I’m more and more convinced that the key to managing costs and improving outcomes for all chronic diseases are behavioral or lifestyle strategies. We’ve got a lot to learn about helping people make important changes in their lives that will help prevent relapses in cardiac care, joint replacements, weight loss, respiratory care, depression, etc. We’ve got even more to learn about helping people maintain these changes for decades.
Addiction treatment is ahead of the curve on a lot of this. We have a lot to offer the rest of medicine and I’m certain we’ll have a lot of opportunities to learn from their research and innovations.
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.
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 FIRSTaid (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.
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.
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.
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.
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.
“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.
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.
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.
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.
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.
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.”
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.
This infographic is from a report on obesity and it’s set off a debate its accuracy. But it gets at a point I’ve made before. And, the more I learn, the clearer it becomes that this general principle applies to medical problems, mental health problems and addiction.
To me, this doesn’t make a case for disengagement from the medical system. Rather it calls for finding some balance between care focused on delivering medications and devices and care that focuses on promoting and supporting health and wellness.
I think addiction recovery has a lot to offer, about maintaining healthy lifestyle changes in particular, but there’s still a lot to learn.
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.