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?

Suboxone Strategy: Protecting Patients Or Profits?

Reckitt Benckiser
Reckitt Benckiser (Photo credit: Wikipedia)

I’m a little late on posting this one, but it still seems worth sharing.

Reckitt Benckiser has decided to pull Suboxone tablets from the market. Why? It’s an evidence-based decision and an expression of their desire to be a good corporate citizen and their concern for children.

Late last month, Reckitt Benckiser created a stir by unexpectedly announcing that its Suboxone tablet for treating opioid dependence will be withdrawn from the US market sometime over the next six months. The reason? The drugmaker, which is based in the UK and actually best known for household cleaning products, expressed concern that children could be accidentally harmed by easy access to tablets that are marketed in bottles.

In making its case, Reckitt cited specially commissioned data showing “consistently and significantly higher rates of accidental unsupervised pediatric exposure” with Suboxone tablets than with Suboxone Film, a newer version of its drug that dissolves under the tongue and can only be accessed by tearing open individual blister packaging. Specifically, the rates for Suboxone tablets were roughly eight times greater (read here).

What’s the big business picture?

To generic drug makers, some physicians and Wall Street analysts, however, the moves amounted to a transparent one-two punch designed to delay lower-cost generic tablets from reaching the market. The patent on Suboxone tablets, in fact, expired two years ago, while patent on Suboxone Film expires in 2022, according to the Reckitt spokesman. “If Reckitt is so concerned about safety,” says one industry source, who asked not to be named, “then why not take the tablets off the market right away? Their tablets are still on the market without blister packing, which they themselves say is unsafe.”

Meanwhile, Reckitt has gradually raised the price of Suboxone Tablets in order to switch patients. The current wholesale average cost (WAC) for a bottle of 30 Suboxone Tablets is $161.70 for the 2 mg dose and $289.80 for the 8 mg dose, according to the Reckitt spokesman. In July, however, the same bottle of the 2 mg dose cost $140.00 and the 8 mg WAC was $252.00, industry sources say. Meanwhile, Suboxone film pricing has held steady: WAC pricing for a carton of 30 Suboxone Film strips remains $117.85 for the 2 mg dose and $211.15 for the 8 mg dose.

More recently, sales of Suboxone tablets fell 19 percent between August 2011 and August 2012, to $658.5 million, according to IMS Health, while sales of Suboxone film doubled to more than $764 million during the same period. “They are (removing the tablets) because generics are expected in 2013 on the tablet,” says Sanford Bernstein analyst Ronny Gal. “The critical question is whether their argument that film is always safer for children will convince FDA not to approve any oral solid generic.”

For these reasons, the back-to-back announcements have been met with outrage. “They have known for years that a generic tablet could destroy their golden calf — and Suboxone is Reckitt Benckiser, from an earnings standpoint. If they do not destroy the tablet, it destroys them,” Jeff Junig, a psychiatrist at the University of Wisconsin Oshkosh Student Health Service and an assistant clinical professor of Psychiatry at the Medical College of Wisconsin, wrote in a letter to Alcoholism & Drug Abuse Weekly.

“I’m sure I sound… paranoid? Cynical?,” wrote Junig, who also authors a blog about Suboxone. “But it is so frustrating when you see marketing trump science. This will discourage generics from making buprenorphine, which will keep the price high, which will cause deaths. Shame on them.”

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.

Following alcoholics for decades

McLeans has an interesting interview with George Vaillant about, “the surprising things you find out about people if you follow them for long enough.”

What’s so different and interesting about this study is that it followed the subjects for decades from a pretty young age. Their subjects were college sophomores when the study began and their selection was not based on any problems or characteristics. So, they studied them before, during and after their active alcoholism.

Here are a few of the better bits.

On alcoholism and recovery:

Q: What, then, are the great lessons to be drawn from the study?

A: Some of the most important ones involved alcoholism. About 50 per cent of alcoholics recover, but a remarkable percentage of those do so with AA. The fact that this study followed up with these men on 60 different occasions with regard to their alcoholism over a period of 50 years did allow us to identify what made a difference.

