ObjectiveThe ideas presented in this paper are based on a presentation at a festschrift event marking the retirement of Professor Gordon Parker from UNSW, Sydney. Drawing on Gordon's depressive subtyping approach and his critiques of a unitary view of major depressive disorder and treatment-resistant depression (TRD), we aim to (i) explore differing models of ketamine for TRD - biomedical...
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...
Treatment-resistant depression is a condition with significant morbidity, despite the current standard of treatment, including traditional pharmacotherapy, psychotherapy, augmentation strategies and electroconvulsive therapy. While novel therapies have emerged, such as ketamine/esketamine, transcranial magnetic stimulation and psilocybin-assisted therapy, the uptake of these treatments is...
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...
Comparing treatments for severe and medication-resistant depression is essential for guiding clinical decision-making. In this meta-analysis, we investigate the efficacy of electroconvulsive therapy (ECT) compared to ketamine for the treatment of major depressive disorder (MDD) and address the discrepant results of prior meta-analyses. We systematically searched PubMED (MEDLINE), Embase, and...
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...
Professional practice guidelines for the use of ketamine in psychiatric practice have been developed by the Royal Australian and New Zealand College of Psychiatrists to provide guidance on the use of ketamine in clinical practice in Australia and Aotearoa New Zealand, based on scientific evidence and supplemented by expert clinical consensus. Articles and information were sourced from existing...
Ketamine and its derivates (e.g. esketamine) are increasingly used in clinical settings for treatment-resistant depression (TRD). Ketamine can give rise to acute, cumulative and longer-term side effects (SEs) across a treatment course. The Ketamine Side Effect Tool (KSET) examines adverse effects though its length has affected feasibility for use in clinical settings. To estimate the frequency...
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...
Ketamine is a restricted and regulated medication in Australia and New Zealand, which has implications when considering treatment for patients with treatment-resistant depression and a history of illicit drug use, abuse or dependence. Regulations governing prescription of ketamine for treatment-resistant depression vary between jurisdictions in Australia and New Zealand, though most restrict...
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...
This systematic review and a meta-analysis synthesised the results from contemporary, randomized and non-randomized controlled studies to assess lasting (one week minimum) changes on cognition/creativity, emotional processing and personality from serotonergic psychedelics. PubMed, Embase and PsycInfo were searched in July 2022. Risk of bias was assessed using Rob 2.0 and ROBINS-I. Ten studies...
In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for...
Ketamine has recently emerged as a highly effective new treatment for people with treatment-resistant depression with rapid antidepressant effects. However, these effects are often short lasting, and the potential cognitive mechanisms underlying the therapeutic effects, such as effects on emotional processing bias, remain poorly understood. In the present study, we explored potential changes in...
Background: Intranasal esketamine has received regulatory approvals for the treatment of depression. Recently a large trial of repeated dose racemic ketamine also demonstrated efficacy in severe depression. However, uncertainties remain regarding comparative efficacy, dosage, and the time course of response. Methods: In this systematic review and meta-analysis, we searched Embase, Medline,...
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 Public and patient expectations of treatment influence health behaviours and decision-making. Aims We aimed to understand how the media has portrayed the therapeutic use of ketamine in psychiatry. Method We systematically searched electronic databases for print and online news articles about ketamine for psychiatric disorders. The top ten UK, USA, Canadian and Australian newspapers...
The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the ‘Clinical Memorandum on...
We aimed to analyze the efficacy and safety of arketamine, the R (−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion...
OBJECTIVE: Ketamine may reduce suicidal ideation in treatment-resistant depression. But it is not known how quickly this occurs and how long it persists. We undertook a systematic review and meta-analysis to determine the short- and long-term effectiveness of ketamine for suicidality. METHOD: CENTRAL, EMBASE, Medline, and PsycINFO were searched until 12 December 2018. Randomised controlled...
BACKGROUND Ketamine and its enantiomers have recently been highlighted as one of the most effective therapeutic options in refractory depression. However, racemic ketamine and esketamine have not been directly compared. The aim of this study is to assess the efficacy and safety of esketamine compared to ketamine in patients with treatment-resistant depression (TRD). METHODS This is a...
Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. This randomised, double-blind, placebo-controlled pilot study compared a 4-week course...
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...
To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60...
Summary Background The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine. Methods In this multicentre, randomised,...