WTH?!?!? (What the heck)

the pharmacy
the pharmacy (Photo credit: nirbhao)

I’m not, in any way, against efforts to develop pharmaceutical treatments for addiction. However, I’m of the opinion that there is a culture problem among researchers and some members of their universe.

Does any serious, knowledgeable person with an eye toward practice believe that a stimulant drug is going to be an effective treatment for alcoholism?

Yet, researchers are toiling away on this, finding that it actually worsened outcomes for some subjects and calling for more research:

Modafinil significantly improved self-report measures of state impulsivity, but had no effect on percentage of abstinent days or percentage of heavy drinking days, nor on the behavioral measures of impulsivity. However, subgroup analysis revealed that modafinil prolonged the time to relapse (p=.022) and tended to increase the percentage of abstinent days (p=.066) in ADP with poor response inhibition at baseline, whereas modafinil increased the percentage of heavy drinking days (p=.003) and reduced the percentage of abstinent days (p=.002) in patients with better baseline response inhibition. Overall results do not favor the use of modafinil in order to reduce relapse or relapse severity in ADP, and caution is required in prescribing modafinil to a non-selected sample of ADP. Further research on the effect of modafinil in ADP with poor baseline response inhibition is warranted.

All for a drug that no practitioner could believe will provide real treatment utility. Why? And, why do we have so much deference to them in our culture?

Acomprosate – A Randomized, Double-Blind, Placebo-Controlled Study

For What It's Worth (Placebo song)
For What It’s Worth (Placebo song) (Photo credit: Wikipedia)

Recently published and found no “evidence of efficacy for acamprosate compared to placebo”.

However, “A goal of abstinence was significantly associated with improved drinking outcomes”.

Efficacy of Acamprosate for Alcohol Dependence in a Family Medicine Setting in the United States: A Randomized, Double-Blind, Placebo-Controlled Study

Background

Acamprosate has been found to enhance rates of complete abstinence and to increase percent days abstinent (PDA) from alcohol relative to placebo treatment. As most U.S. clinical trials of acamprosate have been conducted in alcohol and other drug specialty clinics, there is a need to examine the efficacy of acamprosate in generalist settings. This study tested the efficacy of acamprosate versus placebo on the primary study outcome of PDA in the treatment of alcohol-dependent patients in a family medicine setting. Secondary study outcomes included percent heavy drinking days (%HDD) and gamma glutamyltransferase level (normal or high).

Methods

A randomized, double-blind, placebo-controlled, parallel group design of acamprosate was conducted in 2 family medicine settings (North Carolina and Wisconsin). One hundred volunteers were recruited primarily by advertisement, and participants were assigned to 666 mg (2 pills) oral acamprosate 3 times daily (1,998 mg/d) or matching placebo over a 12-week period. All participants concomitantly received 5 sessions of a brief behavioral intervention from a family/primary care physician.

Results

No significant treatment effect of acamprosate was found on PDA or the secondary outcomes. Significant treatment goal by time interaction effects was found on PDA and %HDD. Participants who had an initial goal of abstinence versus a reduction in alcohol use improved on average over time in PDA and had less %HDD from baseline to the end of treatment.

Conclusions

This clinical trial did not find evidence of efficacy for acamprosate compared to placebo among alcohol-dependent individuals recruited primarily by advertisement as studied in a primary care setting. Drinking outcomes significantly improved regardless of medication condition. A goal of abstinence was significantly associated with improved drinking outcomes, suggesting that alcohol-dependent patients with such a goal may do particularly well with counseling in a family medicine setting.

50% of the equation

Forbes (?!?!) covers Pat Deegan’s efforts to empower mental health patients by guiding them into playing a larger role in their care decisions and participating in their health care records.

…I realized that we are at an important point in the history of medicine. Paper medical records are being replaced by digitized information organized into Electronic Health Records (EHRs). To my dismay, I observed that most EHRs were simply hard coding traditional clinical workflows. This isn’t the vision we started with when we saw the electronic future. The EHRs streamlined clinicians’ work and reflected what mattered to them, but patient priorities and perspectives were not taken into account in these EHRs, despite the fact it would be exceedingly simple to include them. For example, if a person is a recovering addict he or she might want to minimize opiate based pain medication after surgery. Where in the EHR is a place for that patient to voice that preference ? Where in the EHR are patients’ goals for treatment recorded and prominently displayed? If decision support information is available to doctors, why shouldn’t decision support materials be available to patients as well?

