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Depressive Disorders

Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series

August 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

Purpose The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.
Methods We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.
Findings Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.
Conclusions Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Al Shirawi, M. I., Kennedy, S. H., Ho, K. T., Byrne, R., & Downar, J. (2017). Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series. Journal of clinical psychopharmacology, 37(4), 464. 10.1097/JCP.0000000000000717
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Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish

July 28, 2017 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology / By / , , , , , ,

Abstract

The combined infusion of Banisteriopsis caapi stem and Psychotria viridis leaves, known as ayahuasca, has been used for centuries by indigenous tribes. The infusion is rich in N, N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors, with properties similar to those of serotonin. Despite substantial progress in the development of new drugs to treat anxiety and depression, current treatments have several limitations. Alternative drugs, such as ayahuasca, may shed light on these disorders. Here, we present time-course behavioral changes induced by ayahuasca in zebrafish, as first step toward establishing an ideal concentration for pre-clinical evaluations. We exposed adult zebrafish to five concentrations of the ayahuasca infusion: 0 (control), 0.1, 0.5, 1, and 3 ml/L (n = 14 each group), and behavior was recorded for 60 min. We evaluated swimming speed, distance traveled, freezing and bottom dwelling every min for 60 min. Swimming speed and distance traveled decreased with an increase in ayahuasca concentration while freezing increased with 1 and 3 ml/L. Bottom dwelling increased with 1 and 3 ml/L, but declined with 0.1 ml/L. Our data suggest that small amounts of ayahuasca do not affect locomotion and reduce anxiety-like behavior in zebrafish, while increased doses of the drug lead to crescent anxiogenic effects. We conclude that the temporal analysis of zebrafish behavior is a sensitive method for the study of ayahuasca-induced functional changes in the vertebrate brain.
Savoldi, R., Polari, D., Pinheiro-da-Silva, J., Silva, P. F., Lobao-Soares, B., Yonamine, M., … & Luchiari, A. C. (2017). Behavioral changes over time following ayahuasca exposure in zebrafish. Frontiers in behavioral neuroscience, 11. 10.3389/fnbeh.2017.00139
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Side-effects associated with ketamine use in depression: a systematic review

July 27, 2017 / Depressive Disorders, Ketamine, Papers, Psychology / By / , , , ,

Abstract

This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depression. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users. We recommend large-scale clinical trials that include multiple doses of ketamine and long-term follow up to assess the safety of long-term regular use.
Short, B., Fong, J., Galvez, V., Shelker, W., & Loo, C. K. (2017). Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry. 10.1016/S2215-0366(17)30272-9
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The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro

July 13, 2017 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.
Morales-García, J. A., de la Fuente Revenga, M., Alonso-Gil, S., Rodríguez-Franco, M. I., Feilding, A., Perez-Castillo, A., & Riba, J. (2017). The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Scientific reports, 7, 5309. 10.1038%2Fs41598-017-05407-9
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The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro

July 13, 2017 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology / By / , , , , , ,

Abstract

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.
Morales-García, J. A., de la Fuente Revenga, M., Alonso-Gil, S., Rodríguez-Franco, M. I., Feilding, A., Perez-Castillo, A., & Riba, J. (2017). The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Scientific Reports, 7. 10.1038%2Fs41598-017-05407-9
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A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT)

July 7, 2017 / Depressive Disorders, DMT, Papers, Psychology / By / , , , ,

Abstract

N,N-dimethyltryptamine (DMT) is a psychoactive substance that has been gaining popularity in therapeutic and recreational use. This is a case of a physician who chronically took DMT augmented with phenelzine in an attempt to self-medicate refractory bipolar depression. His presentation of altered mental status, mania, and psychosis is examined in regards to his DMT use. This case discusses DMT, the possible uses of DMT, and the theorized mechanism of DMT in psychosis and treatment of depression, particularly involving its agonist activity at 5-HT1A, 5-HT2A, and 5-HT2C. It is also important to recognize the dangers of self-medication, particularly amongst physicians.
Brown, T., Shao, W., Ayub, S., Chong, D., Cornelius, C. A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT). Journal of Psychoactive Drugs. 10.1080/02791072.2017.1344898
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A Physician's Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT)

July 7, 2017 / Depressive Disorders, DMT, Papers, Psychology / By / , , , ,

Abstract

N,N-dimethyltryptamine (DMT) is a psychoactive substance that has been gaining popularity in therapeutic and recreational use. This is a case of a physician who chronically took DMT augmented with phenelzine in an attempt to self-medicate refractory bipolar depression. His presentation of altered mental status, mania, and psychosis is examined in regards to his DMT use. This case discusses DMT, the possible uses of DMT, and the theorized mechanism of DMT in psychosis and treatment of depression, particularly involving its agonist activity at 5-HT1A, 5-HT2A, and 5-HT2C. It is also important to recognize the dangers of self-medication, particularly amongst physicians.
Brown, T., Shao, W., Ayub, S., Chong, D., Cornelius, C. A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT). Journal of Psychoactive Drugs. 10.1080/02791072.2017.1344898
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Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency?

