and we saw separate effects with NMDA and serotonin receptor drugs. This work facilitates future behavioral and pharmacological testing with ketamine usingDrosophila.

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“…Insbesondere im Bereich der Depressionsbehandlung liegen zahlreiche Studien zur Wirksamkeit von Ketamin vor, darüber hinaus auch bei Zwangsstörungen, Autismus, Angststörungen und Abhängigkeitserkrankungen [20]. Für die Behandlung von Patient*innen mit AN liegen nur einzelne Fallserien mit kleinen Fallzahlen vor, welche Hinweise für eine Wirksamkeit auf einzelne Parameter geben [20,21]. Auf theoretischer Ebene geht man von einer positiven Beeinflussung der bei AN pathologisch veränderten Transmittersysteme (Serotonin, Dopamin) und neuropsychologischen Funktionen (Gedächtnis, Körperwahrnehmung) durch Ketamin aus [20].…”

Section: Anorexia Nervosaunclassified

Pharmakotherapie bei Essstörungen

Watolla¹,

Zipfel²,

Stengel³

2023

PSYCH up2date

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Ketamine as a Novel Psychopharmacotherapy for Eating Disorders: Evidence and Future Directions

Cited by 21 publications

References 166 publications

Pharmacological strategies for appetite modulation in eating disorders: a narrative review

Pharmacological strategies for appetite modulation in eating disorders: a narrative review

Microdosing ketamine inDrosophiladoes not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors

Pharmakotherapie bei Essstörungen

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