Oral ketamine augmentation for chronic suicidality in treatment-resistant depression

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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New use for an old drug: oral ketamine for treatment-resistant depression: Table 1

BMJ Case Reports ◽

10.1136/bcr-2016-216088 ◽

2016 ◽

pp. bcr2016216088 ◽

Cited By ~ 5

Author(s):

Kevin M Swiatek ◽

Kim Jordan ◽

Julie Coffman

Keyword(s):

Treatment Resistant Depression ◽

Treatment Resistant ◽

Oral Ketamine ◽

Resistant Depression

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Oral Ketamine as a Treatment Option in Patients With Treatment Resistant Depression and Comorbid Arterial Hypertension

Journal of Clinical Psychopharmacology ◽

10.1097/jcp.0000000000001238 ◽

2020 ◽

Vol 40 (4) ◽

pp. 418-420

Author(s):

Leo R. Silberbauer ◽

Lucie Bartova ◽

Konstantinos Papageorgiou ◽

Rupert Lanzenberger ◽

Siegfried Kasper ◽

...

Keyword(s):

Arterial Hypertension ◽

Treatment Option ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Oral Ketamine ◽

Resistant Depression

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Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study

Psychopharmacology ◽

10.1007/s00213-017-4786-3 ◽

2017 ◽

Vol 235 (2) ◽

pp. 393-398 ◽

Cited By ~ 19

Author(s):

John Hartberg ◽

Simone Garrett-Walcott ◽

Angelo De Gioannis

Keyword(s):

Retrospective Study ◽

Hospital Admissions ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Oral Ketamine ◽

Resistant Depression

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

The British Journal of Psychiatry ◽

10.1192/bjp.bp.115.165498 ◽

2016 ◽

Vol 208 (2) ◽

pp. 108-113 ◽

Cited By ~ 32

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.

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Efficacy of Oral Ketamine Combined with Psychotherapy for Treatment Resistant Depression

European Journal of Medical and Health Sciences ◽

10.24018/ejmed.2021.3.4.979 ◽

2021 ◽

Vol 3 (4) ◽

pp. 106-108

Author(s):

Tatiana Zydb ◽

MIchael Hart

Keyword(s):

Depressive Episode ◽

Low Dose ◽

Major Depressive Episode ◽

Antidepressant Medication ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Major Depressive ◽

Oral Ketamine ◽

Resistant Depression ◽

The Difference

Background: Treatment resistant depression (TRD) is defined as a major depressive episode that does not improve in response to at least two trials, each of a different class, of antidepressant medication. Pharmacotherapy of TRD with low dose ketamines has been shown as relatively successful in recent studies. Effects of such pharmacotherapy can be augmented by combining ketamine with psychotherapeutic interventions such as Zdyb’s Therapeutic Reset of Internal Processes (TRIP) protocol. Method: 10 adult TRD patients (4 men, 6 women) were treated with low dose ketamines and were also receiving psychotherapeutic intervention as per TRIP protocol. All patients were administered the Patient Health Questionnaire, module 9 (PHQ9) which is a measure of a major depressive episode. The PHQ9 was administered twice: on baseline (i.e., prior to treatment) and after the treatment. Results: On average, our patients fell in the moderate range of severity with respect to symptoms of TRD at baseline (pre-TRIP) as by their mean PHQ9 score of 17.9, (SD = 5.1). Their mean PHQ9 score decreased post TRIP treatment to 9.5 (SD = 6.6): the difference is significant in a t-test, t(10) = 4.3172, p = 0002 (two-tailed). The magnitude of the decrease amounts to 46.9% of the average baseline score. Discussion and Conclusions: Our patients experienced significant reductions in symptoms of TRD in this pilot study. Research studies are now needed with control groups of TRD patients on a waiting list or also of those receiving only the ketamine pharmacotherapy.

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