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Depressive Disorders

Clinical Predictors of an Antisuicidal Response to Ketamine

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Suicide is one of the leading causes of death in the United States. Despite treatment efforts, the national suicide rate has increased in recent years. Currently, there are no pharmacological treatments for suicidal ideation (SI). For individuals experiencing a suicidal crisis, rapid acting medications may save lives. Recent studies suggest ketamine, a glutamate modulator, elicits rapid antisuicidal responses. We examined clinical factors that might predict ketamine’s antisuicidal response as a step towards understanding ketamine’s mechanism of action on suicidal thoughts.

Yarrington, J., Ballard, E., Luckenbaugh, D., Niciu, M., Lener, M., Kadriu, B., … & Zarate, C. (2017). 1004-Clinical Predictors of an Antisuicidal Response to Ketamine. Biological Psychiatry, 81(10), S406. 10.1016/j.biopsych.2017.02.731
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Mood Dependent Effects of Ketamine on REM Eye Movements in Patients with Treatment Resistant Depression (TRD)

May 15, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

Both REM and NREM sleep are dysregulated in depression. REM dysregulation in MDD is thought to be partially linked to a deficient inhibitory influence of Process-S, leading to increased REM density (RD) and short REM latency (RL). Consistent with its effects on enhanced synaptic plasticity, ketamine increases SWS and early night slow-wave activity (SWA) in patients with TRD. Here we extend the examination of ketamine effects on rapid mood improvement to RD, an important marker of REM sleep in depression.

Hejazi, N., Yu, K., Park, L., Duncan, W., & Zarate, C. (2017). 861-Mood Dependent Effects of Ketamine on REM Eye Movements in Patients with Treatment Resistant Depression (TRD). Biological Psychiatry, 81(10), S348-S349. 10.1016/j.biopsych.2017.02.586
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Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression

May 11, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a double-blind, randomized, parallel-group, placebo-controlled trial of a single ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype: Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received mood ratings before infusion, after infusion, and for the subsequent 14 days. Plasma ketamine levels and BDNF genotypes were assessed. This study found a significant dose-related ketamine effect on scores on the Hamilton Depression Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on at least 2 days between days 2 and 5) also revealed a significant dose-related effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine for treatment-resistant depression and the first to characterize ketamine effects in a genotyped Chinese population in which most (83%) patients possessed at least one copy of the lower functioning Met allele of the BDNF gene.
Su, T. P., Chen, M. H., Li, C. T., Lin, W. C., Hong, C. J., Gueorguieva, R., … & Krystal, J. H. (2017). Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology. 10.1038/npp.2017.94
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Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression

May 11, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

INTRODUCTION:
Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivates the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine’s antidepressant effects.
METHODS:
Patients who were pursuing ketamine infusion therapy for treatment-resistant depression were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol.
RESULTS:
Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first 2 weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine nonresponders did not appear to benefit from CBT.
CONCLUSIONS:
CBT may sustain the antidepressant effects of ketamine in treatment-resistant depression. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine’s antidepressant effects.
Wilkinson, S. T., Wright, D., Fasula, M. K., Fenton, L., Griepp, M., Ostroff, R. B., & Sanacora, G. (2017). Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression. Psychotherapy and Psychosomatics, 86(3), 162-167. 10.1159/000457960
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Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders

May 8, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Recent research suggests that functional connectivity changes may be involved in the pathophysiology of psychiatric disorders. Hyperconnectivity in the default mode network has been associated with psychopathology, but psychedelic serotonin agonists like psilocybin may profoundly disrupt these dysfunctional neural network circuits and provide a novel treatment for psychiatric disorders. We have reviewed the current literature to investigate the efficacy and safety of psilocybin-assisted therapy for the treatment of psychiatric disorders. There were seven clinical trials that investigated psilocybin-assisted therapy as a treatment for psychiatric disorders related to anxiety, depression, and substance use. All trials demonstrated reductions in psychiatric rating scale scores or increased response and remission rates. There were large effect sizes related to improved depression and anxiety symptoms. Psilocybin may also potentially reduce alcohol or tobacco use and increase abstinence rates in addiction, but the benefits of these two trials were less clear due to open-label study designs without statistical analysis. Psilocybin-assisted therapy efficacy and safety appear promising, but more robust clinical trials will be required to support FDA approval and identify the potential role in clinical psychiatry.
Thomas, K., Malcolm, B., & Lastra, D. (2017). Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders. Journal of Psychoactive Drugs, 1-10. 10.1080/02791072.2017.1320734
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Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications.