You’ll have to read the Natural History of Alcoholism, because he didn’t expound on that in the interview.

On childhood unhappiness and alcoholism:

Q: A lot of long-held theories flew out the window over the decades thanks to your work.

A: One of the simplest examples was the notion that unhappy childhoods cause alcoholism. What a study like this shows is that, first, lots of alcoholics invent an unhappy childhood to justify their drinking. Second: if an alcoholic’s childhood is miserable, it’s because a blood relative has alcoholism. If the unhappy childhood is the result of an alcoholic step-parent, the person doesn’t drink to relieve the misery. So it’s the genetic component of alcoholism that matters.

On alcoholism’s toll (Too bad these lessons need to be re-learned!):

Q: You argue that alcohol abuse is the most ignored causal factor in modern social science. Why?

A: Because it’s much more fun to pay mind to nice people than to angry, passive-aggressive people, and the disease of alcoholism makes people angry and dishonest. If you look at the major books on marriage, alcoholism is mentioned nowhere in the index as a cause of unhappiness. Yet 57 per cent of all the divorces in the Harvard sample occurred when one or other spouse were drinking alcoholically. The alcohol abuse almost always preceded the trouble in the men’s life. Another dramatic example: depression does not lead to alcoholism, whereas alcoholism leads to depression. If you take 100 cases, you can find two or three exceptions, but that’s all. People didn’t really know that before the Grant study.

[hat tip: Jeff Jay]

Correlation does not equal causation

On the oft used phrase, “correlation does not equal causation“:

The correlation phrase has become so common and so irritating that a minor backlash has now ensued against the rhetoric if not the concept. No, correlation does not imply causation, but it sure as hell provides a hint.

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.

Gateway Theory Revisited

 

A small but elegant gate to a meadow path.
(Photo credit: Wikipedia)

 

Keith Humphreys on findings that link marijuana, tobacco and alcohol use with opiate use:

 

The researchers used data from 2006 to 2008 from the National Survey on Drug Use and Health, an annual study representative of the U.S. population, to study 18- to 25-year-olds’ drug use behavior. They found that 12 percent of the survey population reported misusing prescription opioids around the time the survey was conducted.

They also found that both men and women who had smoked marijuana between the ages of 12 and 17 were more than two times more likely to later abuse prescription drugs than those who had not. Young men who drank or smoked cigarettes as teens were 25 percent more likely to abuse prescription drugs — though this link was not found in women surveyed. Fiellin said there was no clear-cut reason why the results differed for men and women.

Keith Humphreys, professor of psychiatry at the Stanford Medical Center, said that this association between “gateway drugs” and prescription pain medication was significant regardless of the exact mechanism behind the link.

“Some people believe the ‘gateway effect’ exists because early drug use primes the human brain for more drug-seeking, others argue that the friends you make using drugs as a youth are a ready source for other drugs later, and still others argue that there are factors, like impulsivity, that causes both early and later drug use,” Humphreys said. “Which camp is correct? Probably, all of them.”

 

 

 

Methadone’s cognitive effects

 

English: Methadone structure, animation
English: Methadone structure, animation (Photo credit: Wikipedia)

Another study on methadone’s cognitive effects:

In one study, on the day after the last exposure to methadone, there was a significant reduction (around 70 per cent) in the level of a signal molecule which is important in learning and memory, in both the hippocampus and in the frontal area of the brain. This reduction supports findings from a previous study (Andersen et al., 2011) where impaired attention in rats was found at the same time. At this time, methadone is no longer present in the brain. This indicates that methadone can lead to cellular changes that affect cognitive functioning after the drug has left the body, which may be cause for concern.

The study was done on rats, not people, but it’s findings aren’t isolated.

Patients and their loved ones may decide that the potential benefits outweigh the costs, but they should be made aware of the costs and know the alternatives.

“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.