Last week, the FDA advisory committee endorsed Janssen Pharmaceutical’s (division of Johnson & Johnson) experimental nasal spray for depression despite a mixed bag of clinical trial results. The panel voted 14-2 to approve Esketamine nasal spray for major depression in patients who have NOT benefited from two or more antidepressants (e.g., Prozac, Paxil, or Zoloft).
This fast-acting nasal spray using esketamine is a chemical mirror image of the anesthetic ketamine, which is often used by veterinarians to sedate animals but is also a schedule III drug known on the street as “Special K” — thanks to its dissociative and hallucinogenic effects.
This new drug was designed in an effort to help the millions of people who suffer from persistent depression and do not respond to current antidepressant products. The nasal spray is seen as a potential substantial improvement over existing therapies for “Treatment Resistant Depression” (TRD), considered a serious or life-threatening condition.
In theory, a drug that provides rapid relief within 24 hours vs the standard 4-6 weeks for the current antidepressants on the market sounds good. However, the disease label of “Treatment Resistant Depression” (TRD) is also the new buzzword allowing drug companies to obtain FDA fast tracking or “breakthrough therapy” designation without having to go through more rigorous testing protocols. Such designation gives the pharmaceutical company the ability to present smaller, fewer clinical trials in order to get their drug to market quicker. While most approved antidepressants currently on the market had to show effectiveness data from at least two positive short-term trials, Janssen only presented one positive short-term trial and the second is an incomplete picture as it is from a withdrawal trial. Janssen’s other trials failed to meet their primary endpoints for efficacy. Additionally, there were also clinical trial participant suicides that occurred during the clinical trials, however these were glossed over and presented as unrelated to the “study” drug. In my opinion, we need more information on the potential link to suicide before an assumption can be made that it’s safe.
Despite all of this, several members of the FDA Advisory Committee perceived this new drug as a potential “game changer” in the way depression is treated. I, however, am NOT one of them. I take my role as the Consumer Representative very seriously and want to make sure that any pharmaceutical drug that the FDA approves shows greater benefit than potential harm. There are real world implications once these drugs are approved and, on the market, advertised with an FDA stamp of approval on them, and counted on without question by the doctors prescribing them and the potential millions of people who will take them.
Too many times I have seen that as soon as one of these controversial drugs gets approved, the drug company’s PR and advertising machine immediately kicks into hyperdrive. The media will be given talking points and tout it as a “breakthrough” treatment for depression that works within mere hours of inhaling the drug, and people will start lining up at their doctor’s offices. In fact, just a day after this meeting, news of this meeting and drug was all over the national media appealing to America’s “quick fix” culture. This “breakthrough treatment” messaging is powerful, especially in the environment of rising antidepressant prescription rates and increased suicides. The media needs to do a better job of questioning these FDA approvals and not just report the “promising” findings off a drug company press release.
Another observation I have had lately is that a majority of new drug application reviews are coming before the FDA Advisory Committees with a Risk Evaluation Mitigation Strategies (REMS) program. The Food and Drug Administration Amendments Act of 2007 gave the FDA authority to require a REMS for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. REMS are not designed to mitigate adverse events of a medication, rather, it focuses on preventing, monitoring and/or managing a specific serious risk by informing, educating and/or reinforcing actions to reduce the frequency and/or severity of the event.
I believe most of the FDA Advisory Committee members vote for these controversial drugs assuming that the REMS program will address any of their potential safety concerns. What they fail to realize is that the REMS program is not enforceable and the drug companies are responsible for managing and reporting to the FDA. I can NOT in good faith cross my fingers and trust the drug companies and FDA to do what they say they will do, just to get the drug approved.
At the end of the day, safety will always be my top priority and I didn’t feel this was similarly the case for the manufacturer as it rushed this esketamine nasal spray to market. I cannot vote for something when the perceived benefits do not clearly and demonstrably outweigh the potential for known harms such as sedation, dissociation, and long-term cognitive or memory loss — this is especially so considering the extremely limited positive clinical trial results.
At one time, the current antidepressants were seen as “game changers” beginning with the launch of Prozac in the late 1980s. Little did the medical establishment and general public know then what we clearly now know today about the questionable efficacy of antidepressants and all the associated dangers such as suicides and withdrawal issues that come with taking these medicines. It is in the rush to market without sound clinical testing and trials that prove efficacy, without potential horrible side effects or outcomes, that we set society up for misuse of medical drugs and create the very real potential for heartache and disappointment for many.
Time will tell, but as I always say, we (the American public) are the real clinical trial. We pay the ultimate price for the lowering of FDA standards for drug approvals.
