Noceboes? How Cute.

I have always been fascinated by neologisms –new words that substitute for more commonly used ones. They can be clever, rude, or just plain silly, but often their point is to get noticed –or perhaps draw attention to their inventors. There was a time –before social media, at least- when we used to applaud people like Shakespeare for turning nouns into verbs, or adjectives into more active participants. And it was a time when elders, if they forgot the word for which they were searching, would simply come up with a new one. Of course, they still do, but it is often  lost in the ebb and flow of media utterage (pardon the neologism). I have written about this before in another context, but the subject continues to intrigue me: https://musingsonretirementblog.com/2016/05/22/what-did-you-say/

This time, however, I was more interested in the clever contrast of nocebo with the word it was replacing, placebo, that was reported in an article in the CBC health news: http://www.cbc.ca/news/health/nocebo-effect-greater-expensive-drugs-1.4358664

I suspect we’re all acquainted with the placebo effect: the ability of a harmless, inactive substitute to have a beneficial effect if it is believed to be the treatment. Again, I have covered this in a previous essay: https://musingsonwomenshealth.com/2016/04/20/rethinking-placebos/

But there seems to be no end to our ability to fool ourselves, and the concept of ‘noceboes’ is yet another illustration. ‘The opposite of the placebo effect — perceived improvement when no active medicine is given — nocebo is the perception of negative side-effects from a benign “medication” in a blind trial.’

The article reports on a study published in the journal Science, which suggests that ‘Expensive medicines can seem to create worse side-effects than cheaper alternatives.’ This particular investigation ‘focused on the pain perceptions of patients who were treated with creams they believed had anti-itch properties but actually contained no active ingredients.’ And, as one could no doubt predict from the title of their publication, Nocebo effects can make you feel pain, ‘Though the scientists ensured the temperatures applied to the two creams were consistent, those who received the expensive cream rated their pain as nearly twice as intense as those who received the cheaper cream. The study suggested that patient expectations related to price can trigger brain responses resulting in higher perception of pain, said Alexandra Tinnermann, a co-author of the study and neuroscientist at University Medical Center Hamburg-Eppendorf.

‘Tinnermann’s team used a functional MRI scanner to identify areas along the spinal cord that were activated during participants’ experience of side-effects. They also pinpointed two brain regions that were more stimulated among participants who believed they received the expensive drug.’

The ethics of using placebos –tricks- is one thing, but what about those of choosing between several recognized and approved medications where the only difference is the price? On the surface, it might seem to be a saving for all concerned. If the data hold up in further studies, why prescribe new and probably higher cost medications, if they’re more likely to have side effects?

Unfortunately the very ethics that require medical practitioners to discuss the possible side effects of any medication, are also known to influence the experience. Knowledgeable patients report more side effects than those who, for whatever reasons, are blissfully unaware of what to expect. Perhaps it’s more a question of which of Pandora’s boxes the practitioner should open -a zero sum game, no matter.

I was sitting on a park bench in the shade of a tree one sunny summer day, trying to finish a book a friend had loaned to me. It wasn’t very interesting, despite her recommendations, and although I was determined to discover what she had liked about it, I found my mind looking for excuses to put it down. My ears soon found a distraction. Two little boys had abandoned their bikes on the  grass nearby and were engaging themselves in scaling the leafy tower of what I had assumed was my own special shade tree. Hidden by several bouquets of leaves fluttering gently in the afternoon breeze, I suppose they thought they were invisible in their private redoubt.

“Thought you were sick, Jay,” one of them said, as if he wondered if he was in danger of catching whatever Jay had.

“I’m on antibiotics, Jordan,” the other answered defensively.

They were silent for a few moments, although I could hear them grunting as they climbed ever higher.

“My mother doesn’t believe in them,” a voice, probably Jordan’s, said very firmly.

“Why?” was Jay’s surprised reply.

Jordan was silent for a moment, clearly trying to remember. “She says they can make you sick.” Even from my position far beneath them, I could almost feel Jordan’s italics.

“How?”

Another, grunt-filled silence as they switched branches. “She says they can make your skin go red…” He hesitated for a minute while he combed through his memory. “And give you… make you wanna throw up.”

Jay seemed to hesitate before answering. “Well, I’m not red or anything, but… uhmm, sometimes I do feel a little like throwing up, I guess. Anyway I have to go to the toilet a lot, so it’s hard to tell.”

“She says that’s what happens with them too, Jay. It’s why I just take vitamin pills.”

“My mother says those don’t usually work… People only think they do.” Jay felt a need to defend his antibiotics. “Mom says we imagine things sometimes…”

“Like what?” Jordan sounded sceptical. For a while, I could only hear the leaves rustling, so I wasn’t sure if they’d already climbed too high to hear.

“Like… Like that vitamins can keep us from getting sick.” I could hear one of them shifting somewhere above as a branch cracked. “And she says some people won’t take antibiotics because they’re afraid of, uhmm…” He hesitated, while he searched for the right word. “…the side-stuff.”

“You mean ‘side-defects’?” Jordan pronounced the words carefully, condescension fairly dripping from his words.

“Yeah. She says if they hear about the defects, they figure they’ll get them.”

“Well my mom says doctors have to tell people about them, though, Jay… It’s the law.” He added smugly.

