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Showing posts with label ethics. Show all posts
Showing posts with label ethics. Show all posts

Thursday, May 28, 2015

More on the Ritalin-Induced Psychosis Study

I'm following up on my last post, I Don't Know What to Think. A friend (not the same one who sent me the Levine piece) had access to one of the full articles, and forwarded it to me. This is the 1987:

Prediction of Relapse in Schizophrenia paper, from Arch Gen Psych. Having read it, what they were trying to do makes more sense to me, but it's still problematic.

The paper's introduction comments:


...A major deficiency in the clinical management of schizophrenia is the lack of proven methods for predicting the subsequent course of illness and identifying those patients who require neuroleptic maintenance to prevent relapse or, alternatively, those who would remain stable for substantial periods of time without drug treatment or while receiving substantially reduced dosages.


There were some previous studies suggesting that behavioral response to psychostimulants could be used as a predictor of relapse. They chose ritalin because it preferentially inhibits uptake of dopamine, and they were trying to find support for the dopamine hypothesis in schizophrenia.

The reason given for conducting the study is:

The application of a psychostimulant provocative test using methylphenidate with stable schizophrenic outpatients undergoing neuroleptic maintenance treatment is an attempt to study whether it may be feasible to exploit this phenomenon for clinical purposes.


That's it. Vague, but it kind of makes sense. It's like a glucose challenge test. You want to know if a specific patient will relapse if you take him off his meds. So you do the ritalin challenge test, and if he responds in a certain way, you know he needs to stay on his meds. And if he responds another way, you can take him off. And what are those "ways"? That's what the study is trying to find out.

They gave most of* the subjects a ritalin infusion, and a placebo infusion, 1 week apart, in random order, while they were still taking meds. They did this in a double blind fashion. They rated the subjects before and after infusions for behavioral, physiological, and physical states and changes.
Then they repeated this process several weeks after discontinuing meds.

This is what the ratings found:



The white bars are before infusion, and the black bars are after.


You'll notice that while it was double blind, you can pretty much tell when the patient got ritalin.

Then they followed the patients for a year, or until they relapsed and needed meds again. And they looked at how response to ritalin infusion correlated with time to relapse. This is what they found:


Patients with greater behavioral and TD changes in response to ritalin, as well as patients with greater baseline TD, had significantly shorter times to relapse. Blink rate and pulse rate were not significantly correlated.

The paper does a bunch of additional analyses, with groups of symptoms rather than individual ones, to get more of what they wanted. But to me, the most interesting result is that patients with more baseline TD relapsed more quickly. That could be a useful piece of data, and it doesn't require a ritalin infusion.

There are technical problems with the study. It had very few subjects, there was a protocol change after the study had begun* (that's why some subjects only had infusions after discontinuing meds), and the paper was written before follow-up had been completed on all the subjects. Also, I can't quite figure out if they did an intent to treat analysis.

They also fudged a bit in the comments section:

...Specific biologic and clinical variables, including behavioral response to methylphenidate, presence of TD, blink-rate response to methylphenidate, and pulse rate response to methylphenidate, under specific pharmacologie conditions, are associated with outcome in terms of time to relapse following neuroleptic withdrawal. 

In the results, blink rate and pulse rate are not so associated.


Here's the ethical problem. Participation in the study could not possibly have benefitted any of the subjects. It only had the potential to do harm. It's not like the authors were positing that a ritalin infusion might delay or prevent relapse.

So I'm skeptical about the consent process. We're not talking about healthy grad students who volunteer to stay awake for 3 days in exchange for $10 and meals. Did the subjects really understand that participation was completely altruistic? That the results could only benefit others, down the road, and maybe not even that?

I would have felt better about it if the idea had been addressed. They mention in the methods section that patients were evaluated for ability to give consent. But I think that somewhere, the authors should have written about the fact that the study was designed in a way that would not benefit the subjects. And that a shorter time to relapse after ritalin infusion might imply a different subgroup, one that might have had a longer time to relapse if they hadn't been given ritalin.

What do you think?


I Don't Know What to Think

A friend forwarded me this piece:

Leading American Psychiatrist Conducted Disturbing Experiments -- and Now He's Smearing Journo Who Uncovered It. (Bruce Levine/Alternet)

It's about experiments conducted by Jeffrey Lieberman. Here are the abstracts:

Arch Gen Psychiatry. 1987 Jul;44(7):597-603.
Prediction of relapse in schizophrenia.
Lieberman JA, Kane JM, Sarantakos S, Gadaleta D, Woerner M, Alvir J, Ramos-Lorenzi J.

