What first began as a veterinary anesthetic and later became an anesthetic for Vietnam war soldiers, ketamine has continued to evolve over the last half century. Maybe you've heard news reports touting warnings about "Special K" being used as a party drug, but now ketamine is emerging as a beacon of hope for those battling severe depression and treatment-resistant depression.

Rise in depression driving research

According to Gallup, 29% of U.S. adults have reported being diagnosed with depression at some point in their lives. That number is almost 10 percentage points higher than what was reported in 2015. As the rates of depression have increased in recent years, so has the search for new forms of treatment.

Common forms of depression treatment include lifestyle changes, therapy and antidepressant medication. Although some people have found success with these treatment options, others feel they aren't effective and see ketamine infusion therapy as a possible solution.

A brief timeline of ketamine and its uses:

1950s: Chemists began working to develop new forms of anesthesia that could alleviate pain. Parke Davis Laboratories of Detroit developed PCP for use in veterinary medicine. While semi-effective in animal use cases, the drug created some problematic side effects such as poor muscle relaxation. When trialed in humans, they experienced similar unfavorable side effects, thus making the drug less effective than similar medications.

1960s: In 1962, ketamine, similar in structure to PCP, was first synthesized. Shortly after synthesization, ketamine was tested on volunteer prisoners who found that the drug was a potent anesthetic with few adverse side effects.

1970s: Clinical trials for ketamine began in France with researchers' findings consistent with those of the prisoners in the '60s. The FDA allowed the drug to be used as an anesthetic for Vietnam soldiers, but because of the potential for ketamine to be abused and its hallucination-creating potential, ketamine was used less in medicine and deemed a Class III substance.

Ketamine for depression in the 21st century

According to Columbia University, "Ketamine targets different subsets of neurotransmitters in the brain than conventional SSRIs, so patients who haven't found therapeutic effects with traditional antidepressants may have better luck with ketamine therapy."

A clinical trial led by Massachusetts General Brigham investigators found that 55% of patients treated with ketamine showed a long-lasting improvement in their depression symptoms without experiencing significant adverse effects.

In 2019, the U.S. Food and Drug Administration approved a ketamine nasal spray to treat depression in adults who have not benefited from other antidepressant medications. The nasal spray is currently only available at a certified doctor's office or clinic.

In a recent study published in the Journal of Clinical Psychiatry, veterans with treatment-resistant depression were treated with ketamine infusions and their results were followed for a year. Almost half of the patients saw a "meaningful drop in scores" on tests that measure their depression, and 15% of patients responded so well to the infusions that they were declared to be in remission.

Researchers at Stanford Medicine researched ketamine's effects on depression by administering either the drug or a placebo when patients with severe depression were under general anesthesia. The researchers discovered that both groups experienced improvements in their depression, leading researchers to believe that patients who believed they received ketamine, even if they hadn't, could improve their depression.

Real-world use cases and testimonials

As reported by NPR, Sarah Gutilla was struggling with depression and had lost hope for all traditional treatment methods. In a last ditch effort, Sarah and her husband decided it was worth the money to send Sarah to receive intravenous ketamine therapy at a ketamine clinic in California. She immediately felt hopeful saying, "The amount of relief I felt after the first treatment was what I think 'normal' is supposed to feel. I've never felt so OK and so at peace."

Perhaps one of the most publicized real-world use cases for ketamine treatments was Matthew Perry and his death following treatment. When Perry's initial toxicology screening linked his death to the acute effects of ketamine, there was increased scrutiny surrounding the use of ketamine clinics for depression treatment. According to a later account, Perry had his final infusion therapy one week prior to his passing. This suggests that, on the day of his death, a high dosage of the drug combined with an opioid and a sedative caused his death rather than the infusion therapy. Although the ketamine treatment wasn't the cause of death, the buzz around the story opened up a conversation about the ethics surrounding using this illicit drug for treatment-resistant depression.

A new frontier for depression treatment

While the research from Stanford Medicine suggests that we still have a long way to go before fully understanding ketamine and its potential to treat depression, the idea that there are new forms of treatment is providing hope for those who have long suffered from severe depression. The drug has come a long way since it was first used in veterinary medicine, and the potential for this "party drug" could hold the future for psychedelics in mental health care.