A Cheerful Development in Fighting Depression

Michael Fumento
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Posted: Aug 09, 2006 12:00 AM

Author William Styron called it “Darkness Visible.” Another writer labeled it “The Noonday Demon.” Successful and beloved people such as William Holden and Ernest Hemingway were never able to shake off the beast called clinical depression.

Depression saps the life from you, so thoroughly destroying hope and happiness that you can’t even imagine why somebody else might smile or laugh. It wrecks dreams figuratively and literally in that it’s often linked with persistent, severe insomnia. It afflicts almost a tenth the adult population each year, is the leading cause of disability for ages 15-44, and frequently involves suicidal fantasies. Sometimes it doesn’t stop at fantasizing. Two weeks ago depression claimed my brother-in-law.

The good news is that most depressives can be treated with drugs, talk therapy, electroconvulsive treatment, or a combination thereof.

Newer drugs tend to have fewer side affects than earlier-generation ones, but all antidepressants provide agonizingly slow results – usually requiring at least 4-6 weeks. Further, the first drug prescribed probably won’t do the trick and there’s no way to know which will be best for each patient. That’s why despite the plethora of anti-depressant medicines, none can rightly be called a “me too” drug.

This is what’s so exciting about a treatment conducted by the National Institute of Mental Health. It’s an injection, not a pill (No, that’s not the exciting part) of a substance called ketamine. Since 1970, ketamine has been used as a general anesthetic for both humans and animals. Given in doses too low to cause anesthesia, it relieved depression in as little as two hours.

The study, appearing in the August Archives of General Psychiatry, comprised 17 depressed patients randomly assigned to receive either an injection of ketamine or a placebo. For 71% of those receiving the real deal, depression improved within a single day. Indeed, 29% became nearly free symptom free. Thirty-five percent of patients who received ketamine were still feeling better a week later. Patients receiving the placebo reported no improvement. No patients had serious side effects.

A week later, in a cross-over study, participants were given the opposite treatment unless they were still benefiting from the ketamine. Those with no benefit from the placebo were now helped while those who had received the real thing the first time but the fake stuff this time had no improvement.

More spectacularly, these were all treatment-resistant patients. They had tried an average of six medicines each without relief.

“To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose,” NIMH Director Dr. Thomas Insel said in a statement. Happily, his knowledge is incomplete. A 2000 study found similar results in seven patients treated with ketamine.

Some researchers believe that current antidepressants set in motion a long series of biochemical reactions; hence the long time period before the patient feels relief. But ketamine, they theorize, bypasses many of these functions. It takes a shortcut.

So when will ketamine be widely available? Actually, it already is. In pill and powder form it’s a “nightclub drug,” popular among the young-and-stupid set. It’s a controlled substance, for good reason. Pharmacologically similar to PCP, it causes hallucinations and euphoria and even psychologically-induced paralysis.

“We don’t want to give anyone the message to run out on the street and use ketamine,” Nuri Farber, a psychiatrist at Washington University in St. Louis told Nature Magazine. “It makes you crazy – that’s why it’s a banned drug.”

There’s no evidence ketamine has the least effect on depression unless injected, yet self-injection can be extremely dangerous because it can stop your lungs. (Of course, that would end your problem.) Further, when you buy from a dealer you never know what you’re getting.

What we need is for the pharmaceutical industry to take this tantalizing research and run with it, developing ketamine-like antidepressants in pill form that more specifically target brain receptors to eliminate or reduce the mental side effects.

Meanwhile, for severe treatment-resistant depressives, the use of ketamine injections themselves should be considered. Ask anyone who has suffered the horror of “darkness visible.”