“These findings may reflect a promising breakthrough in the clinical management of a potentially lethal condition for which there are no approved pharmacotherapies,” the authors wrote.
As the authors themselves point out, however, Phase II trials are only intended as a proof-of-concept. But a Phase III trial of esketamine, which examines safety and efficacy in a larger group of patients and is needed for final FDA approval, is already underway.
But though plenty of doctors and patients are excited about the potential of ketamine, many are also nervous about the unintended consequences of expanding ketamine use.
In an accompanying editorial – co-written by 20 members of the editorial board of the journal – the authors invoked the spectre of the opioid crisis as a worst-case scenario for what could happen.
“The history of pharmacology includes many life-saving drugs. However, it is also replete with examples of drugs whose abuse has outweighed their intended therapeutic effect,” they wrote. “The most recent example is oxycodone, which was developed as an alternative to older abused opioids and then heavily promoted to protect patients from pain after medical and dental procedures.”
As has now become apparent, the manufacturers of oxycodone, Purdue Pharma, wilfully misled doctors and the public about the drug’s addictive potential. The greater availability and access to oxycodone and similar painkillers then helped spark the first wave of the crisis beginning in the late 1990s.
The doses of ketamine given in infusion therapy are less potent than a person would take recreationally to get a high, but the editorial authors noted there have already been reports of depression patients becoming dependent and trying to abuse the drug. Some have shopped around for infusion clinics that will let them dose repeatedly and/or without supervision; others have become addicted to nasal spray formulations of ketamine. And supplies of ketamine used for anaesthesia are already being sold illicitly. These risks could only become greater with an easily obtained version such as esketamine, they warn.
Adding to that, ketamine isn’t a miracle drug for depression either. About 50 per cent to 60 per cent of patients respond to it, and even in these individuals, its unique effects don’t last long. In the current study, though esketamine patients felt less depressed and suicidal than they did in the beginning, they ultimately weren’t any better off than the placebo plus standard treatment group by the end of the 24 days. There were no signs of ketamine dependence in their study sample, the researchers said.
Far from shutting the door on ketamine entirely, the editorial authors instead advocate that a framework for safe treatment be established now, before the genie is completely out of the bottle. Doctors and hospitals could be required to only let patients use esketamine under their direct supervision, they suggested. Or, similar to opioid prescriptions now, patients could have their ketamine prescriptions recorded in a nationwide registry, to prevent people from visiting multiple doctors to get more doses.
These steps “would not be intended to deny therapeutic help to patients with significant need,” the authors wrote. “Rather, the aim is to establish the risk for abuse and the framework within which that treatment will continue to be available to those with need, while the population that is at risk for abuse is protected from an epidemic of misuse.”
In Australia, approximately one in six women and one in eight men will experience depression during their lifetime. Suicide is the leading cause of death for people aged 15 to 44.
If depression is affecting you or someone you know, call Lifeline on 13 11 14.