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Therapeutic Application

Capturing the different health conditions that PAP may adress

A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT)

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)

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?

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 psychiatry78(7), e852-e857. 10.4088/JCP.17f11738
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Ayahuasca: what mental health professionals need to know

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?

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 psychiatry78(6), e674-e677. 0.4088/JCP.17f11681
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Rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review

Abstract

BACKGROUND:
This study evaluated efficacy and safety of intravenous subanesthetic doses of esketamine using an administration time of 10 minutes in patients with treatment-resistant depression and bipolar depression.
METHODS:
A retrospective chart review was conducted to identify patients who met the inclusion criteria for treatment-resistant depression and bipolar depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and these patients received rapid infusion of esketamine between June 2012 and December 2015. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered to measure and score depressive symptom severity before infusion and at 24 hours, 72 hours, and 7 days after infusion. In addition, Clinical Global Impression scale was administered before and 7 days after esketamine infusion.
RESULTS:
Esketamine was administered to 30 patients. A total of 27 patients met the inclusion criteria and had MADRS evaluation data, which showed that 23 had unipolar and 4 had bipolar depression. Thirteen patients (48.1%) showed therapeutic response (MADRS reduction ≥50%) within 1 week (7 days) of intervention. Remission (MADRS <7) was observed in 10 patients (37.0%) in the same period. Therapeutic response and remission frequencies were seen in 16 (59.3%) and 11 (40.7%) patients, respectively, within 24 hours following drug infusion. The most relevant side effect observed during the esketamine infusion was dissociative symptoms ranging from mild to severe, which was reported by 11.1% of patients as a very disturbing experience.
LIMITATIONS:
This study was done retrospectively, had a small sample size, and there was no comparative group.
CONCLUSION:
The present study demonstrates that rapid infusion of esketamine is possibly not the optimal choice to administer this drug for treatment-resistant depression due to tolerability reasons. Further controlled studies are required to investigate efficacy, safety, and tolerability profiles among the different types of ketamines and methods of using this drug in depressed patients.
Correia-Melo, F. S., Argolo, F. C., Araújo-de-Freitas, L., Leal, G. C., Kapczinski, F., Lacerda, A. L., & Quarantini, L. C. (2017). rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review. Neuropsychiatric disease and treatment13, 1627. 10.2147/NDT.S135623
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Low-dose ketamine for treatment resistant depression in an academic clinical practice setting

Abstract

BACKGROUND:
Recent studies demonstrating a rapid, robust improvement in treatment resistant depression (TRD) following a single sub-anesthetic infusion of ketamine have generated much excitement. However, these studies are limited in their generalizability to the broader TRD population due to their subject exclusion criteria which typically limit psychiatric comorbidity, concurrent medication, and level of suicide risk. This paper describes the safety and efficacy of sub-anesthetic ketamine infusions in a naturalistic TRD patient sample participating in a real-world TRD treatment program within a major university health system.
METHODS:
The effects of a sub-anesthetic dose (0.5mg/kg) of ketamine infused IV over forty minutes on TRD patients participating in a treatment program at the University of California, San Diego was investigated by retrospectively analyzing the medical charts of 41 adult TRD patients with a diagnosis of Major Depressive Disorder (MDD) or Bipolar Disorder (BD).
RESULTS:
Subjects were aged 48.6, 78% white, 36.6% female, and 82.9% had MDD. Significant psychiatric comorbidity existed in 73%. Average pre-infusion BDI score was 32.6 ± 8.4 (S.D) and dropped to 16.8 ± 3.1 at 24-h post-infusion (p < 0.001). The 24-h response (≥ 50% reduction from pre-infusion) and remission (BDI <13) rates were 53.7% and 41.5%, respectively. Three quarters of responders maintained responder status at 7-days. Ketamine infusions were well tolerated with occasional nausea or anxiety and mild hemodynamic effects during the infusion.
LIMITATIONS:
Retrospective nature of this study, lack of control group and use of self-report depression ratings scales.
CONCLUSIONS:
This is the first published study of sub-anesthetic ketamine infusions in a real-world TRD population. The results suggest that this treatment is effective and well tolerated in this population.
Feifel, D., Malcolm, B., Boggie, D., & Lee, K. (2017). Low-dose ketamine for treatment resistant depression in an academic clinical practice setting. Journal of affective disorders221, 283-288. 10.1016/j.jad.2017.06.043
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Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia

Abstract

Despite their stigmatisation, psychedelic drugs are once again being clinically researched in Europe and North America. This long-awaited renaissance is showing very promising results and, unlike the pioneering research that occurred before these drugs were outlawed over 30 years ago, the current methodology is rigorous and of a very high standard.
Strauss, N. (2017). Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia. The Medical Journal of Australia206(11), 468-469. 10.5694/mja17.00081
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Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression

Objective:

To identify patients’ perceptions of the value of psilocybin as a treatment for depression.

Method:

Twenty patients enrolled in an open-label trial of psilocybin for treatment-resistant depression participated in a semistructured interview at 6-month follow-up. Thematic analysis was used to identify patients’ experiences of the treatment and how it compared with previous treatments.

Results:

Two main change processes were identified in relation to the treatment. The first concerned change from disconnection (from self, others, and world) to connection, and the second concerned change from avoidance (of emotion) to acceptance. A third theme concerned comparison between psilocybin and conventional treatments. Patients reported that medications and some short-term talking therapies tended to reinforce their sense of disconnection and avoidance, whereas treatment with psilocybin encouraged connection and acceptance.

Conclusion:

These results suggest that psilocybin treatment for depression may work via paradigmatically novel means, antithetical to antidepressant medications, and some short-term talking therapies.
Watts, R., Day, C., Krzanowski, J., Nutt, D., & Carhart-Harris, R. (2017). Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression. Journal of Humanistic Psychology, 0022167817709585.

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Effect of psilocybin on empathy and moral decision-making

Abstract

Background:

Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behaviour. Although the serotonin (5-HT) system has been implicated in modulating empathy and moral behaviour, the relative contribution of the various 5-HT receptor subtypes is still unknown.

Methods:

We investigated the acute effect of psilocybin (0.215mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the Multifaceted Empathy Test (MET) (n=32) and the Moral Dilemma Task (MDT) (n=24).

Results:

Psilocybin significantly increased emotional, but not cognitive empathy compared to placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin.

Conclusions:

These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behaviour. Furthermore, together with previous findings psilocybin appears to promote emotional empathy presumably via activation of 5-HT2A/1A receptors suggesting that targeting 5-HT2A/1A receptors has implications for potential treatment of dysfunctional social cognition.

Pokorny, T., Preller, K. H., Kometer, M., Dziobek, I., & Vollenweider, F. X. (2017). Effect of psilocybin on empathy and moral decision-making. International Journal of Neuropsychopharmacology. 10.1093/ijnp/pyx047

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