An exciting time for pharma

photo credit: carbonNYC

Ugh!

This Join Together article reads like a ad for pharma:

Many people struggling with alcohol dependence who could benefit from medication are not receiving it, according to an expert who spoke at the recent American Psychiatric Association Annual Meeting.

“Antidepressant prescribing is 100 to 200 times as great as prescriptions for medications approved to treat alcohol dependence, despite the fact that the prevalence of disorders for which antidepressants are prescribed—major and minor depression and anxiety disorders—is only two to three times that of alcohol dependence,” says Henry Kranzler, MD, Professor of Psychiatry at the Treatment Research Center at the University of Pennsylvania and the Philadelphia VA Medical Center.

Perhaps I’m the Wrong Tool by Tall Jerome

There’s plenty of room for debate about whether high antidepressant prescribing rates represent money well spent or good medicine, but I’ve covered that before. (See below)

He expresses some enthusiasm about Topamax and then touts a new drug coming from Denmark:

Lundbeck, a Danish pharmaceutical company, has submitted an application for approval by the European Medicines Agency of the medication nalmefene to be used on an as-needed basis to reduce heavy drinking, according to Dr. Kranzler. “This is a novel approach and could have an impact on treatment throughout the European Union and possibly the U.S.,” he adds.

Here’s what a disinterested trade publication had to say about the drug [emphasis mine]:

Danish pharmaceutical company H. Lundbeck A/S yesterday unveiled clinical data on its potential blockbuster drug nalmefene at the 2012 European Congress of Psychiatry clinical in Prague. While Lundbeck and its Finnish partner Biotie Therapeutics Corp. from Turku underline an impressive 66% reduction in total alcohol consumption, a closer look at placebo data is disconcerting. In three placebo-controlled Phase III studies, the drug with the trade name Selincro was given to heavy drinkers who also were given medical advice about their drinking habits. Selincro aims at eliminating the brain’s pleasure response to drinking. After six months, numbers of heavy drinking days (total alcohol consumption) in the first study dropped from 19 to 7 (84g to 30g) in the drug arm, and from 20 to 10 (85g to 43g) in the placebo arm. The numbers of the second study were less convincing and – even worse – in the third study the drug arm barely outperformed the placebo. Nevertheless Biotie-CEO Timo Veromaa thinks that “Selincro has the potential to transform the way alcohol dependence is managed by both patients and physicians.”

Too bad the Join Together article didn’t include a commercial interest disclosure statement* and note that he and/or his projects have received money from the manufacturers of Topamax and nalmefene.

I believe that medications may play a helpful role in the future, but I’m underwhelmed by the current stable of drugs and troubled that so much energy gets put into promoting expensive drugs of dubious value.

This is an exciting time in the treatment of alcoholism, because the field of medication treatment for alcohol dependence is expanding into the arena of personalized medicine, he says.

I’d love to see helpful drugs come along and I think a lot of these docs and researchers have good motives, but they have one tool (the prescription pad) and they seem to consistently oversell it.

* The ASAM event disclosure lists that Dr. Kranzler and/or his projects have recieved money from Alkermes, Roche, Pfizer, Lundbeck, Lilly, Eli Lilly, Janssen, Schering Plough, GlaxoSmithKline, Abbott and Johnson & Johnson. ProPublica does not list him at all. Possible explanations are here.

Hard to kill


Nature has a new article on the troubling shelf life of bad psychology research:

Positive results in psychology can behave like rumours: easy to release but hard to dispel. They dominate most journals, which strive to present new, exciting research. Meanwhile, attempts to replicate those studies, especially when the findings are negative, go unpublished, languishing in personal file drawers or circulating in conversations around the water cooler.

Psychology is not alone in facing these problems. In a now-famous paper, John Ioannidis, an epidemiologist currently at Stanford School of Medicine in California argued that “most published research findings are false”, according to statistical logic. In a survey of 4,600 studies from across the sciences, Daniele Fanelli, a social scientist at the University of Edinburgh, UK, found that the proportion of positive results rose by more than 22% between 1990 and 2007. Psychology and psychiatry, according to other work by Fanelli, are the worst offenders: they are five times more likely to report a positive result than are the space sciences, which are at the other end of the spectrum.

