Ketamine on Depression

Ketamine, known as Special K on the streets, has become a surprise weapon in the war against depression. Pharmaceutical companies are racing to develop drugs that improve upon it, or can be paired with it. NeuroRx has made progress with its drug, Cyclurad which, when paired with ketamine, has the potential to treat bipolar depression which doctors have struggled to treat successfully.

History of Ketamine

Ketamine was first developed in 1962 as a fast-acting anesthetic that is still used widely in operating rooms and for pain management. Beginning in the 1970s ketamine became popular as a recreational drug, known for putting users in a “K-hole,” likened to an out-of-body, near-death experience.

Due to abuses, in 1999 the U.S. Drug Enforcement Administration banned nonmedical uses for ketamine and designated it a Schedule III controlled substance.

According to an article in Bloomberg Business, around the same time, researchers at Yale, including Dennis Charney, who’s now dean of the Icahn School of Medicine at Mount Sinai, stumbled upon the drug’s promise as a mood stabilizer. “We were not thinking at the time that ketamine would be an antidepressant,” Charney says. When patients started reporting that they suddenly felt better, the scientists were surprised.

The group’s findings, published in Biological Psychiatry in 2000, were largely ignored. The study was tiny, and because of ketamine’s reputation as a party drug, scientists were reluctant to follow up. “They didn’t believe you could get better from depression in a few hours,” Charney adds. “They’d never seen that before.” Standard antidepressants such as Prozac and Wellbutrin take weeks or months to kick in. As many as 30 percent of depressed patients don’t respond to conventional antidepressants, according to the National Institute of Mental Health.

Ketamine as Treatment

Six years later, Charney, who’d gone on to work for the National Institutes of Health, initiated a replica study with 17 patients. Within a day of getting one ketamine infusion, 70 percent of the subjects went into remission. Since then, scientists at institutions including Yale, Mount Sinai Hospital, and Baylor College of Medicine have performed dozens more studies that corroborate the findings. Additional studies show that ketamine works by producing long-lasting changes in the brain, reversing neural damage caused by stress and depression and potentially decreasing inflammation and cortisol levels.

Ketamine has continued to gain widespread attention in scientific literature and the media based on the increasing popularity of off-label administration to treat acute depression. Dr. Keith Ablow has sung its praises in his blog for FoxNews, “I have now treated approximately one hundred patients with intravenous ketamine. The results mirror those of research trials on the treatment; more than two thirds of my patients have experienced dramatic recoveries. Their profoundly low mood, lack of energy, decreased self-esteem and even suicidal thinking very frequently yields entirely to the ketamine infusions. And while the results from ketamine may last weeks or months, that is often more than enough time to allow other medications and psychotherapy to permanently rid patients of their suffering.

The ketamine success stories I have witnessed include patients once hobbled by depression and out of work for years who returned to their jobs within weeks of treatment, patients whose anxiety made it nearly impossible to leave the house who can now go on vacations that require travel, and young people who were driven to cutting themselves by underlying stress and self-loathing, but have now stopped cutting and started creating their futures.”

Future Outlook

The FDA’s approval of ketamine for depression hinges on multiphase clinical studies, which are unlikely to happen. Pharmaceutical companies usually pay for clinical trials and can’t make money off a decades-old generic drug. “You can get a few years of exclusivity for a new use, but generally you need more than a few years to recoup the research and development costs of bringing a drug to market,” says Michael Thase, a professor of psychiatry at the University of Pennsylvania who’s consulted for various drug companies developing ketamine-like products.

Instead, companies are spending millions to develop similar, patentable drugs. According to Bloomberg Business, Janssen is seeking approval for a nasal spray made from esketamine, a variation of the ketamine molecule that’s about 20 percent more potent, says Manji. The spray could come on the market in a few years. Cerecor, based in Baltimore, is developing a pill that replicates ketamine’s effects. In June, the startup filed to go public and raise as much as $31.6 million. Pharmaceutical giant Allergan spent $560 million in July to acquire Naurex, an Illinois-based biopharmaceutical company whose main products are two clinical-stage ketamine-like drugs called rapastinel and NRX-1074. Both are designed to modulate the same receptor as ketamine, alleviating depression without inducing hallucination.

Instead of replacing it NeuroRx is trying to work with it. They claim Cyclurad is able to extend the effect of Ketamine in the treatment of acute depression. Writing in the Journal of Clinical Psychiatry, Prof. Dan V. Iosifescu of the Icahn School of Medicine stated, “In this context, the study [of Cyclurad] represents an important addition to the emerging literature on maintaining clinical response after an initial Ketamine treatment… D-cycloserine has several advantages. It can be administered orally and has demonstrated safety and tolerability for long term use.”

Bipolar depression is a leading cause of disability in the United States. Currently, more than three million Americans have Bipolar Depression. 500 people with this condition tragically end their lives each day. Those with bipolar depression are far more likely to commit suicide compared with patients who have other forms of depression. Between 25% and 50% will attempt suicide at some point in their lives. Overall, patients with treatment resistant depression from all causes cost the healthcare system more than $120 billion annually.