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Therapeutic Application

Capturing the different health conditions that PAP may adress

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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Ibogaine for treating drug dependence. What is a safe dose?

September 1, 2016 / Iboga / Ibogaine, Papers, Publications, Substance Use Disorder / By / , , ,

Abstract

The indole alkaloid ibogaine, present in the root bark of the West African rain forest shrub Tabernanthe iboga, has been adopted in the West as a treatment for drug dependence. Treatment of patients requires large doses of the alkaloid to cause hallucinations, an alleged integral part of the patient’s treatment regime. However, case reports and case series continue to describe evidences of ataxia, gastrointestinal distress, ventricular arrhythmias and sudden and unexplained deaths of patients undergoing treatment for drug dependence. High doses of ibogaine act on several classes of neurological receptors and transporters to achieve pharmacological responses associated with drug aversion; limited toxicology research suggests that intraperitoneal doses used to successfully treat rodents, for example, have also been shown to cause neuronal injury (purkinje cells) in the rat cerebellum. Limited research suggests lethality in rodents by the oral route can be achieved at approximately 263mg/kg body weight. To consider an appropriate and safe initial dose for humans, necessary safety factors need to be applied to the animal data; these would include factors such as intra- and inter-species variability and for susceptible people in a population (such as drug users). A calculated initial dose to treat patients could be approximated at 0.87mg/kg body weight, substantially lower than those presently being administered to treat drug users. Morbidities and mortalities will continue to occur unless practitioners reconsider doses being administered to their susceptible patients.
Schep, L. J., Slaughter, R. J., Galea, S., & Newcombe, D. (2016). Ibogaine for treating drug dependence. What is a safe dose?. Drug and alcohol dependence, 166, 1-5. 10.1016/j.drugalcdep.2016.07.005
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The Resurrection Of Psychedelic Psychiatry And Its Role In Addiction Treatment

September 1, 2016 / Ayahuasca, Iboga / Ibogaine, LSD, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

Psychedelic psychiatry, a field which was previously popular between 1950-1970, has recently received a renewed interest as several recent studies have highlighted the potential role of hallucinogens in the treatment of addictions and various mental illnesses. This paper looks at evidence supporting the use of LSD, ibogaine and ayahuasca to treat various addictions and discusses the barriers to further exploration of the therapeutic potential of psychedelic substances.

Skocylas, R. (2016). The resurrection of psychedelic psychiatry and its role in addiction treatment. UBC Medical Journal, 8(1).
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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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