Emotional pain without context

MRI coronal view of the hippocampus
MRI coronal view of the hippocampus (Photo credit: Wikipedia)

Siddhartha Mukherjee provides a brief history of the serotonin hypothesis of depression, its demise and why dismissing serotonin may be an “overcorrection.”

Part of this story is an emerging theory of depression:

A remarkable and novel theory for depression emerges from these studies. Perhaps some forms of depression occur when a stimulus — genetics, environment or stress — causes the death of nerve cells in the hippocampus. In the nondepressed brain, circuits of nerve cells in the hippocampus may send signals to the subcallosal cingulate to regulate mood. The cingulate then integrates these signals and relays them to the more conscious parts of the brain, thereby allowing us to register our own moods or act on them. In the depressed brain, nerve death in the hippocampus disrupts these signals — with some turned off and others turned on — and they are ultimately registered consciously as grief and anxiety. “Depression is emotional pain without context,” Mayberg said. In a nondepressed brain, she said, “you need the hippocampus to help put a situation with an emotional component into context” — to tell our conscious brain, for instance, that the loss of love should be experienced as sorrow or the loss of a job as anxiety. But when the hippocampus malfunctions, perhaps emotional pain can be generated and amplified out of context — like Wurtzel’s computer program of negativity that keeps running without provocation. The “flaw in love” then becomes autonomous and self-fulfilling.

He proposes an alternative understanding of the role serotonin may play:

An antidepressant like Paxil or Prozac, these new studies suggest, is most likely not acting as a passive signal-strengthener. It does not, as previously suspected, simply increase serotonin or send more current down a brain’s mood-maintaining wire. Rather, it appears to change the wiring itself. Neurochemicals like serotonin still remain central to this new theory of depression, but they function differently: as dynamic factors that make nerves grow, perhaps forming new circuits.

This still doesn’t explain the variation in responses to psychotropics. He acknowledges as much and alludes to the need for new typologies of depression. (Remember the dark ages when we talked about endogenous vs. exogenous depressions?)

The layers of speculation can obscure or illuminate just how crude our understandings of depression and the brain are. This, along with the history of psychiatric fads and abuses, makes one wonder if we should proceed a little more cautiously and work a little harder to capitalize on non-pharmacological tools like exercise and social support.

Why we can’t agree

Official portrait of United States Director of...

The Obama administration just released their annual drug control strategy report and all the headlines say it emphasizes treatment over incarceration.

Sounds great, but the stories are short on details.

Others, from the Drug Policy Alliance are dismissing it as more of the same.

More of the same? Really? I think Obama’s safely within the herd on this, but one doesn’t have to go back very far to reach a time when it would be a certain death sentence for a national politician to say that we should incarcerate fewer people for drug crimes. Change may not be coming as quickly as the DPA would like, but to say that the current state of affairs is “same old, same old” is pretty silly.

All of this is mildly interesting. What is was much more interesting was this quote:

Is it a disease of the brain? I asked Columbia University psychology professor Carl Hart, who is also a board member of Drug Policy Alliance. Hart laughed. “A behavioral disease, therefore the brain is involved? OK, we can say that about everything.”

I admit, the addiction-is-an-illness line never worked for me. It leaves out personal will. It sanitizes destructive decision making. It suggests that people cannot get clean without a health care professional.

Art Caplan, director of the Center for Bioethics at the University of Pennsylvania, came up with the best explanation I’ve heard for the disease argument. People don’t want to see addicts jailed, he said, so they’ve come up with a scenario to spare users from incarceration. Ergo: “The whole drug establishment is invoking the disease model as an antidote to the criminal-justice model.”

I think it goes a long way toward explaining the difficulty in explaining the difficulty in finding any common ground on drug policy.

  • The question of free will is an important and under-addressed matter. Though I’m pretty confident it’s under-addressed because it’s not empirically knowable.
  • The suspicion of the disease model is a huge barrier. If there are profound disagreements about the nature of the issue, it’s very difficult to even begin to come up with solutions that address each other’s concerns.
  • The suspicion of each other’s motives is a huge barrier—”so they’ve come up with a scenario”. This paints advocates of the disease model as disingenuous. We’re manufacturing the model we need rather than describing what is.