I began to realize that in this historic window of opportunity, those of us who are patients had to get at the table to insure that the EHR reflected our concerns, our strengths and views. Remember, patients are the other 50% of the healthcare equation. I thought about what would a truly person-centered EHR might look like. How can the patient’s voice best be accommodated in the EHR? What does bi-directional decision support look like? How can an EHR support informed medical decision making and shared decision making for people with long-term disorders. These are some of the important questions I developed the CommonGround web application to explore.

Primary care is a misnomer. Primary care happens in the context of daily life, not only in the physician’s office, but in the community and increasingly online. Traditionally, clinicians are gatekeepers of information, but if they don’t talk about recovery patients don’t hear about it. We decided to develop software with important information for current mental health patients provided by recovering patients. We start with the notion that those with mental disorders can and do recover, and we built a body of knowledge to help those currently struggling. The main thing for us is to help people be better informed about their conditions and their options for dealing with them in the broader context of functional and quality life.

Beware of misleading headlines

Caution Tape
Caution Tape (Photo credit: Picture Perfect Pose)

A new article discussing the expanding use of medications in addiction treatment has the following sub heading:

Experts are pushing for a truly medical approach to treating addiction as a disease rather than relying solely on longtime unproven therapies like 12-step programs.

Unproven?

I’m certain a day will come when we have effective pharmacological tools to help addicts initiate and maintain recovery but, beyond detox, I find the current meds pretty underwhelming as a group and troubling in some cases.

When you hear the push for these “scientific”, “medical” and “evidence-based” treatments, keep these exhibits in mind:

A Doctor’s Dilemma: When Crucial New-Drug Data Is Hidden

The positive spin surrounding industry-funded studies — which are, after all, the studies that the government uses to approve drugs — isn’t the only ongoing problem. Goldacre further describes how drug companies hide data about medication risks that affect children, how they attempt to intimidate the employers of researchers who produce results they don’t like, and how they routinely withhold safety data in various other ways that do harm to patients.

A Call for Caution on Antipsychotic Drugs

You will never guess what the fifth and sixth best-selling prescription drugs are in the United States, so I’ll just tell you: Abilify and Seroquel, two powerful antipsychotics. In 2011 alone, they and other antipsychotic drugs were prescribed to 3.1 million Americans at a cost of $18.2 billion, a 13 percent increase over the previous year, according to the market research firm IMS Health….several recent large randomized studies, like the landmark Catie trial, failed to show that the new antipsychotics were any more effective or better tolerated than the older drugs.

It was also soon discovered that the second-generation antipsychotic drugs had serious side effects of their own, namely a risk of increased blood sugar, elevated lipids andcholesterol, and weight gain. They can also cause a potentially irreversible movement disorder called tardive dyskinesia, though the risk is thought to be significantly lower than with the older antipsychotic drugs.

Nonetheless, there has been a vast expansion in the use of these second-generation antipsychotic drugs in patients of all ages, particularly young people. Until recently, these drugs were used to treat a few serious psychiatric disorders. But now, unbelievably, these powerful medications are prescribed for conditions as varied as very mild mood disorders, everyday anxiety, insomnia and even mild emotional discomfort.

Top 10 Drug Company Settlements

Record-breaking multibillion-dollar settlements against big drug companies have become routine in the U.S. In recent years, pharmaceutical companies seem to have been playing a game of one-upmanship, each surpassing yet a new milestone of wrongdoing — fraudulently marketing their drugs or making misleading claims about their safety — and the threat of massive payouts appears to have offered little deterrent.

Following the evidence

Ouch:

Fluoxetine HCl 20mg Capsules (Prozac)
Fluoxetine HCl 20mg Capsules (Prozac) (Photo credit: Wikipedia)

Abstract: This paper raises the question about whether the data on the medications we call antidepressants justify the label of antidepressant. The authors argue that a true antidepressant should be clearly superior to placebo, should offer a risk/benefit balance that exceeds that of alternative treatments, should not increase suicidality, should not increase anxiety and agitation, should not interfere with sexual functioning, and should not increase depression chronicity. Unfortunately, these medications appear to fall short on all of these dimensions. Many of the “side effects” of these medications have larger effect sizes than the antidepressant effect size. To call these medications antidepressants may make sense from a marketing standpoint but may be misleading from a scientific perspective. Consumers deserve a label that more accurately reflects the data on the largest effects and helps them understand the range of effects from these medications. In other words, it may make just as much sense to call these medications antiaphrodisiacs as antidepressants because the negative effects on libido and sexual functioning are so common. It can be argued that a misleading label may interfere with our commitment to informed consent. Therefore, it may be time to stop calling these medications antidepressants.

