Category Archives: health

An early warning system for health threats: the invaluable work of ProMED

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ProMED Mail is one of the most important information resources on the net, and most of us have never heard of it. It’s an email list which describes itself as a “global electronic reporting system for outbreaks of infectious diseases and acute exposures to toxins that affect human health, including those in animals and in plants grown for food or animal feed”.

Unlike the official clearinghouses run by WHO and CDC, ProMED is, in its own words, “open to all sources” and its reports are freely available to us all. ProMED was first to raise concern about the aggressive respiratory disease spreading in China in 2003, which became known as SARS. Before the Chinese authorities had permitted their officials to report the disease to WHO, Catherine Strommen, an elementary school teacher in Fremont, California, spotted a post in an international teachers’ chat room from a concerned teacher in China describing “an illness that started like a cold, but killed its victims in days”.

Alarmed, Strommen emailed an old neighbor and friend, Stephen Cunnion, M.D., a retired Navy physician and epidemiologist who now lived in Maryland. A practical, no-nonsense man, Cunnion started searching the web. With no success, he tried a new tack—sending an email to ProMED-mail, a global electronic reporting system for outbreaks of emerging infections and toxins. After quoting Strommen’s missive, he asked: “Does anyone know anything about this problem?”

The tiny ProMED staff conducted its own web search. It, too, came up empty-handed. On February 10, it sent out to tens of thousands of subscribers a posting headed: “PNEUMONIA – CHINA (GUANGDONG): RFI,” or Request for Information.

Thus did the world first learn of SARS, the new and deadly infection that would kill 774 people and infect 8,000 in 27 countries.

From an article by Madeline Drexler in The Journal of Life Sciences.

H1N1 Reports (Swine-avian-human Influenza A)

To keep up on H1N1 flu [I agree with the pig farmers, “swine flu” sounds like your big risk is getting it from pigs and pork, not human sneezes and handshakes] check the ProMED main page. While all the media is now frothing over with “news” about this disease, some of it sounds as reliable as alien abduction accounts. ProMED is timely and scientifically accurate but understandable by non-biologists. It includes valuable, and interesting, commentary on reports and questions: “this has been reported, but here’s what we don’t know, or here are local factors that must be considered in evaluating it”.

What ProMED does

ProMED is a program of the International Society for Infectious Diseases which began in 1994. It does not simply print whatever comes in—this is an extremely well-moderated list. A group of specialists checks and filters the reports, seeks more information from local sources and other experts, and provides judicious commentary. This group also “scans newspapers, the internet, health department and government alerts, and other information sources for inklings that an infectious disease, perhaps not yet reported widely, is threatening animal, plant and/or human health.”

I think I first signed up to receive the digests back when “mad cow disease” was emerging, and have since used ProMED to follow diseases such as anthrax and Ebola.
A topic of interest to me recently concerns outbreaks of measles and mumps in Western nations due to falling rates of vaccination. And as a former zookeeper I keep up on diseases of wildlife and zoo animals, including the fungal disease threatening whole populations of wild bats in the Eastern US. ProMED also covers plant diseases (mostly of crops).

All of this, infectious diseases of humans, wildlife, and crops, is of greatly increased urgency because climate change, global transport, and destruction of wild areas all lead to the spread of familiar diseases to new locales and the emergence of “new” diseases previously only found in remote wild areas. With regard to contaminants and toxins, governments are unable to deal with this effectively due to the political power of corporations and lack f oversight in producing countries. ProMED can’t make your food and furniture non-toxic, but it can sound alarms that might otherwise be silenced.References to a topic’s prior appearances on the list are attached to current reports, and archives are easy to access. Editions in French, Portuguese, Russian and Spanish are now available.

“Each posting is limited to 25 KB bandwidth—to ensure that it slips through an old-fashioned dial-up modem in the most remote areas of the world (where new infectious threats tend to smolder). ‘We use technology that was state-of-the-art in 1994. We use email—plain-text email at that. We don’t use fancy fonts,’ Madoff says. ‘The power of the Internet is its ubiquity and speed; it’s not necessarily in all the neat things you can do.’ [from Drexler’s article cited above]

You can subscribe here.

Toxins and contaminants

ProMED also collects, evaluates, and disseminates reports of health problems related to toxins and contamination of food and medicines. These can be quite unusual. For example, the case of the toxic leather sofas in Britain:

toxicsofaleg.jpg

Photo: Effect on leg of reaction to toxic chemical contained in sofas. From BBC.

A judge [in the UK] is expected to order several retailers to pay millions of
pounds to people who suffered burns and rashes from faulty leather
sofas….

More than 1600 people claim to have been affected by the problem. Tens
of thousands more people could have burns not yet traced to sofas.
The High Street stores, along with 11 others, may have to pay more
than 10 million pounds [USD 14.3 million] in compensation and legal
costs, the shoppers’ lawyers say. They claim that makes it “the
largest group compensation claim ever seen in British Courts.”

The sofas, which were manufactured in China, were packed with sachets
of an anti-mould chemical called dimethyl fumarate to stop them from
going moldy during storage in humid conditions.