Abstract
Despite the proven efficacy of neuroleptic drugs in the acute and maintenance pharmacotherapy of schizophrenia, practical methods for identifying patients who require neuroleptic treatment to prevent relapse are lacking. This study evaluated the use of a methylphenidate challenge test to predict the outcome in 34 stable outpatients with schizophrenia receiving neuroleptic treatment. Patients received two infusions, one of methylphenidate and one of placebo, in randomized order one week apart while receiving neuroleptic treatment and again three weeks after drug withdrawal. Behavioral, cardiovascular, and neurologic responses were evaluated before and after infusion under double-blind conditions. Patients were then followed up without medication for 52 weeks or until symptom recurrence. The results indicate that specific measures, including behavioral response to methylphenidate, presence of tardive dyskinesia, and, under specific pharmacologic conditions, tardive dyskinesia, blink-rate, and pulse-rate responses to methylphenidate, are associated with time and propensity to relapse following neuroleptic withdrawal. These measures may be potentially useful in the identification of candidates for neuroleptic withdrawal and/or dosage-reduction treatment strategies.
PMID: 2886110 [PubMed - indexed for MEDLINE]



Psychopharmacol Bull. 1990;26(2):224-30.
Behavioral response to methylphenidate and treatment outcome in first episode schizophrenia.
Jody D1, Lieberman JA, Geisler S, Szymanski S, Alvir JM.
Sandoz Pharmaceuticals, Sandoz Research Institute, East Hanover, NJ 07936-1951.

Abstract
In order to examine the relationship of behavioral response to psychostimulants and acute treatment response, we administered methylphenidate (0.5 mg/kg i.v.), an indirect dopamine (DA) agonist, to 38 patients who met Research Diagnostic Criteria (RDC) for definite or probable schizophrenia or schizoaffective disorder, were experiencing their first acute episode of psychosis, and had received less than 12 weeks or no prior lifetime neuroleptic exposure. Following baseline methylphenidate infusions, patients received a standardized regimen of acute neuroleptic treatment. Methylphenidate produced an increase in psychopathology reflected by a worsening of both positive and negative symptoms. Using a priori criteria, 61 percent of patients exhibited psychotic symptom activation, and 39 percent showed no change. Activation during methylphenidate infusion during the initial acute phase of illness was not correlated with time to achieve antipsychotic treatment response but was associated with side-effect vulnerability.
PMID: 2236460 [PubMed - indexed for MEDLINE]


In the 1987 study, they were trying to figure out which patients with schizophrenia require maintenance treatment with neuroleptics to prevent relapse. So they took 34 stable outpatients who were on meds and gave them IV ritalin, so they might get psychotic. Then they kept them off meds for a year or until they got psychotic. They learned that certain responses to ritalin are associated with a tendency to relapse. I don't have access to the full article, so I don't know which responses.

How did using the ritalin help answer their question? They could have just taken them off their meds and followed them. Sure, that would have been uncontrolled. But how does trying to make stable patients unstable tell you which stable patients will relapse off meds? It only tells you which stable patients given ritalin will relapse off meds.

In the 1990 study, they took 38 first break patients and gave them IV ritalin, which made 61% of them sicker. Then they looked at how these patients responded to antipsychotics. 

Also back in 1987, Lieberman wrote a review of 36 studies that established the pscyhotogenic potency of ritalin. So the authors of the two studies above were aware that ritalin would likely make the patients psychotic.

According to the Levine piece,

On April 26, 2015, Jeffrey Lieberman, former president of the American Psychiatric Association, stirred up controversy by calling investigative journalist Robert Whitaker a “menace to society” on CBC radio because Whitaker, in his book Anatomy of an Epidemic, had challenged the long-term effectiveness of psychiatric medication...

In Whitaker’s Globe 1998 series in the segment “Testing Takes Human Toll,” he interviewed Lieberman about his and other psychotic symptom exacerbation and provocation experiments. Lieberman asserted, “To say that increasing a particular symptom—like hearing voices for a couple of hours in somebody who has been hearing voices for 10 years—is causing [suffering] rather seems like a stretch.”