From the conclusion:

If we do not call these medications antidepressants, what are some alternative labels that may better fit the existing data? The effect sizes for many of the “side effects” are larger than the antidepressant effect sizes. Using labels like antiaphrodisiac medications, agitation enhancers, insomnia inducers, suicidality inducers, mania stimulators, or gas busters obviously would not offer the same marketing appeal. Though tongue in cheek, we consider these possible labels to be more accurate than the commonly used label of “antidepressant.” It could be argued that the outcomes with the largest effect sizes should be offered as the primary label for a medication.

These guys are pretty sarcastic. And, their sarcasm is unlikely to be a conversation starter, but I suspect that there is more of this backlash to come.

It brings to mind a comment from a recent episode of On Being [emphasis mine]:

…individuals are hopelessly biased, they cannot perceive the truth by themselves.

Science is not just an individual activity. We expect our scientists, we exhort them, to be as objective as they can and a good scientist tries to do so very earnestly, but still fails. So therefore, there must be a social process that causes science to work to be a truth-discovering process.

This thing about scientific truth-discovery being a social process  puts it’s finger on something very important. It’s one of the things that so frustrating about hearing people tout evidence-based policies.

Consider the arguments for naloxone distribution. I’ve honestly got no quarrel with it, I just believe that it’s a woefully inadequate response. Of course it’s true that it’s an evidence based policy. I’m sure it saves lives. My problem is that advocates draw a straight line from this truth to universal implementation, AND anyone who balks is anti-science. The problem is that these advocates don’t ask what else we know to be true. For example, treatment also reduces overdose deaths. We fail to discuss what else improves this measure (overdose deaths), we also fail to discuss what other measures are important. If we have that conversation, then we can discuss why it sh0uld or shouldn’t jump to the top of the list without accusing others of being anti-science.

Another example are the evidence-based arguments that opiate substitution medications should be the front-line treatment for opiate addiction. To be sure, these medications reduce opiate misuse. However, there also exists a model, with evidence, that eliminates opiate use in 78% of patients over 5 years. Why not discuss that? Why not allow discussion of whether reduced opiate use is even a good measure? Or, the best measure?

This social aspect of truth-discovery is too often too exclusive. Of course, we can not and should not give equal standing to every goofball with a pet theory, but the points in the antidepressant paper above and the recent GSK scandal demonstrate that the current custodians of evidence are all too capable of leading us into policies based on something other than truth while scolding anyone who questions their evidence.

UPDATE: Just to clarify two things.

First, we’re not anti-medication, but we do believe that their benefits are overstated, the adverse effects are understated, that other methods are just as effective or more effective (And, provide additional benefits.) and that they too often constitutes risk management rather than real treatment.

Second, I see naloxone as first aid. I have no interest in interfering with access to first aid of any kind to anyone with any kind of physical crisis. However, first aid should be FIRST aid (Not last aid or only aid.), and meaningful treatment for the real problem should follow. I tend to bristle because these calls for naloxone programs never seem to include calls for access to treatment of adequate quality, intensity and duration following the overdose.

GlaxoSmithKline’s corruption

GlaxoSmithKline
(Photo credit: Ian Wilson)

The details are simultaneously exactly what you’d expect and shocking.

And some people wonder why we’re reluctant to embrace the latest and greatest pharmacological fad. Keep all of this in mind next time someone suggests that medicalizing addiction treatment will improve professionalism, ethics and reliance on scientific evidence.

Sham advisory boards:

Glaxo also used sham advisory boards and speakers at lavish resorts to promote depression drug Wellbutrin as an option for weight loss and a remedy for sexual dysfunction and substance addiction, according to the government. Customers were urged to use higher-than-approved dosages, the government said.

