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Therapeutic Application

Capturing the different health conditions that PAP may adress

Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report

April 28, 2017 / Iboga / Ibogaine, Papers, Psychology, Substance Use Disorder / By / , , , , , ,

Abstract

Background and aims

Ibogaine is a natural alkaloid that has been used in the last decades as an adjuvant for the treatment of opiate withdrawal. Despite the beneficial results suggested by animal studies and case series, there is a lack of clinical trials to assess the safety and efficacy of ibogaine. Moreover, the majority of reports described cases of heroin-dependent individuals, with and without concomitant use of methadone, using high doses of ibogaine. Therefore, it is not clear if ibogaine at low doses could be used therapeutically in people on methadone maintenance treatments (MMT).

Methods

Case report of a female on MMT for 17 years who performed a self-treatment with several low and cumulative doses of ibogaine over a 6-week period.

Results

The patient successfully eliminated her withdrawals from methadone with ibogaine. Each administration of ibogaine attenuated the withdrawal symptoms for several hours, and reduced the tolerance to methadone until all signs of withdrawal symptoms disappeared at the end of the treatment. No serious adverse effects were observed, and at no point did the QTc measures reach clinically significant scores. Twelve months after the treatment, she was no longer on MMT.

Conclusions

To our knowledge, this is the first case report describing an ibogaine treatment using low and cumulative doses in a person on MMT. Although preliminary, this case suggests that low and cumulative doses of ibogaine may reduce withdrawal symptoms in patients undergoing MMT.

Wilkins, C., dos Santos, R. G., Solá, J., Aixalá, M., Cura, P., Moreno, E., … & Bouso, J. C. (2017). Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report. Journal of Psychedelic Studies, 1(1), 29-34. 10.1556/2054.01.2017.005
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Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial

April 28, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

OBJECTIVES: To evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored.

METHODS: Sixteen participants with bipolar depression and a Scale for Suicidal Ideation (SSI) score of ≥4 were randomized to ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg). Current pharmacotherapy was maintained excluding benzodiazepines within 24 hours. The primary clinical outcome was SSI score on day 1 post-infusion.

RESULTS: Results supported feasibility. Mean reduction of SSI after ketamine infusion was almost 6 points greater than after midazolam, although this was not statistically significant (estimate=5.84, SE=3.01, t=1.94, P=.074, 95% confidence interval ([CI)]=-0.65 to 12.31). The number needed to treat for response (SSI <4 and at least 50% below baseline) was 2.2, and for remission (SSI=0) was 3.2. The strongest neurocognitive correlation was between memory improvement on the Selective Reminding Test (SRT) and reduction in SSI score on day 1 after ketamine (ρ=-.89, P=.007). Pre- to post-infusion decrease in serum brain derived neurotrophic factor (BDNF) correlated with reduction in SSI from baseline to day 1 after ketamine (n=5, ρ=0.90, P=.037) but not midazolam (P=.087).

CONCLUSIONS: The study demonstrated feasibility. Suicidal thoughts were lower after ketamine than after midazolam at a trend level of significance, likely due to the small pilot sample. Memory improvement and BDNF are promising biomarkers. Replication is needed in an adequately powered full-scale trial.

Grunebaum, M. F., Ellis, S. P., Keilp, J. G., Moitra, V. K., Cooper, T. B., Marver, J. E., … & Mann, J. J. (2017). Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam‐controlled randomized clinical trial. Bipolar Disorders. 10.1111/bdi.12487

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Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders

April 26, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Papers, Psychology / By / , , , , ,

Abstract

The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in treatment-resistant depression, post-traumatic stress disorder and obsessive compulsive disorder. Due to similarities in brain network activity in depression and anxiety disorders, we hypothesized that ketamine might also be active in other refractory anxiety disorders. We evaluated the efficacy and safety of ketamine in 12 patients with refractory generalized anxiety disorder and/or social anxiety disorder who were not currently depressed, using an ascending single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which persisted for up to seven days. A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate, with minor changes at 0.25 mg/kg, and progressively greater and more durable changes at the higher doses. Ten of 12 patients were treatment responders at 0.5–1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be a potential therapeutic alternative for patients with refractory generalized anxiety disorder/social anxiety disorder. Along with its demonstrated effectiveness in patients with treatment-resistant depression, obsessive compulsive disorder and post-traumatic stress disorder, these data raise the intriguing possibility that ketamine may have broad efficacy in disorders characterized by negative emotional states, and that these disorders may share a common precipitating neurobiology.
Glue, P., Medlicott, N. J., Harland, S., Neehoff, S., Anderson-Fahey, B., Le Nedelec, M., … & McNaughton, N. (2017). Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. Journal of Psychopharmacology, 0269881117705089.
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Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report

April 24, 2017 / Anxiety Disorders / PTSD, Ayahuasca, Papers, Psychology / By / , , ,

Abstract

Background and aims

Ayahuasca is a dimethyltryptamine- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of Northwest Amazonian for ritual and therapeutic purposes. Animal and human studies suggest that ayahuasca has antidepressant and anxiolytic potentials and has a good safety profile. However, anxiety-like reactions may also occur after ayahuasca intake, although they are rare.

