Older Person with Parkinson's

Nuplazid (pimavanserin) is a fascinating example of the FDA’s confusing drug authorization process. We suspect that many people think a stamp of approval from the Food and Drug Administration means a medication has received very thoughtful review and passed high hurdles with flying colors. Sometimes, though, the way in which drugs get a green light is a lot more complicated.

Safe and Effective? What Does That Mean?

The FDA’s fundamental criteria for approving new drugs is surprisingly simple. Manufacturers must prove that a medicine is “safe and effective” before they can market it. This is a key component of the Food Drug and Cosmetic Act.

The problem with this concept is that no one bothers to define what “safe” or “effective” really means. This vagueness creates confusion in the minds of many consumers and health professionals.

Every night on television, people watch prescription drug commercials that mention a long list of serious drug side effects. Not infrequently they hear about adverse reactions such as depression, suicidal thoughts, confusion, weight gain, trouble breathing, heart attacks, cancer, fatal infections and death.

Nuplazid Commercial:

The concern over drug safety and effectiveness bubbled up recently in Congressional hearings on a medicine called pimavanserin (Nuplazid). It was approved by the FDA two years ago to treat hallucinations and delusions associated with Parkinson’s disease.

Here is a link to a Nuplazid “commercial” that is not a Nuplazid commercial. It’s what the industry refers to as a disease awareness campaign. Nowhere in the ad is the drug Nuplazid mentioned.

What you see is an older man in a dark room. While eerie music plays in the background and voices whisper in the background you hear the man saying:

“They appear out of nowhere…my secret visitors. Appearing next to me in plain sight.”

A cat dashes past and disappears. While the eerie music continues to play the announcer says:

“Hallucinations and delusions. These are the unknown parts of living with Parkinson’s disease.”

The man in shadows then says:

“What stories they tell…but for my ears only. What plots they unfold but only in my mind.”

The voice-over announcer then shares:

“Over 50 percent of people with Parkinson’s will experience hallucinations or delusions during the course of their disease and these can worsen over time, making things even more challenging.”

Sounds scary! Then the reassuring female announcer’s voice tells us:

“But there are advances that have led to treatment options that can help.”

The viewer is told to “Talk to your Parkinson’s specialist” and

“Learn more at MORETOPARKINSONS.com”

Nowhere during the commercial is Nuplazid mentioned. Because disease awareness campaigns do not tell you to ask your doctor if the drug is right for you, they don’t have to mention Nuplazid side effects.

Nuplazid Side Effects:

Here is what you will find in the official Nuplazid prescribing information:

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

  • Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
  • NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.

“Antipsychotic drugs increase the all-cause risk of death in elderly patients with dementia-related psychosis. Analyses of 17 dementia-related psychosis placebo-controlled trials (modal duration of 10 weeks and largely in patients taking atypical antipsychotic drugs) revealed a risk of death in the drug-treated patients of between 1.6- to 1.7-times that in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in placebo-treated patients.

“Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.”

Other Nuplazid Side Effects:

Nuplazid side effects include fluid buildup in extremities (peripheral edema), digestive upset (nausea, constipation), confusion and unsteadiness (gait disturbance). Other adverse reactions may include sleepiness, skin rash and tongue swelling.

Institute for Safe Medication Practices (ISMP):

QuarterWatch (Nov. 2, 2017) (an independent drug industry watchdog publication of ISMP) reported on the safety and effectiveness of Nuplazid. This report noted that the initial approval of this drug was based on one clinical trial:

“Three previous trials had failed to demonstrate a benefit in reducing hallucinations and other symptoms of psychosis. FDA’s medical reviewer recommended against the approval of Nuplazid. He noted that, although other psychiatric drugs were often approved with limited evidence of benefit, in the case of Nuplazid, treatment had more than doubled the risk of death and/or serious adverse events in its only positive trial.”

Despite the FDA’s own reviewer’s objections, the agency decided that the potential benefits outweighed the risks for this drug.

A CNN Report:

Since then, concerns about this drug’s safety and effectiveness have mounted. Hundreds of people have died while taking Nuplazid. The FDA points out, however, that many of these patients were old and sick and taking other medications as well. Consequently, the agency is investigating to see whether this drug was directly responsible for their deaths.

