Ketamine, often associated with street drug "Special-K" and also a hospital-grade anesthetic, could be a breakthrough, fast-acting therapy for major depression in a nasal spray form, according to a new study.
But a small "proof of concept" study of 66 people, conducted by Yale Department of Psychiatry and Janssen Research at 11 hospitals around the U.S., suggests a possible remedy.
Within four hours, the 35 people who received esketamine showed rapid improvement of depressive symptoms and suicidal thoughts, with much better scores on a depression symptom scale than the 31 people who received regular care and a placebo nasal spray. After the first dose, only 29 percent of the esketamine group had "common" or "explicit" suicidal thoughts, compared to 58 percent in the group that had received the placebo.
How esketamine could help bridge the 'efficacy gap'
Esketamine and other ketamine derivatives are attracting interest from many doctors because they could be used to bridge the "efficacy gap" -- the time between the appearance of severe depression and the time standard antidepressant drugs begin to have an effect.
Now that this small study has shown the drug’s potential to rapidly help counteract severe depression faster, larger scale studies can now be done.
Esketamine is probably not a long-term solution for the majority of people with depression; after four weeks, the anti-depressant effect was no different than standard care, and there are side effects. Ketamine is known to cause hallucinations and feelings of "dissociation" -- feeling detached from the immediate surroundings, or even from all physical or emotional experiences.
At the doses used in this study, most patients who got esketamine reported this effect after each dose, though their symptoms were less intense with repeat doses. Five of the 35 patients had to stop taking the drug due to other side effects: Agitation, aggression, dizziness and abnormal heart rhythm.
Regulating the use of ketamine to prevent addiction
Prolonged use of ketamine can also lead to addiction. In the world outside the hospital, people abuse ketamine and its derivatives to get high. One of the questions becomes: How can it be safely prescribed to treat depression?
Like oxycodone, the editorial noted that esketamine could become a drug "whose abuse has outweighed their intended therapeutic effect."
The medication can also be highly beneficial, also like oxycodone and other opioid painkillers, when used for the right person and for the right length of time.
"Just as it is considered irresponsible to ask patients to tolerate pain, it is irresponsible to deny a suicidal patient the fullest range of effective interventions," Freedman added in the editorial.
That’s why, if it receives FDA approval, doctors would need to take steps to ensure ketamine would be used responsibly. The first step would likely be to identify patients who will best benefit from the drug: Those with the most severe and treatment-resistant depression.
Just as importantly, individuals prescribed the drug would need to be re-assessed frequently.
Ketamine drugs could be administered in the same fashion. Urine drug screening could be used to ensure that ketamine levels are low enough to actually need a repeat dose. A national registry of esketamine prescriptions could identify those receiving multiple doses from multiple prescribers. Limiting prescriptions to approved facilities might prevent inappropriate use by patients and physicians alike.
Research shows that esketamine could have major potential to help severe depression in people at high risk for suicide or who have not responded to other therapies. With careful study and awareness of its potential downfalls, it may become a valuable component of mental healthcare for people with immediate need.
Dr. Kelly Arps is a resident physician in internal medicine at Johns Hopkins Hospital. Kelly is working with the ABC News Medical Unit.