OPEN Foundation

Depression

Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression

October 29, 2015 / Depression, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , ,

Abstract

Among treatments currently assessed in major depression, ketamine, has been proposed of great interest, especially because of its very rapid action. However, the time-course of the antidepressive action of ketamine remained unclear. In the present meta-analysis, we provided a clear and objective view regarding the putative antidepressive effect of ketamine and its time-course. We searched the MEDLINE and PsycINFO databases through December 2013, without limits on year of publication, using the key words ketamine and synonyms for mood disorder or episode. Six randomized, double-blind and placebo-controlled trials of ketamine in major depression (n=103 patients) were thus identified. Authors were contacted and they all provided original data necessary for this meta-analysis. Standardized mean differences (SMD) were calculated between the depression scores in ketamine and placebo groups at days 1, 2, 3–4, 7 and 14. Ketamine showed an overall antidepressive efficacy from day 1 to day 7. However, the maintenance of its efficacy over time failed to reach significance in bipolar depression after day 3–4. Significant SMDs were not explained by demographic or clinical characteristics of included samples. The present meta-analysis provides a high level of evidence that ketamine has a rapid antidepressive action during one week, especially in unipolar disorder.

Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2015). Meta-analysis of short-and mid-term efficacy of ketamine in unipolar and bipolar depression. Psychiatry research.  http://dx.doi.org/10.1016/j.psychres.2015.10.032
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Kappa Opioids, Salvinorin A and Major Depressive Disorder

October 1, 2015 / Depression, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Salvia / Salvinorin A / By / ,

Abstract

Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b – endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant- based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile , with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research.

T Taylor and Francesca Manzella, G. Kappa Opioids, Salvinorin A and Major Depressive Disorder. Current Neuropharmacology, 13. http://dx.doi.org/10.2174/1570159X13666150727220944
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Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders

October 1, 2015 / Depression, Ketamine, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Major depressive disorder (MDD) is a leading cause of disability worldwide. Despite a plethora of established treatments, less than one third of individuals with MDD achieve stable remission of symptoms. Given limited efficacy and significant lag time to onset of therapeutic action among conventional antidepressants, interest has shifted to treatments that act outside of the monoamine neurotransmitter systems (e.g., serotonin, norepinephrine, and dopamine). Preclinical and clinical research on the glutamate system has been particularly promising in this regard. Accumulating evidence shows support for a rapid antidepressant effect of ketamine—a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. The present article reviews the pharmacology, safety, and efficacy of ketamine as a novel therapeutic agent for mood and anxiety disorders. The majority of clinical trials using ketamine have been conducted in patients with treatment-resistant forms of MDD; recent work has begun to examine ketamine in bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder. The impact of ketamine on suicidal ideation is also discussed. The current status and prospects for the identification of human biomarkers of ketamine treatment response and hurdles to treatment development are considered. We conclude by considering modulators of the glutamate system other than ketamine currently in development as potential novel treatment strategies for mood and anxiety disorders.

Costi, S., Van Dam, N. T., & Murrough, J. W. (2015). Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders. Current Behavioral Neuroscience Reports, 1-10. https://dx.doi.org/10.1007/s40473-015-0052-3
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Ketamine for depression: evidence, challenges and promise

September 25, 2015 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / ,

Abstract

Major depressive disorder and bipolar depression are among the most prevalent and disabling mental disorders worldwide. Real-world effectiveness trials in major depressive disorder have underscored that most pharmacological options target monoamines, which are involved in a minority (15-20%) of synaptic contacts in the mammalian brain.

Most synapses (∼50%) use the amino acid glutamate as their primary neurotransmitter, and preclinical models of depression have implicated aberrant glutamatergic neurotransmission for 25 years. More recently, the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine was shown to produce rapid and robust antidepressant effects in patients with treatment-resistant major depressive disorder and bipolar depression.

Zarate, C. A., & Niciu, M. J. (2015). Ketamine for depression: evidence, challenges and promise. World Psychiatry, 14(3), 348-350. http://dx.doi.org/10.1002/wps.20269
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Psychedelic medicine: A re-emerging therapeutic paradigm

December 6, 2021 / Anxiety disorders / PTSD, Ayahuasca, Cacti / Mescaline, Depression, DMT, Ketamine, LSD, MDMA, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , ,

Introduction

In clinical research settings around the world, renewed investigations are taking place on the use of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder (PTSD). Since the termination of a period of research from the 1950s to the early 1970s, most psychedelic substances have been classified as “drugs of abuse” with no recognized medical value. However, controlled clinical studies have recently been conducted to assess the basic psychopharmacological properties and therapeutic efficacy of these drugs as adjuncts to existing psychotherapeutic approaches. Central to this revival is the re-emergence of a paradigm that acknowledges the importance of set (i.e., psychological expectations), setting (i.e., physical environment) and the therapeutic clinician–patient relationship as critical elements for facilitating healing experiences and realizing positive outcomes [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][…]