May 3, 2017 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , ,

Abstract

Current therapeutic approaches to depression fail for millions of patients due to lag in clinical response and non-adherence. Here we provide new support for the antidepressant effect of an anesthetic drug, ketamine, by Inverse-Frequency Analysis of eight million reports from the FDA Adverse Effect Reporting System. The results of the examination of population scale data revealed that patients who received ketamine had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain. The analysis also revealed that patients who took ketamine had significantly lower frequency of reports of pain and opioid induced side effects, implying ketamine’s potential to act as a beneficial adjunct agent in pain management pharmacotherapy. Further, the Inverse-Frequency Analysis methodology provides robust statistical support for the antidepressant action of other currently approved therapeutics including diclofenac and minocycline.
Cohen, I. V., Makunts, T., Atayee, R., & Abagyan, R. (2017). Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications. Scientific Reports, 7. 10.1038/s41598-017-01590-x
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Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

May 1, 2017 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology / By / ,

Abstract

Over more than 60 years, monoamine oxidase (MAO) inhibitors are available for therapy of central nervous diseases. Although they have shown to be efficacious specifically in the treatment of major depressive disorders and treatment-resistant depression, they became less a therapeutic choice for the physicians mostly due to severe side effects, such as liver failure and hypertensive crisis associated specifically with the first generation of inhibitors. Nevertheless, this class of drugs is still being used for treatment specifically as more selective and reversible inhibitors became available and will provide clinicians with additional treatment options. The current review revisits monoamine oxidase inhibitors and their potential in the treatment of human diseases, such as anxiety, depression, mood and personality disorders, and pain and introduces current ideas and developments.
Entzeroth, M., & Ratty, A. K. (2017). Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle. Open Journal of Depression, 6(02), 31. 10.4236/ojd.2017.62004
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1001. Neurocognitive Effects of Repeated Ketamine Infusions in Co-Occurring Posttraumatic Stress Disorder and Treatment-Resistant Depression

April 29, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Albott, C., Lim, K., Forbes, M., Erbes, C., Thuras, P., Tye, S., … & Shiroma, P. (2017). 1001-Neurocognitive Effects of Repeated Ketamine Infusions in Co-Occurring Posttraumatic Stress Disorder and Treatment-Resistant Depression. Biological Psychiatry, 81(10), S405. 10.1016/j.biopsych.2017.02.728
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Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial

April 28, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

OBJECTIVES: To evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored.

METHODS: Sixteen participants with bipolar depression and a Scale for Suicidal Ideation (SSI) score of ≥4 were randomized to ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg). Current pharmacotherapy was maintained excluding benzodiazepines within 24 hours. The primary clinical outcome was SSI score on day 1 post-infusion.

RESULTS: Results supported feasibility. Mean reduction of SSI after ketamine infusion was almost 6 points greater than after midazolam, although this was not statistically significant (estimate=5.84, SE=3.01, t=1.94, P=.074, 95% confidence interval ([CI)]=-0.65 to 12.31). The number needed to treat for response (SSI <4 and at least 50% below baseline) was 2.2, and for remission (SSI=0) was 3.2. The strongest neurocognitive correlation was between memory improvement on the Selective Reminding Test (SRT) and reduction in SSI score on day 1 after ketamine (ρ=-.89, P=.007). Pre- to post-infusion decrease in serum brain derived neurotrophic factor (BDNF) correlated with reduction in SSI from baseline to day 1 after ketamine (n=5, ρ=0.90, P=.037) but not midazolam (P=.087).

CONCLUSIONS: The study demonstrated feasibility. Suicidal thoughts were lower after ketamine than after midazolam at a trend level of significance, likely due to the small pilot sample. Memory improvement and BDNF are promising biomarkers. Replication is needed in an adequately powered full-scale trial.

Grunebaum, M. F., Ellis, S. P., Keilp, J. G., Moitra, V. K., Cooper, T. B., Marver, J. E., … & Mann, J. J. (2017). Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam‐controlled randomized clinical trial. Bipolar Disorders. 10.1111/bdi.12487

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Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders

April 26, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Papers, Psychology / By / , , , , ,

Abstract

The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5–1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be a potential therapeutic alternative for patients with refractory generalized anxiety disorder/social anxiety disorder. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology.
Glue, P., Medlicott, N. J., Harland, S., Neehoff, S., Anderson-Fahey, B., Le Nedelec, M., … & McNaughton, N. (2017). Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. Journal of Psychopharmacology, 0269881117705089.
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