Commonly known as DMF, the toxic, fine white powder has been used by
some manufacturers to protect leather goods like furniture and shoes
from mold. Even very small amounts can be harmful.

One sofa customer, who is well aware of the health problems caused by
her purchase, is a customer who bought a leather sofa suite from
Argos in April 2007. Almost a year later, she started to notice a
rash developing on her arms and legs. After a few weeks, her skin
started flaking off. She says the irritation was so bad, she was off
work for 2 months. This customer was seen by more than a dozen
doctors, who couldn’t work out what was causing the rash.

She said: “It was very, very painful; I couldn’t sleep at night; I
couldn’t walk about; I couldn’t drive; every time I did walk about,
the skin would fall off, and I would leave a trail of it, therefore,
I couldn’t go to work.”

Reliable histories of outbreaks/events

ProMED doesn’t just present breaking news and requests for additional reports; it frequently publishes very useful summaries of what’s been learned, and what action governmental agencies have taken. For example, “Melamine contaminated food products – Worldwide ex China” and “Prion disease Update 2009 (01)” (Mad Cow Disease and its human infectious disease, the fatal “variant Creutzfeldt-Jakob disease”.

Supporting ProMED

Believe it or not, ProMED is supported by individuals, with not a penny of funding from any government. That means they are independent (remember the movie Jaws, where the city council wants to suppress news of the shark attacks?) and fast to react. They sift a lot of news from all sorts of sources, put out calls for more information, and disseminate news in a responsible way.

If the work of this group seems like something you’d like to support, here’s your chance. They’re having a brief Spring fundraising campaign. To quote their email,

Your gift funds quick information every day – The economical, low-tech computer programs we use enable us to speed ProMED to your mailboxes, to post it online where anyone can find it, , and to provide the administrative services (accounting, office space, cell phone connections, etc.) required to support a small, agile worldwide enterprise.

ProMED-mail reaches over 50,000 public health officials, students, journalists, agricultural specialists, infectious disease professionals and others around the globe. Because it is free, subscribers in more than 187 countries have an equal opportunity to know when a disease outbreak occurs — and can spring into action when necessary to prevent or minimize its spread.

If the Spring campaign is past, here’s the main donations page.

Bad Science: Housework helps combat anxiety and depression

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I’m a subscriber to New Scientist, the British weekly magazine of science news for the rest of us. I subscribed to Science for a while too, because it publishes researchers’ actual articles, but decided I’d rather have more numerous reports with less math. New Scientist contains short reports and a few longer articles as well as interviews, and a great feature at the end where people write in requesting explanations for odd observations (very British, I think, in the tradition of the journal Notes and Queries (1849 – present), or letters to the London Times from country parsons reporting the first sighting of a bird).

Anyway, though I still find NS interesting and valuable, I’ve begun to feel they are sometimes sacrificing science for snappy headlines. Here’s an example that is from a while ago, but quite illustrative.

Housework helps combat anxiety and depression

FEELING down? You might be able to dust away your distress. Just 20 minutes a week with the vacuum cleaner or mop is enough to help banish those blues, and sport works even better.
That’s the message from Mark Hamer and his colleagues at University College London, who wanted to find out what benefits arise from different types of physical activity. They examined data from questionnaires filled in by almost 20,000 Scottish people as part of the Scottish Health Surveys, carried out every few years. Some 3200 respondents reported suffering from anxiety or depression, but those who regularly wielded the mop or the tennis racket were least likely to suffer, the researchers report (British Journal of Sports Medicine, DOI: 10.1136/bjsm.2008.046243).

One 20-minute session of housework or walking reduced the risk of depression by up to 20 per cent. A sporting session worked better, reducing risk by a third or more. Failing housework or sport, says Hamer, try to find something physical to do. “Something – even for just 20 minutes a week – is better than nothing.”

––From issue 2652 of New Scientist magazine, 19 April 2008, page 4-5. Abstract of original available free, entire article requires fee to BJSM.

Why we shouldn’t believe this

In New Scientist’s brief bit, there’s absolutely no evidence for a causal relationship between exercising and being less depressed. It’s an example of the frequent, but quite false, assumption that because two things are associated, one causes the other. Other relationships are quite possible. Does physical activity really reduce depression and anxiety, or are the people who actually do housework or sports simply the ones who have less severe symptoms to start with? Or is there some other connexion altogether? Nothing in the New Scientist, or the article abstract, addresses that question. But it makes an eye-catching headline, to say that housework cures depression.

To investigate the question scientifically, it is necessary to take a large number of depressed people and randomly assign them to one of three groups: an exercise group, a control group given some other task like filling in a weekly questionnaire or reading about depression, and a third group who don’t get any new activity or other attention from the researchers. (Ideally those doing the testing and analysis don’t know which group is which.) Then, at the beginning and end of the study, measure psychological state using some accepted reliable tests and see what changes. Finally, use statistical analysis to see if the changes are significant or might be due to chance. [Even after that, other factors may make the apparent conclusions false: maybe the exercise was not enough to have an effect, or during the study the country went to war and everybody stayed depressed, or the social aspects of being in an exercise group had more effect than the actual jumping and sweating did.]

