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Depressive Disorders

Antidepressant actions of ketamine: from molecular mechanisms to clinical practice

February 1, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

In the past decade the emergence of glutamate N-methyl-d-aspartate (NMDA) receptor blockers such as ketamine as fast-acting antidepressants fostered a major conceptual advance by demonstrating the possibility of a rapid antidepressant response. This discovery brings unique mechanistic insight into antidepressant action, as there is a substantial amount of basic knowledge on glutamatergic neurotransmission and how blockade of NMDA receptors may elicit plasticity. The combination of this basic knowledge base and the growing clinical findings will facilitate the development of novel fast acting antidepressants.

Monteggia, L. M., & Zarate, C. (2015). Antidepressant actions of ketamine: from molecular mechanisms to clinical practice. Current opinion in neurobiology, 30, 139-143. https://dx.doi.org/doi:10.1016/j.conb.2014.12.004
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Classic psychedelic use is associated with reduced psychological distress and suicidality

December 6, 2021 / Anxiety Disorders / PTSD, Depressive Disorders, Psychology, Publications / By

A8_thumbnail_500x400In a population-based survey study that was published earlier this month, an association was found between the use of classic psychedelics and reduced psychological distress and suicidality [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”][1]. The researchers included the data of 191.382 individuals that participated in the annual National Survey on Drug Use and Health (NSDUH) [2] between 2008 and 2012, and made a comparison between the psychological well being of classic psychedelic users and non-users. Classic psychedelic users were categorized as such if they met the criteria of having used ayahuasca, mescaline, LSD, peyote or San Pedro and/or psilocybin at least once in their lifetime. To rule out the possibility that differences between the groups of users and non-users could be attributed to factors other than classic psychedelics, the researchers statistically controlled the demographical factors age, gender, ethno-racial identity, educational attainment, annual household income, marital status, self-reported risky behavior and lifetime illicit drug use. No solid claim can be made about causality from this correlation, but the results are in line with earlier hypotheses that the effects of psychedelics may have qualities that could be helpful in modulating suicide risk [3]. As a current estimate, about 7% of the population worldwide suffers from mental health disorders [4]. The results of this study are a hopeful answer to the request from the National Action Alliance for Suicide Prevention (2014) to develop novel interventions that aim at suicide prevention.

 
[1] Hendricks et al. (2015).
[2] The NSDUH survey is the annual survey that is conducted by the United States Department of Health and Human Services. The survey aims at estimating the prevalence of substance use and mental illnesses.
[3] An extensive overview of earlier research can be found in the third and fourth paragraph of the article of Hendricks et al. (2015).
[4] This is based on the estimate of the World Health Organization (2001) that about half a billion people worldwide experience mental health problems and that the current world population is estimated at 7.2 billion (United States Census Bureau, 2015)
 
References

Hendricks, P. S., Thorne, C. B., Clark, C. B., Coombs, D. W., & Johnson, M. W. (2015). Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology. [Abstract]
National Action Alliance for Suicide Prevention: Research Prioritization Task Force (2014). A prioritized research agenda for suicide prevention: An action plan to save lives. National Institute of Mental Health and the Research Prioritization Task Force, Rockville, Maryland.
United States Census Bureau (2015). U.S. and World Population Clock. As retrieved on January 17. from http://www.census.gov/popclock/
World Health Organization (2001). The World health report 2001: Mental health: New understanding, new hope. Geneva, Switzerland: World Health Organization[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population

January 13, 2015 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Mental health problems are endemic across the globe, and suicide, a strong corollary of poor mental health, is a leading cause of death. Classic psychedelic use may occasion lasting improvements in mental health, but the effects of classic psychedelic use on suicidality are unknown. We evaluated the relationships of classic psychedelic use with psychological distress and suicidality among over 190,000 USA adult respondents pooled from the last five available years of the National Survey on Drug Use and Health (2008–2012) while controlling for a range of covariates. Lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81 (0.72–0.91)), past year suicidal thinking (weighted OR=0.86 (0.78–0.94)), past year suicidal planning (weighted OR=0.71 (0.54–0.94)), and past year suicide attempt (weighted OR=0.64 (0.46–0.89)), whereas lifetime illicit use of other drugs was largely associated with an increased likelihood of these outcomes. These findings indicate that classic psychedelics may hold promise in the prevention of suicide, supporting the view that classic psychedelics’ most highly restricted legal status should be reconsidered to facilitate scientific study, and suggesting that more extensive clinical research with classic psychedelics is warranted.

