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Depressive Disorders

Role of psilocybin in the treatment of depression

October 27, 2016 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

Psilocybin is a naturally occurring alkaloid, pharmacologically similar to the classic hallucinogen lysergic acid diethylamide (LSD). Although primarily used as a recreational drug or an entheogen in particular cultural settings, recent population based studies have shown that it does not lead to serious physical or mental health problems or dependent use. In view of recent work demonstrating psilocybin’s potential to increase subjective sense of wellbeing and because of its novel mechanism of 5-HT2A serotonin receptor agonism, it is being explored for possible therapeutic utility in mood and anxiety disorders.

Mahapatra, A., & Gupta, R. (2016). Role of psilocybin in the treatment of depression. Therapeutic Advances in Psychopharmacology, 2045125316676092.
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Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression

October 18, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , ,

Abstract

Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.

Papp, M., Gruca, P., Lason-Tyburkiewicz, M., & Willner, P. (2016). Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression. Behavioural Pharmacology. 10.1097/FBP.0000000000000259

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A Double-Blinded, Randomized, Placebo-Controlled Sub-Dissociative Dose Ketamine Pilot Study in the Treatment of Acute Depression and Suicidality in a Military Emergency Department Setting

October 1, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background: Rates of completed suicide in the military have increased. Options are limited for acute relief of depression and suicidal ideation. Traditional treatments’ effects take weeks to months. A novel, rapid, therapeutic target has emerged with the N-methyl-D-aspartate antagonist ketamine. Previous studies suggest that a single dose of intravenous (IV) ketamine rapidly alleviates depression and suicidality.

Methods: In this proof of concept study, an active duty convenience sample population presenting to the emergency department (ED) meeting criteria for inpatient psychiatric admission as a result of depression and suicidal thinking were randomized to receive either a subdissociative dose (0.2 mg/kg) of IV ketamine or equivalent volume of normal saline (placebo). Subjects were evaluated for symptoms throughout a 4-hour ED course, at hospital discharge, and 2 weeks postdischarge.

Results: Methodological problems limited analyzable data to 10 subjects. Two of three who received ketamine experienced dramatic decreases in suicidality and hopelessness within 40 minutes. No such improvements were seen in any of seven controls over the 4-hour observation in the ED. At discharge from the hospital, there was no clinically significant difference. No subjects described adverse symptoms.

Conclusion: Despite methodology difficulties noted in this pilot study, there was statistical improvement in intervention group versus controls.

Burger, J., Capobianco, M., Lovern, R., Boche, B., Ross, E., Darracq, M. A., & McLay, R. (2016). A Double-Blinded, Randomized, Placebo-Controlled Sub-Dissociative Dose Ketamine Pilot Study in the Treatment of Acute Depression and Suicidality in a Military Emergency Department Setting. Military Medicine, 181(10), 1195-1199. 10.7205/MILMED-D-15-00431
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Psychedelics in the treatment of unipolar mood disorders: A systematic review

October 1, 2016 / Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Unipolar mood disorders, including major depressive disorder and persistent depressive disorder (dysthymia), confer high rates of disability and mortality and a very high socioeconomic burden. Current treatment is suboptimal in most cases and there is little of note in the pharmaceutical development pipeline. The psychedelic drugs, including lysergic acid diethylamide and psilocybin, were used extensively in the treatment of mood disorders, and other psychiatric conditions, before their prohibition in the late 1960s. They are relatively safe when used in medically controlled environments, with no reported risk of dependence. Here, we present a systematic review of published clinical treatment studies using psychedelics in patients with broadly defined unipolar mood disorder, and consider their place in psychiatry. Whilst all the included studies have methodological shortcomings, of 423 individuals in 19 studies, 335 (79.2%) showed clinician-judged improvement after treatment with psychedelics. A recently completed pilot study in the UK favours the use of psilocybin with psychological support in treatment resistant depressive disorder. The evidence overall strongly suggests that psychedelics should be re-examined in modern clinical trials for their use in unipolar mood disorders and other non-psychotic mental health conditions.

Rucker, J. J., Jelen, L. A., Flynn, S., Frowde, K. D., & Young, A. H. Psychedelics in the Treatment of Unipolar Mood Disorders: A Systematic Review.
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The Relationship between depression and use of ecstasy among adolescents in Taiwan

October 1, 2016 / Depressive Disorders, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Introduction: The aim of this cross-sectional study was to examine the relationship between depression and ecstasy use among adolescents in Taiwan by controlling for the effects of demographic characteristics and cannabis use.