I don't know what to think. I don't truly believe Lieberman is a monster. A jerk, maybe, but not a monster. But first break patients haven't been hearing voices for 10 years.

Maybe the idea was that they could learn a lot about who did and didn't need meds by causing a little bit of extra suffering, and that ultimately, that knowledge would help a lot of people. The same way it hurts to be vaccinated, but it's helpful. 

Maybe it was easy to get stuff like this by an IRB in the late 80's and early 90's.

Maybe the patients were able to give consent, and understood what was being done to them. To me, that, "Rather seems like a stretch." You're hearing voices that are frightening you? We'll just give you something to make those voices worse, and by doing so, we'll know exactly how to treat you. 

Maybe it's the same kind of logic that comes up in Shrinks. We'll do a scan of your brain, and then we'll know exactly what's causing your mental illness.

Levine wants to blame the APA. He states, "Why would the American Psychiatric Association elect Lieberman president in 2012? Because psychiatry sees nothing wrong with these psychotic symptom exacerbation and provocation experiments."

Obviously, I don't agree with that opinion. And I also don't equate the APA with psychiatry.

There just seems to be so much stuff that comes up around this one guy.

I just don't know.



Thursday, October 23, 2014

Let's Talk about the ACA

I got a lot of responses to my recent post, Reinvention. I have to say, I was really touched by the concern people expressed, and I appreciate the suggestions for augmenting my soon-to-be-depleted income. I want to assure everyone that I am not on the verge of starvation.

One of the commenters focused on the Affordable Care Act (ACA), or Obamacare, and remarked, correctly, that not all the problems with healthcare can be blamed on the ACA. There was also a question of whether or not any of the NY exchanges covers out of network providers, because apparently, there's at least one that does in Massachusetts. Well, I checked, and there is no out of network coverage in the NY Exchange, except for immediate, emergent care.

Back in January, The Carlat Report published an article entitled, An Ethical Perspective on the Affordable Care Act, which I wrote. The contract I signed with them indicates that once 6 months has passed since the publication, I'm allowed to publish or use it myself, and since it's been that long, I thought I'd includea version of it here:

An Ethical Perspective on the Affordable Care Act

The Patient Protection and Affordable Care Act (PPACA), commonly referred to as the “ACA” or “Obamacare”, was signed into law on March 23, 2010. It’s mission: to secure health care for all US citizens, irrespective of age, gender, race, medical history, or socioeconomic status. This article will present a brief review of the ACA, and then discuss its ethical considerations, especially as they pertain to psychiatry.

First, An Ethics Refresher:

There are generally considered to be four principles of medical ethics:
Autonomy, which implies respect for a patient’s ability to make decisions for himself or herself; Justice, which allows for equal treatment of all, including fair allocation of scarce resources; Beneficence, or acting for the good of the patient; and Non-Maleficence which is the principle of primum non nocere, first, do no harm.

Ideally, any interaction with or treatment of a patient obeys all four principles, but in reality this is often not possible. For instance, the tension between autonomy and beneficence comes into question when determining patient capacity.

Provisions of the ACA are set to take effect by 2020, and generally fall into two categories: increasing access to healthcare (by mandating insurance coverage), and improving the quality and efficiency of health care delivery. Table 1 lists all the provisions scheduled through 2015, divided roughly into these two categories.





For the most part, potential ethical dilemmas for psychiatrists will occur in the quality and efficiency improvement category. Particular areas of concern are new innovations to improve quality and bring down costs, integrated health systems, linking payments to quality outcomes, payment bundling, and paying physicians based on value rather than outcome.

The Collaborative Care Model:

The Collaborative Care Model, developed by Wayne Katon, M.D., and Jürgen Unützer, M.D., at The University of Washington, is a type of integrated health system. Its implementation highlights many of the ethical pitfalls of the ACA, particularly as they pertain to psychiatrists.  In this model, primary care clinic patients are screened for psychiatric illness using simple rating scales. If the screen is positive, they are referred to a care manager, usually a MSW or other behavioral health provider, who oversees their psychiatric care. The care manager is, in turn, supervised by a psychiatrist, who reviews cases at regular intervals, but does not see the patients, except under unusual circumstances. Patient progress is measured by rating scales, until clinical goals are achieved. And providers are reimbursed based on clinical outcomes. (Link)

There have been some reports of success with this model. A study by Katon, et. al examined 214 participants with poorly controlled diabetes, coronary heart disease, or both and coexisting depression, randomized to usual care or collaborative care management by a medically supervised nurse. The intervention combined support for self-care using motivational and encouraging coaching, with pharmacotherapy, either citalopram or buproprion. At 12 months, patients in the intervention group had significantly greater overall improvement compared to controls. There was a significant difference in scores on the SCL-20 depression scale alone, but non-significant differences in the other individual outcome measures (HgbA1C, LDL, systolic BP).

