The Pharmaceutical companies have been hard pressed to develop fast-acting anti-depressant and anti-anxiety drugs to meet the growing demand. In fact, there are no new drugs entering the pipe line. Older psychotropic drugs are merely being molecularly altered and are being re-branded as, “new and more effective” treatments for depression and anxiety. The drugs, currently being prescribed do not provide relief to all patients – only about 70% respond – and for those who do respond the medication ceases to be effective after an indefinite period of time. Other less fortunate patients experience no relief of symptoms. These groups constitute the majority of patients who seek ketamine therapy. Even for those whose medication “works” may not tolerate the side effects. Emotional blunting and sexual dysfunction (low libido) are a few of those undesirable “benefits.”
Companies are racing to develop fast-acting anti- depression drugs — but the process is tricky
Ketamine has started to fill the gap. Since the early 2000s, small studies suggested that ketamine might have potential as a depression drug. Unlike traditional antidepressants that target the brain’s serotonin and noradrenaline systems, ketamine appears to block a receptor called NMDA, which is activated by the neurotransmitter glutamate.
The evidence is promising: A dose much smaller than what’s used for anesthesia — given through an IV — stems symptoms of severe depression and anxiety in some patients with treatment-resistant depression, often within hours.
So, what is different about Ketamine that makes it more effective than the currently prescribed ant-depressant and anxiolitic drugs?
As noted, traditional anti-depressants target the brain’s serotonin and noradrenaline systems. This assumes that these neurotransmitters are those most responsible for depression and anxiety. So why don’t they work reliably and consistently for depressed and anxious patients? Examine the diagram below. Brain imaging reveals the level of stimulation to the brain centers involved when these medications are delivered.
Anti-depressants:
Ketamine:
The illustration above shows how ketamine stimulates brain activity on a global scale. This broad stimulation is caused by a glutamate boost which is the main mechanism of action produced by ketamine during infusion.
What is glutamate, and what role does it play in the treatment of depression and anxiety?
Glutamate is a powerful excitatory neurotransmitter that is released by nerve cells in the brain. It is responsible for sending signals between nerve cells, and under normal conditions it plays an important role in learning and memory.
An illustration of the glutamate burst experienced upon administration of ketamine during an infusion:
ketamine increases glutamate release in the prefrontal cortex, and according to the studies, is implicated in the induction of rapid antidepressant effects. The glutamate burst, then, has a two-fold benefit. The reduction and eventual remission of depressive and anti-anxiety symptoms is paramount. The facilitation of new learning is a significant secondary benefit. Old, ingrained behaviors which are detrimental to healthy functioning, can be replaced with new, more effective ways of coping with the day-to-day stressors that invariably arise. This adaptation is made possible by neurogenesis; the ability to increase the number of neurons in the brain – thereby making it possible to develop new connections and enhance communication between brain cells.