July 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By /

Abstract

BACKGROUND:
Ketamine, administered in subanesthetic doses, is an effective off-label treatment for severe and even treatment-refractory depression; however, despite dozens of studies across nearly 2 decades of research, there is no definitive guidance on matters related to core practice issues.
METHODS:
This article presents a qualitative review and summary about what is known about ketamine dosing, rate of administration, route of administration, duration of treatment, and frequency of sessions.
RESULTS:
Ketamine is most commonly administered in the dose of 0.5 mg/kg, but some patients may respond to doses as low as 0.1 mg/kg, and others may require up to 0.75 mg/kg. The ketamine dose is conventionally administered across 40 minutes; however, safety and efficacy have been demonstrated in sessions ranging between 2 and 100 minutes in duration. Bolus administration is safe and effective when the drug is administered intramuscularly or subcutaneously. Whereas the intravenous route is the most commonly employed, safety and efficacy have been described with other routes of administration, as well; these include oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous routes. Patients may receive a single session of treatment or a course of treatment during the acute phase, and treatment may rarely be continued for weeks to years to extend and maintain treatment gains in refractory cases. When so extended, the ideal frequency is perhaps best individualized wherein ketamine is dosed a little before the effect of the previous session is expected to wear off.
CONCLUSIONS:
There is likely to be a complex interaction between ketamine dose, session duration, route of administration, frequency of administration, and related practice. Until definitive studies comparing different doses, rates of administration, routes of administration, and other considerations are conducted, firm recommendations are not possible. From the point of view of clinical practicability, subcutaneous, intranasal, and oral ketamine warrant further study. If domiciliary treatment is considered, the risk of abuse must be kept in mind.
Andrade, C. (2017). Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency?. The Journal of clinical psychiatry, 78(7), e852-e857. 10.4088/JCP.17f11738
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Ayahuasca: what mental health professionals need to know

July 1, 2017 / Anxiety Disorders / PTSD, Ayahuasca, Biology & Ethnobotany, Depressive Disorders, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Background

Ayahuasca is a psychoactive ethnobotanical concoction that has been used for decades by indigenous groups of the Northwestern Amazon and by syncretic religious organizations for ritual and therapeutic purposes. In the last two decades, it is being used worldwide in evolving practices. Ayahuasca seem to therapeutic effects, but controlled studies are lacking. Moreover, its safety and toxicity are not completely understood.

Objectives

To present an overview of the effects of ayahuasca based on the most recent human studies.

Methods

Narrative review.

Results

Ayahuasca administration in controlled settings appears to be safe from a subjective and physiological perspective, with few adverse reactions being reported. More frequent adverse reactions occur in non-controlled settings. Prolonged psychotic reactions are rare and seem to occur especially in susceptible individuals. Ayahuasca showed antidepressive, anxiolytic, and antiaddictive effects in animal models, observational studies, and in open-label and controlled studies.

Discussion

Ayahuasca administration in controlled settings appear to be safe. Moreover, ayahuasca seem to have therapeutic effects for treatment-resistant psychiatric disorders that should be further investigated in randomized controlled clinical trials. However, medical complications and cases of prolonged psychotic reactions have been reported, and people with personal or family history of psychotic disorders should avoid ayahuasca intake.

Santos, R. G. D., Bouso, J. C., & Hallak, J. E. C. (2017). Ayahuasca: what mental health professionals need to know. Archives of Clinical Psychiatry (São Paulo), 44(4), 103-109. 10.1590/0101-60830000000130
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Ketamine for Depression, 3: Does Chirality Matter?

June 22, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By /

Abstract

Ketamine is a racemic mixture of the enantiomers R-ketamine and S-ketamine (esketamine). S-ketamine has greater analgesic and anesthetic effects than R-ketamine and is less likely to cause psychotomimetic and other adverse effects. There is therefore an emerging interest favoring the use of S-ketamine over racemic ketamine when the drug is used for analgesia or anesthesia. This article examines preclinical and clinical literature on the antidepressant properties of S-ketamine. Animal data suggest potential advantages for R-ketamine over S-ketamine. Case reports, case series, and some small randomized controlled trials suggest that single or repeated intravenous infusions (0.2-0.4 mg/kg) or intranasal administrations (28-84 mg) of S-ketamine have antidepressant action in patients with medication-refractory depression and that the observed benefits are similar in magnitude to the antidepressant benefits reported with racemic ketamine. However, there are no direct comparisons between S-ketamine and either R-ketamine or racemic ketamine in depressed patients; therefore, it is not possible to make an informed choice when considering the enantiomers and the racemate for the indication of depression.
Andrade, C. (2017). Ketamine for Depression, 3: Does Chirality Matter?. The Journal of clinical psychiatry, 78(6), e674-e677. 0.4088/JCP.17f11681
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