The FDA reviewer, Dr. Paul Andreason, has left the agency. In a CNN report he is quoted as saying:

“This is exactly what I thought was going to happen.”

Questions have also been raised about its effectiveness. According to CNN, more than 1,000 reports have been submitted to the FDA claiming that the drug did not eliminate hallucinations.

Congressional Hearings:

U. S. Representative Rosa DeLauro questioned the Commissioner of the Food and Drug Administration during recent hearings:

“How many more adverse events do we have to have reported? How many people, quite frankly, have to die? Why does the industry always take precedence over public health and safety?”

The Commissioner, Dr. Scott Gottlieb, told Congress that the agency would “take another look” at the safety profile of Nuplazid. We wish the FDA would take another look at a lot of other medications as well.

The FDA and “Safe and Effective”:

If all FDA-approved drugs are supposed to be safe and effective, why do so many come with warnings about deadly adverse effects? The FDA seems to believe it’s off the hook as long as the official prescribing information contains cautions about potential hazards. The idea is that informed physicians and patients will be able to make balanced decisions based on this kind of data.

Long lists of scary side effects can quickly overwhelm physicians and pharmacists as well as patients, even sophisticated ones. Frequent exposure to such recitations in commercials may desensitize people to the dangers of drugs.

The FDA considers it a patient’s responsibility to be informed about the risks of any medicine she takes. One could argue that in the case of Nuplazid, elderly patients who are hallucinating and may be cognitively impaired should not be expected to shoulder this burden. Even desperate family members may not be qualified to assess the balance of benefits and harms. Isn’t that what the FDA should be doing?

Past Disasters:

Despite the assurance that a drug must be proven safe and effective before it is approved, the FDA has a long track record of problem medications. The arthritis drug Vioxx (rofecoxib) flamed out because of an association with heart attacks and strokes. It was removed from the market after about five years.

Bextra (valdecoxib) was somewhat similar to Vioxx. It disappeared after almost four years.

The cholesterol-lowering drug Baycol (cerivastatin) caused severe muscle breakdown (rhabdomyolysis) and was also linked to an excessive number of deaths. It took roughly four years before Baycol was pulled.

The diabetes drug Rezulin (troglitazone) bit the dust after about three years. The FDA reviewer who analyzed the original safety data did not recommend approval. He was concerned about liver toxicity. He was overruled by the agency. Eventually, the drug’s potential to cause serious liver toxicity was proven and Rezulin disappeared from the market.

How Do You Interpret Words Such as “Safe and Effective”?

What does the phrase “safe and effective” mean to you? We really want to understand how patients and family members perceive safety and effectiveness. If a drug “works” in 4 out 10 patients and a placebo sugar pill works in 3 out of 10 patients, the FDA might consider the medicine effective, even if 6 out of 10 got no benefit at all. Would you consider that drug effective?

Even if a medicine causes potentially life-threatening reactions like suicidal thoughts, heart attacks, strokes or cancer, the FDA might well consider it “safe.” Would you? Please share your thoughts in the comment section below.

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  1. Gerri
    Chicago illinois
    Reply

    I personally will not take any drug until it’s been on the market for 5 years at least, prefer not to be a guinea pig.

  2. Gael
    Virginia
    Reply

    It looks like people would be well advised not to take any drug that has not been on the market for at least 5 years, possibly longer. The early patients are guinea pigs.

  3. Larry L.
    Wisconsin
    Reply

    I think that no prescription drug is 100 percent safe. Therefore, if I’m correct, no such drug should be described as 100 percent safe. Regulators should institute rules that require the manufacturer to describe relevant, specific safety information as the information becomes known.

    For example, if adverse effects from a given new drug include elevated levels of some enzyme, this information (specific level and the estimated risk) should be made known to the market and updated from time to time.

    I agree with Marty.

  4. Antoon
    New zealand
    Reply

    I am 85 years old and in great fettle, I have never taken doctors prescription medicine because of the potential destructive side issues. I control my health through diet.

    Most of our health concerns are driven through nutrition, I had high BP and cholesterol also type 2 diabetes and peripheral arterial disease I control these conditions by reducing the consumption of glucose producing foods such as sugar; grains and potatoes.

