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...
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...
Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in...
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...
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...
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,...
Abstract Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to...
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...
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent...
There is an urgent need for rapidly acting antidepressants. Current therapies share a delayed onset of action, contrasting with drugs of abuse that have rapid psychotropic effects but cause tolerance and dependence. A key uncertainty is whether there is a finite speed limit imposed by the critical role of homeostatic adaptive mechanisms that underpin the efficacy and onset of available...
BACKGROUND: The primary objective of this randomised controlled trial (RCT) is to establish the effectiveness of a novel online quality of life (QoL) intervention tailored for people with late stage (≥ 10 episodes) bipolar disorder (BD) compared with psychoeducation. Relative to early stage individuals, this late stage group may not benefit as much from existing psychosocial treatments. The...