Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression

Zheng, Wei; Gu, Li-Mei; Zhou, Yanling; Wang, Chengyu; Lan, Xiaofeng; Zhang, Bin; Shi, Haishan; Wang, Danfeng; Ning, Yuping

doi:10.3389/fpsyt.2021.780975

Cited by 7 publications

(4 citation statements)

References 39 publications

(66 reference statements)

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“…The depression symptom was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) [ 31 ]. In line with the methodology of previous studies [ 18 , 32 - 34 ], the evaluation of anhedonia symptoms was based on the MADRS anhedonia item, including items 1 (apparent sadness), 2 (reported sadness), 6 (concentration difficulties), 7 (lassitude), and 8 (inability to feel) at baseline, day 1 and week 2 after the last ketamine infusion (days 13 and 26). Patients were determined as antianhedonic responders when the reduction rate of anhedonia symptoms was ≥ 50% on day 13 from baseline, while others were determined as antianhedonic nonresponders [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Baseline Plasma BDNF Levelsare Associated with Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Major Depressive Disorder

Zheng

Zhou

et al. 2023

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Objectives: Evidence has shown that brain-derived neurotrophic factor (BDNF) is associated with anhedonia symptoms in MDD patients, while the rapid antianhedonic effects of ketamine may occur independently of depressive symptoms. To our knowledge, the relationship between plasma BDNF (pBDNF) and the effect of repeated-dose intravenous ketamine on anhedonic symptoms has not been investigated. Methods: Seventy-five Chinese individuals with major depressive disorder (MDD) received ketamine treatments. Anhedonia and pBDNF concentrations were evaluated with a subscale of the Montgomery–Åsberg Depression Rating Scale (MADRS) and enzyme-linked immunosorbent assay (ELISA) at baseline, day 13 and day 26. Results: Baseline pBDNF levels were associated with changes in anhedonic symptoms on day 13 (r=0.30, P=0.008). Interestingly, pBDNF concentrations were associated with changes in anhedonia symptomson day 26 (r=0.10, P=0.02). Baseline pBDNF levels were higher in antianhedonic responders than in antianhedonic responders (F=4.2, P=0.04). Ketamine reduced anhedonia symptoms in antianhedonic responders compared to nonresponders on days 13 and 26 (all Ps<0.05). The baseline high BDNF group had a lower level of anhedonia than the low BDNF group on days 13 (P<0.001) and 26 (P=0.01). Conclusion: Our study suggests that baseline pBDNF concentrations may predict the antianhedonic effect in individuals with MDD treated with repeated doses of ketamine.

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Section: Methodsmentioning

confidence: 99%

Baseline Plasma BDNF Levelsare Associated with Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Major Depressive Disorder

Zheng

Zhou

et al. 2023

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“…Clinical ratings of the severity of anhedonic symptoms measured in a sample of individuals with melancholic and non-melancholic depression at baseline, at 4 and 24 h after each infusion of the study agent, and at 2 weeks postinfusion (day 26) using the Montgomery–Åsberg Depression Rating Scale (MADRS). Following the methodology of previous studies ( 20 – 22 ), the anhedonia items of the MADRS, including assessments of apparent sadness, concentration difficulties, lassitude, reported sadness, and inability to feel, were utilized to assess the severity of anhedonic symptoms ( 23 , 24 ). The coprimary endpoints were the comparison of antianhedonic response and remission (≥50 and ≥75% reduction of the MADRS anhedonia subscale scores at day 13, respectively) ( 25 , 26 ) between individuals with melancholic and non-melancholic depression.…”

Section: Methodsmentioning

confidence: 99%

A comparison of the antianhedonic effects of repeated ketamine infusions in melancholic and non-melancholic depression

Zheng

Yang

et al. 2022

Front. Psychiatry

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ObjectivesMelancholic depression may respond differently to certain treatments. The aim of this study was to compare the antianhedonic effects of six intravenous injections of 0.5 mg/kg ketamine in patients with melancholic and non-melancholic depression, which remain largely unknown.MethodsIndividuals experiencing melancholic (n = 30) and non-melancholic (n = 105) depression were recruited and assessed for anhedonic symptoms using the Montgomery–Åsberg Depression Rating Scale (MADRS). The presence of melancholic depression was measured with the depression scale items at baseline based on DSM-5 criteria.ResultsA total of 30 (22.2%) patients with depression fulfilled the DSM-5 criteria for melancholic depression. Patients with melancholic depression had a non-significant lower antianhedonic response (43.3 vs. 50.5%, t = 0.5, p > 0.05) and remission (20.0 vs. 21.0%, t = 0.01, p > 0.05) to repeated-dose ketamine infusions than those with non-melancholic depression. The melancholic group had significantly lower MADRS anhedonia subscale scores than the non-melancholic group at day 26 (p < 0.05).ConclusionAfter six ketamine infusions, the improvement of anhedonic symptoms was found in both patients with melancholic and non-melancholic depression, and the efficacy was similar in both groups.

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“…Item analysis indicates that ketamine and esketamine not only significantly improve overall symptoms of TRD, but also specific depressive symptoms that are over-represented in adults with TRD, such as anhedonia [196][197][198][199] . Meta-analytic data also indicate that glutamatergic treatment strategies may be superior to antipsychotic agents in adults with TRD 200,201 .…”

Section: Ketamine/esketaminementioning

confidence: 99%

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

McIntyre,

Alsuwaidan,

Baune

et al. 2023

World Psychiatry

112

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Treatment‐resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision‐making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision‐making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo‐resistant (e.g., due to inadequacy of treatment trials or non‐adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non‐response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co‐administered with an antidepressant) are established as efficacious in the management of TRD. Some second‐generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine‐fluoxetine combination has been studied in FDA‐defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA‐approved for individuals with TRD, with accelerated theta‐burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non‐inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual‐based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

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Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression

Cited by 7 publications

References 39 publications

Baseline Plasma BDNF Levelsare Associated with Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Major Depressive Disorder

Baseline Plasma BDNF Levelsare Associated with Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Major Depressive Disorder

A comparison of the antianhedonic effects of repeated ketamine infusions in melancholic and non-melancholic depression

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

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