Conventional treatment for depression usually consists of the use of antidepressant medications, therapy, or a combination of both.

Despite their widespread use, antidepressant medications are not without risk or controversy. One only has to look at recent headlines to see the possible serious risks linked to the drugs:

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In addition, antidepressants aren’t always helpful: the medications usually take at least two weeks to show any effect, and for some people, they don’t work at all.

Experts say that a drug that is fast-acting and provides sustained relief from depression was available, the risk of suicide among patients would be reduced.

A new research finding adds to the growing body of evidence that a controversial party drug may be the answer those experts (and those who suffer from depression) have been looking for.

That drug is ketamine, which is also known as the recreational drug “Special K.”

Ketamine is an anesthetic that was developed in the early 1960s. It is one of the most widely used drugs in modern medicine, and is on the World Health Organization’s List of Essential Medicines. In the US, ketamine is classified as a Drug Enforcement Administration (DEA) Schedule III drug, which means it is believed to have  moderate to low potential for physical and psychological dependence.

In the late 1990s, Yale researchers at the Connecticut Mental Health Center made the first observation that ketamine helped depressed patients feel better.

Gerard Sanacora MD, PhD, director of the Yale Depression Research Program, recalls the discovery:

Unexpectedly, a single dose of ketamine produced a rapid, robust antidepressant response in several patients. It started as early as a few hours after the drug was given and lasted for days, or even weeks.

Research on ketamine at Yale – and elsewhere – is ongoing.

Dr. Thomas Insel, the former director of the National Institute of Mental Health, wrote a blog post about ketamine in October 2014. Here’s an excerpt:

Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades. Three findings are worth noting. First and most important, several studies demonstrate that ketamine reduces depression within six hours, with effects that are equal to or greater than the effects of six weeks of treatment with other antidepressant medications. The shift from six weeks to six hours has already transformed what we could and should expect of antidepressant treatments.

Second, ketamine’s effects have been noted in people with treatment-resistant depression. Most of the studies to date have tested ketamine in people for whom other treatments were not effective, including both medications and psychotherapy. This promises a new option for people with some of the most disabling and chronic forms of depression, whether classified as major depressive disorder or bipolar depression.

Third, it appears that one of the earliest effects of the drug is a profound reduction in suicidal thoughts.

Ketamine typically relieves depression within two hours and its beneficial effect on patients may last as long as a week.

It can be addictive and may send recreational users into hallucinations and delusions. Some have experienced disorientation that they call the “K-hole.”

Because of the potential for misuse and addiction, explained researcher Daniel Lodge, Ph.D., of The University of Texas Health Science Center at San Antonio, “You have a novel, highly effective treatment for depression, but you can’t give it to people to take at home or on a routine basis.”

The Ketamine Advocacy Network was founded by ketamine clinical trial volunteers at the National Institutes of Health in 2012 . These individuals personally experienced the power ketamine has to rapidly relieve the excruciating pain of refractory (treatment-resistant) depression. The organization’s website offers a wealth of information on the drug, research findings, and patient experiences.

Almost all of the research studies done on ketamine so far have used intravenous infusion (an IV drip) as the method of delivery for the drug. This is to ensure it goes directly into the bloodstream at a carefully controlled rate and straight to your brain without first being metabolized by the body. Ketamine must be administered in a very precise way – the reasons for which are eloquently outlined in this article from the Ketamine Advocacy Network: Route of Administration: Critical to Achieving Relief.

So far, ketamine’s success rate in treating people with depression, bipolar disorder, and post-traumatic stress disorder (PTSD) is promising, according to the Ketamine Advocacy Network:

About 70% of patients with treatment-resistant depression (including bipolar patients) experience rapid relief after a low-dose ketamine infusion.  Similar success rates have been seen in returning combat veterans suffering from PTSD.  These patients’ cases are the worst of the worst, lasting years or even decades, and which have not responded to any other treatments. Many have hovered on the verge of suicide for years, many have actually attempted suicide, and all have endured a very poor quality of life.

While that success rate is high, the organization points out that the degree of relief can vary among patients, and that it doesn’t work for everyone.

Researchers say the problem with ketamine is that the drug acts on receptors located throughout the brain, which makes it difficult to control its effects.

Here’s how ketamine works:

Ketamine is completely different from SSRIs, tricyclics, MOAI inhibitors, benzos, or any other antidepressant or anti-anxiety medication.  The exact mechanism that causes ketamine to relieve depression is still under study, and is quite complex.  In short, when ketamine is administered in a very precise way it triggers a cascading sequence of events in the brain, which ultimately results in the re-growth of neurons that previously died off.  It is thought by some researchers that prolonged exposure to stress causes these neurons die off in the first place, resulting in depression, but ketamine causes them to rapidly re-grow within hours, relieving the depressive symptoms.  This is an oversimplification of a very complex topic, and the latest research hints there may be several other mechanisms involved that also play important roles. (source)

Dr. Lodge and colleagues from the Health Science Center’s Department of Pharmacology used state-of-the-art research techniques in rats to identify a brain circuit that brings about the beneficial effects of ketamine. The circuit sends signals between the hippocampus and the prefrontal cortex. The researchers found that activating the circuit in rats causes antidepressant-like effects similar to those caused by ketamine, whereas preventing activation of the circuit eliminates the antidepressant-like effects of ketamine.

Flavia R. Carreno, Ph.D., lead author of the study, said:

The idea is, if one part of the brain contributes to the beneficial effects of ketamine, and another part contributes to its abuse and effects such as hallucinations, now we can come up with medications to target the good part and not the bad.

Identifying this mechanism now gives scientists a target, Dr. Lodge explained:

The next step is finding a drug that interacts selectively with it. And we have some ideas how to do that.

Currently, ketamine therapy is not widely available. There are only a few clinics in the US that offer it for depression, bipolar, PTSD, and other mood disorders.

When used in a medical setting, ketamine is very safe. It is the only anesthetic that does not suppress the body’s cardiovascular and respiratory systems. However, it does have the potential to elevate heart rate and blood pressure, so the patient’s vitals must be monitored during treatment.

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