Depression affects approximately 17% of the population at some point in life. First line treatment options normally consist of a class of drugs known as Selective Serotonin Reuptake Inhibitors (SSRIs). While SSRIs are highly effective at resolving depression in some patients, they come with significant limitations. These limitations include low response rates, treatment resistance, high incidence of relapse, and a delay in efficacy that requires patients to take one of many SSRIs for weeks to months before seeing any benefit. This lag-time in efficacy can be fatal in cases where suicidal ideations also occur, which is very common in depressed patients. Ketamine has been found to relieve the symptoms of depression within hours, rather than the usual weeks most antidepressants can take.
Depression has long been thought to be due to a neurochemical imbalance, which is why SSRIs are thought to help. The truth is that all mood disorders, including depression, are very complex and vary widely from case to case. This is evidenced by the low response rate for various SSRIs in depression. A key change is neuronal atrophy, characterized by the loss of synaptic connections in key cortical and limbic brain regions—which are important for mood. This neuronal atrophy is thought to occur due to decreased expression of growth factors, such as brain-derived neurotrophic factor (BDNF). Recent studies have demonstrated that ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, increases spine synapses in the prefrontal cortex and can also reverse the deficits caused by chronic stress. Many have hypothesized and basic research has shown that this occurs by transient disinhibition of glutamate transmission, followed by compensatory glutamate bursts at the neuronal synapse. This leads to a concomitant increase in BDNF, initiating a cascading signal pathway that ultimately increases neuronal spine formation. Resulting in an easing of depression symptoms.