scholarly journals Using Oral and Intranasal Dosage Forms of Ketamine for Managing Treatment-Resistant Depression: A Review of the Literature

2016 ◽  
Vol 4 (2) ◽  
pp. 64-71 ◽  
Author(s):  
Patrick Arthur Twohig ◽  
Vaughn Huckfeldt
Keyword(s):  
Health Care ◽  
Side Effects ◽  
Care Setting ◽  
Dosage Forms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Similar Reduction ◽  
Aspartate Receptor ◽  
Pubmed Database ◽  
Resistant Depression

A lack of effective treatment for patients with treatment-resistant depression (TRD) has led to the evaluation of ketamine, an N-methyl- D-aspartate receptor antagonist. Despite the demonstrated short-term benefits of using intravenous (IV) ketamine, side effects and the difficulty in administering ketamine outside the health-care setting has raised interest in alternative dosage forms. Research articles evaluating oral or intranasal (IN) ketamine were retrieved from the PubMed database. Patients who received oral or IN ketamine experienced a similar reduction in depressive symptoms within 24 hours of treatment and fewer side effects compared to patients who received IV ketamine. Novel administration forms of ketamine provide an opportunity for patients with TRD to achieve remission with fewer adverse side effects. Future studies should continue to evaluate these administration strategies in the hope of promoting ketamine’s use outside health-care settings and for longer time periods.

scholarly journals Ketamine: A tale of two enantiomers

2020 ◽  
pp. 026988112095964
Author(s):  
Luke A Jelen ◽  
Allan H Young ◽  
James M Stone
Keyword(s):  
Side Effects ◽  
Receptor Antagonist ◽  
The United States ◽  
Receptor Activation ◽  
Racemic Mixture ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Aspartate Receptor ◽  
Antidepressant Effects ◽  
Resistant Depression

The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and abuse potential. Ketamine is a racemic mixture, composed of equal amounts of (S)-ketamine and (R)-ketamine. An (S)-ketamine nasal spray has been developed and approved for use in treatment-resistant depression in the United States and Europe; however, some concerns regarding efficacy and side effects remain. Although (R)-ketamine is a less potent N-Methyl-D-Aspartate receptor antagonist than (S)-ketamine, increasing preclinical evidence suggests (R)-ketamine may have more potent and longer lasting antidepressant effects than (S)-ketamine, alongside fewer side effects. Furthermore, a recent pilot trial of (R)-ketamine has demonstrated rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research is ongoing to determine the specific cellular and molecular mechanisms underlying the antidepressant actions of ketamine and its component enantiomers in an effort to develop future rapid-acting antidepressants that lack undesirable effects. Here, we briefly review findings regarding the antidepressant effects of ketamine and its enantiomers before considering underlying mechanisms including N-Methyl-D-Aspartate receptor antagonism, γ-aminobutyric acid-ergic interneuron inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor activation, brain-derived neurotrophic factor and tropomyosin kinase B signalling, mammalian target of rapamycin complex 1 and extracellular signal-regulated kinase signalling, inhibition of glycogen synthase kinase-3 and inhibition of lateral habenula bursting, alongside potential roles of the monoaminergic and opioid receptor systems.

scholarly journals Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression

2020 ◽  
Vol 263 ◽  
pp. 568-575 ◽  
Author(s):  
Elia E. Acevedo-Diaz ◽  
Grace W. Cavanaugh ◽  
Dede Greenstein ◽  
Christoph Kraus ◽  
Bashkim Kadriu ◽  
...  
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Comprehensive Assessment ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

scholarly journals Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

2019 ◽  
Author(s):  
Eleanor J. Cole ◽  
Katy H. Stimpson ◽  
Brandon S. Bentzley ◽  
Merve Gulser ◽  
Kirsten Cherian ◽  
...  
Keyword(s):  
Side Effects ◽  
Rating Scale ◽  
Neuropsychological Testing ◽  
Anterior Cingulate ◽  
High Dose ◽  
Delayed Response ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resting Motor Threshold ◽  
Resistant Depression

AbstractBackgroundCurrent treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed ‘Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)’.MethodsTwenty-one participants with TRD received open-label SAINT. FcMRI was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.ResultsNineteen of 21 participants (90.48%) met criteria for remission (≤10 on the Montgomery-Åsberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events.DiscussionOur accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.Trial registrationClinicalTrials.gov NCT03240692

scholarly journals Esketamine in Treatment Resistant Depression: The Way to Remission