    I have not eaten breakfast cereals for 15 years and eat no bread. My BP and cholesterol are well within the accepted range. My diabetes is under control as the peripheral arterial disease.

    Approximately 3300 years ago mankind was given a blueprint for healthy living, “LET YOUR FOOD BE YOUR MEDICINE AND YOU MEDICINE BE YOUR FOOD”

  5. Pat
    Texas
    Reply

    Pat has been having hallucinations for over a year, the only reason anyone can come up with is a heart pill he took damaged his optic nerve which is causing the hallucinations. He ha been on nuplizd, memantine, excelon patch and Risperidone. Cut the patch last month and reduced nuplizd until was off, but hallucinations seemed worse so went back on with 1 pill a day. Says he fells better. He is 81, diabetic and the only diagnosis we have gotten is maybe beginning of Lewy Body. If anyone has advice please help.

  6. Julius
    Houston, TX
    Reply

    I have suffered seizures and strokes from FDA approved drugs, and the problems are multiplying exponentially.

    When my health insurance carrier began to approve generics exclusively regardless of doctor’s rationale for the original, it turned out to be a cost issue only as all their new generics were made in India and the FDA did almost zero assessments or inspections of manufacturing. Even labels listed incorre4ct contents.

    My call to the pharmacy manager of my health insurer, and the FDA rep I called both just hung up on me, refusing even to hear of any problem.

  7. Elmo
    USA
    Reply

    CNN already discredited. No homework was done for this article. Many will suffer if they follow your advice!

    • Kathy
      WA
      Reply

      I think you should read(or re-read) the CNN report! It does not discredit what the Graedons have written. Look closely, the drug in question is an antipsychotic drug. These drugs might work for some and not others and WILL have side effects.

      The FDA indication for this drug is for Parkinson’s with hallucinations. Article states it would be used in advanced stages. That’s the clincher—-1. Patient’s overall health in decline(side effects more dangerous) and 2. Patient’s family possibly has “false hope” of a successful outcome.

      The patient study numbers for this drug are too small, I’ll leave it at that. I am a retired pharmacist.

  8. Diana
    OK
    Reply

    Thank you! I have been looking for a place to voice my frustration. With so many drugs being recalled, you can’t help but suspect someone hand is being padded. My mother has been on several arthritis medications that she later found out instead of building bone, they actually caused her teeth to crumble. Another side effect is breaking of the hip bone. Why can’t we fire the FDA? We need a more reliable system.

  9. Jan
    Houston
    Reply

    I’m on the side of “look always for natural assistance in the alternate arena than the FDA approval”. In my opinion, the FDA is only out to make as much money as it can, resulting in horrible damage to WAY, WAY, WAY too many products and prescriptions on the market that cause harm, rather than help the patient!

  10. Cathy
    Bainbridge Island, WA
    Reply

    Other things to consider:
    Is the person for whom the drug is prescribed cognitive enough to consider the risks vs advantages of taking the drug? Or does this person have somebody that he/she can trust to consider these things for him/her? Is he/she capable of taking note of and reporting any possible side effects encountered, or does he/she live with someone who can do that for him/her? As much as we might trust our doctors and believe that our doctors and pharmacists will take care of us in these regards, they also depend upon us to report to them any side effects, and they often fail to follow up on patients for whom they’ve prescribed drugs. It is up to the patient to tell them of any perceived side effects, and patients often fail to do so. Those with cognitive failure or suspected cognitive failure should not be prescribed risky drugs unless there is someone at home to watch for effectiveness and side-effects.

    Another thing to consider is the age of the patient, because our bodies’ abilities to metabolize drugs change as we get older. I am an in-home caregiver and have been told again and again that anyone over age 60 should start most newly- prescribed drugs at a lower dosage than would be normally prescribed, and yet I have seen, again and again, clients with serious side effects at full dosage, whose doctors then reduce the dosage for them. Shouldn’t some warning about this be given on the prescribing information that comes from the pharmacy? Shouldn’t that be one of the first things that we see and take into consideration?

  11. James
    Flower Mound, TX
    Reply

    I am concerned that some drugs do not list some of their less common adverse effects. My dermatologist prescribed Lamasil for toe nail fungus. He did a blood test to verify I was not experiencing liver issues (which the manufacturer cautions are possible).

