Diminished GABAA Receptor-Binding Capacity and a DNA Base Substitution in a Patient with Treatment-Resistant Depression and Anxiety

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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Validity of the Maudsley Staging Method in Predicting Treatment-Resistant Depression Outcome Using the Netherlands Study of Depression and Anxiety

The Journal of Clinical Psychiatry ◽

10.4088/jcp.17m11475 ◽

2018 ◽

Vol 79 (1) ◽

pp. 17m11475 ◽

Cited By ~ 3

Author(s):

Sjoerd M. van Belkum ◽

Hanneke Geugies ◽

Thom S. Lysen ◽

Anthony J. Cleare ◽

Frenk P. M. L. Peeters ◽

...

Keyword(s):

The Netherlands ◽

Depression And Anxiety ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Resistant Depression

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Critical review of available treatment options for treatment refractory depression and anxiety - clinical and ethical dilemmas

Medicinski pregled ◽

10.2298/mpns1606171k ◽

2016 ◽

Vol 69 (5-6) ◽

pp. 171-176 ◽

Cited By ~ 2

Author(s):

Dusan Kolar ◽

Michael Kolar

Keyword(s):

Anxiety Disorders ◽

Ethical Dilemmas ◽

Treatment Options ◽

Depression And Anxiety ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Symptoms Of Depression ◽

Mood And Anxiety Disorders ◽

Resistant Depression ◽

Treatment Refractory

Treatment-resistant mood and anxiety disorders require an intensive therapeutic approach, and it should balance benefits and adverse effects or other potential detrimental effects of medications. The goal of treatment is to provide consistent and lasting improvement in symptoms of depression and anxiety. Benzodiazepines are effective for anxiety symptoms, but with no sustained treatment effects. Other medication treatment options for anxiety disorders are outlined. Ketamine is usually very effective in treating major depressive disorder but without sustained benefits. Long-term use may pose a significant risk of developing tolerance and dependence. Stimulant medication augmentation for treatment-resistant depression is effective for residual symptoms of depression, but effects are usually short-lasting and it sounds more as an artificial way of improving energy, alertness and cognitive functioning. Synthetic cannabinoids and medical marijuana are increasingly prescribed for various medical conditions, but more recently also for patients with mood and anxiety disorders. All of these treatments may raise ethical dilemmas about appropri?ateness of prescribing these medications and a number of questions regarding the optimal treatment for patients with treatment-resistant depression and treatment refractory anxiety disorders.

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The prominence of anhedonia in treatment resistant depression and links to dopamine receptor binding

10.26226/morressier.5785edc9d462b80296c998ff ◽

2016 ◽

Author(s):

Sakina Rizvi

Keyword(s):

Dopamine Receptor ◽

Receptor Binding ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Resistant Depression ◽

Dopamine Receptor Binding

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Does anxiety moderate the effectiveness of mirtazapine in patients with treatment-resistant depression? A secondary analysis of the MIR trial

Journal of Psychopharmacology ◽

10.1177/0269881120965939 ◽

2020 ◽

Vol 34 (12) ◽

pp. 1342-1349

Author(s):

Raphael Rifkin-Zybutz ◽

Stephanie MacNeill ◽

Simon JC Davies ◽

Christopher Dickens ◽

John Campbell ◽

...

Keyword(s):

Primary Care ◽

Reuptake Inhibitor ◽

Secondary Analysis ◽

Anxiety Symptoms ◽

Generalized Anxiety ◽

Depression And Anxiety ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Likelihood Ratio Testing ◽

Resistant Depression

Background: There is a lack of evidence to guide treatment of comorbid depression and anxiety. Preliminary evidence suggests mirtazapine may be effective in treating patients with both depression and anxiety symptoms. Methods: We undertook a secondary analysis of mirtazapine (MIR): a placebo-controlled trial of the addition of mirtazapine to a selective serotonin reuptake inhibitor or serotonin–norepinephrine reuptake inhibitor in treatment-resistant depression (TRD) in primary care. We subdivided participants into three groups by baseline generalized anxiety disorder score (GAD-7): severe (GAD-7 ⩾ 16), moderate (GAD-7 = 11–15), no/mild (GAD-7 ⩽ 10). We used linear regression including likelihood-ratio testing of interaction terms to assess how baseline anxiety altered the response of participants to mirtazapine as measured by 12-week GAD-7 and Beck Depression Inventory II (BDI-II) scores. Results: Baseline generalized anxiety moderated mirtazapine’s effect as measured by GAD-7 ( p = 0.041) and BDI-II ( p = 0.088) at 12 weeks. Participants with severe generalized anxiety receiving mirtazapine had lower 12-week GAD-7 score (adjusted difference between means (ADM) −2.82, 95% confidence interval (CI) −0.69 to −4.95) and larger decreases in BDI-II score (ADM −6.36, 95% CI −1.60 to −10.84) than placebo. Conversely, there was no anxiolytic benefit (ADM 0.28, 95% CI −1.05 to 1.60) or antidepressant benefit (ADM −0.17, 95% CI −3.02 to 2.68) compared with placebo in those with no/mild generalized anxiety. Conclusions: These findings extend the evidence for the effectiveness of mirtazapine to reduce generalized anxiety in TRD in primary care. These results may inform targeted prescribing in depression based on concurrent anxiety symptoms, although these conclusions are constrained by the post-hoc nature of this analysis.

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