No doubt such a study has been done, probably more than once; advising depressed people to get more exercise is a standard approach and insurance companies would love to fund the research to support it. Mark Hamer might have cited previous work in the full text of his article in the British Journal of Sports Medicine (which New Scientist should have read before writing their brief and provocative piece) but we readers have no way of knowing this.

In this particular case––the effect of exercise on individuals––researchers would have to be vigilant about the distortion of results due to participants dropping out or failing to comply with the activity levels. Even the method of choosing participants can affect reliability of results: if the depressed people are chosen from those who show up at clinics, their symptoms may be overall less severe than the symptoms of people too depressed even to go to a clinic.

A similar example: exercise and fibromyalgia

I have fibromyalgia, and some researchers have pronounced aerobic exercise to be beneficial for reducing the symptoms of this condition’s chronic pain and fatigue. Exercise is fundamentally a good thing, I agree. It distracts one from symptoms, adds an interest, may confer a feeling of control over one’s illness, strengthens muscles, promotes growth of new neurons in the brain, and can improve flexibility.

But. In moderate to severe cases of fibromyalgia, even mild exertion can cause greatly increased pain and exhaustion. Unlike the familiar “weekend athlete” reaction, the increased pain and fatigue may last a week or several weeks. This means that for some individuals the goal of walking briskly for a few blocks could take years to attain, since we are knocked back to the starting point when we overdo, or when something else in our lives like a cold or interrupted sleep aggravates our symptoms.

Some time ago I read a review article which gathered the results of a number of studies on exercise and fibromyalgia, and I noted that in some the dropout rate was high but wasn’t mentioned in interpreting the data. And then there are people, like myself, who would never enroll in an aerobic exercise program because we’ve “been there, done that” and it was painful and unproductive. If we’re not counted, and a high dropout rate is glossed over, then to whom do the results apply?

What can we say about exercise, then?

I am skeptical of the efficacy of exercise as a general one-size-fits-all prescription for fibromyalgia or depression. I would suggest the fibromyalgia studies really show that exercise appears to be helpful for those people able to endure it, but, while all patients should be encouraged to do appropriate activities as tolerated, there’s a need to be gradual and cautious. Some patients may never be able to attain exercise levels that make appreciable improvements to their symptoms, despite sincere efforts. (This doesn’t mean that exercise is without benefits to them, though. My level of physical activity doesn’t seem to help my pain, fatigue, or quality of sleep, but I’m much happier when I get out for a walk or a bit of gardening.) At an education class on fibromyalgia, I heard someone ask “How can I exercise when even walking around the house is too strenuous?” The reply was, “Can you get up and walk all the way around your kitchen table? Good. Start with that and work up.” Sensible advice, but actual improvement in symptoms may be a very long time in coming for that person.

For depressed people, exercise is unlikely to be harmful and may indeed help––I myself believe that it does––but there’s no evidence of that in the New Scientist account of Mark Hamer’s work.

I felt this was worth writing about for two reasons, one general and one particular. It’s a good example of how the media gives us accounts of scientific research without the details needed to evaluate them. And, invisible conditions like fibromyalgia and depression are different from most other health problems. They are regarded by many as non-ailments or personal weakness/malingering, so it is easy for “exercise may help” to become “quit complaining, pull up your socks and get on with it”. From there it’s a short step to “all these patients could feel better but they just won’t do the work necessary; they cling to their disease.”

And I have to admit that the example used, housework, was particularly galling to me. While there are people who can enjoy housework as a zen activity, or feel great satisfaction at making their floors and sinks shine, most of us (male or female) do not get much pleasure at all from it. Every time you do it, next day there it is again, dirty dishes, laundry piling up, dog hair floating across the floor. Truly, housework is never done. And, given that housework is still seen more as a woman’s responsibility than a man’s, and that women have a higher rate of depression than men, the “FEELING down? You might be able to dust away your distress” line seems offensively sexist and dismissive.

B Vitamins may reduce risk of macular degeneration

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I get “headline summaries” of health-related research from docguide.com, and one of last week’s headlines was “Vitamin B Combination Plus Folic Acid May Reduce Risk of Age-Related Vision Loss”. Age-related macular degeneration, or AMD, is pretty common on older people: one large study found that people in middle-age have about a 2 percent risk of getting AMD, but this risk increased to nearly 30 percent in those over age 75. There are increased-risk factors such as gender (female), race (white), smoking, obesity, and family history of the disease.

My husband’s mother has AMD, so I’ve seen its effects and I immediately went to read the article as summarized at docguide:

Taking a combination of vitamins B6 and B12 and folic acid appears to decrease the risk of age-related macular degeneration (AMD) in women, according to a study published in the February 23 issue of Archives of Internal Medicine.

William G. Christen, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts, and colleagues conducted a randomised, double-blind trial involving 5,442 women aged 40 years and older who already had heart disease or at least 3 risk factors. Of these, 5,205 did not have AMD at the beginning of the study.

