OPEN Foundation

Menu
Search
Close this search box.

Depressive Disorders

Ketamine for Treatment-Resistant Unipolar and Bipolar Major Depression: Critical Review and Implications for Clinical Practice

April 6, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , ,

Abstract

There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side-effects are generally mild and transient. The data investigating the adjunctive use of concurrent ketamine in the course of electroconvulsive therapy (ECT) for depression do not suggest efficacy or tolerability. The therapeutic potential of ketamine has stimulated considerable excitement among clinicians, patients, and industry, and has led to the increasing use of ketamine as an off-label substitute for ECT and other antidepressive treatments. This clinical review of ketamine will assess the evidence-based use of ketamine and initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.

Bobo, W. V., Voort, J. L. V., Croarkin, P. E., Leung, J. G., Tye, S. J., & Frye, M. A. (2016). KETAMINE FOR TREATMENT‐RESISTANT UNIPOLAR AND BIPOLAR MAJOR DEPRESSION: CRITICAL REVIEW AND IMPLICATIONS FOR CLINICAL PRACTICE. Depression and Anxiety. http://dx.doi.org/10.1002/da.22505
Link to full text

Ketamine for treatment-resistant depression: recent developments and clinical applications

April 6, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , ,

Abstract

Approximately one-third of patients with major depressive disorder (MDD) do not respond to existing antidepressants, and those who do generally take weeks to months to achieve a significant effect. There is a clear unmet need for rapidly acting and more efficacious treatments. We will review recent developments in the study of ketamine, an old anaesthetic agent which has shown significant promise as a rapidly acting antidepressant in treatment-resistant patients with unipolar MDD, focusing on clinically important aspects such as dose, route of administration and duration of effect. Additional evidence suggests ketamine may be efficacious in patients with bipolar depression, post-traumatic stress disorder and acute suicidal ideation. We then discuss the safety of ketamine, in which most neuropsychiatric, neurocognitive and cardiovascular disturbances are short lasting; however, the long-term effects of ketamine are still unclear. We finally conclude with important information about ketamine for primary and secondary physicians as evidence continues to emerge for its potential use in clinical settings, underscoring the need for further investigation of its effects.

Schwartz, J., Murrough, J. W., & Iosifescu, D. V. (2016). Ketamine for treatment-resistant depression: recent developments and clinical applications. Evidence-based mental health. http://dx.doi.org/10.1136/eb-2016-102355

Link to full text

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

March 24, 2016 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , ,

Abstract

Objective:

To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline).

Methods:

Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection.

Results:

Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression.

Conclusion:

Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & Hallak, J. E. (2016). Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies. Revista Brasileira de Psiquiatria, 38(1), 65-72. http://dx.doi.org/10.1590/1516-4446-2015-1701
Link to full text

Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide

March 24, 2016 / Depressive Disorders, LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured interviews performed shortly after the functional magnetic resonance imaging (fMRI) scans (approximately 2.5 h post-administration). Within each report, specific linguistic references to mental spaces for the past, present and future were identified. Results revealed significantly fewer mental spaces for the past under LSD and this effect correlated with the general intensity of the drug’s subjective effects. No differences in the number of mental spaces for the present or future were observed. Consistent with the previously proposed role of the default-mode network (DMN) in autobiographical memory recollection and ruminative thought, decreased resting-state functional connectivity (RSFC) within the DMN correlated with decreased mental time travel to the past. These results are discussed in relation to potential therapeutic applications of LSD and related psychedelics, e.g. in the treatment of depression, for which excessive reflection on one’s past, likely mediated by DMN functioning, is symptomatic.

Speth, J., Speth, C., Kaelen, M., Schloerscheidt, A. M., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2016). Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide. Journal of psychopharmacology (Oxford, England), 30(4), 344. http://dx.doi.org/10.1177/0269881116628430

Link to full text

Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years

March 18, 2016 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., Riba, J., Zuardi, A. W., & Hallak, J. E. (2016). Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. Therapeutic Advances in Psychopharmacology, 2045125316638008.

Link to full text

Ayahuasca: pharmacology, neuroscience and therapeutic potential

March 11, 2016 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one’s own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders.

Domínguez-Clavé, E., Soler, J., Elices, M., Pascual, J. C., Álvarez, E., de la Fuente Revenga, M., … & Riba, J. (2016). Ayahuasca: pharmacology, neuroscience and therapeutic potential. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.03.002
Link to full text

From mice to men: can ketamine enhance resilience to stress?

February 15, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By /

Abstract

The rapid antidepressant properties of intravenous ketamine have ignited high hopes from researchers, clinicians, and patients alike. While bottom-up patient demand has led some clinicians to offer repeated ketamine infusions directly to patients, academic commentators have warned against premature clinical adoption (1), at times likening the field’s enthusiasm to the misguided use of stimulants or opiates to induce short-term depression relief. The rapidity of ketamine’s antidepressant onset (2-hours post-infusion) is impressive, but effects dissipate almost as rapidly (3-7 days).

Price, R. B. (2016). From mice to men: can ketamine enhance resilience to stress?. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2016.02.011
Link to full text

Should ketamine be used for the clinical treatment of depression?

February 5, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , ,

Abstract

OBJECTIVE: There has been widespread interest from the public and media in the potential of ketamine as a novel treatment for depression. This paper reviews whether current evidence supports the use of ketamine for the clinical treatment of depression.

CONCLUSIONS: Clinical trials have investigated the use of intravenous ketamine for the treatment of depressive symptoms over the past 15 years. However, there remain many unanswered questions regarding its effectiveness, safety, and the route, dose and regimen for repeated administration. Experts have also raised concerns regarding ketamine’s adverse effects, abuse potential and the risk of addiction. At this stage, the use of ketamine in the treatment of depression remains in the realm of research settings.

Arunogiri, S., Keks, N. A., & Hope, J. (2016). Should ketamine be used for the clinical treatment of depression?. Australasian Psychiatry, http://dx.doi.org/10.1177/1039856216629839.

Link to full text

Psychedelics

February 3, 2016 / Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network.

Nichols, D. E. (2016). Psychedelics. Pharmacological reviews, 68(2), 264-355. http://dx.doi.org/10.1124/pr.115.011478

Link to full text

Oral ketamine for the treatment of pain and treatment-resistant depression

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

Abstract

Background

Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications.

Aims

To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain.

Method

Searches in PubMed with the terms ‘oral ketamine’, ‘depression’, ‘chronic pain’, ‘neuropathic pain’, ‘intravenous ketamine’, ‘intranasal ketamine’ and ‘subcutaneous ketamine’ yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality.

Results

Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects.

Conclusions

Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials.

Schoevers, R. A., Chaves, T. V., Balukova, S. M., aan het Rot, M., & Kortekaas, R. (2016). Oral ketamine for the treatment of pain and treatment-resistant depression. The British Journal of Psychiatry, 208(2), 108-113. http://dx.doi.org/10.1192/bjp.bp.115.165498

Link to full text

interested in becoming a trained psychedelic-assisted therapist?

Management of Psychedelic-Related Complications - Online Event - Nov 20th

REGISTER NOW