The collaborative care model raises numerous ethical questions. It provides access to psychiatric care to many more patients than could be seen individually by psychiatrists, particularly in remote rural areas, thus allowing for the just distribution of scarce resources. At the same time, beneficence, and even non-maleficence, need to be considered, because care is being provided by people with limited training-in the Katon study, nurses attended a 2 day training course on depression management and behavioral strategies. And in a 2006 meta-analysis of collaborative care for depression, Gilbody, et. al found that, “...effect size was directly related to ...the professional background and method of supervision of case managers.”

In addition, types of treatment may be limited to medication, and follow-up to screening questionnaires, often conducted via telephone. 

What are the ethical implications of overseeing care for many patients who will never be interviewed in person? As a psychiatrist, would you be comfortable signing off on such care?
There is the question of putting an additional burden on primary care providers.
And there is the broader question of wasting resources by not utilizing the psychiatrist’s hard-earned skills. Which psychiatrists will find this work appealing, and will the model influence which medical students chose to pursue careers in psychiatry?

Other models of integrated care exist, such as the Collaborative Medicine and Behavioral Health (CoMeBeh) project at the University of Iowa, in which primary care is provided by physicians rotating through the psychiatry clinic, rather than the other way around. This excellent model is, unfortunately, limited by the fact that it targets a smaller population than the Katon model—those patients already in psychiatric care.

Value vs. Volume:

There are several innovations of the ACA which are intended to encourage not only better quality care, but better quality care at equal or lesser cost. In other words, greater value. 

The motivation for this idea seems clear. It acknowledges that a high volume of patients does not allow for much individual time or attention, so it attempts to incentivize physicians to provide better quality care for each patient.
Given that a goal of the ACA is to ensure coverage for all, it is paradoxical to expect doctors to spend more time with and provide better care for each patient, and to simultaneously reduce cost, when there are more patients to be cared for. But even assuming it is possible to get more for less, how does one go about implementing these innovations? How is value measured? And what ethical quagmires does one encounter in the process? 


PQRS:

The Physician Quality Reporting System (PQRS) was designed by the Centers for Medicare and Medicaid Services (CMS) as a way to improve the quality of care of Medicare beneficiaries by tracking practice patterns and providing incentive payments. It was implemented on a voluntary basis in 2007, for Medicare Part B Fee For Service (FFS) beneficiaries. But beginning in 2015, there will be payment adjustments for Medicare providers who do not satisfactorily report data. 

The PQRS is ponderous. Providers can report via one of five methods, some of which require a vendor. Beginning in 2014, providers are required to report at least 9 measures within at least 3 domains (e.g. Patient Safety, Person and Caregiver-Centered Experience and Outcomes, Communication and Care Coordination, Effective Clinical Care, Community/Population Health, Efficiency and Cost Reduction), at a certain frequency. 

One example of a measure pertinent to psychiatry is PQRS #9, Anti-depressant Medication Management: 

Percentage of patients 18 years of age and older who were diagnosed with major depression, and who remained on antidepressant medication treatment. Two rates are reported
Effective Acute Phase Treatment: Percentage of patients who remained on an antidepressant medication for at least 84 days (12 weeks) 
Effective Continuation Phase Treatment: Percentage of patients who remained on an antidepressant medication for at least 180 days (6 months) 

Clearly, this "measure of quality" has nothing to do with how well the patient is doing, and everything to do with coming up with something that can be easily measured-how long the patient has been taking medication. What if the patient is responding poorly, or taking an ineffective dose, or should be tapered off meds? Is that an example of "ineffective treatment"?


Similarly, “value-based purchasing holds providers of health care accountable for both cost and quality of care... [It involves]: measuring and reporting comparative performance; paying providers differentially based on performance; and designing health benefit strategies and incentives to encourage individuals to select high value services and providers and better manage their own health and health care.”
But how is performance determined, and will the patient's role be considered in this determination? Patients sometimes make poor choices. Should the physician’s income be adversely affected by those choices? Will doctors “cherry-pick” patients they think will be “good”? And is the patient’s autonomy diminished if the doctor is held responsible for his or her decisions?



