Emerging Uses Of Ketamine Treatment For Depression

Known to some as 'Special K,' low-dose ketamine is a controlled substance known for producing hallucinations and a high similar to an out-of-body experience. However, recent studies have shown that ketamine, which was initially discovered as an anesthetic and pain reliever, could be an effective alternative for treatment-resistant depression. 

History Of Ketamine In Medicine

Ketamine was first synthesized by a professor at Wayne State University in Detroit, Michigan in the 1960s. After receiving FDA approval for use in humans in 1970, ketamine was used as an analgesic and sedative during the Vietnam War. In large doses, ketamine is an effective anesthetic and was used for many years on humans as well as on animals. Compared to other anesthetics, ketamine had fewer side effects on breathing and blood pressure.

However, it was also discovered that ketamine has some psychoactive properties, causing hallucinations or a "spaced out" feeling. This discovery prompted ketamine's use as a recreational drug, which resulted in stricter rules regarding its distribution and use. Outside a medical setting, unregulated use of ketamine can cause serious side effects to a person’s physical and mental health. Nonetheless, a recent serendipitous discovery suggests that ketamine may have remarkable effects on depression.

The Highs And Lows Of Depression

Major depressive disorder is one of the most prevalent, severe, and debilitating of the psychiatric illnesses. Globally, an estimated 350 million people live with depression. Current mainstream antidepressants, the so-called selective serotonin reuptake inhibitors (SSRIs such as fluoxetine) and serotonin-norepinephrine reuptake inhibitors (SNRIs such as venlafaxine), were discovered some 60 years ago. How SSRIs work is still unclear, and importantly, they don't work for everyone. Indeed,  only about 35% of patients on SSRIs achieve full remission, leaving as many as 5 million people in the U.S. with so-called “treatment-resistant depression”.

Another limitation is that for patients who do experience therapeutic benefits from SSRIs, the effects take several weeks to kick in and there is a high rate of relapse. This means that for many patients, depression can come back. This fact highlights an unmet need for antidepressants with more rapid relief, particularly for patients with stubborn depression or who have active suicidal thoughts. 

Moreover, several studies have shown that SSRIs may not work any better than a placebo (a sugar pill) for treating mild to moderate depression. And for those with severe depression, SSRIs only had a small and clinically insignificant benefit over placebo. 

If you are thinking about suicide, considering harming yourself or others, feeling that any other person may be in any danger, or if you have any medical emergency, you must immediately call the emergency service number (1-800-273-8255 in the US and 0800-689-5652 in the UK) and notify the relevant authorities. Seek immediate in-person assistance.

A New Wonder Treatment?

For many, ketamine appears to be effective at improving symptoms of depression. Studies suggest that a sub-anesthetic dose of ketamine may be effective for lessening suicidal thoughts and for treatment-resistant depression. Research studies published to date suggest that 60-70% of patients with treatment-resistant depression respond to ketamine. Importantly, the response appears to be almost immediate – within hours of administration – and can be sustained for up to two weeks in some patients.

These initial findings have sparked interest in ketamine as a treatment for depression. As of now, the FDA has approved a non-psychedelic ketamine treatment to be investigated in clinical trials for depression. And some doctors have prescribed ketamine off-label to severely depressed patients. There are also ongoing late-stage clinical trials, but most of them are with small sample sizes, so much more research needs to be done.

How Does Ketamine Work?

The short answer is we're not sure. The anesthetic properties of ketamine are thought to occur by its blockade of NMDA glutamate receptors in the brain. Glutamate is the major neurotransmitter in the brain and is a fast-acting excitatory molecule. This contrasts with monoaminergic systems such as serotonin, which are more localized and slow moving. Ketamine appears to work through the fast-acting glutamate system, which is consistent with its rapid onset of action.

For the antidepressant effects of ketamine, studies suggest that it is not only ketamine's blockade of NMDA receptors but also its simultaneous enhancement of another type of glutamate receptor: AMPA receptors. The block of NMDA and enhancement of AMPA receptors, together, may cause a rapid release of glutamate in the brain, which is thought to kick-start neuroplasticity, (the ability of the brain to grow new neurons and new connections).

Contemporary theories of depression suggest that neuroplasticity is impaired in people with depression and that interventions that promote neuroplasticity can help to alleviate depression. Conventional antidepressants as well as behavioral interventions (such as exercise) have been shown to increase neuroplasticity. But because ketamine appears to work on the glutamate system, it seems to work more rapidly and more powerfully. For people who are suicidal, this rapid effect can be lifesaving.

A Note Of Cautious Optimism

Although the use of ketamine in treating depression is promising so far, there are some remaining questions and challenges. While a recent systematic review suggests that ketamine is a safe treatment for depression in the short term, questions remain about the long-term risks and potential side effects of ketamine treatment and effects for long-term use. Similarly, people can become dependent on it, and long-term recreational abuse of ketamine is linked to cognitive dysfunction and bladder toxicity.

Another consideration is that ketamine's effects appear to be temporary; depression often creeps back up over the course of days or weeks. This requires regular infusions of ketamine to keep depressive symptoms at bay. Since insurance rarely covers the treatments, these infusions are costly, ranging from $400 to $800 per infusion. This means that patients can expect to spend more than $10,000 per year out of pocket.

The Bottom Line

For those who have exhausted contemporary antidepressants (e.g., SSRIs and SNRIs) and still struggle with severe depression and suicidal thoughts, ketamine may be a good option. The research is promising, but the jury is still out on long-term effects. Never use street or illegal drugs as a treatment for mental health conditions as it could be dangerous. Always discuss your options with a licensed and certified mental health professional. 

For many people with treatment-resistant depression, even leaving the house can be a struggle. This can make meeting with a mental health professional like a counselor or therapist in person nearly impossible. That’s where online therapy can play an important role. With internet-based counseling, you can discuss your symptoms with a licensed therapist from the comfort of your home. This form of treatment can also be more convenient since appointments are available day or night. 

Researchers in the field of mental health have been investigating the effects of online counseling for more than a decade. One study found that individuals undergoing remote therapy for depression experienced greater symptom reduction when compared to participants on a waitlist. 

Takeaway

If you’re experiencing symptoms of depression, you should know that a variety of treatment options are available. A professional therapist like those at BetterHelp can help you evaluate these options and choose the best course of action for your particular situation. Simply answer a few questions and you can get matched with a qualified counselor within 48 hours.