In April 1998, the women were randomly assigned to take a placebo or a combination of folic acid 2.5 mg per day, vitamin B6 50 mg per day, and vitamin B12 1 mg per day. Participants continued the therapy through July 2005 and were tracked for the development of AMD through November 2005.…

Women taking the supplements had a 34% lower risk of any AMD and a 41% lower risk of visually significant AMD. “The beneficial effect of treatment began to emerge at approximately 2 years of follow-up and persisted throughout the trial,” the authors wrote.

Because the findings apply to the early stages of disease development, these supplements appear to represent the first identified way––other than not smoking––to reduce the risk of AMD in individuals at an average risk. “From a public health perspective, this is particularly important because persons with early AMD are at increased risk of developing advanced AMD, the leading cause of severe, irreversible vision loss in older Americans,” wrote the authors.

Beyond lowering homocysteine levels, potential mechanisms for the effectiveness of B vitamins and folic acid in preventing AMD include antioxidant effects and improved function of blood vessels in the eye, the authors noted. [or see the full text as published in Archives of Internal Medicine]

A reliable study?

As you can see, this study has a lot of factors that give its findings credence: a large sample size (albeit all female), random assignment of the subjects to receive vitamins or placebo, and double-blinded protocol (neither the participants nor the medical professionals working with them knew whether they were taking placebo or vitamins). And the study lasted for 7 years, allowing time both for the development of AMD, and for the vitamins’ preventive action, if any, to have an effect. Longer is generally better in epidemiological studies; given the expense of long-term studies, though, 7 years is longer than many. The authors caution that “… our findings could be due to chance and need to be confirmed in other populations” but that doesn’t indicate misgivings on their part, it’s a standard caveat of good scientists. One swallow does not make a summer, as Aristotle observed. Being able to replicate results is a fundamental part of the scientific method.

One non-random element was that the women “already had heart disease or at least 3 risk factors” for it, so they may be expected to have a higher than average incidence of circulatory problems. If that means they had a greater-than-average risk of getting AMD, which is in part a circulatory disease, then the efficacy of the vitamins may appear more dramatic than if administered to a truly random population where only some individuals have heart disease or risk factors for heart disease.

Practical implications

What about the amounts of B6, B12, and folic acid that were given? I went at once to see how much we get from the two vitamins we take each day, a multi-B and a regular multi-vitamin/mineral combination. Here’s what I found out:

BVitChart.jpg

The supplements we take at our house supply much less than the amounts used in the study.

That brings up two new questions:

Would it be safe to take such high levels? and
How much do we need to take to get the effect (assuming that the effect seen in the study is real)?

The second question is easier to answer: we don’t know. The study used high amounts, no doubt to be more certain of seeing any possible connexion. Lower levels might work, but that must await another study.

The first question has no definitive answer either. If you want my guess, it is that yes, it’s probably safe, but I’ve never even played a scientist on TV, so who am I to say? Below, I present the results of some quick research on safe levels of these vitamins, which indicate that probably the high levels are safe.

But first let’s consider some common-sense indicators. We can give some weight to where the authors work: Brigham and Women’s Hospital, Harvard Medical School; Departments of Biostatistics and Epidemiology, Harvard School of Public Health; and the National Eye Institute, Bethesda. The study participants were female health care professionals, not poor women in a remote country. While the potential conflict of interest statements at the end of the article reveal some funding from pharmaceutical companies, such companies generally don’t make much from vitamin preparations because they can’t really be patented to prevent others from selling similar products. Cynically, I conclude that respected ivy-league docs, with fellow health-care professionals as their guinea pigs, and no big money to tempt them, are probably not going to take risks by knowingly pushing the limits on safe levels of the study drugs.

Now for some numbers. The “Safe” levels in the chart above are from the Council for Responsible Nutrition, self-proclaimed to be “the leading trade association representing dietary supplement manufacturers and ingredient suppliers”. Those levels are conservative.

Two other kinds of data are known as NOAEL: No-observed-adverse-effects-level, and
LOAEL: Lowest-observed-adverse-effect level. Vitamin B6 has been tested up to levels of 200 mg/day without seeing any adverse effects, and for B12 up to 5 mg/day has been given before adverse effects were observed. These levels are well above the amounts used in the study. For folic acid, while “safe” levels have been named, there appears to be no research which has established NOAEL or LOAEL. [data from US Government sources compiled by Judy A. Driskell, Professor of Nutritional Science and Dietetics at the University of Nebraska]

Another reassuring fact is that all three of these vitamins are water-soluble, so they do not accumulate in the fatty tissues; excess is excreted in the urine.

Why are supplements necessary for these vitamins?

No one is likely to get the amounts used in the study, solely from unsupplemented foods. (See US Government charts of food nutrients, B6, B12, Folic Acid (folate).)

For example, to get 50 mg of B6, you’ll need to eat about 70 bananas or medium baked potatoes––and these are the two foods highest in that vitamin. Cold cereals are highly fortified, but it takes about 30 cups of fully fortified cereal to give you 50 mg, according to the government chart. For 2.5 mg of folic acid, get to work on putting away more than 2 pounds of cooked beef liver each day, or about 5 cups of fully fortified breakfast cereal.

