Written by Johanna Ryan, May 9, 2015
This column is partly a report on the marketing of Abilify, the atypical antipsychotic that has become America’s best-selling drug. It’s also an appeal for advice and feedback from the RxISK and Mad in America communities, and a call for some brainstorming about strategy. The plans laid out by drugmakers Otsuka and Lundbeck for Abilify’s future, and the cooperation they’re getting from leading universities, are alarming enough to me that reporting on them seems inadequate. We need action, although I’m not sure exactly what kind.
Over the past month, RxISK.org has featured a series of articles on Abilify. I kicked it off with “Dodging Abilify”, a look at the drug’s huge popularity with U.S. doctors and my own efforts to avoid taking it for depression. “Abilify from the Inside Out” shared what RxISK had learned from the first 34 reports we received from people on Abilify. The third, “Abilify, Tourette’s and Me” was written by “DG”, a young man who described his own disastrous Abilify experience. In the fourth, “Abilify, Tourette’s and You” DG described attempts to reach out to the FDA as it considered approving Abilify for Tourette’s syndrome. I added a note about the legal shenanigans behind Otsuka’s effort to get Abilify approved for Tourette’s, just as the patent on the drug was about to expire.
I began the project as an Abilify skeptic. The huge profits from the drug, which costs from $800 to $1,000 per month in the U.S., seemed to be driving its expanding use. Its alleged advantages were being hyped, while its problems weren’t being talked about. Abilify was costing states a fortune – $57 million in one year for the Medicaid program in Illinois – even as they cut vitally needed services. By April, I had decided I’d be cheering when Abilify’s patent expired at the end of the month and cheaper generics hit the market. Maybe the marketing machine would stop just long enough for people to figure out who, if anyone, actually needed this drug.
Otsuka has one plan up its sleeve that’s already much-discussed in the business and financial press: Brexpiprazole, a new drug that’s only slightly different from Abilify (aripiprazole). This is a time-worn tactic for Pharma; for instance, Janssen’s new antipsychotic Invega (paliperidone) is actually just the main metabolite of its old drug Risperdal (risperidone). Otsuka already has researchers running trials on brexpiprazole and praising it in the pages of medical journals – but the financial press notes they’re still having trouble “differentiating” it from Abilify. Nothing new there.
Then I stumbled across an article in New York Newsday that stopped me in my tracks. A new for-profit clinical trial group called Vanguard Research had just signed a $28 million contract with Otsuka to test Abilify Maintena, the depot injection form of Abilify, in “early-stage schizophrenia.” People aged 18 to 35 who were suffering their first psychotic episode would be randomly placed on monthly long-acting injections of Maintena, and kept on them for two full years. (A control group would get “usual care,” meaning they’d get whatever daily antipsychotic pill their doctor felt was best for them.)
This is a big departure from the conventional wisdom, in which doctors reserve depot injections for chronically psychotic patients who have repeatedly “failed” to take their pills as prescribed. The justification given was that “medication adherence” was the key to maximizing recovery. Maybe monthly injections could get new patients on the path to success right away, protecting them from relapse. To emphasize this, Vanguard’s trial has been christened the PRELAPSE Study.
The real reason for the study, however, was spelled out with brutal clarity in the Newsday article. Losing the patent on Abilify would cost billions – but Otsuka “could help offset revenue lost from the oral version if they can shift patients to Abilify Maintena… Vanguard’s clinical trial seeks to show that Abilify Maintena’s monthly injection reduces chances of a relapse in the early stages of schizophrenia compared with oral versions.” The study hadn’t started, but the “right result” was predetermined. That’s the polar opposite of real science – not to mention a doctor’s sacred oath to put the patient’s welfare first. Yet the article had been proudly posted on the website of Long Island Jewish Medical Center. Not only was this “nonprofit” hospital the majority owner of for-profit Vanguard Research. Its chief of psychiatry, John M. Kane, owned the minority stake – and would also be the Principal Investigator on the PRELAPSE Study!
There are good reasons why even hard-core biological psychiatrists don’t use these injections for everyone. They lock you in to a specific drug and dose (usually a high one) for a month at a time. If you need a change of meds or a dose reduction, too bad. Often they pack a particularly unpleasant wallop on the day of the shot. They’re coercive; the main point is to defeat patients’ efforts to reduce or stop their meds, and patients know it. They’re the method of choice when patients are court-ordered to either take their meds or be committed to a hospital. Even when there is no court order, it’s hard for doctors to say they have a “therapeutic relationship” with someone they’re basically forcing to accept treatment.
For young people having their first psychotic episode, I knew, this could be disastrous. For many, there’s no reason to assume they are in the first stages of a lifelong illness – especially if their voices, delusions or other extreme states come in response to a traumatic experience, drug use or a sudden big life change. Doctors used to recognize a problem called “brief reactive psychosis” that might strike a person only once or twice in a lifetime, under unusual stress. It wasn’t that uncommon, and often it would lift without any medication at all. In other cases medications could be used for a short time, and discontinued as soon as the crisis was over.
