Fig 2 - uploaded by Abigail Calder
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Relationship between effect sizes and the continuous variables of timing, percentage of missing values, and average participant age for studies administering any psychoplastogen. Shading shows 95% confidence intervals. The effect of hours post-administration was significant but minimal (SMD = 0.0005, p = 0.038). Studies with a higher percentage of missing data reported significantly greater effect sizes (SMD = 0.77, p = 0.028).
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Background
Peripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test wheth...
Contexts in source publication
Context 1
... combined effect size across all psychoplastogens was not significant (SMD = 0.024, p = 0.64). There was a relatively low level of heterogeneity (I 2 = 22.64%) and no evidence of publication bias (p = 0.15, Supplementary Fig. S2). Subgroup analyses found no significant effects for plasma or serum alone, as well as no effect for healthy subjects or depressed patients alone. ...
Context 2
... on short-term changes in plasma and long-term changes in serum; this did not change any of the results. Meta-regressions found no significant effect of age, study design, BDNF immunoassay sensitivity, or overall risk of bias on change in BDNF. Later BDNF measurements were associated with minimally larger effect sizes (SMD = 0.0005, p = 0.038, Fig. 2). Studies comparing change from baseline BDNF between a treatment and placebo group reported significantly lower effect sizes than studies using only a baseline BDNF measurement as a control group (SMD = -0.31, p = 0.031). Additionally, studies with a higher percentage of missing data reported greater effect sizes (SMD = 0.77, p = ...
Context 3
... combined effect size across all psychoplastogens was not significant (SMD = 0.024, p = 0.64). There was a relatively low level of heterogeneity (I 2 = 22.64%) and no evidence of publication bias (p = 0.15, Supplementary Fig. S2). Subgroup analyses found no significant effects for plasma or serum alone, as well as no effect for healthy subjects or depressed patients alone. ...
Context 4
... on short-term changes in plasma and long-term changes in serum; this did not change any of the results. Meta-regressions found no significant effect of age, study design, BDNF immunoassay sensitivity, or overall risk of bias on change in BDNF. Later BDNF measurements were associated with minimally larger effect sizes (SMD = 0.0005, p = 0.038, Fig. 2). Studies comparing change from baseline BDNF between a treatment and placebo group reported significantly lower effect sizes than studies using only a baseline BDNF measurement as a control group (SMD = -0.31, p = 0.031). Additionally, studies with a higher percentage of missing data reported greater effect sizes (SMD = 0.77, p = ...
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Citations
... Sleep-promoting antidepressants like trazodone and mirtazapine also require several days of treatment to show antidepressant properties [13]. In this context, the lack of effects of both drugs on plasma BDNF levels is not surprising, as recent evidence has challenged the robustness, and the biological and clinical utility of blood BDNF measures [34]. Future investigations including repeated administrations are therefore warranted to clarify potential effects of GHB on subjective sleep quality, affective state, and depressive symptoms. ...
In major depressive disorder (MDD), main clinical features include insomnia and increased daytime sleepiness. However, specific treatment options to promote sleep in MDD are limited. Gamma-hydroxybutyrate (GHB, administered as sodium oxybate) is a GHB/GABA B receptor agonist used clinically in narcolepsy, where it promotes restorative slow-wave sleep (SWS) while reducing next-day sleepiness. Hence, we performed a randomized, placebo- and active comparator-controlled, double-blind, crossover trial to investigate the sleep-promoting properties of GHB in individuals with MDD. Outpatients aged 20–65 years fulfilling the DSM-5 criteria for MDD were enrolled. A single nocturnal dose of GHB (50 mg/kg) was compared with a single evening dose of the clinical competitor trazodone (1.5 mg/kg) and placebo. Of 29 randomized patients, 23 received at least one intervention and were included in the analysis. Primary outcomes were nocturnal slow wave sleep ([SWS] assessed by polysomnography), next-day vigilance (median response time and number of lapses on the psychomotor vigilance test [PVT]), next-day working memory (median speed and accuracy on an N-back task), and next-day plasma brain-derived neurotrophic factor (BDNF) levels. GHB robustly prolonged SWS compared to both trazodone and placebo. GHB also prolonged total sleep time and enhanced sleep efficiency, while reducing sleep stages N1, N2, and wake-after-sleep-onset. While the median response time on the next-day PVT was unaffected, GHB reduced the number of lapses compared to trazodone and placebo. No effects on next-day working memory performance and BDNF levels were observed. No serious adverse events occurred. Overall, a single nocturnal dose of GHB effectively promotes SWS and shows more favorable effects on next-day vigilance than trazodone and placebo. Future studies should investigate GHB in clinical settings, including repeated administration.
... Additionally, ketamineinduced elevations in rodent peripheral plasma BDNF levels have been shown to not correspond to central BDNF levels, putting into question the usability of peripheral BDNF as a biomarker of central BDNF concentrations following psychedelic treatment (Le Nedelec et al., 2018). A meta-analysis of all human psychedelic/psychoplastogen studies measuring peripheral BDNF illustrated there is no evidence that peripheral BDNF is elevated following administration of psychedelics in humans, suggesting this is not a reliable marker of post-dose changes in neuroplasticity (Calder et al., 2024). This is also indicative of challenges in translating between molecular and psychological levels of inquiry. ...
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... In some studies, increases in BDNF have been associated with the neurotrophic properties of ketamine [41]. In contrast, a recent meta-analysis showed no changes in peripheral BDNF in humans associated with the use of psychoplastogens, suggesting that signaling may not be the best marker of neuroplasticity [42]. Future research may clarify this discrepancy. ...
Background
Eating disorders (EDs) significantly impair physical health and psychosocial functioning. Few effective therapeutic approaches exist for EDs, particularly in Anorexia Nervosa (AN). The use of ketamine, already characterized as a noncompetitive NMDA antagonist anesthetic in depression and suicidal ideations, could be an innovative adjuvant treatment for the AN spectrum.
Methods
We describe a case series of eight patients treated with intravenous Ketamine Adjuvant Treatment (KAT) combined with usual care. We also review the literature and discuss the theoretical mechanisms behind the influence of KAT in EDs. Our patients were all female, with a diagnosis of AN spectrum, and aged between 16 and 44. We offered KAT attempting to remodel rigid food-centered thoughts. Some sessions were guided by psychomotor or psychological support, thus working on self-image, body perceptions, self-esteem, and sensorial re-exposure to “forbidden” food.
Results
KAT significantly improved BMI, with a coefficient of 0.71 (0.23–1.20, p = 0.002), with a tendency to improve weight regain dynamics from the fourth or fifth infusion onwards. It could also reduce AN psychopathology and obsessive-compulsive-like symptoms (ruminations, cognitive rigidity, guilt), improving clinical evolution.
Conclusions
Our findings underscore the potential of KAT as a therapeutic approach for restrictive EDs as an adjuvant treatment or after failure of first-line treatments. It particularly addresses rigid thought patterns and neurocognitive biases that are notoriously difficult to target. Ketamine’s “pro-plasticity” and “pro-neurogenesis” properties may facilitate this effect. KAT represents a potential tool after failure of first-line treatments. Future research in controlled studies is imperative to corroborate its effect.