If you are like me, you are wondering how people were ever healthy when all they had to eat was plain old food without any vitamin supplements, and no fortified cereal, bread, and milk. One answer, of course, is that our forebears often did suffer from vitamin deficiencies. It wasn’t just sailors on long voyages getting scurvy. And some conditions, like AMD, turn up more frequently now because more people live to the age where they occur. It is intriguing to wonder, though, what other factors may be at work when mega-levels of nutrients (far beyond those found in food) seem to protect against ailments. Perhaps the overall nutrient and micro-nutrient levels of our food are lowered by depleted soil in which crops (including animal feedstuffs) are grown, loss of nutrients during shipping and storage, and other elements of the modern commercial food business. Maybe we don’t get some as yet unknown nutrients which potentiate our use of other nutrients.

For my part, I’m going looking for supplements with higher doses of these three B vitamins. I may not end up with quite the levels used in the study, but I’ll see how close I can get within the limits of budget and willingness to swallow a bunch of pills.

Dr. House’s writers betray pain patients

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As a chronic pain patient who took methadone for years, and experienced a lot of misunderstanding from medical professionals and laypersons about addiction, I greeted the House series with hope when I first saw it. It’s smart and interesting as tv goes, and Hugh Laurie is a fine actor who has done well with the unusual role. But beyond that, I thought having a chronic pain sufferer as a main character presented a great opportunity to break the stereotype that “taking pain meds longterm = addiction”. Dr. Gregory House is certainly well-informed about medical science as opposed to drug war hysteria, and no one can deny that he’s assertive!

Dr-gregory-house.jpg

Source unknown, appears only on generic odd picture sites. Found with Google image search.
House’s halo may fade as you read on.

However, the writers and producers are promoting the familiar hackneyed clichés about addiction–––worse, these clichés are false and are no longer accepted in current medical thought. And House, of all people, is represented as knowing no better, and accepting the label of “addict”.

Two of the doctors House works with (his boss Cuddy and his friend Wilson) say frequently that House’s professional and personal abilities are being damaged by his “addiction” (his everyday use of vicodin for constant severe pain in his leg), and this conflict has played out in many episodes in the first three years. [We never seem to watch the Fox channel, so we see House in reruns on other channels; if there has been a drastic change in the last season I wouldn’t know about it. But I doubt there’s been a change in a theme which has been used so often.]

I was moved to write this by seeing again the old episode titled “Detox” (episode 11, season 1, 2005). Cuddy challenges him to go a week without vicodin to “prove he’s not an addict”. House accepts the challenge, his prize being a month of no clinic duty, and he also accepts the premises: that if he shows signs of physical withdrawal it means he is addicted. He does show these signs, though he tries to hide or deny them, and he also suffers greatly increased pain. Feeling nauseated, he’s told that it’s withdrawal, and replies “No, I’m in pain. Pain causes nausea.” Maybe so, but withdrawal from opioids does too. Finally the pain and withdrawal symptoms make it impossible for him to function as his usual professional self: hyper-smart and intuitive diagnostician. A patient is depending on him, and so are his diagnosticians-in-training, and one of the latter gives him some vicodin and tells him to take it because he’s not able to do what needs to be done.

At the end, asked what he has learned, House says (close paraphrase): I’m an addict….But I’m not going to quit…I pay my bills, I work, I function.

His friend Wilson says, You’ve changed, you’re miserable and you’re afraid to face yourself…Everything’s the leg, nothing’s the pills?

House: They let me do my job, and they take away my pain.

So, House won’t abandon the vicodin because he cannot function without pain relief, but he caves to the notion that he is an addict.

There are so many things wrong with this, and the writers of a medical show ought to know better.

Addiction Versus Dependence

The refusal to distinguish between these two terms has cursed our management of pain for fifty years or more. But in the last couple of decades medicine has, at last, officially separated the two. Here is a discussion of the terminology from an authoritative source, a Consensus Document issued jointly by The American Academy of Pain Medicine, The American Pain Society and the American Society of Addiction Medicine, called Definitions Related to the
Use of Opioids for the Treatment of Pain. [I quote at length, so it will be clear that this represents exactly and completely the sense of this document. Emphasis is added.]

BACKGROUND

Clear terminology is necessary for effective communication regarding medical issues. Scientists, clinicians, regulators and the lay public use disparate definitions of terms related to addiction. These disparities contribute to a misunderstanding of the nature of addiction and the risk of addiction, especially in situations in which opioids are used, or are being considered for use, to manage pain. Confusion regarding the treatment of pain results in unnecessary suffering, economic burdens to society, and inappropriate adverse actions against patients and professionals.

Many medications, including opioids, play important roles in the treatment of pain. Opioids, however, often have their utilization limited by concerns regarding misuse, addiction and possible diversion for non-medical uses.

Many medications used in medical practice produce dependence, and some may lead to addiction in vulnerable individuals. The latter medications appear to stimulate brain reward mechanisms; these include opioids, sedatives, stimulants, anxiolytics, some muscle relaxants, and cannabinoids.

