The touting of ketamine as a wonder drug for depression has both puzzled and distressed me. There were all kinds of reasons premature ketamine exuberance seemed wrong and potentially dangerous:
- It was fast-tracked by the FDA without the usual expectation that it first prove its efficacy and safety.
- The studies supporting its efficacy were very few, small, short-term, and had mixed results.
- Its safety was being evaluated only in highly controlled and very expensive treatment environments. There were six deaths in the ketamine patients, including three suicides; none in the placebo group. And an additional very dangerous, unintended consequence was completely ignored; that many depressed people, hearing the hype and unable to afford official treatment, might get into serious trouble self-medicating with street “Special K”.
- Ketamine’s strongest boosters all had possible financial and/or intellectual conflicts of interest. Clinicians were making big bucks from the ketamine centers they quickly opened all around the country. Researchers enjoyed being on the grant gravy train. Pharma saw ketamine as a potential blockbuster drug in the making. And leading psychiatrists welcomed the introduction of a novel antidepressant, with a completely different mechanism of action, to fill what had previously been a very dry pipeline of new drug discovery.
I assumed that the ketamine craze was no more than the typical triumph of hope over experience- the glitter of the new that always fades with familiarity. In a previous blog, I questioned its magical efficacy and pointed out its serious safety risks.
The Remarkable Political Back Story
I consider myself a cynic when it comes to new drugs, always questioning the claims that surround them and the motives of the touts. But a wonderful piece of investigative journalism has uncovered a mind-boggling political push behind the ketamine craze that proves me to have been childishly naive when it comes to ketamine.
On March 5, 2019, President Trump issued an executive order to reduce suicide among Vets, who constitute a large and important group of voters. On the very same day, the FDA gave a fast track approval to Janssen’s version of ketamine. Articles appeared all over the media that ketamine was remarkable, effective, and safe.
Soon the word was out among administrators in the VA system that the president wanted vets to have quick and ready access to the new wonder drug. The VA bureaucratic wheels usually grind very slowly, but the president’s boosting has greased them remarkably. And beyond verbal encouragement, he has offered the VA special funding to buy the drugs and set up the ketamine clinics.
Trump, Janssen, and Marketing Ketamine to Vets
It remains something of a mystery how President Trump became such an enthusiastic psychopharmacologist. But it is known that two of his Mar-a-Lago buddies advise him informally on VA affairs and also have contacts with Janssen.
Janssen has a long history of heavy lobbying to politicians generally and to the military and VA specifically. It has targeted the Armed Services and VA concern with military suicides as a golden marketing opportunity. And it is not shy about charging outrageous prices for a “me-too” version of ketamine developed only to establish patent rights and a monopoly pricing grip. The VA should also note that Janssen has frequently been forced to pay big fines for its underhanded marketing techniques.
The VA refused the journalists’ requests for interviews to discuss its policies re: ketamine and how and when they will be implemented. Instead, it issued a statement that it had approved “the use of intranasal esketamine for adults with treatment-resistant depression (when used in conjunction with an oral antidepressant). The VA has not yet administered esketamine to any patients, and is in the process of designing a clinical implementation plan optimized for safety and efficacy.”
It is always dangerous to “ready, fire, aim.” And ketamine is a very dangerous drug, not to be trifled with. I have seen it cause self-mutilation, suicide attempts, and psychosis. The deaths occurring in the initial studies confirm the concerns raised by my personal clinical experience. And there is no guarantee that vets will receive ketamine only in the highly supervised VA clinics. Once the buzz is out that it is effective, many may choose the much riskier rout of self-medication.
I am not the only person concerned about the ketamine craze. Many other clinicians and researchers have also expressed strong reservations before, during, and after the rushed FDA approval.
The VA should catch its breath before succumbing to political pressure. The president does not have clinical expertise and should not be driving treatment guidelines. FDA approval does not guarantee that ketamine will be safe and effective for vets.
Before putting ketamine on formulary and establishing clinics to supervise its delivery, the VA should conduct an independent review of the evidence. To do otherwise is courting large scale clinical disaster.
Those who don’t learn from past mistakes repeat them. It would be foolhardy in the extreme not to learn from the FDA’s mistakes in promoting the recent opioid and vaping epidemics. Commercial and political interests should not contaminate clinical common sense. Fools rush in where angels fear to tread.