Background/Objectives: Psilocybin shows therapeutic promise for several psychiatric disorders, but the acute perceptual and cognitive alterations produced by conventional doses (10–25 mg) require in-clinic supervision, which limits scalability. Whether the therapeutically relevant pharmacology of psilocybin can be safely separated from its hallucinogenic activity remains unresolved. To address...
The dose-response profile of racemic ketamine in internalizing disorders is poorly characterized. This was a secondary analysis of outcome responses in patients with treatment-resistant depression, post-traumatic stress disorder, generalized and/or social anxiety, or obsessive-compulsive disorder. For each disorder, they received single intramuscular doses of racemic ketamine (0.5 and 1.0...
Psilocybin shows therapeutic promise for several psychiatric disorders, but the acute perceptual and cognitive alterations produced by conventional doses (10-25 mg) require in-clinic supervision, which limits scalability. Whether the therapeutically relevant pharmacology of psilocybin can be separated from its hallucinogenic activity remains unresolved. To address this gap, we conducted a Phase...
BACKGROUND: Longer-term outcome and safety data of repeated subcutaneous racemic ketamine for treatment-resistant depression (TRD) is lacking, as is knowledge of the impact of prior ketamine treatment on subsequent response. AIMS: To evaluate the effectiveness and safety of a 4-week course of subcutaneous racemic ketamine over 6 months and investigate whether prior ketamine treatment influences...
BACKGROUND: Neurotic disorders - major depressive disorder (MDD), panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and specific phobia - have differing pharmaceutical profiles. But all, even when resistant to conventional treatment (TR), respond quickly to low dose (0.5-1.0 mg/kg I.M.) ketamine....
Ketamine is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. It was approved by the US Food and Drug Administration for anesthesia in 1970. The only other related US regulatory approval since then has been for esketamine nasal spray for depression in 2019. Over this time ketamine has been repurposed by mainly academic researchers, reporting clinical activity...
Ketamine has disputed effects on suicidal ideation scores in depressed populations. This study assessed effectiveness of ketamine in adults with treatment resistant depression, examining a secondary outcome of suicidal ideation. Phase III, double-blind, randomized, active-controlled, multicenter trial. Participants were randomized to twice-weekly subcutaneous racemic ketamine or midazolam for 4...
Anomalous perceptual experiences (APEs) have been reported anecdotally in ultra-endurance athletes. These experiences occur in the absence of psychiatric illness and may reflect the effects of extreme physiologic and environmental stressors. However, the literature is fragmented and terminology inconsistent, limiting understanding of the nature, prevalence, and mechanisms of these experiences....
The neurotic disorders (e.g., depression, dysthymia, generalized anxiety disorder, panic disorder, agoraphobia, social anxiety, post-traumatic stress disorder, and obsessive-compulsive disorder) are costly and difficult to treat. Diagnosis is based on symptoms not biological causes. Here, we summarize New Zealand-based work developing EEG biomarkers and novel treatments. Working at the...
Ketamine is effective for treatment resistant depression (TRD); but cost-effectiveness evidence remains limited. To evaluate the cost-effectiveness of subcutaneous ketamine for TRD from health sector and societal perspectives. A cost-utility analysis alongside the KADS randomised controlled trial (RCT) involved 174 participants receiving ketamine or midazolam (active control) twice weekly for 4...
We provide preliminary support for the efficacy and tolerability of i.m. ketamine in a community sample of individuals with PTSD. Further work is required to establish the optimal dosing regimen and longer-term role of ketamine in treatment of PTSD, but our findings are encouraging given the well-known of treatments in this area.
Abstract Background Ketamine, a rapidly acting antidepressant, requires dosing in clinic because of strong symptoms of dissociation and sedation after IV/IN dosing. This need for dosing in clinic limits capacity to treat patients with Treatment Resistant depression (TRD). We hypothesize that ketamine formulations that maximize ketamine’s first pass metabolism and delay absorption will have...
We previously completed a double-blind randomised crossover study assessing intramuscular ketamine for treatment-resistant depression (TR-D), post-traumatic stress disorder (TR-PTSD) and obsessive-compulsive disorder (TR-OCD). Here, we report an extension study to explore the ongoing benefits and tolerability of maintenance oral ketamine. All participants from the original study were eligible...
Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties. To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD. The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active...
Obsessive-Compulsive Disorder (OCD) may respond to ketamine treatment. To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl. This was a randomised double-blind psychoactive-controlled study with single doses of racemic ketamine 0.5 mg/kg, 1.0 mg/kg or fentanyl 50 µg (psychoactive control). Pre-dosing with 4 mg oral...
Background: The underlying mechanism(s) of action of psychedelic-assisted therapy (PAT) to reduce distress, depression, and/or anxiety symptoms in life-threatening illness are poorly understood. It has been postulated that addressing death anxiety, and components of spiritual and existential distress, may be mediating factors. Method: This systematic review describes the current evidence base...
Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery-Asberg Depression...
Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms,...
Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish...
Background The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care. Aim To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services. Method We consulted with...
Background Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. Aims To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. Method This phase 3,...
BACKGROUND: Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse. AIM: To identify all studies combining psychotherapy with ketamine for the treatment of psychiatric disorders to summarise their effects and make recommendations for future research....
Ketamine has rapid anxiolytic effects in treatment-resistant obsessive compulsive, post-traumatic stress, generalised anxiety and social anxiety disorders. This study aimed to assess changes following acute and maintenance ketamine therapy on the Fear Questionnaire (FQ) subscales and the Spielberger State Anxiety Inventory (SSAI). This secondary analysis used data from a mixed open-label and...
Background: We previously reported that ketamine has anxiolytic effects in patients with treatment-resistant generalized anxiety and social anxiety disorders. Aims: The purpose of this study was to replicate our earlier report about ketamine‘s anxiolytic activity, using a more robust study design. Methods: This was a double-blind, psychoactive-controlled ascending dose study in 12 patients with...
Parenteral ketamine has fast‐onset antidepressant and antianxiety effects; however, it causes dissociation, hypertension, and tachycardia shortly after dosing. Ketamine's antidepressant effects may be due to active metabolites rather than to ketamine itself. We hypothesized that oral controlled‐release ketamine tablets would improve safety and tolerability compared with injected ketamine by...