Physical dependence, tolerance and addiction are discrete and different phenomena that are often confused. Since their clinical implications and management differ markedly, it is important that uniform definitions, based on current scientific and clinical understanding, be established in order to promote better care of patients with pain and other conditions where the use of dependence-producing drugs is appropriate, and to encourage appropriate regulatory policies and enforcement strategies.

RECOMMENDATIONS

The American Society of Addiction Medicine (ASAM), the American Academy of Pain Medicine (AAPM), and the American Pain Society (APS) recognize the following definitions and recommend their use:

ADDICTION

Addiction is a primary, chronic, neurobiologicneurobiological disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.

PHYSICAL DEPENDENCE

Physical dependence is a state of adaptation that often includes tolerance and is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist…

TOLERANCE

Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time.


DISCUSSION

Most specialists in pain medicine and addiction medicine agree that patients treated with prolonged opioid therapy usually do develop physical dependence and sometimes develop tolerance, but do not usually develop addictive disorders. However, the actual risk is not known and probably varies with genetic predisposition, among other factors. Addiction, unlike tolerance and physical dependence, is not a predictable drug effect, but represents an idiosyncratic adverse reaction in biologically and psychosocially vulnerable individuals. Most exposures to drugs that can stimulate the brain’s reward center do not produce addiction. Addiction is a primary chronic disease and exposure to drugs is only one of the etiologic factors in its development.

Addiction in the course of opioid therapy of pain can best be assessed after the pain has been brought under adequate control, though this is not always possible. Addiction is recognized by the observation of one or more of its characteristic features: impaired control, craving and compulsive use, and continued use despite negative physical, mental and/or social consequences. An individual’s behaviors that may suggest addiction sometimes are simply a reflection of unrelieved pain or other problems unrelated to addiction. Therefore, good clinical judgment must be used in determining whether the pattern of behaviors signals the presence of addiction or reflects a different issue.

Behaviors suggestive of addiction may include: inability to take medications according to an agreed upon schedule, taking multiple doses together, frequent reports of lost or stolen prescriptions, doctor shopping, isolation from family and friends and/or use of non-prescribed psychoactive drugs in addition to prescribed medications. Other behaviors which may raise concern are the use of analgesic medications for other than analgesic effects, such as sedation, an increase in energy, a decrease in anxiety, or intoxication; non-compliance with recommended non-opioid treatments or evaluations; insistence on rapid-onset formulations/routes of administration; or reports of no relief whatsoever by any non-opioid treatments.

Adverse consequences of addictive use of medications may include persistent sedation or intoxication due to overuse; increasing functional impairment and other medical complications; psychological manifestations such as irritability, apathy, anxiety or depression; or adverse legal, economic or social consequences. Common and expected side effects of the medications, such as constipation or sedation due to use of prescribed doses, are not viewed as adverse consequences in this context. It should be emphasized that no single event is diagnostic of addictive disorder. Rather, the diagnosis is made in response to a pattern of behavior that usually becomes obvious over time.

Pseudoaddiction is a term which has been used to describe patient behaviors that may occur when pain is undertreated. Patients with unrelieved pain may become focused on obtaining medications, may “clock watch,” and may otherwise seem inappropriately “drug seeking.” Even such behaviors as illicit drug use and deception can occur in the patient’s efforts to obtain relief. Pseudoaddiction can be distinguished from true addiction in that the behaviors resolve when pain is effectively treated.

Physical dependence on and tolerance to prescribed drugs do not constitute sufficient evidence of psychoactive substance use disorder or addiction. They are normal responses that often occur with the persistent use of certain medications. Physical dependence may develop with chronic use of many classes of medications. These include beta blockers, alpha-2 adrenergic agents, corticosteroids, antidepressants and other medications that are not associated with addictive disorders.

How important are definitions?

Few things are more important. We interact with the world through language. Words cause emotional reactions, compose our thoughts, represent us to others. Would you want to be introduced to a group of strangers as an “addict” or as a “pain patient”?

Let’s look at the decision to replace “addiction” with “dependence” in the fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This thick volume is the official dictionary and guide for defining mental disorders, including addictive behaviors. (Change in the DSM can contribute to profound social and legal change––as when, after a series of redefinitions, homosexuality was finally removed from the list of disorders in 1987.) An editorial in the American Journal of Psychiatry (2006) discusses this decision to use “dependence” not only to describe physical dependence, but also for addiction, as differentiated in the document quoted above.

All of the authors of this editorial are involved in the next revision of the DSM (DSM-V), and one has been part of the revisions since the 1980’s. They favor changing back to a distinction between “addiction” and “dependence,” and describe how the decision was made to merge both into “dependence”:

Those who favored the term “dependence” felt that this was a more neutral term that could easily apply to all drugs, including alcohol and nicotine. The committee members argued that the word “addiction” was a pejorative term that would add to the stigmatization of people with substance use disorders. A vote was taken at one of the last meetings of the committee, and the word “dependence” won over “addiction” by a single vote.

It was a victory for Political Correctness!

