Ketamine for Anxiety

Ketamine was approved as an anesthetic by FDA in 1970 and has been used mostly in the operation room and emergency department. It has also been used in combination with psychotherapy for the treatment of depression and anxiety. The traditional antidepressants affect chemical brain chemicals and improve the mood of the patients, but ketamine alters levels of glutamate in the brain, leading to rapid improvement in symptoms of anxiety and depression.

Ketamine is legal when prescribed by licensed medical professionals in the United States. It has been widely used in the hospital since its approval by FDA in 1970.  The FDA approved esketamine, a form of ketamine, for treating depression in 2019. In just the past few years, there have been many clinical trials studying ketamine’s role in various mental health conditions. In light of these findings, doctors have begun prescribing ketamine-assisted therapy as a treatment for depression, anxiety, PTSD, and chronic pain. Ketamine is listed as a Schedule III drug in the Drug Enforcement Administration (DEA) guidelines. Any drugs that are classified as schedules I through V count as controlled substances. Controlled substances aren’t necessarily harmful; they just need to be closely monitored by a doctor. Their rating results from a combination of factors including the potential for mental or physical addiction, the accepted stance of the medical community, and the risk of adverse side effects. These drugs all require prescriptions to be legally used. Schedule III classification means that the drug has been widely accepted by the scientific community as having medicinal value and it is not unusual for a clinician to prescribe it to patients. However, ketamine is only legal when prescribed by a licensed medical practitioner.

Anxiety disorders are one of the most prevailing mental health problems in the United States. About 40 million adults in the United States suffer from anxiety disorders each year, making up 18.1% of the population. Only 37.9% of them receive treatment for anxiety. Among patients who receive treatment, 30-40% are unable to get relief from symptoms of anxiety through standard therapeutic approaches. As treatment of mental health issues evolved, some new drugs showed promising effects, and Ketamine is one of these medications. Ketamine is an FDA-approved anesthetic agent that has also been used off-label to treat treatment-resistant depression and anxiety disorders.

Jerome H Taylor et al. conducted a randomized, placebo-controlled crossover trial to assess the treatment efficacy of ketamine for social anxiety disorder. Eighteen individuals with DSM-5 SAD were given IV Ketamine infusions (0.5 mg/kg over 40 min) compared to the control group who received a placebo (saline infusion). Ratings of anxiety symptoms were assessed after 3 hours of infusion, followed for 14 days on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). After two weeks of ketamine administration, patients exhibited a significant treatment response to ketamine infusion as compared to placebo. On LSAS, response to ketamine infusion was 33.3%, and in contrast, placebo response was 0%. The VAS response was 88.89% and 52.94% to ketamine infusion and placebo, respectively. This response provided supportive evidence of the treatment efficacy of ketamine in reducing social anxiety.

Paul Glue et al. studied an exploratory double-blind psychoactive-controlled replication study to determine the treatment effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders in 12 patients who were not currently depressed. Ketamine was administered in ascending doses (0.25, 0.5, and 1 mg/kg) at an interval of 7 days, and the control group was given midazolam 0.01 mg/kg. Ratings, dissociation, tolerability, and safety were detected for ketamine infusion. Rating of anxiety improved after one hour of ketamine infusion, which persisted for 7 days (1 week). In contrast, midazolam had a minor treatment effect on the improvement of anxiety symptoms. Ketamine infusions were safe and well-tolerated. This study indicates ketamine acts as a potential therapeutic agent for reducing symptoms of treatment-refractory generalized anxiety and social anxiety disorders.

A continuation of the above-mentioned study detected the effect of the maintenance dose of ketamine in 20 patients with generalized anxiety disorders (GAD) and social anxiety disorder (SAD). In this study, 18 out of 20 patients showed significant improvement in social functioning during the maintenance treatment of ketamine. The researchers of this study concluded that ketamine might be an alternative treatment for patients with treatment-refractory GAD or SAD.