Methods: A total of 10,262 adolescents aged 12-18 years completed research questionnaires that assessed their severity of depression, status of ecstasy use, and history of cannabis use. The participants were grouped into non-users, ex-users, and current users. Severity of depression among these three adolescent groups was compared using analysis of covariance (ANCOVA), considering the history of cannabis use and demographic characteristics as covariates.
Results: After controlling for history of cannabis use and age, the study found that current ecstasy users experienced more severe depressive symptoms than ex-users and non-users. The difference between ex-users and non-users was not significant.
Conclusion: This study found that current ecstasy users had more severe depressive symptoms than non-users and ex-users. Psychological health professionals must monitor depressive symptoms among adolescent ecstasy users and provide emotional regulation strategies and psychological intervention for those with significant depression.
Lee, K. H., Su, C. H., Hsiao, R. C., Yen, C. N., & Yen, C. F. (2016). The Relationship between depression and use of ecstasy among adolescents in Taiwan. Neuropsychiatry (London), 6(4), 124-127. 10.4172/Neuropsychiatry.1000130
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Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review

September 9, 2016 / Depressive Disorders, Ketamine, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , ,

Abstract

OBJECTIVE: The aim of this review was to determine the clinical and biological predictors of the ketamine response.

METHODS: A systematic research on PubMed and PsycINFO database was performed without limits on year of publication.

RESULTS: The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients.

CONCLUSIONS: In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in attention tests were also predictive to a good response. These predictive factors could be more specific to ketamine. With these different predictor factors (clinical and biological), it could be interesting to develop clinical strategies to personalize ketamine’s administration.

Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2016). [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”][Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review]. L’Encephale. 10.1016/j.encep.2016.06.005
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Ketamine Treatment and Global Brain Connectivity in Major Depression

September 8, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Capitalizing on recent advances in resting state functional connectivity magnetic resonance imaging (rs-fcMRI) and the distinctive paradigm of rapid mood normalization following ketamine treatment, the current study investigated intrinsic brain networks in major depressive disorder (MDD) during a depressive episode and following treatment with ketamine. Medication-free patients with MDD and healthy control subjects (HC) completed baseline rs-fcMRI. MDD patients received a single infusion of ketamine and underwent repeated rs-fcMRI at 24 h post-treatment. Global brain connectivity with global signal regression (GBCr) values were computed as the average of correlations of each voxel with all other gray matter voxels in the brain. MDD group showed reduced GBCr in the prefrontal cortex (PFC), but increased GBCr in the posterior cingulate, precuneus, lingual gyrus, and cerebellum. Ketamine significantly increased GBCr in the PFC and reduced GBCr in the cerebellum. At baseline, 2174 voxels of altered GBCr were identified, but only 310 voxels significantly differed relative to controls following treatment (corrected α<0.05). Responders to ketamine showed increased GBCr in the lateral PFC, caudate, and insula. Followup seed-based analyses illustrated a pattern of dysconnectivity between the PFC/subcortex and the rest of the brain in MDD, which appeared to normalize post-ketamine. The extent of the functional dysconnectivity identified in MDD and the swift and robust normalization following treatment, suggest that GBCr may serve as a treatment response biomarker for the development of rapid acting antidepressants. The data also identified unique prefrontal and striatal circuitry as putative marker of successful treatment and target for antidepressants development.

Abdallah, C. G., Averill, L. A., Collins, K. A., Geha, P., Schwartz, J., Averill, C., … & Iosifescu, D. V. (2016). Ketamine Treatment and Global Brain Connectivity in Major Depression. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 10.1038/npp.2016.186

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Ketamine: Future Treatment For Unresponsive Depression?

September 1, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / ,

Abstract

Major Depressive Disorder (MDD) is a debilitating mental health condition which accounts for a significant portion of worldwide disability. Historically, the suggested pharmacotherapy to treat MDD have been monoaminergic-acting antidepressants, such as SSRIs or SNRIs. These drugs can provide relief, but often take weeks to noticeably improve depressive symptoms and are not always effective, leading to a condition known as Treatment-Resistant Depression (TRD). It is believed that 50% MDD sufferers in Ireland suffer from TRD, and thus the development of improved pharmacotherapies is necessary. One emerging therapy is low dose, intravenous (R-S)-Ketamine (ketamine). While the molecular basis of ketamine’s therapeutic effect has not been fully determined, it has shown to effectively and swiftly mitigate the symptoms of TRD. Barriers do exist preventing the legal prescription of ketamine, including its questionable safety profile and risk of inducing dependence. Despite this, ketamine remains a promising pharmacotherapy for TRD and further investigation is required.

Frere, M., & Tepper, J. (2016). Ketamine: Future Treatment For Unresponsive Depression?. Irish Medical Journal. 10147/620895
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Ketamine for Depression: An Update

August 24, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By /

Abstract

A decade has now passed since research into the antidepressant effects of ketamine began in earnest, after the clinical trial reported by Zarate et al. in 2006 (1). In that proof-of-concept study, 18 medication-free patients with treatment-resistant major depressive disorder (TRD) showed a large reduction in core depressive symptoms within hours of receiving a single low-dose 0.5 mg/kg intravenous infusion of ketamine as measured by the 21-item Hamilton Depression Rating Scale compared with saline placebo.

Murrough, J. W. (2016). Ketamine for Depression: An Update. Biological Psychiatry, 80(6), 416-418. http://dx.doi.org/10.1016/j.biopsych.2016.07.005
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