Last week, the FDA advisory committee endorsed Janssen Pharmaceuticalās (division of Johnson & Johnson) experimental nasal spray for depression despite a mixed bag of clinical trial results.Ā The panel voted 14-2Ā to approve Esketamine nasal spray for major depression in patients who have NOT benefitedĀ from two or more antidepressants (e.g., Prozac, Paxil, or Zoloft).
This fast-acting nasal spray using esketamine is a chemical mirror image ofĀ theĀ anestheticĀ ketamine, which is often used by veterinarians to sedate animals but is also a schedule III drug known on the street as āSpecial KāĀ ā thanks to its dissociative and hallucinogenic effects.
This new drug was designed inĀ anĀ 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 therapiesĀ forĀ āTreatment Resistant DepressionāĀ (TRD), considered a serious or life-threatening condition.
In theory, a drug that provides rapid relief within 24 hours vsĀ the standard 4-6 weeks forĀ the currentĀ antidepressants on the market sounds good.Ā However,Ā the disease label ofĀ āTreatment Resistant Depressionā (TRD) is also the new buzzword allowing drug companies toĀ obtainĀ FDA fast trackingĀ orĀ ābreakthrough therapyā designationĀ without having to go through more rigorous testing protocols. Such designationĀ gives theĀ pharmaceuticalĀ 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,Ā Janssen only presented one positive short-term trialĀ and the second isĀ anĀ incomplete picture as it isĀ from a withdrawal trial. JanssenāsĀ other trials failed to meet their primary endpoints for efficacy. Additionally, there were alsoĀ clinical trial participantĀ suicides that occurred during the clinical trials, however theseĀ were glossed over and presented asĀ unrelatedĀ to the āstudyā drug. In my opinion, we need more information on the potential link to suicide before an assumption can be made that itās safe.
Despite all of this, several members of the FDA Advisory Committee perceivedĀ this new drug as a potential āgame changerā in the way depression is treated. I, however,Ā amĀ NOT one of them. I take my role as the Consumer Representative very seriouslyĀ and want to make sure thatĀ anyĀ pharmaceuticalĀ drugĀ thatĀ theĀ FDA approvesĀ showsĀ greaterĀ benefit thanĀ potential harm. There are real world implications once these drugsĀ are approved and, on the market,Ā advertised withĀ an FDA stamp of approval on them, and counted on without question by the doctors prescribing them and the potentialĀ millionsĀ of people who willĀ takeĀ them.
Too many timesĀ I have seenĀ that as soon as one of these controversial drugs gets approved, the drug companyās PR and advertising machineĀ immediatelyĀ kicks into hyperdrive. TheĀ media willĀ be given talking points andĀ tout it asĀ aĀ ābreakthroughā treatmentĀ for depressionĀ thatĀ worksĀ withinĀ mereĀ hours of inhaling the drug,Ā and people will start lining up at their doctorās offices. In fact, just a day after this meeting, news of this meeting and drugĀ was all over the national media appealing to Americaās āquick fixā culture. This ābreakthrough treatmentā 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 āpromisingā findings off a drug company press release.
AnotherĀ observationĀ I haveĀ 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 myĀ topĀ priority and I didnāt feel this wasĀ similarlyĀ the case forĀ the manufacturer as it rushed thisĀ esketamine nasal sprayĀ to market. IĀ cannotĀ vote for something when the perceived benefitsĀ doĀ notĀ clearly and demonstrablyĀ outweigh the potential forĀ knownĀ harmsĀ such asĀ sedation, dissociation, and long-term cognitive or memory lossĀ ā this isĀ especiallyĀ soĀ considering theĀ extremely limitedĀ positive clinical trial results.
At one time, the current antidepressants were seen as āgame changersāĀ beginning with theĀ launch of Prozac in the late 1980s. Little did theĀ medical establishment and generalĀ public know then what weĀ clearly nowĀ know today about the questionable efficacy of antidepressants and all theĀ associatedĀ 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 theĀ loweringĀ ofĀ FDA standards for drug approvals.
