Anxiety disorders affect a substantial proportion of the population, with a lifetime prevalence of approximately 34% of adults in the United States. These disorders, characterized by fear and anxiety, significantly impact daily functioning, and vary in triggers, ranging from specific situations to general distress. Anxiety symptoms are pervasive across various clinical settings, including generalized anxiety disorder, major depressive disorder, chronic pain, advanced cancer, and palliative care.
Ketamine, known for its effectiveness as a glutamate-based antidepressant, has garnered attention for its potential anxiolytic effects. Emerging evidence suggests that ketamine may provide fast-acting relief for anxiety symptoms lasting up to two weeks after a single dose in conditions such as social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and treatment-refractory anxiety (Glue et al., 2018; Taylor et al., 2018; Liriano et al., 2019; Tully et al., 2022).
Despite previous supportive studies, the time course of ketamine's anxiolytic action remains underexplored. Today we will discuss findings of a recent systematic review and meta-analysis that aim to fill this gap, examining the effect of ketamine on anxiety symptoms for various diagnoses.
Treatment options for anxiety, such as the use of selective serotonin reuptake inhibitors (SSRIs), have limitations, including a slow onset of action and side effects (e.g., weight gain, decreased libido, and sleep disturbances), as well as the potential for worsening anxiety symptoms. Benzodiazepines provide rapid relief but are associated with tolerance, dependence, and potential addiction. The prevalence of treatment-resistant anxiety underscores the urgent need for novel, rapidly acting anxiolytic agents.
This systematic review and meta-analysis involved fourteen studies, with seven focusing on PTSD, five on mood disorders, and two on anxiety disorders or chronic pain. Results indicated that ketamine's anxiolytic effects manifested rapidly, typically within three to four hours, and remained significantly superior to placebo at 24 hours and 7-14 days post-administration.
While the studies showed some heterogeneity, particularly in acute time points, the sustained anxiolytic effects of ketamine were consistent across various settings. Notably, studies assessing effects beyond 14 days suggested a continued superiority of ketamine over placebo, emphasizing its potential for prolonged anxiolytic efficacy.
This groundbreaking review provides an exploration of ketamine's anxiolytic effects, shedding light on its temporal profile across multiple clinical settings. The findings support the notion that ketamine provides both rapid and sustained relief for anxiety symptoms. This is an additional benefit to its potential antidepressant effect, as suggested by previous studies discussing efficacy, where up to 83% improvement was observed in patients with treatment-resistant depression who received ascending repeated doses of intravenous ketamine.
Despite some limitations, this review highlights the need for future research to better understand ketamine's sustained anxiolytic efficacy beyond two weeks. Moreover, the correlation between improvements in anxiety and depression scores suggests a shared mechanism for these therapeutic effects, warranting further investigation.
In conclusion, this new research provides valuable insights into the potential of ketamine as a rapid and enduring anxiolytic agent. Furthermore, low doses of ketamine have been shown to effectively treat other types of anxiety, including refractory social anxiety, with only minor adverse effects, as demonstrated by other studies indicating the safe and effective use of ketamine administration. By highlighting the potential use of ketamine for various diagnoses, this work sets the stage for future research to refine administration patterns and explore repeated dosing for optimized therapeutic outcomes in anxiety disorders.
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