Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis

Expert Opinion on Drug Safety, Journal Year: 2022, Volume and Issue: 21(6), P. 853 - 866

Published: March 1, 2022

Background Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy safety of racemic for depression.Research design methods conducted a PRISMA-guided relevant randomized controlled trials or unipolar bipolar major depression from database inception through 2021. random-effects meta-analyses using pooled rate ratios (RRs) Cohen's standardized mean differences (d) with their 95% confidence intervals (CI).Results found 36 studies (2903 participants, 57% female, 45.1 +/- 7.0 years). Nine used esketamine, while rest ketamine. The overall study quality was high. Treatment any form associated improved response (RR=2.14; CI, 1.72-2.66; I2=65%), remission (RR=1.64; 1.33-2.02; I2=39%), severity (d=-0.63; -0.80 -0.45; I2=78%) against placebo. Overall, there no association between treatment retention in (RR=1.00; 0.99-1.01; I2<1%), dropouts due adverse events (RR=1.56; 1.00-2.45; number reported per participant (OR=2.14; 0.82-5.60; I2=62%) Conclusions Ketamine are effective, safe, acceptable treatments individuals living depression.

Language: Английский

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Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 8, 2023

Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering several factors, and has been suggested to reverse neuropathological patterns seen depression. These come at a time great need for novel approaches, as prevalence is rising current treatment options remain inadequate large number people. The rapidly growing literature on ketamine's antidepressant potential yielded multiple proposed mechanisms action, many which have implications recently elucidated aspects depressive pathology. This review aims provide reader an understanding pathology how act it. Literature was identified through PubMed Google Scholar, reference lists retrieved articles. When reviewing evidence pathology, picture emerges four elements interacting each other facilitate progressive worsening, namely stress, inflammation, neurotoxicity neurodegeneration. Ketamine acts all these levels rapid potent reductions symptoms. Converging suggests that works increase stress resilience stress-induced dysfunction, modulate systemic inflammation neuroinflammation, attenuate neurotoxic processes glial synaptogenesis rather than Still, much remains be revealed about research lacking durability effect. findings discussed herein calls more longitudinal approaches when determining efficacy its relation could relevant considerations clinical implementation.

Language: Английский

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Discovering the Potential Mechanisms of Medicinal Mushrooms Antidepressant Activity: A Review

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 623 - 623

Published: March 2, 2023

Major Depression Disease is a common mental illness that affects more than 322 million people worldwide and it one of the leading causes physical disability. The etiology depression complex interplay psychological, social, biological factors. Currently, psychopharmacotherapy based mainly on monoamine theory, which states caused by an insufficient level monoamines such as serotonin, norepinephrine, and/or dopamine. Due to relatively low efficacy typical antidepressant high prevalence treatment-resistant (~30%), seeking new ways prophylaxis, adjuvant therapy, or novel compounds with activity, priority. According studies analyzed mushroom consumption patterns prevalence, was concluded ingestion lowers odds depression. Medicinal mushrooms are considered functional foods because their ability synthesize accumulate different types metabolites, enhance health-promoting properties. review aims explain activity edible/medicinal elucidating mechanism from perspectives: edible source serotonin precursors psilocybin rapid-acting antidepressant. These exhibit anti-neuroinflammatory antioxidant activities impact neurotrophin expression, neurogenesis process, influence gut–brain axis.

Language: Английский

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Molecular mechanisms of rapid-acting antidepressants: New perspectives for developing antidepressants

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106837 - 106837

Published: June 26, 2023

Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds the patients are prone relapse symptoms or completely ineffective in antidepressant treatment. The recent success N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as rapid-acting has propelled extensive research on action mechanism antidepressants, especially relation its role synaptic targets. Studies have revealed that not limited antagonism postsynaptic NMDA receptors GABA interneurons. Ketamine produces powerful and rapid effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic receptors, adenosine A1 L-type calcium channels, among others synapse. More interestingly, 5-HT2A agonist psilocybin demonstrated potential for depressed mouse models clinical studies. This article focuses review new pharmacological target studies emerging drugs such hallucinogens (e.g., psilocybin) briefly discusses possible strategies targets with view shed light direction future research.

Language: Английский

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Clinical specificity profile for novel rapid acting antidepressant drugs

International Clinical Psychopharmacology, Journal Year: 2023, Volume and Issue: 38(5), P. 297 - 328

Published: June 29, 2023

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants not effective in all patients and often show a relevant response latency, range of adverse events, including weight gain sexual dysfunction. Novel rapid agents were developed the aim overcoming at least part these issues. drugs target glutamate, gamma-aminobutyric acid, orexin, other receptors, providing broader pharmacodynamic mechanisms, that is, expected to increase possibility personalizing treatments on individual profile. These new combining action, tolerable profile, higher effectiveness specific symptoms, which relatively poorly targeted by standard antidepressants, such as anhedonia reward, suicidal ideation/behaviours, insomnia, cognitive deficits, irritability. This review discusses specificity profile namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), zuranolone (SAGE-217). The main is provide an overview efficacy/tolerability compounds mood having different symptom/comorbidity patterns, help clinicians optimization risk/benefit ratio when prescribing drugs.

Language: Английский

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