Phony continuing education programs:

GSK paid millions to doctors to promote the drug off-label during meetings sometimes held at swanky resorts, the government said. The company relied on pharmaceutical sales reps, “sham advisory boards,” and continuing medical education programs that appeared independent but were not.

Misleading doctors:

The company went to extreme lengths to promote the drugs, such as distributing a misleading medical journal article and providing doctors with meals and spa treatments that amounted to illegal kickbacks, prosecutors said.

Bribing doctors:

“GSK’s sales force bribed physicians to prescribe GSK products using every imaginable form of high priced entertainment, from Hawaiian vacations to paying doctors millions of dollars to go on speaking tours to a European pheasant hunt to tickets to Madonna concerts, and this is just to name a few,” said Carmin M. Ortiz, U.S.attorney in Massachusetts.

Widespread:

Crimes and civil violations like those in the GlaxoSmithKline case have been widespread in the pharmaceutical industry and have produced a series of case with hefty fines. One reason some have said the industry regards the fines as simply a cost of doing business is because aggressively promoting drugs to doctors for uses not officially approved — including inducing other doctors to praise the drugs to colleagues at meetings — has quickly turned numerous drugs from mediocre sellers into blockbusters, with more than $1 billion in annual sales.

Stories have noted that Pfizer agreed to a $2.3 billion settlement in 2009. Also, Johnson & Johnson settled with Arkansas for $1.2 billion for several violations, including:

…for not disclosing the risks of the antipsychotic Risperdal.

Withholding data on Paxil:

GSK allegedly participated in the publishing of medical journal articles that stated paroxetine was effective in patients under 18, when, in fact, the data showed that the opposite was true. At the same time, the company withheld study data in from two other studies in which Paxil also failed to demonstrate efficacy in treating depression in patients under 18, according to a press release from the Justice Department.

Kept safety issues secret:

…the company kept secret data on raised cardiovascular effects.

The medical model and recovery

Yesterday’s post about the disease model and recovery got me thinking about complaints that treatment is not medical enough. It’s worth noting that mental health treatment has a medical model and these patients believe it’s been harmful to them. What they want is something more like the holistic lifestyle approach, peer support and talk therapy that one might find in a good addiction treatment program.

This may help explain why addiction treatment guards itself from the encroaching medical model so tenaciously. (Worth noting that mental health system guards its model pretty vigorously too.)

Of course, none of this means that there aren’t lousy treatment providers or that there isn’t room for improvement in addiction treatment. Just that there is something worth protecting there and patients in the mental health system see it.

“Disease” and recovery

“Once I became my diagnosis, there was no one left to recover.”

1212mentalhealth-RW
(Photo credit: Robbie Wroblewski)

Yesterday’s Pat Deegan post led me to Dr. Daniel Fisher’s work on mental illness recovery. He promotes an “empowerment” model of recovery that he contrasts with a “rehabilitation” model of recovery.

According to this vision, one is capable of recovering from the mental illness itself, not merely regaining functioning while remaining mentally ill. … We realize that the idea that people can recover from mental illness will create more work on the part of entitlement programs. Instead of a single, once-in-a-lifetime determination of disability, episodic periods of disability will need to be supported.

In this model, treatment is part of self-managed care. The goal of treatment here is assisting people in gaining greater control of their lives and assisting them in regaining valued roles in society. The primary goal of treatment should not be to control the person’s behavior. The use of medication does not itself mean that a person has not recovered from mental illness. It depends upon the degree to which the person and those around them see the medication as constantly needed. Ideally, each person should learn to take medication on an as-needed basis, after having learned to self-monitor. Many people also embrace holistic health as an alternative to medication.

One of the things I find fascinating about this movement is that they challenge the brain disease model of mental illness.

Not surprisingly, many researchers have concluded that medication alone is best for the treatment for mental illness. Despite recent convincing research showing the usefulness of psychotherapy in treating schizophrenia, psychiatric trainees are still told “you can’t talk to a disease.” This is why psychiatrists today spend more time prescribing drugs than getting to know the people taking them.

I, too, used to believe in the biological model of mental illness. Thirty-one years ago, as a Ph.D. biochemist with the National Institute of Mental Health, I researched and wrote papers on neurotransmitters such as serotonin and dopamine. Then I was diagnosed with schizophrenia — and my experience taught me that our feelings and dreams cannot be analyzed under a microscope.

