Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study

被引:24
作者
Glue, Paul [1 ]
Medlicott, Natalie J. [2 ]
Neehoff, Shona [3 ]
Surman, Peter [4 ]
Lam, Fred [5 ]
Hung, Noelyn [5 ]
Hung, Cheung-tak [5 ]
机构
[1] Univ Otago, Sch Med Sci, Hazel Buckland Chair Psychol Med, POB 913, Dunedin 9054, New Zealand
[2] Univ Otago, Sch Pharm, Dunedin, New Zealand
[3] Univ Otago, Psychol Med, Dunedin, New Zealand
[4] Douglas Pharmaceut Ltd, Auckland, New Zealand
[5] Zenith Technol Ltd, Dunedin, New Zealand
关键词
anxiety; depression; dissociation; extended-release ketamine tablet; first-in-patient; pharmacodynamics; pharmacokinetics; safety; STATES;
D O I
10.1177/2045125320922474
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页数:6
相关论文
共 20 条
[1]   Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? [J].
Andrade, Chittaranjan .
JOURNAL OF CLINICAL PSYCHIATRY, 2017, 78 (07) :E852-E857
[2]   Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS) [J].
Bremner, JD ;
Krystal, JH ;
Putnam, FW ;
Southwick, SM ;
Marmar, C ;
Charney, DS ;
Mazure, CM .
JOURNAL OF TRAUMATIC STRESS, 1998, 11 (01) :125-136
[3]  
Glue P, 2019, US Patent Office, Patent No. [10,441,544 B2, 10441544]
[4]   Ascending-Dose Study of Controlled-Release Ketamine Tablets in Healthy Volunteers: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability [J].
Glue, Paul ;
Medlicott, Natalie J. ;
Surman, Peter ;
Lam, Fred ;
Hung, Noelyn ;
Hung, C. Tak .
JOURNAL OF CLINICAL PHARMACOLOGY, 2020, 60 (06) :751-757
[5]   Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study [J].
Glue, Paul ;
Neehoff, Shona ;
Sabadel, Amandine ;
Broughton, Lucy ;
Le Nedelec, Martin ;
Shadli, Shabah ;
McNaughton, Neil ;
Medlicott, Natalie J. .
JOURNAL OF PSYCHOPHARMACOLOGY, 2020, 34 (03) :267-272
[6]   Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders [J].
Glue, Paul ;
Medlicott, Natalie J. ;
Harland, Sarah ;
Neehoff, Shona ;
Anderson-Fahey, Bridie ;
Le Nedelec, Martin ;
Gray, Andrew ;
McNaughton, Neil .
JOURNAL OF PSYCHOPHARMACOLOGY, 2017, 31 (10) :1302-1305
[7]   Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression [J].
Haile, C. N. ;
Murrough, J. W. ;
Iosifescu, D. V. ;
Chang, L. C. ;
Al Jurdi, R. K. ;
Foulkes, A. ;
Iqbal, S. ;
Mahoney, J. J., III ;
De La Garza, R., II ;
Charney, D. S. ;
Newton, T. F. ;
Mathew, S. J. .
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2014, 17 (02) :331-336
[8]   THE ASSESSMENT OF ANXIETY-STATES BY RATING [J].
HAMILTON, M .
BRITISH JOURNAL OF MEDICAL PSYCHOLOGY, 1959, 32 (01) :50-55
[9]   Acute low-dose ketamine produces a rapid and robust increase in plasma BDNF without altering brain BDNF concentrations [J].
Le Nedelec, Martin ;
Glue, Paul ;
Winter, Helen ;
Goulton, Chelsea ;
Broughton, Lucy ;
Medlicott, Natalie .
DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 2018, 8 (03) :780-786
[10]  
Liebowitz M R, 1987, Mod Probl Pharmacopsychiatry, V22, P141