Repeated ketamine administration redeems the time lag for citalopram's antidepressant-like effects
G.-F. Zhang, W.-X. Liu, L.-L. Qiu, J. Guo, X.-M. Wang, H.-L. Sun, J.-J. Yang, Z.-Q. Zhou
European Psychiatry June 1, 2015 DOI: 10.1016/j.eurpsy.2014.11.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Chronic unpredictable mild stress (CUMS) rats |
| Interventions | Ketamine Citalopram |
| Dose | Ketamine 10 mg/kg intraperitoneal; citalopram 20 mg/kg oral |
| Duration | 21 days |
| Measures | Sucrose preference test, forced swimming test, open field test |
| Topics | Esketamine Ketamine |
| Key points | In CUMS rats, all four repeated ketamine regimens (10 mg/kg) showed antidepressant-like effects without altering locomotor activity or stereotypy; intermittent schedules produced longer-lasting effects than consecutive daily dosing. Adding ketamine (10 mg/kg every 7 days) to citalopram (20 mg/kg daily) for 21 days produced more rapid and sustained antidepressant-like effects than citalopram alone, which the authors propose may overcome the delayed onset of classic antidepressants. |
Abstract
Abstract: Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 8
- Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine Scientific Reports June 5, 2017
- Ketamine for depression: evidence, challenges and promise World Psychiatry September 25, 2015
- Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One? Frontiers in Psychiatry May 11, 2021
- Cognitive and psychotic effects of ketamine "short- vs. long-term" therapy in a rat model of depression: Hippocampal TrkB/Akt/GSK-3β/mTOR/autophagy trajectories. Progress in Neuro-Psychopharmacology and Biological Psychiatry September 1, 2025
- An Update of Ketamine Illicit Use Ketamine Revisited - New Insights into NMDA Inhibitors September 14, 2022
and 3 more in the library
Cites 16
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized, Placebo-Controlled, Crossover Pilot Trial of the Oral Selective NR2B Antagonist MK-0657 in Patients With Treatment-Resistant Major Depressive Disorder Journal of Clinical Psychopharmacology June 20, 2012
- Long-Lasting Antidepressant Action of Ketamine, but Not Glycogen Synthase Kinase-3 Inhibitor SB216763, in the Chronic Mild Stress Model of Mice PLoS One February 4, 2013
and 11 more in the library