Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Background: Ketamine’s defining side effects are dissociation and increased blood pressure/heart rate. An oral formulation with delayed absorption could minimize these effects. We recently reported safety and tolerability data for an extended release ketamine tablet in healthy volunteers. Methods: To assess safety, tolerability, efficacy, and pharmacokinetics of an extended release oral ketamine tablet in patients with treatment-resistant depression/anxiety. This was a multiple dose open-label flexible dose uncontrolled study in seven patients with treatment-resistant depression/anxiety, who had all previously demonstrated mood improvement to subcutaneous ketamine. Assessments included ratings of anxiety, depression and dissociation, safety and tolerability, and blood samples for ketamine pharmacokinetics and brain-derived neurotrophic factor (BDNF) concentrations. Results: Improvements in anxiety and depression ratings occurred gradually over 96 h; all patients had >50% improvements in mood ratings. Ketamine was safe and well tolerated, with no changes in vital signs, and a single brief report of dissociation. Ketamine may induce its own metabolism, as the ratio of norketamine to ketamine increased out to 96 h. Serum BDNF concentrations did not change during the study. Conclusion: Ketamine’s safety/tolerability may be improved with an extended release oral formulation. Onset of mood improvement is slightly delayed compared with parenteral dosing. These data support the further development of extended release ketamine tablets for treatment of resistant depression and anxiety disorders.

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Effectiveness and tolerability of citalopram for the treatment of depression and anxiety disorders in children and adolescents: an open-label study

Journal of Neural Transmission ◽

10.1007/s00702-009-0330-x ◽

2009 ◽

Vol 117 (1) ◽

pp. 139-145 ◽

Cited By ~ 16

Author(s):

Shella Schirman ◽

Sefi Kronenberg ◽

Alan Apter ◽

David Brent ◽

Nadine Melhem ◽

...

Keyword(s):

Anxiety Disorders ◽

Children And Adolescents ◽

Depression And Anxiety ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Treatment Of Depression

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The Use of Transcranial Focused Ultrasound for the Treatment of Depression and Anxiety

Case Medical Research ◽

10.31525/ct1-nct04250441 ◽

2020 ◽

Author(s):

Keyword(s):

Focused Ultrasound ◽

Depression And Anxiety ◽

Treatment Of Depression ◽

Transcranial Focused Ultrasound

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Faculty Opinions recommendation of Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718255811.793519373 ◽

2016 ◽

Author(s):

William St Clair

Keyword(s):

Disease Activity ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Proof Of Concept ◽

Primary Sjogren’S Syndrome ◽

Open Label ◽

Primary Sjögren's Syndrome ◽

Early Primary ◽

Sjögren‘S Syndrome

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Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study

Translational Psychiatry ◽

10.1038/s41398-021-01230-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adem T. Can ◽

Daniel F. Hermens ◽

Megan Dutton ◽

Cyrana C. Gallay ◽

Emma Jensen ◽

...

Keyword(s):

Suicidal Ideation ◽

Low Dose ◽

Suicide Ideation ◽

Well Being ◽

Primary Outcome Measure ◽

Open Label ◽

Oral Ketamine ◽

High Level ◽

Chronic Suicidality

AbstractRecently, low-dose ketamine has been proposed as a rapid-acting treatment option for suicidality. The majority of studies to date have utilised intravenous (IV) ketamine, however, this route of administration has limitations. On the other hand, oral ketamine can be administered in a range of settings, which is important in treating suicidality, although studies as to safety and feasibility are lacking. n = 32 adults (aged 22–72 years; 53% female) with chronic suicidal thoughts participated in the Oral Ketamine Trial on Suicidality (OKTOS), an open-label trial of sub-anaesthetic doses of oral ketamine over 6 weeks. Participants commenced with 0.5 mg/kg of ketamine, which was titrated to a maximum 3.0 mg/kg. Follow-up assessments occurred at 4 weeks after the final dose. The primary outcome measure was the Beck Scale for Suicide Ideation (BSS) and secondary measures included scales for suicidality and depressive symptoms, and measures of functioning and well-being. Mean BSS scores significantly reduced from a high level of suicidal ideation at the pre-ketamine (week 0) timepoint to below the clinical threshold at the post-ketamine (week 6) timepoint. The proportion of participants that achieved clinical improvement within the first 6 weeks was 69%, whereas 50% achieved a significant improvement by the follow-up (week 10) timepoint. Six weeks of oral ketamine treatment in participants with chronic suicidality led to significant reduction in suicidal ideation. The response observed in this study is consistent with IV ketamine trials, suggesting that oral administration is a feasible and tolerable alternative treatment for chronic suicidality.

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Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽

10.1186/s13063-021-05033-x ◽

2021 ◽

Vol 22 (1) ◽

Cited By ~ 1

Author(s):

Iwein Gyselinck ◽

◽

Laurens Liesenborghs ◽

Ewout Landeloos ◽

Ann Belmans ◽

...

Keyword(s):

Clinical Trial ◽

Standard Of Care ◽

Ordinal Scale ◽

Cytokine Signaling ◽

Nasopharyngeal Swab ◽

The Novel ◽

Proof Of Concept ◽

Open Label ◽

Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

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