A hallucinogenic drug known on the street as "Special K" offers new hope to those suffering from severe, treatment-resistant depression.
Ketamine, which was originally developed in the 1960s as a milder version of PCP, already has a well-established medical use as a sedative or pain killer. But since 2000, small but high-quality studies have demonstrated its uses as a powerful and fast-acting treatment for major depression.
The growing body of evidence has emboldened doctors to begin prescribing Ketamine for depression, despite the fact that the drug has not been approved for such a use and the long-term effects are still unknown. To address those unknowns, various pharmaceutical companies are formulating their own versions of the drug and testing them in clinical trials, as The New York Times recently reported, but advocates say that the trials are simply an attempt to make money on tweaked versions of a generic drug.
Ketamine doesn't work like common, widely-used antidepressant medications like Prozac, Zoloft or Lexapro, which are selective serotonin reuptake inhibitors that change the balance of the neurotransmitter serotonin. Instead, Ketamine targets receptors of glutamate, an amino acid.
Scientists first noticed that targeting glutamate had an antidepressant effect more than 50 years ago, when doctors administered a glutamate-modulating antibiotic to tuberculosis patients and saw their moods lift, according to Dr. Robert Howland, an associate professor of psychiatry at the University of Pittsburgh School of Medicine.
Howland recently published a review of 25 peer-reviewed studies (that had a total of 416 participants) in the journal Neuropharmacology that examined the effects of Ketamine treatment on people with treatment-resistant depression.
All 25 studies suggested that Ketamine was indeed an "active and rapid antidepressant" for people with treatment-resistant depression (approximately 10 to 20 percent of those who have depression), wrote Howland in his review. Three of those studies even showed that Ketamine appeared to reduce suicidality (suicide ideation) in people treated with the drug. This confirms that glutamate plays an active role in this mental illness, according to Howland.
But serious questions remain about the drug's long-term effects, as well as its ability to sustain the same levels of antidepressant over time without upping the dose. After all, people can become addicted to "Special K," and large doses of the drug could cause hallucinations, aggressive or violent behavior and even death from overdose, according to the University of Maryland's Center for Substance Abuse Research.
"Although limited to initial observations, ketamine may be effective not only in TRD patients but also on suicidality," concluded Howland in his study review. "However, future studies are recommended in order to test the efficacy of ketamine when compared with other active comparators such as electroconvulsive therapy or antidepressant-antipsychotic drugs combinations."