The authors criticize the widening of the term because of the negative effect on pain patients:

This [redefinition] has resulted in confusion among clinicians regarding the difference between “dependence” in a DSM sense, which is really “addiction,” and “dependence” as a normal physiological adaptation to repeated dosing of a medication. The result is that clinicians who see evidence of tolerance and withdrawal symptoms assume that this means addiction, and patients requiring additional pain medication are made to suffer. Similarly, pain patients in need of opiate medications may forgo proper treatment because of the fear of dependence, which is self-limiting by equating it with addiction.

A Canadian article (2006) describes the reluctance of many physicians to prescribe opioids for pain, and why they are reluctant:

In a recent national survey, 35% of Canadian family physicians reported that they would never prescribe opioids for moderate-to-severe chronic pain, and 37% identified addiction as a major barrier to prescribing opioids. This attitude leads to undertreatment and unnecessary suffering.

This is over one-third of Canada’s doctors who will never “prescribe opioids for moderate-to-severe chronic pain” no matter what. We cannot know how many would do the ethical thing and refer such patients to someone more experienced in treating pain, and how many just leave the patients to their own devices. If 35% would never prescribe opioids, some additional percentage would fall into the “rarely” category, which also results in undertreatment of pain.

Why does medical opinion on a fictional TV show matter?

Current medical “best practices” and principles regarding the differentiation of addiction from dependence have been slow to reach doctors and other medical professionals, let alone the public. Of course doctors should not be getting their medical information and attitudes from television, but television has a strong influence on viewers who know little about the topic presented–that’s all of us who are not medically trained. A person who believes that taking opioids results in addiction is far less likely to push for adequate pain treatment for him/herself, or family, and may even reject it if offered. If friends, relatives, and employers of pain patients share the confusion about addiction, they will exercise social pressure or threaten loss of employment. So the attitudes promoted by a popular TV show––in the US, House was the most-watched scripted program on TV during the 2007–08 television season––can have profound effects on the health care people receive.

When House stops taking the vicodin, he suffers headaches, sleeplessness, nausea, inability to concentrate, and irritability. All are symptoms of physical dependence, as in the definition paper cited above. That these same symptoms are felt by addicts is beside the point: addicts and chronic pain patients both are physically dependent, and both will suffer similar withdrawal symptoms as a result. For the pain sufferer, the symptoms of increased pain are added.

As a pain patient, I have experienced withdrawal from methadone. It is hell. It gave me much more compassion for addicts. Yet, in trying to get off methadone “cold turkey” when my doctors claimed they could not assist me, I went through seven days and nights of absolutely no sleep, intense physical and mental suffering from the withdrawal, and increased pain. There’s the pain you were medicating, and in addition the cessation of methadone makes all your bones ache, worse than any flu. And all this time the methadone was on the shelf. Untouched. Not typical addict behavior. On the eighth day with no sleep I realized that there had been no lessening of my symptoms, and that I could not endure it another 24 hours, so with distaste and reluctance I began taking the methadone again. I resolved then that I needed to find different doctors, who would help me through this, and subsequently did so with complete success. (I wrote about this in an earlier post.)

In my case the pain being treated had changed (improved, by a nerve block) during my time on opioids; the increased pain I had during withdrawal was nothing like that which House suffered from his leg. He showed great fortitude and self-control, but while dramatic it was medically pointless. The man has pain so bad he cannot function if it is not controlled; if nothing else works other than opioids, then that’s what he needs to use. Current medical thought recognizes this; the writers of the show do not.

Some of the behaviors relative to pain medication shown by House are reprehensible, such as stealing medication and forging prescriptions. This seems like classic drug addict behavior. But see the paragraph above on Pseudoaddiction, including the statement “Even such behaviors as illicit drug use and deception can occur in the patient’s efforts to obtain relief. Pseudoaddiction can be distinguished from true addiction in that the behaviors resolve when pain is effectively treated.” In fact, much of House’s often-criticized behavior has to be considered in light of the fact that even the vicodin never adequately relieves his leg pain. Irritability, mental and physical restlessness, combativeness, and harsh remarks can be the signs of unrelieved physical pain.

pain behavior chart.jpg

Chart from “Pain Assessment in Older Adults” (2006). The source references mentioned at the bottom of the chart are : 8. The management of persistent pain in older persons. American Geriatric Society (AGS) panel on persistent pain in older persons. J Am Geriatr Soc. 2002;50:S205-S224; and 9. Ferrell BA, Chodosh J. Pain management. In: Hazzard WR, Blass JP, Halter JB, et al. Principles of Geriatric Medicine and Gerontology. 5th ed. New York: McGraw-Hill Inc; 2003:303-321.

We have been told that even before his leg injury, House wasn’t a sunny sociable person. But he’s gotten worse since then, and in the show the doctors around House nearly always blame his pills––his addiction–not his pain.

