Ketamine is recognized as a rapid and sustained antidepressant, particularly for major depression unresponsive to conventional treatments. Anhedonia is a common symptom of depression for which ketamine is highly efficacious, but the underlying circuits and synaptic changes are not well understood. Here, we show that the nucleus accumbens (NAc) is essential for ketamine's effect in rescuing...
In this issue of Neuron, Pignatelli et al.1 find that ketamine reverses stress-induced changes in excitatory synapses in nucleus accumbens D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs) and that these changes are necessary for the treatment of anhedonia-like behavior.
Long-term opioid use is associated with pharmacological tolerance, a risk of misuse and hyperalgesia in patients with chronic pain (CP). Tapering is challenging in this context, particularly with comorbid opioid-use disorder (OUD). The antihyperalgesic effect of ketamine, through N-methyl-D-aspartate (NMDA) antagonism, could be useful. We aimed to describe the changes in the dose of opioids...
Abstract Purpose of the review Treatment-resistant depression (TRD) is a challenging condition characterized by minimal improvement despite two or more antidepressant trials. Ketamine-assisted psychotherapy (KAP) integrates the rapid antidepressant effects of ketamine with psychotherapy to enhance and sustain therapeutic outcomes. This systematic review evaluates the effectiveness of KAP in...
Intensive care medicineMay 5, 2025Ary Serpa Neto, Marcus Young, Jian Wen Chan et al.9 citations
Ketamine use is a potentially modifiable risk factor for hallucinations. We aimed to use target trial emulation to investigate the association between low-dose ketamine and development of hallucinations in critically ill patients in the intensive care unit (ICU). Retrospective study using data from a university affiliated ICU in Melbourne, Australia. Application of marginal structural models...
Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. This mechanism may differentiate ketamine from other NMDA receptor antagonists. Animal models that reflect OR-dependent behavioral effects of ketamine may shed light on the...
Recent studies in mouse models have demonstrated that ketamine and rapastinel induce rapid-acting and sustained antidepressant effects in major depressive disorder (MDD). However, it remains unclear how ketamine's and rapastinel's opposing mechanisms of action-NMDAR antagonist and NMDAR positive allosteric modulator, respectively-result in similar antidepressant-like effects. Furthermore,...
Ketamine has garnered attention for its rapid efficacy in alleviating depressive symptoms in treatment-resistant depression, offering a novel mechanism as a non-monoaminergic agent. Despite its potential, limited research has explored mental health professionals' perspectives on its use. This study assesses the attitudes, knowledge, and concerns of Portuguese psychiatrists and psychologists...
SUMMARYThis critical appraisal of a Cochrane Review assesses the efficacy of ketamine for treating unipolar major depressive disorder. The review included 31 randomised controlled trials involving ketamine. Results indicate that intravenous (i.v.) ketamine significantly improves antidepressant response compared with i.v. saline and, to a lesser extent, i.v. midazolam within 24–72 h. However,...
Cephalalgia ReportsMay 1, 2025Jonathan A. Leighton, Chieh Grace Lau, Aisha Savdo et al.2 citations
Background Cluster headache is an excruciating condition for which standard treatments are usually insufficient. Evidence has accumulated that serotonergic psychedelic indoleamines including psilocybin and LSD can be effective in preventing attacks. Methods In this case series, nine patients with episodic and chronic cluster headache that didn’t respond to conventional treatments were treated...