The effect of intranasal (R,S)-ketamine on symptoms of fatigue in severe major depressive disorder or bipolar depression with and without comorbid alcohol use disorder: Results from a randomized, double-blind, placebo-controlled trial

Article

作者: Lane, Scott D. ; Jones, Gregory H ; Henter, Ioline D. ; Vecera, Courtney M. ; Soares, Jair C. ; Henter, Ioline D ; Vecera, Courtney M ; Jones, Gregory H. ; Courtes, Alan C ; Ruiz, Ana C. ; Machado-Vieira, Rodrigo ; Zarate, Carlos A ; Soares, Jair C ; Ruiz, Ana C ; Lane, Scott D ; Zarate, Carlos A. ; Courtes, Alan C.

BACKGROUNDFatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal (IN) ketamine in individuals with fatigue. This study sought to evaluate the anti-fatigue effects of a single 50 mg dose of IN ketamine in individuals with major depressive disorder (MDD) or bipolar depression (BDep), both with and without comorbid alcohol use disorder (AUD).METHODSTwenty-eight individuals with primary diagnoses of MDD or BDep I/II currently experiencing a depressive episode with active suicidality were enrolled; approximately 60 % had comorbid AUD. Changes in the NIH-Brief Fatigue Inventory (NIH-BFI) were assessed at baseline and at 4, 24, and 48 h post-treatment.RESULTSThe group x time interaction for NIH-BFI score was significant (F = 3.44, p = 0.022), favoring IN ketamine over placebo. IN ketamine was well-tolerated with minimal adverse effects.LIMITATIONSLimitations include the limited sample size, short duration, and single, fixed dose.CONCLUSIONSIN ketamine appears to induce rapid anti-fatigue effects in individuals with severe MDD and BDep both with and without comorbid AUD. This suggests that IN ketamine holds potential as an alternative, rapid-acting, anti-fatigue option for different medical conditions.

2024-12-01·Science of The Total Environment

Unveil the toxicity induced on early life stages of zebrafish (Danio rerio) exposed to 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers

Article

作者: Gonçalves, Virgínia M.F. ; Gonçalves, Virgínia M F ; Langa, Ivan ; Ribeiro, Cláudia ; Félix, Luís ; Tiritan, Maria Elizabeth ; Ribeiro, Ondina ; Carrola, João Soares ; Torres-Ruiz, Monica

The increased detection of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) in aquatic ecosystems, has raised concern worldwide about its possible negative impacts on wildlife. MDMA is produced as racemate but its enantioselective effects on non-target organisms are poorly understood. Therefore, this study aimed to provide a comprehensive study of the toxicity of MDMA and its enantiomers in the early life stages of zebrafish (Danio rerio). Zebrafish embryos (≈3 h post fertilization) were exposed to different concentrations (0.02, 0.2, 2, 20, and 200 μg/L) of (R,S)-MDMA and both pure enantiomers. Both enantiomers induced effects on embryonic development, DNA integrity, and behaviour and enantioselective effects were noted. (S)-MDMA exhibits higher toxic effects on embryonic development level with increased mortality and severity of teratogenic effects, and behavioural abnormalities in acoustic startle-habituation response. (R)-MDMA affected general activity and avoidance behaviour, showing greater inhibitory effects on behavioural activity. Additionally, (R,S)-MDMA induced higher genotoxic effects than the two isolated enantiomers. These results are of concern at populational levels since effects on mortality, development, and behaviour were observed even at environmentally relevant concentrations, which can cause a reduction of larval viability and in the number of individuals in each generation, and an increase in the risk of predation of the organisms. Yet, the bioaccumulation studies showed that MDMA is not accumulated in zebrafish. Therefore, this work demonstrated for the first time the occurrence of MDMA enantiotoxicity in the early life stages of zebrafish, which should be considered in further environmental risk assessments involving fish species or other non-target aquatic organisms.

2022-03-01·Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Response to intravenous racemic ketamine after switch from intranasal (S)‐ketamine on symptoms of treatment‐resistant depression and post‐traumatic stress disorder in Veterans: A retrospective case series

作者: Ramanathan, Dhakshin ; Mehaffey, Eamonn ; Printz, David ; Martis, Brian ; Bentley, Sean ; Bismark, Andrew ; Baker, Dewleen G. ; Mishra, Jyoti ; De Peralta, Sharon ; Sojourner, Kevin ; Artin, Hewa ; Liu, Fred ; Lee, Ellen E.

AbstractBackgroundRacemic (R,S)‐ketamine is a glutamatergic drug with potent and rapid acting antidepressant effects. An intranasal formulation of (S)‐ketamine was recently approved by the US Food and Drug Administration (FDA) to be used in individuals with treatment‐resistant depression (TRD). There are no data directly comparing outcomes on depression or other comorbidities between these two formulations of ketamine. However, recent meta‐analyses have suggested that IV racemic ketamine may be more potent than IN‐(S)‐ketamine.MethodsWe retrospectively analyzed clinical outcomes in 15 Veterans with comorbid TRD and post‐traumatic stress disorder (PTSD) who underwent ketamine treatment at the VA San Diego Neuromodulation Clinic. All Veterans included in this analysis were given at least 6 intranasal (IN)‐(S)‐ketamine treatments prior to switching to treatment with IV racemic ketamine.ResultsVeterans receiving ketamine treatment ( across both IN‐(S)‐ketamine and IV‐(R,S)‐ketamine) showed significant reductions in both the Patient Health Questionnaire‐9 (PHQ‐9), a self‐report scale measuring depression symptoms (rm ANOVA F(14,42) = 12.6, p < 0.0001), and in the PTSD checklist for DSM‐5 (PCL‐5), a self‐report scale measuring PSTD symptoms (rm ANOVA F(13,39) = 5.9, p = 0.006). Post hoc testing revealed that PHQ‐9 scores were reduced by an average of 2.4 ± 1.2 compared to baseline after (S)‐ketamine treatments (p = 0.1) and by an average of 5.6 ± 1 after IV‐ketamine treatments (p = 0.0003) compared to pretreatment baseline scores. PCL‐5 scores were reduced by an average of 4.3 ± 3.3 after IN (S)‐ketamine treatments (p = 0.6) and 11.8 ± 3.5 after IV‐ketamine treatments (p = 0.03) compared to pretreatment baseline scores.ConclusionsThis work suggests that off‐label IV‐(R,S)‐ketamine could be considered a reasonable next step in patients who do not respond adequately to the FDA‐approved IN‐(S)‐ketamine. Further double‐blinded, randomized controlled trials are warranted to assess whether IV racemic ketamine is more effective than IN‐(S)‐ketamine.

100 项与 (R, S)-16s(Zhejiang University) 相关的药物交易

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