Addicts and pain patients, differences and similarities

I intended to include some data here about the low actual rate of addiction (not dependency) in pain patients as a result of taking pain meds. I remember reading figures that ranged from 5% to 10%. When I did a quick search for substantiation I found that many of the research articles online are only available for a fee. The rates I did see varied so much, I must assume that the studies are not all using the same standards. Different researchers have different definitions of addiction vs. dependence; there is also an overlap of characteristics or symptoms between addicts and those who are physically dependent. If I had had no legal access to relief when I was in extremis after seven days of no methadone, I probably would have lied or stolen, if necessary to end the withdrawal. Nothing violent; I would have gotten myself somehow to the emergency room instead. But if turned away there, who knows?

This is the sort of mental and physical suffering that confronts the organism with a stark choice: solve this, or die. (If you are too debilitated to protect yourself or find food, you will die, as far as the primitive part of our brain is concerned.) Once physical dependency has been established, both addicts and pain patients are motivated to get their drugs, driven more powerfully than anyone can imagine who has not experienced it. The distinctions between addict and dependent patient must be made on criteria other than the evidence of physical dependence, since this is the same for both.

The chart below presents some criteria that seem to square with my experience and reading, although the source does not give scholarly or research citations for it.

Chart,addict-patient.jpg

[The last item under Addicts should read “The life of an addict is a continuous downward spiral.”]

Individual responses to potentially addictive drugs vary. Not everyone who tries heroin becomes addicted. Different responses are based on biological and psychological factors we are only beginning to glimpse: everything’s neurological in the end, I suppose, but increasingly it appears that experience (from conditions in utero to nutrition, upbringing, and exercise) can cause physical changes in the brain and nervous system, and therefore in thinking, emotion, and behavior [see note 1]. Even the physical brain, where our sense of “I” resides, is changeable throughout our lives: adapting, adding complexity, growing (or shrinking) based on what happens to us. The activity of our genes themselves can be enhanced, reduced, suppressed entirely, depending on outside conditions from before birth to the day we die.

How should society regard people with chronic pain?

When a starving person steals bread, we do not say that he should have simply endured his hunger, or that he is “addicted” to food. Believe me, the situation of a person in great pain, or even moderate chronic pain, is also desperate and unbearable, and the organism will get relief.

The compassionate and socially responsible action is to meet these needs in an appropriate way. Can we assist this starving person in earning money so as to feed himself or herself? If not, most of us agree that the helpless, the elderly, the people so injured by life as to be unemployable, should receive aid rather than be allowed to starve or freeze to death. The pain patient deserves the same action: the question to be asked is: How can the pain best be alleviated? There may be surgical options, transfer to a different job, physical therapy, use of TENS units and the like, as appropriate. Meditation, mild exercise, and cognitive training may offer some relief too. But the response to pain must not be limited to only non-drug approaches.

The patient is the final judge of what works, and how much pain is too much, and the patient should not be silenced with threats and accusations of addiction.

A question that needs to be asked about drug addiction is Why? Why do so many of our fellow citizens seek out heroin, cocaine, methamphetamine, illegal prescription drugs, too much alcohol? What is their pain? Not physical, perhaps, but certainly psychological or spiritual: despair, lack of meaning in life, lack of true positive connexion to other human beings and to the natural world. Until we approach drug addiction in this way we will never understand how to reduce its occurrence. Neither after-the-fact tactics (punishment, ostracism, rehab), nor prevention (education and interdiction) have worked very well. But asking Why? about addiction would reveal aspects of our society that are senseless and cruel to many, but pleasant and profitable for a few. Danger, ssssshh!

We have been so cowed and brainwashed by the continually failing War on Drugs and our native streak of puritanism that we even permit medical professionals to deny adequate pain relief to terminal cancer patients. Is it really because they “might get addicted” in the weeks before they die? Or is it the imposition of society’s fears and prejudices upon the most helpless among us? Clearly, we have made little progress in reducing the numbers of illegal drug users over the past forty years––but law-abiding people who go to doctors, they can be denied and controlled.

And so, apparently, can Dr. Gregory House, who is pitched to us as the independent thinker extraordinaire, smart and brave, ready to track truth to its lair and drag it out into the daylight. I wish his writers would let him do exactly that on the issue of pain and addiction.

1. Further reading on the “plasticity” of the brain (an unsystematic quick gathering)

  • Scientists map maturation of the human brain (2003), a short overview
  • Brain changes significantly after age 18 (2006), “The brain of an 18-year-old college freshman is still far from resembling the brain of someone in their mid-twenties. When do we reach adulthood? It might be much later than we traditionally think.”
  • Research finding persistent physical and functional changes in human brains caused by smoking, chemotherapy,
  • Empirical research on structural brain changes affecting social cognitive development after childhood (2007);
  • Various environmental factors can cause “epigenetic changes…reversible heritable changes in the functioning of a gene can occur without any alterations to the DNA sequence. These changes may be induced spontaneously, in response to environmental factors…” and be associated with development of schizophrenia and other psychiatric disorders or the quality of an individual’s performance as a parent
  • Childhood lead exposure can predict criminality(2008), even after controlling for factors such as socioeconomic status of the family; “Lead can interfere with the brain by impairing synapse formation and disrupting neurotransmitters, such as dopamine and serotonin. It also appears to permanently alter brain structure.”