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. 

Interestingly, ketamine has been identified as a fast acting antidepressant.  Ketamine has been shown in numerous clinical studies to rapidly reduce depression and suicidality.  Therefore, it is currently being evaluated by pharmaceutical companies who seek to get a labelled indication on a ketamine drug product for the treatment of depression. Fortunately, ketamine is already an FDA-approved drug and is available for off label use as a physician sees fit. Numerous case studies and even double-blind placebo controlled clinical trials have shown that intravenous (IV) ketamine can be employed to treat depression that is resistant to first line therapies such as SSRIs. 

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.  Scientists have identified many other changes that are thought to contribute to or cause 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 cause 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. 

Thus, ketamine may be effective at treating depressed patients that do not respond to first line therapies.  In addition, the onset of therapeutic action for ketamine occurs much more rapidly than with SSRIs.  Many patients begin to feel better after a single IV infusion session, however, others do require prolonged infusion sessions.  Moreover, as with SSRIs, ketamine is not always effective at resolving depression in every patient.