Methods

Case report.

Results

Here, we describe a case of a non-medicated, symptom-free young female with generalized anxiety disorder, who experienced intense anxiety, panic, and hopelessness during and for 3 days after participating in an ayahuasca ritual. The symptoms appeared in the first hours after ayahuasca intake and were gradually reducing in the following hours/days, but were intense enough to cause significant suffering to her, who needed to seek psychiatric help and restarted pharmacological treatment.

Conclusions

Although “bad/horror trips” with anxiety features may occur during the acute effects of ayahuasca and other hallucinogens, to the best of our knowledge, this is the first report of a subacute/prolonged anxiety-like reaction to this substance. Ayahuasca should be used with caution in people with a history of anxiety disorders.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & C. Hallak, J. E. (2017). Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report. Journal of Psychedelic Studies, 1(1), 35-39. 10.1556/2054.01.2017.004
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Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment

April 23, 2017 / Depressive Disorders, Ketamine, Neuroscience, Papers / By / , , , , , ,

Abstract

Background

Prefrontal global brain connectivity with global signal regression (GBCr) was proposed as a robust biomarker of depression and was associated with ketamine’s mechanism of action. Here, we investigated prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Then, we conducted a set of pharmacological challenges in healthy subjects to investigate the glutamate neurotransmission correlates of GBCr.

Methods

In the cohort A study, we used functional magnetic resonance imaging to compare GBCr between 22 patients with TRD and 29 healthy control subjects. Then, we examined the effects of ketamine and midazolam on GBCr in patients with TRD 24 hours posttreatment. In the cohort B study, we acquired repeated functional magnetic resonance imaging in 18 healthy subjects to determine the effects of lamotrigine (a glutamate release inhibitor), ketamine, and lamotrigine-by-ketamine interaction.

Results

In the cohort A study, patients with TRD showed significant reduction in dorsomedial and dorsolateral prefrontal GBCr compared with healthy control subjects. In patients with TRD, GBCr in the altered clusters significantly increased 24 hours following ketamine (effect size = 1.0, confidence interval = 0.3 to 1.8) but not following midazolam (effect size = 0.5, confidence interval = −0.6 to 1.3). In the cohort B study, oral lamotrigine reduced GBCr 2 hours postadministration, while ketamine increased medial prefrontal GBCr during infusion. Lamotrigine significantly reduced the ketamine-induced GBCr surge. Exploratory analyses showed elevated ventral prefrontal GBCr in TRD and significant reduction of ventral prefrontal GBCr during ketamine infusion in healthy subjects.

Conclusions

This study provides the first replication of the ability of ketamine to normalize depression-related prefrontal dysconnectivity. It also provides indirect evidence that these effects may be triggered by the capacity of ketamine to enhance glutamate neurotransmission.

Abdallah, C. G., Averill, C. L., Salas, R., Averill, L. A., Baldwin, P. R., Krystal, J. H., … & Mathalon, D. H. (2017). Prefrontal Connectivity & Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 10.1016/j.bpsc.2017.04.006
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Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study