Hendricks, P. S., Thorne, C. B., Clark, C. B., Coombs, D. W., & Johnson, M. W. (2015). Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114565653

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Rapid-onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression

December 26, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Summary

What is known and objective

The current pharmacotherapeutic treatment of major depressive disorder (MDD) generally takes weeks to be effective. As the molecular action of these drugs is immediate, the mechanistic basis for this lag is unclear. A drug that has a more rapid onset of action would be a major therapeutic advance and also be a useful comparator to provide valuable mechanistic insight into the disorder and its treatment.

Comment

Recent evidence suggests that ketamine produces rapid-onset antidepressant action. Important questions are as follows: is it specific or coincidental to other effects; is there a dose–response relationship; and is the mechanism related to that of current antidepressants. NMDA receptor antagonism is unlikely the explanation for ketamine’s antidepressant action.

What is new and conclusion

It is not an exaggeration to state that the new findings, if validated, might produce a revolution in understanding and treating depressive disorders.

Drewniany, E., Han, J., Hancock, C., Jones, R. L., Lim, J., Nemat Gorgani, N., … & Raffa, R. B. (2014). Rapid‐onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression. Journal of Clinical Pharmacy and Therapeutics. https://dx.doi.org/10.1111/jcpt.12238
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Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

December 17, 2014 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current study, 62 patients (mean age=46.2±12.2) with TRD free of concomitant antidepressant medication underwent neurocognitive assessments using components of the MATRICS Consensus Cognitive Battery (MCCB) before and after a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in a 2:1 fashion under double-blind conditions and underwent depression symptom assessments at 24, 48, 72 h, and 7 days post treatment using the Montgomery–Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment was conducted once at 7 days. Neurocognitive performance improved following the treatment regardless of treatment condition. There was no differential effect of treatment on neurocognitive performance and no association with antidepressant response. Slower processing speed at baseline uniquely predicted greater improvement in depression at 24 h following ketamine (t=2.3, p=0.027), while controlling for age, depression severity, and performance on other neurocognitive domains. In the current study, we found that ketamine was devoid of adverse neurocognitive effects at 7 days post treatment and that slower baseline processing speed was associated with greater antidepressant response. Future studies are required to further define the neurocognitive profile of ketamine in clinical samples and to identify clinically useful response moderators.

Murrough, J. W., Burdick, K. E., Levitch, C. F., Perez, A. M., Brallier, J. W., Chang, L. C., … & Iosifescu, D. V. (2014). Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial. Neuropsychopharmacology. https://dx.doi.org/10.1038/npp.2014.298

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Medical Drug or Shamanic Power Plant: The Uses of Kambô in Brazil

December 11, 2014 / Anthropology & Sociology, Biology & Ethnobotany, Depressive Disorders, Papers, Psychiatry & Medicine, Publications / By / ,

Abstract

The secretion from the frog Phyllomedusa bicolor, known in Portuguese as kambô, has traditionally been used as a stimulant and an invigorating agent for hunting by indigenous groups such as the Katukina, Yawanawa, and the Kaxinawa in the southeast Amazon. Since the mid 90s, its use has expanded to large cities in Brazil and, since the late 2000s, abroad to Europe and the US. The urban diffusion of the use of kambô has taken place via healing clinics offering alternative therapies, by way of members of the Brazilian ayahuasca religions, and through travel, mainly by Amazonian rubber tappers, the Katukina, and the Kawinawa Indians. In this article, we present an ethnography of the expansion and reinvention of the use of kambô. We describe the individuals who apply the substance, who are a diverse group, including indigenous healers, ex-rubber tappers, holistic therapists, and doctors. We argue that the frog secretion has a double appeal among this new urban clientele: as a “remedy of science,” in which its biochemical properties are stressed; and as a “remedy of spirit,” in which its “indigenous origin” is more valued, as if kambô was a kind of shamanic power plant analogous to peyote and ayahuasca.

Labate, B. C., & Lima, E. C. D. (2014). Medical Drug or Shamanic Power Plant: The Uses of Kambô in Brazil. Ponto Urbe. Revista do núcleo de antropologia urbana da USP, (15).
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Nitrous Oxide for Treatment-Resistant Major Depression: a Proof-of-Concept Trial

December 9, 2014 / Depressive Disorders, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background

NMDA receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and NMDA receptor antagonist, may also be a rapidly acting treatment for TRD.

