Ketamine as a Novel Drug for Depression Treatment.

BACKGROUND Depression is one of the most common mental disorders. Currently used antidepressants, acting on the monoaminergic system, are insufficient for depression treatment. In recent years, potential application of NMDA receptor modulators in the treatment of drug-resistant depression has gained attention. Administration of ketamine, being a non-competitive NMDA receptor antagonist, contributes to a faster remission of symptoms. SUBJECTS AND METHODS The aim of this paper is to review current studies on the use of ketamine in the treatment of drug-resistant depression, compare results of various administration methods - intravenous, intranasal or oral, as well as compare its effectiveness with that of other antidepressants. RESULTS Numerous studies show the drug is effective and well tolerated, particularly in patients with increased suicidal thoughts. However, there are concerns on increasing tolerance to the drug and the possibility of implementing a long-term treatment. CONCLUSION Oral and intranasal forms of the drug are particularly promising due to their non-invasiveness and ability to self-administer. In March 2019, S-ketamine nasal spray was registered by the FDA for the treatment of drug-resistant depression.

[1]  S. Dursun,et al.  Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers , 2020, Therapeutic Advances in Psychopharmacology.

[2]  D. Blumberger,et al.  Management of Treatment-Resistant Depression: Challenges and Strategies , 2020, Neuropsychiatric disease and treatment.

[3]  Yuko Fujita,et al.  Phencyclidine-induced cognitive deficits in mice are ameliorated by subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine: Role of BDNF-TrkB signaling , 2019, Pharmacology Biochemistry and Behavior.

[4]  M. aan het Rot,et al.  Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial , 2019, BMC Psychiatry.

[5]  K. Hashimoto,et al.  Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites , 2019, Translational Psychiatry.

[6]  A. Włodarczyk,et al.  Suicidality in treatment resistant depression: perspective for ketamine use. , 2019, Psychiatria Danubina.

[7]  S. Dursun,et al.  Esketamine for treatment-resistant depression , 2020, Drug and Therapeutics Bulletin.

[8]  M. Fava,et al.  Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) , 2019, The international journal of neuropsychopharmacology.

[9]  C. Andrade.  Oral Ketamine for Depression, 2: Practical Considerations. , 2019, The Journal of clinical psychiatry.

[10]  C. Andrade.  Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. , 2019, The Journal of clinical psychiatry.

[11]  T. Hendler,et al.  Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study , 2018, British Journal of Psychiatry.

[12]  A. Ghajar,et al.  Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial. , 2018, Journal of affective disorders.

[13]  K. Hashimoto,et al.  Is (S)-norketamine an alternative antidepressant for esketamine? , 2018, European Archives of Psychiatry and Clinical Neuroscience.

[14]  Jennifer W. Evans,et al.  Ketamine normalizes brain activity during emotionally valenced attentional processing in depression , 2018, NeuroImage: Clinical.

[15]  D. E. Olson,et al.  Psychedelics Promote Structural and Functional Neural Plasticity , 2018, Cell reports.

[16]  R. Shelton,et al.  Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial , 2017, JAMA psychiatry.

[17]  E. Ballard,et al.  The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. , 2017, The American journal of psychiatry.

[18]  John Hartberg,et al.  Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study , 2017, Psychopharmacology.

[19]  G. Mion.  History of anaesthesia: The ketamine story - past, present and future. , 2017, European journal of anaesthesiology.

[20]  S. Kennedy,et al.  Oral Ketamine in Treatment-Resistant Depression A Clinical Effectiveness Case Series , 2017 .

[21]  M. Afarideh,et al.  Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: A double-blind, randomized, controlled trial. , 2016, Journal of affective disorders.

[22]  K. Olkkola,et al.  Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy , 2016, Clinical Pharmacokinetics.

[23]  J. Dilger,et al.  Ketamine enantiomers in the rapid and sustained antidepressant effects , 2016, Therapeutic advances in psychopharmacology.

[24]  K. Hagi,et al.  Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories , 2016, Psychological Medicine.

[25]  C. Clark,et al.  Ketamine for Treatment-Resistant Unipolar Depression: Current Evidence , 2016 .

[26]  J. Potash,et al.  Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. , 2015, The American journal of psychiatry.

[27]  C. Reilly.  Stoelting's Pharmacology and Physiology in Anesthetic Practice , 2015 .

[28]  Y. Hsu,et al.  Possible pathophysiology of ketamine‐related cystitis and associated treatment strategies , 2015, International journal of urology : official journal of the Japanese Urological Association.

[29]  D. Charney,et al.  A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder , 2014, Biological Psychiatry.

[30]  M. Furey,et al.  Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. , 2014, Journal of psychiatric research.

[31]  Madhuri S. Kurdi,et al.  Ketamine: Current applications in anesthesia, pain, and critical care , 2014, Anesthesia, essays and researches.

[32]  R. Lam,et al.  A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes , 2014, Psychological Medicine.

[33]  Damiaan Denys,et al.  Mental health: A road map for suicide research and prevention , 2014, Nature.

[34]  R. Nelesen,et al.  Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial. , 2013, Journal of palliative medicine.

[35]  Edwin D Boudreaux,et al.  Trends in US emergency department visits for attempted suicide and self-inflicted injury, 1993-2008. , 2012, General hospital psychiatry.

[36]  T. Vos,et al.  Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature , 2012, Psychological Medicine.

[37]  Jan Fawcett,et al.  THE IMPORTANCE OF ANXIETY IN BOTH MAJOR DEPRESSION AND BIPOLAR DISORDER , 2012, Depression and anxiety.

[38]  J. Mann,et al.  Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. , 2012, Archives of general psychiatry.

[39]  G. Sanacora,et al.  Towards a glutamate hypothesis of depression An emerging frontier of neuropsychopharmacology for mood disorders , 2012, Neuropharmacology.

[40]  E. Kavalali,et al.  NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses , 2011, Nature.

[41]  R. Henkin,et al.  Intranasal delivery to the brain , 2011, Nature Biotechnology.

[42]  T. Messer,et al.  Therapieresistente Depressionen , 2009, Fortschritte der Neurologie-Psychiatrie.

[43]  A. Meyer-Lindenberg,et al.  Oral administration of the NMDA receptor antagonist S-ketamine as add-on therapy of depression: a case series. , 2010, Pharmacopsychiatry.

[44]  H. Çankaya,et al.  Nasal obstruction as a common side-effect of sildenafil citrate. , 2006, The Tohoku journal of experimental medicine.

[45]  R. Baldessarini,et al.  Suicidal risk during treatment with clozapine: a meta-analysis , 2005, Schizophrenia Research.

[46]  M. Sharpe,et al.  Psychological autopsy studies of suicide: a systematic review , 2003, Psychological Medicine.

[47]  T. Meert,et al.  Dextromethorphan and ketamine potentiate the antinociceptive effects of μ- but not δ- or κ-opioid agonists in a mouse model of acute pain , 2002, Pharmacology Biochemistry and Behavior.

[48]  M. Michel,et al.  S (+)-Ketamine Increases Muscle Sympathetic Activity and Maintains the Neural Response to Hypotensive Challenges in Humans , 2001, Anesthesiology.

[49]  H. Meltzer,et al.  Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression , 1995, European Neuropsychopharmacology.

[50]  P. White,et al.  Pharmacology of Ketamine Isomers in Surgical Patients , 1980, Anesthesiology.

[51]  A. Beck.  THINKING AND DEPRESSION. I. IDIOSYNCRATIC CONTENT AND COGNITIVE DISTORTIONS. , 1963, Archives of general psychiatry.