A recent meta-analysis suggests that subanesthetic doses of ketamine can offer rapid and sustained anxiety relief, becoming noticeable within a few hours and lasting up to two weeks. Despite the promising results, the research highlights the necessity for further research with larger patient cohorts to solidify the evidence base. The study has been published in the Journal of Psychopharmacology.
Ketamine is a dissociative anesthetic that has been used in medical settings for decades. In recent years, research has suggested that subanesthetic doses of ketamine may have rapid and robust antidepressant effects. Preliminary evidence suggests that ketamine may also have fast-acting anxiety-reducing effects in conditions like social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and treatment-refractory anxiety.
“Ketamine is a prototypical example of an emerging class of rapidly acting antidepressants,” explained study author Laith Alexander, an academic clinical fellow in translational psychiatry at King’s College London. “There was emerging evidence that ketamine might also be useful as an anti-anxiety (aka. anxiolytic) drug. In this study, we sought to synthesize evidence across several high-quality studies to see if low doses of ketamine could provide rapid and sustained relief of anxiety symptoms across a range of clinical settings.”
The researchers conducted a meta-analysis of 11 randomized controlled trials. These trials all met predefined criteria and provided data on the effects of ketamine on anxiety symptoms.
In a meta-analysis, researchers statistically combine data from multiple studies to draw overall conclusions. In this case, the researchers pooled and analyzed the standard mean differences in anxiety scores between the ketamine and placebo groups at different time points. By synthesizing data from multiple randomized controlled trials, the meta-analysis provided a more robust and comprehensive assessment of ketamine’s effect on anxiety compared to individual studies.
The researchers found that the anxiolytic effects of ketamine became noticeable relatively quickly after it was administered. Specifically, these effects began to manifest within a few hours, typically around 3 to 4 hours, following the administration of ketamine. The effects of ketamine were not just short-lived but had a lasting impact. After the initial 3-4 hour period, these effects continued to be significant for up to 2 weeks after the administration of ketamine.
“Our study suggests that low doses of ketamine, when used in appropriate clinical settings, may indeed provide rapid and relatively sustained relief of anxiety symptoms. However, further work using larger patient cohorts is needed to bolster the evidence base,” Alexander told PsyPost.
“Interestingly, some animal studies suggest that low doses of ketamine may not be as effective in alleviating anxiety symptoms compared to other depression-related symptoms. Our study contradicts these findings somewhat, and suggest that ketamine may indeed be useful for anxiety symptoms in patients.”
The researchers also investigated the relationship between dissociation and anxiety scores. Dissociation is an altered state of consciousness where a person may feel disconnected from their thoughts, feelings, or surroundings. It’s a known side effect of ketamine. But Alexander and his colleagues did not find any statistically significant correlation between the degree of dissociation people experienced as a result of ketamine and their anxiety scores.
So what accounts for the potential therapeutic effects of the drug? Ketamine acts as an NMDA receptor antagonist, leading to changes in synaptic plasticity and potentially triggering the release of brain-derived neurotrophic factor (BDNF). These neurochemical changes are thought to contribute to mood improvement.
“Drugs like ketamine might be effective because they are potent inducers of neural plasticity – that is, they make neuronal connections more malleable,” Alexander explained. “This is a critical requirement for new learning, which might take place during therapy. The combination of these medications with psychotherapy may therefore be particularly effective in ameliorating anxiety symptoms.”
The research provides important insights into ketamine’s potential as an anxiolytic agent. But there are some limitations that should be taken into consideration when interpreting its findings. “Caveats include the small numbers of patients in individual studies included in our analysis,” Alexander said. “Additionally, we still don’t understand how ketamine would be dosed in clinical settings – how often, optimum route, monitoring requirements, etc.”
The study, “A transdiagnostic systematic review and meta-analysis of ketamine’s anxiolytic effects“, was authored by Hannah Hartland, Kimia Mahdavi, Luke A Jelen, Rebecca Strawbridge, Allan H Young, and Laith Alexander.