Methods

In this blinded, placebo-controlled crossover trial 20 TRD patients were randomized to a 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). Primary endpoint was the change on HDRS-21 24 hours after treatment.

Results

Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) minutes at a median inspiratory concentration of 44% (37 – 45%, IQR). In two patients nitrous oxide treatment was briefly interrupted and in three discontinued. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared to placebo (mean HDRS-21difference at 2 hours: -4.8 points, 95% CI -1.8 to – 7.8 points, p= 0.002; at 24 hours: -5.5 points, 95% CI -2.5 to -8.5 points, p<0.001; comparison between nitrous oxide and placebo: p<0.001). Four patients (20%) had treatment response (reduction ≥50% on HDRS); three patients (15%) a full remission (HDRS ≤ 7 points) after nitrous oxide, compared to one patient (5%) and none after placebo (odds ratio [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”][OR] for response 4.0, 95% CI 0.45 – 35.79; OR for remission 3.0, 95% CI 0.31 – 28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity.

Conclusions

This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with treatment-resistant depression.

Nagele, P., Duma, A., Kopec, M., Gebara, M. A., Parsoei, A., Walker, M., … & Conway, C. (2014). Nitrous Oxide for Treatment-Resistant Major Depression: a Proof-of-Concept Trial. Biological Psychiatry. https://dx.doi.org/10.1016/j.biopsych.2014.11.016
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A single infusion of ketamine improves depression scores in patients with anxious bipolar depression

November 14, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Objective

Patents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine’s ability to decrease symptoms of depression.

Methods

Thirty-six patients with anxious (n = 21) and non-anxious (n = 15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5 mg/kg) over 40 min. Post-hoc analyses compared changes in the Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14 days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of ≥ 7.

Results

A linear mixed model revealed a significant effect of anxiety group on the MADRS (p = 0.04) and HDRS (p = 0.04). Significant drug effects (all p < 0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p > 0.28).

Conclusions

Both anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine’s novel role in the treatment of anxious bipolar depression.

Ionescu, D. F., Luckenbaugh, D. A., Niciu, M. J., Richards, E. M., & Zarate, C. A. (2014). A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar disorders. https://dx.doi.org/10.1111/bdi.12277

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Ketamine and other potential glutamate antidepressants

November 12, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl-d–aspartate (NMDA) receptor antagonist anaesthetic agent, can alleviate depressive symptoms in patients within hours of administration. The mechanism of action appears to be in part through glutamate release onto non-NMDA receptors including α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic receptors. However these are also reported effects on 5-HT, dopamine and intracellular effects on the mammalian target of rapamycin (mTOR) pathway. The effects of SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants may also involve alterations in NMDA function. The article reviews the effect of current antidepressants on NMDA and examines the efficacy and mechanism of ketamine. Response to ketamine is also discussed and comparison with other glutamate drugs including lamotrigine, amantadine, riluzole, memantine, traxoprodil, GLYX-13, MK-0657, RO4917523, AZD2066 and Coluracetam. Future studies need to link the rapid antidepressant effects seen with ketamine to inflammatory theories in MDD.

Dutta, A., McKie, S., & Deakin, J. W. (2014). Ketamine and other potential glutamate antidepressants. Psychiatry research, 225(1-2), 1-13. https://dx.doi.org/10.1016/j.psychres.2014.10.028

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LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects

November 11, 2014 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Papers, Psychology, Publications / By / , ,

Abstract

Objective: A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up.

Method: 12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A Qualitative Content Analysis (QCA) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes.

Results: None of the participants reported lasting adverse reactions. The significant benefits as measured with the STAI were sustained over a 12-month period. In the QCA participants consistently reported insightful, cathartic and interpersonal experiences, accompanied by a reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations of subjective experiences suggest facilitated access to emotions, confrontation of previously unknown anxieties, worries, resources and intense emotional peak experiences à la Maslow as major psychological working mechanisms. The experiences created led to a restructuring of the person’s emotional trust, situational understanding, habits and world view.

Conclusions: LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease. Explanatory models for the therapeutic effects of LSD warrant further study.

Gasser, P., Kirchner, K., & Passie, T. (2014). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114555249
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