The role of ketamine in treatment-resistant depression: a systematic review
This review (24 studies; n=416) found that ketamine is a reliable fast-acting anti-depressant for patients suffering from treatment-resistant depression (TRD). Long-term effects, however, remain to be studied.
Authors
- Serafini, G.
- Howland, R. H.
- Rovedi, F.
Published
Abstract
Background
At least 10-20% of the patients suffering from depression meet criteria for treatment-resistant depression (TRD). In the last decades, an important role of glutamate in mood modulation has been hypothesized and ketamine, a non noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, has been demonstrated to be effective in both MDD and TRD. However, concerns emerged about the optimal dosage, and frequency of administration of this treatment.
Methods
aiming to systematically review the current literature focusing on the main pharmacological properties and impact of ketamine in TRD, a detailed literature search in PubMed/Medline and ScienceDirect databases was conducted. Twenty-four manuscripts including a total of 416 patients fulfilled inclusion criteria.
Results
Most studies demonstrated that the NMDA antagonist ketamine has rapid antidepressant effects in TRD patients, confirming the active role of glutamate in the pathophysiology of this complex condition. Ketamine has been demonstrated to be rapidly effective and was associated with a significant clinical improvement in depressive symptoms within hours after administration. Also, ketamine was also found to be effective in reducing suicidality in TRD samples.
Limitations
The long-term efficacy of ketamine has not been investigated by most studies. The psychotomimetic properties may complicate the application of this pharmacological agent.
Conclusions
Ketamine may be considered a valid and intriguing antidepressant option for the treatment of TRD. Further studies are needed to evaluate its long-term antidepressant efficacy in patients with TRD.
Research Summary of 'The role of ketamine in treatment-resistant depression: a systematic review'
Introduction
Treatment-resistant depression (TRD) affects 10–20% of patients with major depressive disorder and is associated with frequent relapses, persistent functional impairment, and elevated suicide risk. The predominance of monoaminergic antidepressants in clinical practice, combined with their limited efficacy in TRD, prompted investigation of alternative neurobiological targets. Accumulating evidence implicating glutamatergic dysregulation in mood disorders led to clinical evaluation of ketamine — a non-competitive NMDA receptor antagonist — which demonstrated rapid antidepressant effects where conventional agents had failed. This systematic review aimed to critically evaluate the evidence on the efficacy, neurobiological mechanisms, and tolerability of ketamine in patients specifically meeting criteria for TRD, integrating case reports, open-label studies, and randomised controlled trials published through November 2013.
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Study Details
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- APA Citation
Serafini, G., Howland, R., Rovedi, F., Girardi, P., & Amore, M. (2014). The role of ketamine in treatment-resistant depression: a systematic review. Current Neuropharmacology, 12(5), 444-461. https://doi.org/10.2174/1570159X12666140619204251
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