Forcing these young people to take a high-dose antipsychotic for two whole years would subject them to all the damaging effects for no good reason, while misleading them and their families as to the nature of their problem. It might well condemn some to a long-term disability they would never have had otherwise. Even for those who did appear to have a long-term problem that might be at least partly biological, long-term meds were a flawed answer at best. The PRELAPSE Study would not just “risk” doing grave, possibly irreversible harm to some of its subjects. It would be practically guaranteed.
In recent years people with psychotic experiences themselves, in alliance with open-minded professionals, are developing alternative ways to help people recover either with no meds at all or using the least amount practicable. These initiatives are now recognized and even encouraged in academic medical centers across the country, where “recovery” is declared to be psychiatry’s goal, and patient-centered care is everyone’s watchword. Why, then, are so many respected academic medical centers signed up to participate in the PRELAPSE Study? According to ClinicalTrials.gov, they include Stanford University; Georgia Regents University; Emory University (in collaboration with Atlanta’s Grady Hospital); the University of Iowa; St. Louis University; the University of Florida; Creighton University in Omaha; and the University of Minnesota. There are others, possibly including Dartmouth, Michigan State and the University of Cincinnati, which may be supervising PRELAPSE Study sites located at community mental health centers.
The University of Minnesota ought to be especially ashamed. The decade-long coverup of the death of Dan Markingson in the CAFE Trial of atypical antipsychotics has finally led to a suspension of all psychiatric research, pending an investigation of the department’s treatment of human subjects. None of the universities, however, seem to share Dr. Kane’s taste for publicity around PRELAPSE. While the seven community research sites have all begun recruiting, not one of the eight university sites has started yet, according to ClinicalTrials.gov. A Minnesota activist told me PRELAPSE was not on the list of research studies put on pause by the investigation, because it was still awaiting ethical approval from the university’s Institutional Review Board (IRB).
Could we get some or all of these universities to withdraw from PRELAPSE by campaigning to have this study rejected on ethical grounds? It would not be easy. Public opinion in the U.S. has been carefully shaped for years to see mental illnesses as brain diseases that science is well on its way to curing, and “people going off their meds” as the root of much of the misery and homelessness they associate with mental illness. Even some people who question the overdiagnosis of depression or ADHD still assume that “schizophrenics” really do need their meds, period.
Yet many people with first-hand knowledge of the issues will be surprised and disgusted that their local medical school has partnered with Otsuka on this study. A little education could bring others onto our side. If we succeeded, even at a few schools, it could not only deal a modest blow to Big Pharma, but help change the public discussion as well. (It’s worth noting that Lundbeck, Otsuka’s European partner, has not dared conduct a study like this in Europe. Instead they’ve backed a modified study targeting patients of all ages who have been diagnosed with schizophrenia for at least one year but less than seven years.)
But I’ve never been diagnosed with psychosis, or spent much time at a top academic medical center. That’s why I’m looking for input from those who have. What do you think we should do?
I met some people who were taking Abilify and were doing all right; they felt it caused less sedation and weight gain than the other antipsychotic drugs they’d been on. Yet all of them were glad someone was writing about the side effects, and were concerned about its long-term impact on their health.
In the course of researching this I learned something wonderful about the Randomized Controlled Trial, that “gold standard” route to the truth that supposedly trumps all other evidence. It turns out that a lot of experts who pledge allegiance to the sacred RTC when it tells them what they want to hear, turn into big-time skeptics when it does not.
A large “meta-analysis” of randomized controlled trials published last year found no advantage for monthly injections over daily pills for preventing “relapse” in schizophrenia.
So what did the authors do–accept their own findings? Hell no. They rattled on about how RCT’s were “less representative of real-world patients” than naturalistic studies. The oral-meds group might have included too many highly-cooperative patients. The study’s organizers might even have (OMG!) excluded patients “expected to have poor adherence.” (None of this made a great deal of sense. After all, if the groups were randomly chosen, wouldn’t the injection group be abnormally cooperative as well?)
They concluded they needed “large and long pragmatic studies” to prove what they just knew was true: that injections produced better results in the “real world.” I found this especially touching, having heard them scoff so often at the idea that we should follow people for more than six to twelve weeks if we really wanted to know whether medications “worked.” Good lads, I wanted to say; now you’re starting to think! Can I interest you in a really good article or two by David Healy?
Probably not. Instead, the authors pointed hopefully to an analysis of “mirror-image” studies that had found a benefit for injections. These were n=1 studies, but of a special kind. Apparently they all involved patients who initially “failed” or dropped out of pill-based treatment, then came back and were put on injections. By definition, only those known to have bombed on Condition One (pills) were being tested on Condition Two (shots)! They struck me as potentially no better than those “Before and After” testimonials you see in cheesy ads for “miracle” weight loss and muscle-building products. The white-coated scientists who usually sneer at “anecdotes” were serving up anecdotes that might make the average patient complaint look like Nobel Prize material.