Schizophrenia is more often due to a loss of dreams than a loss of dopamine. At the NEC, we try to reach out across the chasm of chaos. I know there are many people who feel they have done all they can, have struggled against mental illness to no avail, and we understand their pain. Yet we believe that recovery is eventually possible for everyone — although it can take a long time to undo the negative messages of past treatments. We can offer hope from first-hand experience.

Another post identifies common factors in these recovery experiences. I’ve summarized them. It’s worth noting that that author reports that people achieving recovery reported that traditional psychiatric treatment was a barrier to achieving these factors.

Factor #1Hope in the possibility of real recovery. All participants in all three of my research studies expressed that in order to even begin the journey towards real recovery, they first had to believe that such recovery is actually possible.

Factor #2Arriving at an understanding of their psychosis alternative to the brain disease theory. Every participant went through a process of developing a more hopeful understanding of their psychotic experiences, generally coming to see their psychosis as a natural though very risky and haphazard process initiated by their psyche in an attempt to cope and/or heal from a way of being in the world that was simply no longer sustainable for them.

Factor #3Finding meaning. All participants expressed how important it was for them to connect with meaningful goals/activities that made their life worth living—that provided them with some motivation to greet each new day with open arms and to channel their energy productively.

Factor #4Connecting with their aliveness. All participants reported how important it was for them to connect more deeply with themselves—particularly with their feelings, needs, and sense of self agency.

Factor #5Dealing with their relationships. All participants expressed the importance of healing and/or distancing themselves from unhealthy relationships and cultivating healthy ones.

Rethink Mental Illness
Rethink Mental Illness (Photo credit: Wikipedia)

It seems that the biggest objection to the disease model is that mental health consumers experience this model as something that puts them in a passive position, waiting for someone or something to come along and hopefully mend their broken brain just enough to allow them to get through life with something less than full personhood.

This article in Friday’s Wall Street Journal gets at the same thing with respect to much less severe mental illness as experienced by young people.

When I first began to take antidepressants, I understood that doing so meant I had a chemical imbalance in my brain. I knew that, arguably, I should find that comforting—it meant that what I was going through wasn’t my fault—but instead it made me feel out of control. I wanted my feelings to mean something. The idea that my deepest emotions were actually random emanations from my malfunctioning brain didn’t uplift me; it just further demoralized me.

In my 20s, I sought out talk therapy, partly to deal with the questions that using antidepressants raised for me and partly because the effects of the drugs, spectacular in the short term, had waned over time, leaving plenty of real-world problems in their wake. Only then did I begin to notice just how nonrandom my feelings were and how predictably they followed some simple rules of cause and effect.

Looking back, it seems remarkable that I had to work so hard to absorb an elementary lesson: Some things make me feel happy, other things make me feel sad. But for a long time antidepressants were giving me the opposite lesson. If I was suffering because of a glitch in my brain, it didn’t make much difference what I did. For me, antidepressants had promoted a kind of emotional illiteracy. They had prevented me from noticing the reasons that I felt bad when I did and from appreciating the effects of my own choices.

What’s so interesting about this is that people with addictions have a completely different experience. Within the context of addiction recovery, discovering that one has the illness of addiction means that one has a lot of work to do and a lot of responsibility for their recovery. This model is not without its limitations, but it’s amazing how many people find an admission of powerlessness  to be so empowering.

I have two thoughts.

First, there seems to be a parallel here. People band together in response to the failure of existing institutions and, together, find an alternative path to recovery. The institutions use their size, wealth, connections, research and publications to de-legitimize this path to recovery. It’s probably a very good thing that PhRMA didn’t have a stake in addiction treatment in 1935.

Second, as the Affordable Care Act is implemented and we need to start really grappling with the cost of chronic diseases, this empowerment model of recovery fits very well with a lifestyle medicine approach. Unfortunately, our medical system is not structured (staffing, reimbursement, monitoring, research, etc.) to support this approach.

I think mental health and addiction treatment have a lot to learn from lifestyle medicine, but I also think addiction and mental illness recovery movements have a lot to teach lifestyle medicine about how patients can maintain wellness over decades.

NOTE: Dawn Farm is not anti-medication, though we do have concerns about the way they are used. More information here.