April 12, 2017 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

BACKGROUND:
The psychoactive indole alkaloid ibogaine has been associated with encouraging treatment outcomes for opioid dependence. The legal status of ibogaine in New Zealand provides a unique opportunity to evaluate durability of treatment outcomes.
OBJECTIVE:
To examine longitudinal treatment effects over a 12-month period among individuals receiving legal ibogaine treatment for opioid dependence.
METHOD:
This observational study measured addiction severity as the primary outcome in 14 participants (50% female) over 12 months post-treatment using the Addiction Severity Index-Lite (ASI-Lite) following a single ibogaine treatment by either of two treatment providers. Secondary effects on depression were assessed via the Beck Depression Inventory-II (BDI-II). The Subjective Opioid Withdrawal Scale (SOWS) was collected before and immediately after treatment to measure opioid withdrawal symptoms.
RESULTS:
Nonparametric comparisons via Friedman Test between baseline and 12-month follow-up for participants completing all interviews (n = 8) showed a significant reduction for the ASI-Lite drug use (p = 0.002) composite score. Reductions in BDI-II scores from baseline to 12-month follow-up were also significant (p < 0.001). Significant reductions in SOWS scores for all participants (n = 14) were also observed acutely after treatment (p = 0.015). Patients with partial data (n = 4) also showed reductions in ASI-Lite drug use scores and family/social status problems. One patient enrolled in the study died during treatment.
CONCLUSION:
A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months. Ibogaine’s legal availability in New Zealand may offer improved outcomes where legislation supports treatment providers to work closely with other health professionals.
Noller, G. E., Frampton, C. M., & Yazar-Klosinski, B. (2017). Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse, 1-10. 10.1080/00952990.2017.1310218
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New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

April 11, 2017 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future.
Huang, Y. J., Lane, H. Y., & Lin, C. H. (2017). New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity. Neural plasticity, 2017. 10.1155/2017/4605971
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Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain

April 7, 2017 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

The rapidly-acting antidepressant properties of ketamine are a trend topic in psychiatry. Despite its robust effects, these are ephemeral and can lead to certain adverse events. For this reason, there is still a general concern around the off-label use of ketamine in clinical practice settings. Nonetheless, for refractory depression, it should be an indication to consider. We report the case of a female patient admitted for several months due to a treatment-resistant depressive bipolar episode with chronic suicidal behaviour. After repeated intravenous ketamine infusions without remarkable side effects, the patient experienced a complete clinical recovery during the 4 weeks following hospital discharge. Unfortunately, depressive symptoms reappeared in the 5th week, and the patient was finally readmitted to hospital as a result of a suicide attempt.
López-Díaz, Á., Fernández-González, J. L., Luján-Jiménez, J. E., Galiano-Rus, S., & Gutiérrez-Rojas, L. (2017). Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain. Therapeutic advances in psychopharmacology, 7(4), 137-140. 10.1177/2045125316675578
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A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial

April 4, 2017 / Ketamine, Papers, Psychology, Substance Use Disorder / By / , , , , ,

Abstract

Background

Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group.

Methods/design

This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life.

Discussion

This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems.

McAndrew, A., Lawn, W., Stevens, T., Porffy, L., Brandner, B., & Morgan, C. J. (2017). A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial. Trials, 18(1), 159. 10.1186/s13063-017-1895-6
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Clinical predictors of antidepressant response to ketamine in unipolar treatment-resistant depression

April 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology / By / , , , , , ,

Abstract

Introduction

The non-competitive N-methyl-d-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in treatment-resistant depression (TRD). However, only a few studies have investigated which clinical characteristics predict a response to ketamine.

Objectives

To assess sociodemographic variables and clinical markers that predict response to ketamine in unipolar TRD patients.

Methods

Searches of Pubmed, NCBI and Google Scholar were conducted for clinical trials and systematic reviews, through October 2016, using the keywords:
ketamine, N-methyl-d-aspartate receptor antagonist, rapid-acting antidepressant, depression, treatment-resistant depression, clinical predictors.

Results

Findings support the following clinical predictors:
– sociodemographic variables: positive family history of alcohol abuse disorder in first-degree relative (increased antidepressant response and fewer depressive symptoms for up to 4 weeks post-infusions), higher BMI (improvement in depression severity at 230 minutes and one day post-infusion), negative history of suicide attempt (greater improvement at day 7);
– infusion-associated events: greater dissociation during infusion (better antidepressant response at 230 minutes and one week post-infusion); rapid response to first infusion (sustained response to subsequent infusions in one-third responders for up to 83 days);
– symptomatology: anxious depression (fewer depression symptoms at day one up to 25 associated with longer time to relapse); neurocognitive performance (lower attention) predicts change in severity of depressive symptoms over six infusions.

Conclusions

Findings suggest that specific clinical characteristics are predictors of ketamine response in TRD. Future studies confirming reliable predictors will assist clinicians to implement efficacious and individualized treatment for TRD patients.

Del Sant, L. C., Magalhães, E., Lucchese, A. C., Alves, H. P., Sarin, L. M., Del Porto, J. A., & de Lacerda, A. T. (2017). Clinical predictors of antidepressant response to ketamine in unipolar treatment-resistant depression. European Psychiatry, 41, S525-S526. 10.1016/j.eurpsy.2017.01.704
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