    Fortunately, I had a scheduled annual physical with my primary care physician several weeks into the treatment. He was surprised to find that my white blood cell count was depressed to almost nil. He redid the blood test and told me to stop taking Lamasil immediately. He again tested my blood after I stopped Lamasil, and my white cell count had returned to normal.

    My primary care doctor sent in a report to the FDA, but neither of us ever heard back. To my knowledge, Lamasil’s warnings did not include possible adverse effects on white blood cell counts.

  12. Elizabeth
    Sounthern CA
    Reply

    Our FDA is a joke.
    They are not to be trusted to watch out for patients. They are on the side of the drug companies.
    Too many drugs are not approved that are safe and beneficial, and too many are approved that should not be approved ever that do more harm than good.

    After my Mom suffered some extremely severe side effects her Drs never bothered to even warn us about some new medicines she was given. My Cousin was living in England at the time, and she told me how many drugs available in the US were not available in England, also how many things sold here as over-the- counter required a prescription or authorization by a pharmacist to be purchased in England. We felt that the version of the FDA in England cared more about patients’ well-being than drug companies’ profits at their expense.

    I started checking to see if the drugs my Mom was prescribed were available in the United Kingdom. If a drug was banned in the U.K. I would tell the Dr that Mom will not take it. If it was approved in the U.K. she would take it. This saved my Mom from some horrible side effects of drugs that were approved by our FDA but were not approved in England.

  13. Jam
    Bellingham WA
    Reply

    The FDA seems to rule heavily on the side of profits for Big Pharma. People should be aware of the ties people in charge of these decisions have to Big Pharma, how deep those (monetary) connections are. “Approved by the FDA” is not the same as “safe and effective” at all, but too many are swayed by the belief that Big Brother knows best. Best for lining his pockets, is all.

  14. Jane S.
    Colorado
    Reply

    None of this should surprise anyone. There has been an apparent collision of big pharma and a big govnerment in Washington DC for a very long time. Of course, the driving force is big money. If only there was a way to find out just how much the welfare of the American citizens is sold for annually. Money equals power, and power equals corruption, a pretty simple equation.

  15. Kerry
    Mt Pleasant, SC
    Reply

    I would expect a greater than 50/50 chance that a medication will have a positive effect. To say something that works at a rate of 4 of 10 is ludicrous if you then call it “effective”. Perhaps a category of: “for those really desperate” is needed where 4 in 10 is better than no ideas. Personally, to be called effective I’d rather see medications with a greater than 60% chance of success. I am sure if the rate of 40% effective had been posted with the information to doctors and patients, its use would have been much less likely.

    As for “safe,” I look at all medications skeptically these days because of the recent safety recalls. If the data is there indicating “not safe,” it should not get on the market. If it takes 3 or 4 times to get past a review there is a safety problem. Again, maybe have a category for desperate situations where risk is worth the possible out come. But approving such a drug implies a level of safety it does not have.

  16. Robert
    Seattle
    Reply

    I always questioned the way that the statistics were applied to drug trials. If less than 1/2 the subjects saw improvements due to the medication, it really didn’t seem important how many were improved by the placebo. The drug was ineffective. It’s an example of the old saw, ‘Do figures lie or do liars figure?’

  17. Marty
    Florida
    Reply

    I have fibromyalgia, and over the last 15 years have been on litterally dozens of Rx medications. Most with troubling side affects and very few that have helped. So, in my case, overall, they have been neither safe nor effective. As in any life choice we have to weigh the cost and the benefit. I think it would be very helpful (at least for me) if effectiveness and rate of occurrence of each side affect was published. For example: ABC drug is XX% effective will xyz problem and, XX% of those participating in the trials experienced qrf side affect.

  18. Walter
    Athens, GA
    Reply

    This type of disgraceful governmental, politically-influenced behavior, on the part of the FDA, which is supposed to protect us, is indicative of the gradual slide of America into a complete corporate kleptocracy where Big Pharma and Big Health Insurance buy off the American medical establishment in order to control health-care in the U.S. for their own financial gain, to the detriment of American citizens.

  19. Mark
    Florida
    Reply

    Is the FDA’s definition of “safe and effective” some kind of a joke?

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