Hope and Recovery

Pat Deegan reflects on her own experience an shares about the need for hope in recovery:

He said, I should retire from life and avoid stress. I have come to call my psychiatrist’s pronouncement a “prognosis of doom”. He was condemning me to a life of handicaptivity wherein I was expected to take high dose neuroleptics, avoid stress, retire from life and I was not even 18 years old! My psychiatrist did not understand that boredom is stressful! A life devoid of meaning and purpose is stressful! A vegetative life is stressful. A life in handicaptivity, lived out within the confines of the human services landscape, where the only people who spend time with you, are people who are paid to be with you – that is stressful! Living on disability checks from the government is stressful.

When I was diagnosed I needed hopeful messages and role models. I needed to hear that there were pathways into a better future for me. I needed to connect with others who had been diagnosed with schizophrenia and who had recovered lives of meaning and purpose. I needed to find others who had completed college and who had jobs and who got married and had families, and had an apartment and a car.

Why is hope important to recovery? Because hope is the root of life’s energy. In order to recover, I had to turn away from the wish that psychiatrists could fix me. I had to turn away from the myth that psychiatric treatments could cure me. Instead, I had to mobilize all of the energy I had. I had to become an active partner in my recovery. I had to learn to work collaboratively with my treatment team and to draw strength from the wisdom of my peers. I had to begin striving for my goals, not when I was “all better”, but from day one. I had to believe that there was a life for me beyond the confines of the mental health system. That is hope. Hope is the tenacious pursuit of pathways to a better life, despite the odds. Without hope, there is no recovery.

Amen. Please go and read the whole post at her blog and spend some time poking around her posts.

Deconstructing “it works”

Healthcare, etc. has a great post deconstructing what it means to say a treatment works:

What exactly does it mean when we say that a treatment works? Do we mean the same thing for all treatments? Are there different ways of assessing whether and how well a treatment works? I am sure you’ve guessed that I wouldn’t be asking this question if the answer were simple. And indeed, the answer is “it depends.”

What I am talking about is examining outcomes. I did a post a couple of years ago here, where I use the following quote from a Pharma scientist:

“The vast majority of drugs – more than 90 per cent – only work in 30 or 50 per cent of the people,” Dr Roses said. “I wouldn’t say that most drugs don’t work. I would say that most drugs work in 30 to 50 per cent of people. Drugs out there on the market work, but they don’t work in everybody.”Here is that word “work” again. What does this mean? well, let’s take such common condition as heart disease. What does heart disease do to a person? Well, it can do many things, including give him/her such symptoms as a chest pain, shortness of breath, dizziness and palpitations, to name a few. These symptoms may have at least two sets of implications: 1) they are bothersome to the individual, and in this way may impair his/her enjoyment of life, and 2) they may signal either a present or a future risk of a heart attack. Why are heart attacks important? Well, they are important because one may kill the person who is having it, or one (or several) may weaken the heart to the point of a substantial disability and thus a deterioration in the quality of life. So, there certainly seems to be a good rationale to prevent heart disease either from happening in the first place or from at least worsening when it’s already established.

Now, what’s available to us to prevent heart disease? Well, some think that lowering one’s cholesterol is a good thing. OK, let’s go with that. What is the sign that the statins (cholesterol-lowering drugs) “work”? What would it look like if it was about lowering the cholesterol? Say, your total cholesterol is 240. You go on a statin and in 6 months your total cholesterol is 238. Your cholesterol was lowered, it worked! Well, yes, but if you are asking what this 2-point drop really accomplishes, you are beginning to understand the meaning of “work.” So, just intuitively we can say that there needs to be a certain, perhaps “clinically significant,” drop in the total cholesterol in order for us to say that the drug “worked.”

Great! Now we are sidling up to the real issue: What constitutes a “clinically significant” drop in cholesterol? Is it some arbitrary number that looks high enough? Probably not. How about some drop that correlates to a drop in the risk of the actual condition we are trying to impact, heart disease? Say, a 40-point drop, or getting to below 200, may be the right threshold for the “works” judgment. Ah, but there is yet another question to ask: How often does this type of a drop lead to a reduction in heart disease? Is it always (not likely), or is it the majority of the time (rarely) or at least some of the time (most likely in clinical medicine)? And what portion of that time do we consider satisfactory — 60%? 40%? 20%? 2%?

There’s more. Read the rest here.