Tupper, K. W., Wood, E., Yensen, R., & Johnson, M. W. (2015). Psychedelic medicine: a re-emerging therapeutic paradigm. CMAJ: Canadian Medical Association journal= journal de l’Association medicale canadienne, 187(14), 1054. https://dx.doi.org/10.1503/cmaj.141124
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Ketamine for depression: the highs and lows

September 1, 2015 / Depression, Ketamine, Papers, Psychiatry, Psychology, Publications / By /

Abstract

Long used as an anaesthetic and analgesic, most people familiar with ketamine know of it for this purpose. Others know it as a party drug that can give users an out-of-body experience, leaving them completely disconnected from reality. Less well known is its growing off-label use in the USA for depression, in many cases when other options have been exhausted.

Kirby, T. (2015). Ketamine for depression: the highs and lows. The Lancet Psychiatry, 2(9), 783-784. http://dx.doi.org/10.1016/S2215-0366(15)00392-2
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Psilocybin, psychological distress, and suicidality

September 1, 2015 / Depression, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Hendricks et al. (2015) found that having ever used any classic psychedelic substance—namely, dimethyltryptamine (DMT), ayahuasca, lysergic acid diethylamide (LSD), mescaline, peyote or San Pedro, or psilocybin—was associated with a significantly reduced likelihood of past month psychological distress (weighted OR = .81 (.72–.91)), past year suicidal thinking (weighted OR = .86 (.78–.94)), past year suicidal planning (weighted OR = .71 (.54–.94)), and past year suicide attempt (weighted OR = .64 (.46–.89)) in the United States adult population. Although these findings comport with an emerging literature suggesting classic psychedelics may be effective in the treatment of mental health conditions and prevention of self-harm, they do not speak to the potential risk profile or therapeutic applications of psilocybin in particular, which is the most commonly examined classic psychedelic in contemporary clinical research. Considering that psilocybin may be a candidate for future approved medical use in the United States, the United Kingdom, and other nations (Bogenschutz et al., 2015; Grob et al., 2011; Johnson et al., 2014; see also Nutt et al., 2013), an analysis of the specific relationships of psilocybin use with psychological distress and suicidality may help inform decisions by the United States Food and Drug Administration and regulatory bodies of other nations. The objectives of the current research, therefore, were to extend the analysis of Hendricks et al. (2015) by evaluating the associations of lifetime psilocybin use, per se, with past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population.

Hendricks, P. S., Johnson, M. W., & Griffiths, R. R. (2015). Psilocybin, psychological distress, and suicidality. Journal of Psychopharmacology, 29(9), 1041-1043. http://dx.doi.org/10.1177/0269881115598338
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R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

September 1, 2015 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF-TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF-TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability.

Yang, C., Shirayama, Y., Zhang, J. C., Ren, Q., Yao, W., Ma, M., … & Hashimoto, K. (2015). R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Translational psychiatry, 5(9), e632. http://dx.doi.org/10.1038/tp.2015.136

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Psychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other Approaches

August 1, 2015 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , ,

Abstract

Suicide is a major global public health problem and the leading cause of injury mortality in the USA. Suicide is a complex phenomenon involving several systems and neurobiological pathways, with interacting genetic and environmental mechanisms. The literature on the neurobiology and pharmacotherapy of suicide has been limited. To date, no medications have proven efficacious for treating acute suicidal crises. There is an emerging literature supporting a rapid anti-suicidal effect of ketamine, a non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, among depressed patients with suicidal ideation. Potential ketamine’s anti-suicidal effect mechanisms are linked to interruption of the kynurenine pathway and modulating pro-inflammatory cytokines exacerbation. However, available data are not sufficient for its routine integration in clinical practice, and larger and replicated randomized control studies are needed.

Al Jurdi, R. K., Swann, A., & Mathew, S. J. (2015). Psychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other Approaches. Current psychiatry reports, 17(10), 1-10. https://dx.doi.org/10.1007/s11920-015-0614-9

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The potential utility of some legal highs in CNS disorders

July 29, 2015 / Addiction, Anxiety disorders / PTSD, Depression, Ketamine, LSD, MDMA, Medicine, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / ,

Abstract

Over the last decade there has been an explosion of new drugs of abuse, so called legal highs or novel psychoactive substances (NPS). Many of these abused drugs have unknown pharmacology, but their biological effects can be anticipated from their molecular structure and possibly also from online user reports. When considered with the findings that some prescription medications are increasingly abused and that some abused drugs have been tested clinically one could argue that there has been a blurring of the line between drugs of abuse and clinically used drugs. In this review we examine these legal highs/NPS and consider whether, based on their known or predicted pharmacology, some might have the potential to be clinically useful in CNS disorders.

Davidson, C., & Schifano, F. (2015). The potential utility of some legal highs in CNS disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. https://dx.doi.org/10.1016/j.pnpbp.2015.07.010
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