Accountable Care Organizations (ACO’s) are groups of doctors, hospitals, and other providers who have agreed to work together to improve care and reduce costs. ACO’s that successfully demonstrate quality care and reduced costs “share in the savings” they create for Medicare. In addition, selected ACO’s can participate in the advance payment model , which provides upfront and monthly payments that can be invested in the ACO infrastructure. 

Ethical considerations for all the value measurement provisions include who is being served by these measures of value, and whether they truly measure value, or simply take up time and energy better spent with patients.


The Bundled Payments for Care Initiative involves paying a lump sum, rather than individually, for an “episode of care”. For example, if a patient is admitted for a course of ECT, rather than separately reimbursing the hospital, anesthesiologist, and psychiatrist who performs the ECT, all three will be reimbursed in one lump sum, presumably to be divided in a mutually agreed upon way. The intention seems to be to encourage collaboration between providers, and limiting of costs and overhead. But the effect may be limiting who is willing to participate, and "turfing" of work.


Coverage vs. Care:

Leaving aside questions about quality and efficiency, the ACA’s goal of health coverage for all presents its own ethical dilemma.  An expectation of medical care goes along with insurance coverage, but there is a discrepancy between the number of patients seeking treatment that will be paid for by their insurance, and the number of practitioners who will accept their insurance. In this respect, psychiatrists in private practice are in an unusual position. A study by Bishop et. al, published in JAMA Psychiatry Online on December 11, 2013, notes that psychiatrists are significantly less likely than physicians in other specialties to accept private noncapitated insurance (55.3% v. 88.7%, respectively, p<.001), Medicare (54.8% v. 86.1%, p<.001), and Medicaid (43.1% v. 73.0%, p<.001). 

The reasons for the discrepancy are unclear. One possibility suggested by the article is that while reimbursement rates for office-based psychiatric treatment are similar to those for office-based medical evaluation/management, psychiatrists don’t see as many patients per day as physicians from other specialties, resulting in less income for those who accept insurance. 
Another possibility is the fact that there are more psychiatrists than doctors from other specialties in solo practice (60.1% v. 33.1%), and solo practices require less infrastructure than larger practices, so there is less motivation to hire staff to interact with insurance companies, which is necessary to dispute claims and ensure reimbursement.
The article also cites a 14% decline in the number of graduates of psychiatry training programs between 2000 and 2008, and an aging workforce, as reasons the demand for psychiatrists exceeds the supply, and allows psychiatrists to not accept insurance. 

This is an ethical conundrum. Do we, as physicians, have a moral obligation to accept insurance, even if we lose income as a result? Or to provide care for patients who are unable to pay our full fees? Should we donate some percentage of our services, free of charge, to those who could not otherwise afford care? Or is it more ethical to treat patients who are free of the session limits and formulary restrictions that come with insurance coverage, even at greater financial cost to the patient? 

In regard to the doctor’s need to make a living, Freud writes, “It seems to me more respectable and ethically less objectionable to acknowledge one's actual claims and needs rather than...to act the part of the disinterested philanthropist—a position which one is not, in fact, able to fill, with the result that one is secretly aggrieved, or complains aloud, at the lack of consideration and the desire for exploitation evinced by ones patients.” (On Beginning the Treatment (Further Recommendations on the Technique of Psycho-Analysis I). The Standard Edition of the Complete Psychological Works of Sigmund Freud, Volume XII (1911-1913): The Case of Schreber, Papers on Technique and Other Works, Pp. 131-132


The ACA has taken on the challenge of guaranteeing affordable and quality health care for all Americans. This is a noble undertaking, with vast challenges, and unpredictable ramifications, including ethical dilemmas for doctors. What are the moral implications of refusing to accept insurance? Does that harm or help our patients? Is it possible to provide better care at lesser expense, and will we or our patients suffer as a consequence? How do we know what constitutes better care, and are measures of care helpful, or simply time-consuming? Is it more ethical to provide full care for the few, or limited care for the many? Perhaps we can view these dilemmas as opportunities to re-examine our values, and the reasons we chose to become doctors in the first place.