Can Ketamine be used for Treatment of Anxiety and Post Traumatic Stress Disorder?

ketamine

Ketamine was originally approved by the United States Food and Drug Administration (US. FDA) as an anesthetic. But the drug has found major use for the management of mood disorders such as refractory depression (also called treatment-resistant depression). The drug is also employed for the management of anxiety disorders, suicidal ideation, and post-traumatic stress disorder. According to Drugbank.com, Ketamine is an NMDA receptor antagonist with potent anesthetic properties. It was originally developed in the early 1960s as a replacement for phencyclidine (PCP) by Calvin Stevens at Parke Davis Laboratories. It started being used for veterinary purposes in Belgium and in 1964 was proven that compared to PCP, it produced minor hallucinogenic effects and shorter psychotomimetic effects. Ketamine works via the glutamate pathway, a neurotransmitter that is widely distributed throughout the body. This pathway mediates responses to stress and in the formation of traumatic memories. The mechanism of antidepressant and anti-anxiety effects of Ketamine occur through the activation of synaptic plasticity which causes an increase in the levels of brain-derived neurotrophic factor translation and secretion and also by inhibiting glycogen synthase kinase-3 and stimulating mammalian target of rapamycin signaling. Brain-derived neurotropic Brain-derived neurotrophic factors have been shown to participate in behavioral responses to classical antidepressants. However, their impact on synaptic plasticity may take several weeks to manifest. In contrast, ketamine-mediated synaptic plasticity changes appear to occur within a matter of hours after ketamine administration. Hence, this proves the potential for Ketamine to have a role in the treatment of anxiety and post-traumatic stress disorder.

The effects of Ketamine on mood disorders such as general anxiety disorders and post-traumatic stress disorder has been extensively studied. The role of Ketamine in General Anxiety Disorder and Social Anxiety Disorders have been studied extensively.

For instance, a small study of patients with GAD and SAD (n=12) compared three ascending ketamine doses to midazolam. Each was given at 1-week intervals, with midazolam counterbalanced in dosing position across patients. Ketamine was found to dose-dependently improve scores on the Fear Questionnaire. Moreover, its impact on decreasing theta frequency in the right frontal sites assessed via electroencephalogram (EEG) was comparable to that of conventional anxiolytics. This study was taken up by Glue and colleagues; they evaluated the efficacy and safety of ketamine in 12 patients with refractory GAD and SAD who were not currently depressed using an ascending single-dose at weekly intervals study design. Within 1 hour of dosing, patients reported reduced anxiety, which persisted for up to 7 days.

Furtherance of that study evaluated the impact of maintenance treatment ketamine in patients with GAD and SAD (n=20) and found that 18 of the 20 patients reported ongoing improvements in social functioning and/or work functioning during maintenance treatment. The researchers concluded that maintenance therapy might be a therapeutic alternative for patients with treatment-refractory GAD/SAD.

For this reason, various researchers have established that Ketamine for treatment-resistant depression has a veritable evidence base and converging lines of evidence suggest its use and effectiveness for the treatment of anxiety disorders.