The company-sponsored experts who advocate maintenance drugging for everyone refuse to treat either research subjects or “real-world” patients as individuals. They end up abusing the research subjects, the better to abuse the rest of us after the tainted research is published. And it turns out the only side they are loyal to in the great “RCT vs. clinical practice” debate is whichever side their bread happens to be buttered on.
I was kept on a depot injection for a few years even though I was being prescribed lithium and the even though doctors had realized I wasn’t schitzophrenic. I was sleeping 14 hours a day in this chemical straightjacket and suffered a great deal. Prof.David Healy convinced me to come off the depot injection. At first I was very wary because of the fear of another breakdown. I became much brighter and healthier and I have not had a psychotic event for the past 20+ years. What if doctors have wrongly diagnosed some one and pout them on an erroneous regime of depot injections without ever questioning the situation ? It is a frightening scenario and should be top of the list of priorities when considering such a regime of medication.
Last month I added a comment about the drug industry’s failure to show that injections led to better long-term results in Randomized Controlled Trials. This week JAMA Psychiatry has published a study that claims to show just that. And it’s being hailed as a “game changer” for treatment of patients in a first psychotic episode. It’s so important, they gotta let you read it for free:
The study compared Risperdal pills with Risperdal Consta injections in a program that offered cognitive therapy and a supported-employment program as well as drugs. I see two BIG problems in this study that Janssen was able to exploit to make its high-priced injection look good. They’re not subtle–they’re loopholes big enough to drive a Mack truck through.
The first problem? It was not “blinded.” Both the treating physicians and the raters knew who was on pills, and who was on injections. And this was in a study with a very big psycho-social treatment component! In working with each individual patient, and rating his or her progress, the research team was free to let their Janssen-sponsored hopes and dreams run wild. If they “just knew” Team Injection deserved to win, they could easily make it so–either deliberately, or without consciously realizing what they were doing.
The second problem? You won’t see it unless you check out their registration on ClinicalTrials.gov (Nos. 00333177 and 00330551). This study was supposed to center on “work and school performance” as its key outcome measure. Yet when the article was written, PRESTO CHANGE-O! The Performance measure had disappeared, and the measure of patient success had become “fewer psychotic symptoms and/or relapse”. Wanna make a bet on what those work-performance ratings showed? The ones they decided not to talk about? Probably very disappointing. This is like setting up a Little League Baseball pitching contest, and then changing it to a batting contest when your kid turns out to be a lousy pitcher.
The work performance ratings were no doubt included to demonstrate the real-world difference that the injection program was making. Not just better rating scales — Results that Matter! Their unexplained disappearance is the best evidence that injection patients were no better off in a real-world sense. In that case, locking in patients with a first psychotic episode to a regimen of long-term antipsychotics, which can carry such a dreadful physical and medical burden, is inexcusable.
I have been on various psychiatric drugs over the past 10 years including abilify tablets and depot. They have ruined my 20s, had the whole range of side effects apart from sudden death.. yet. Recently I have been getting chest pain that is lasting longer and longer. I am only on abilify depot 400mg a month and have read about some cardiovascular issues. I’m not massively overweight but have a very sedentary lifestyle due to the loss of enjoyment of day to day life. I have expressed my wishes to go back onto the tablets and reduce my meds but my psychiatrist is very reluctant. I know the half life of the depot is around 46 days and takes a long time to get out your system but is that enough time to taper down or do I need to go back onto tablets? I want to avoid tardive psychosis and withdrawal effects as much as possible.. but I don’t want a heart attack as a result of these drugs.
Suppress a Statistic I was eventually told I have B-polar. Covid risk technically says the GP but not for pyschiatrist drugs over the 14years i have been prescribed and taken first an antidepressant ? then another? thats when it started then,diazepam, olanzapine, tegratol, risperidone, seroquel, quetiapine, aripiprazole, haloperidol. lithium, amisulpride, promazine ,back to seroquel ,back to aripiprazole put on a CTO forced meds of paliperadone depot and now abilify mantena depot. Im lost for words. I disagree with the Bipolar diagnosis. Take away the drugs even the street drug speed that i found helpful to manage the sedative side of meds put at risk from the begining as these drugs have an adverse effect on me or shall i say im allergiced to all of the above my GP and pychiatrict Dr say im sensitive to these now where do i begin painful headachs, dizzy, nausea, tiered, sinus,dry mouth over salavation tooth decay, edema, weeping edema or heavy sweats, muscle stifness, dificulty walking , breathing difficulty or asthma, bloated stomach, constapation bladder retention, weight gain 3 stone, tearfull, poor memory poor, consantration , tounge rolling or i stick it to the top of my mouth, ive had hives or edema with adhesions diagnosed with osteopania because prolactin levels where high. low stats high thyroid high white blood cell count,infection, inflamation all this to keep me well and out of hospital. I dont want to go to the GP but im always there i dont want to go to hospital to be told im not well and maybe i should complain when i am well when would I ever be considerd well when im dead maybe or killed. Thats a bit much maybe but what differance does it make my experiance my life i have to deal with it, my handle. Keep it clean for the covid.