2021 ◽  
pp. 35-39
Author(s):  
João Facucho-Oliveira ◽  
Daniel Esteves-Sousa ◽  
Bruno Prates ◽  
Rui Neves ◽  
Pedro Varandas
Keyword(s):  
Depressive Symptoms ◽  
Behavioral Therapy ◽  
Symptomatic Relief ◽  
European Medicines Agency ◽  
Caucasian Woman ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Aspartate Receptor ◽  
Resistant Depression

Major depressive disorder affects an estimate of 5% of the population with nearly 1‑third of patients failing to achieve remission with conventional pharmacological treatment. Esketamine, a novel rapid‑acting antidepressant, with a noncompetitive antagonism on N‑methyl‑D‑Aspartate receptor, have been recently approved by Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment‑resistant depression. Here, we report a clinical case of a 42‑year‑old Caucasian woman who endured many years with severe depressive symptoms and high functional impairment. Previous treatments included cognitive behavioral therapy, numerous pharmacological trials with antidepressants and augmentation agents, and neurostimulation approaches. Upon treatment with esketamine, the patient presented remarkable clinical recovery. Psychometric assessments determined an acute reduction on the MADRS score after 1 week and progressive recovery of the depressive symptoms on the following weeks. Likewise, PHQ‑9 scale assessments, evaluating the relative frequency of depressive symptoms. and the Sheehan scale, assessing functional recovery, also determined a pronounced symptomatic relief.

scholarly journals A Review of the Mechanism of Antagonism of N-methyl-D-aspartate Receptor by Ketamine in Treatment-resistant Depression

Cureus ◽  
2018 ◽  
Author(s):  
Yasar Sattar ◽  
John Wilson ◽  
Ali M Khan ◽  
Mahwish Adnan ◽  
Daniel Azzopardi Larios ◽  
...  
Keyword(s):  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Aspartate Receptor ◽  
Resistant Depression

scholarly journals Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature

2017 ◽  
Vol 7 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Sarah E. Grady ◽  
Travis A. Marsh ◽  
Allison Tenhouse ◽  
Kelsey Klein
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Bipolar Depression ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Randomized Controlled ◽  
The Past ◽  
Aspartate Receptor ◽  
Resistant Depression

Abstract Introduction: Over the past decade, ketamine has been studied for major depressive disorder and bipolar depression. Ketamine is believed to exert its antidepressant properties through N-methyl-D-aspartate receptor antagonism. Methods: Study authors completed a literature review of seven randomized controlled trials of ketamine usage in major depressive disorder and bipolar depression. Results: Ketamine demonstrated a statistically significant improvement over placebo or midazolam in major depressive disorder. Ketamine also exhibited a statistically significant improvement over placebo in bipolar depression. Discussion: Ketamine has shown promise in quickly reducing symptoms in patients with treatment resistant depression and bipolar depression. Using ketamine may be helpful for patients that have exhausted other therapeutic options.

scholarly journals Oral ketamine for the treatment of pain and treatment-resistant depression

2016 ◽  
Vol 208 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Robert A. Schoevers ◽  
Tharcila V. Chaves ◽  
Sonya M. Balukova ◽  
Marije aan Het Rot ◽  
Rudie Kortekaas
Keyword(s):  
Chronic Pain ◽  
Side Effects ◽  
Negative Consequences ◽  
Treatment Resistant Depression ◽  
Dosing Regimen ◽  
Treatment Resistant ◽  
Oral Ketamine ◽  
Study Results ◽  
Resistant Depression ◽  
Time Periods

BackgroundRecent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications.AimsTo review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain.MethodSearches in PubMed with the terms ‘oral ketamine’, ‘depression’, ‘chronic pain’, ‘neuropathic pain’, ‘intravenous ketamine’, ‘intranasal ketamine’ and ‘subcutaneous ketamine’ yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality.ResultsOverall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects.ConclusionsOral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials.

scholarly journals Incremental Health Care Burden of Treatment-Resistant Depression Among Commercial, Medicaid, and Medicare Payers

2020 ◽  
Vol 71 (6) ◽  
pp. 593-601 ◽  
Author(s):  
Anshu Shrestha ◽  
Meaghan Roach ◽  
Kruti Joshi ◽  
John J. Sheehan ◽  
Prodyumna Goutam ◽  
...  
Keyword(s):  
Health Care ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Care Burden ◽  
Burden Of Treatment ◽  
Health Care Burden ◽  
Resistant Depression
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