Therapeutic Advances in Chronic Disease
April 13, 2015
Nicolas D. Iadarola, Mark J. Niciu, Erica M. Richards et al.
202 citations
A single subanesthetic dose infusion of the noncompetitive NMDA receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression, unlike current monoaminergic antidepressants which have a delayed onset and limited efficacy. Preclinical studies inspired by ketamine's clinical effects reveal enhanced synaptic plasticity and synaptogenesis through mechanisms including release of local translational inhibition of brain-derived neurotrophic factor, mammalian target of rapamycin activation, and glycogen synthase kinase-3 inhibition. Current efforts aim to extend ketamine's efficacy, uncover neurobiological mechanisms in biologically enriched subgroups, and identify biomarkers for personalized treatment. Other NMDA receptor antagonists show modest antidepressant effects but potentially fewer dissociative or psychotomimetic effects, prompting development of novel glutamatergic antidepressants with greater target specificity and fewer adverse effects.
The Journal of Clinical Psychiatry
September 25, 2014
Dawn F. Ionescu, David A. Luckenbaugh, Mark J. Niciu et al.
111 citations
Patients with treatment-resistant major depressive disorder who also have high anxiety (anxious depression) responded better to a single infusion of ketamine than those without high anxiety, contrary to expectations based on traditional antidepressants. Over 28 days of follow-up, the anxious group showed significantly fewer depression symptoms at multiple time points and relapsed much later (median 19 days versus 1 day). No significant differences in side effects were observed. These results suggest that ketamine, an NMDA receptor antagonist, may be especially effective for the anxious depression subtype, which is typically difficult to treat with standard antidepressants.
Journal of Clinical Psychiatry
February 1, 2023
Balwinder Singh, S. Kung, Vanessa K. Pazdernik et al.
64 citations
In adults with treatment-resistant depression, intravenous (IV) ketamine and intranasal (IN) esketamine produced similar rates of symptom improvement and remission, but remission was reached in fewer treatment sessions with IV ketamine. Over up to six IV or eight IN treatments, depressive symptoms were measured before and 24 hours after each session. Among 62 participants (median age 50, 65% female), neither the change in symptom scores nor the proportion achieving response or remission differed significantly between groups. However, time to remission—adjusting for age, sex, body mass index, and baseline severity—was five times faster with IV ketamine than with IN esketamine. A randomized controlled trial is needed to confirm these results.
The International Journal of Neuropsychopharmacology
December 19, 2014
Mark J. Niciu, David A. Luckenbaugh, Dawn F. Ionescu et al.
55 citations
A single low-dose infusion of the anesthetic ketamine produces rapid antidepressant effects in people with treatment-resistant major depressive disorder. In this trial, depressed individuals with a family history of alcohol use disorder showed a longer-lasting antidepressant response to ketamine compared to those without such a family history. Adding the drug riluzole did not extend or enhance ketamine's antidepressant durability. The findings suggest that family history of alcohol use disorder may predict a more durable ketamine response, which should be accounted for in future ketamine depression studies.
Pharmaceuticals
August 1, 2023
B. Joseph, N. Nuñez, S. Kung et al.
14 citations
For adults with treatment-resistant depression, taking lamotrigine alongside intravenous ketamine or intranasal esketamine does not significantly reduce the antidepressant effect of the treatments. In a historical cohort study, response and remission rates were similar whether patients were on lamotrigine or not. There was a trend toward lower dissociation scores among those taking lamotrigine, especially with IV ketamine. The study was limited by only 13 patients on lamotrigine, so the evidence is insufficient to conclude that lamotrigine attenuates the antidepressant effect, but it may reduce dissociation.
Journal of Affective Disorders
January 1, 2024
Liliana Patarroyo-Rodriguez, Vanessa M. Pazdernik, Jennifer L. Vande Voort et al.
12 citations
Sleep disturbances affect 94% of patients with treatment-resistant depression, with middle and early insomnia being the most common. Patients who experience hypersomnia (excessive sleep) before treatment show higher response rates and greater improvement in depressive symptoms after receiving intravenous ketamine or intranasal esketamine. Additionally, 15% of patients have an atypical depression phenotype, and most of them also achieve a positive response with greater symptom reduction. A trend toward faster response is seen in both the hypersomnia and atypical depression groups. These sleep-related features may help predict which patients will benefit from ketamine-based treatments.
The Journal of Clinical Psychiatry
September 17, 2025
Liliana Patarroyo-Rodriguez, Vanessa K. Pazdernik, Jennifer L. Vande Voort et al.
1 citation
Ketamine and esketamine reduced long-term emergency department visits for suicidality among individuals with treatment-resistant depression. Further research with longer follow-up is needed to determine whether these benefits depend on mood state or reflect an independent mechanism.