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.
Universities on the Take
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).
What Can We Do?
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.