Jay seemed to think about it for a second. “Then no wonder, eh?” he said, as if he finally understood.

“No wonder what?”

“No wonder people get ‘em,” Jay answered, triumphantly.

From the mouths of babes.

Advertisements

Rethinking Placebos

Placebo. I love the word; it comes from the Latin verb placere: to please, and in the first person future indicative –placebo– translates as ‘I will please’. Wonderful.

I’ve been thinking about it a lot lately, probably since rereading a Dec. 31/14 article in Medscape entitled ‘Should Doctors Use More Placebos?’ http://www.medscape.com/viewarticle/835197 The answer, of course, is ambiguous –no one seems to want to commit to the use of a technique favoured in the days when there were few other options; times when there were no antibiotics, no condition-specific medications –no detailed knowledge of the physiology of the body, let alone diseases. Those were times when naming the problem and being able to give a likely prognosis was an important part of Medicine. I suppose it still is. But the other, equally important component nowadays, of course, is solving the problem so named –solving, as well as hopefully curing it with specifically targeted medications or therapies.

Placebos have usually been construed as inert, essentially harmless substances with little or no known properties that might otherwise be helpful in restoring bodily health. No pharmacological effect… So why would anyone wish to use them anymore? Or do we?

In this informed era of medical ethics –and of course, social media- would it even be possible to use placebo treatment, except, maybe, in a study where a treatment is being compared to no -or likely ineffective- treatment (placebo treatment) and where the participants are unaware which substance they are receiving (so as not to bias the results) and have understood and accepted this? Not something likely to occur in the average visit to a doctor’s office for an illness.

And the ethics that need to be considered? Well, amongst others, the concept of autonomy –the right of an individual to make both their own treatment decision and an informed choice. And then, of course, there is the ethical requirement for Informed Consent. How can you give someone a treatment without telling her that you may well end up using something that is pharmacologically inert? A non-medication, as it were.

A placebo is usually a trick –you think you have been given something specifically designed to help; you take it on trust; you have faith in the doctor… If you found out that what you had been given –lied to about, in fact- was inert, wouldn’t that undermine your confidence, and especially your trust, in that doctor? Even if it worked? Or maybe especially if it worked –it would mean he thought your condition was more psychological than physiological –i.e. ‘all in your head’. Not very likely to foster a continuing relationship.

But what if the doctor told you he was going to use a placebo for your condition? Would it work if you knew? Well, here’s where it can get interesting; there is a difference between using a placebo and using the placebo effect: the approach to the patient matters as well as what is given to attack the problem. Such things as actually hearing the patient –listening to what they have to say- rather than immediately reaching for the prescription pad; being reassuring and sympathetic. Friendly. Understanding. The demeanour and hope with which any treatment is administered has been shown to effect the results –the art of Medicine.

But nowadays, we all know about this. The fact that there is some theatre to medicine, and a play of characters is not a secret –although I suspect that most of us prefer not to think about it when we ourselves have an illness. The play within the play…

It got me thinking about placebos in my specialty, though. Are there any placebos in gynaecology, for instance, and do we ever use them? We certainly use the placebo effect in obstetrics –we are constantly reassuring our patients about the never-ending and always-changing symptoms occasioned by their growing bodies. Most of them don’t need investigations or tests- nor do they need any specific medication -just an acknowledgment by the doctor that whatever the patient has noticed is not something to be worried about. It is not something malevolent, nor likely to affect the baby, but merely something that happens in pregnancy –part of the spectrum. Something to be expected. It’s a trust issue. That’s why they came to you after all.

And what about gynaecology? All medicine involves placebo effects –we’ve just discussed that- but what about placebos? Are we kidding ourselves to think that gyaecology is exempt from their use? I suppose it depends on how you define a placebo. As we’ve already seen, a placebo is classically defined as a substance that is not likely to have any measurable pharmacological effects and so is considered inert. But what about a substance that is not yet proven by scientists to have an effect –for example by well-designed studies that compare various treatments? Of course, it may simply be that no one has actually studied the substance so far; there are many complementary and alternative medicines that Western Medicine has not subjected to analysis. So their use by the doctor would not necessarily be as a therapy, but maybe as an acquiescence to a patient’s request, in the absence, perhaps, of any other recognized treatment options.

How about a substance that has some effects, and yet likely not enough, nor sufficiently consistently to be considered a mainstay treatment, but which might be sold, say, in a health food store? Some of the phytoestrogens found in materials like clover or soy have estrogenic effects, but may attach weakly or ineffectively to certain estrogen receptors -and in some organs but not others…

And then there are medications that are useful for other conditions –perhaps related, but not necessarily so- but are re-packaged for a new life. The use of ovulation inducers in infertility treatment, even when the patient is known to be ovulating –a just-in-case therapy. Or an antibiotic for a new-onset, ultrasound negative –but as yet undiagnosed- pelvic pain in a woman when she shows up in a busy emergency department. Maybe it’s an infection… Or vitamin pill use for the busy woman who doesn’t have time for a healthy diet every day. It can’t hurt and it may help… Surely these are placebos.

Or substances that have switched their roles over the years –were they inadvertent placebos that have been since promoted? Acetylsalicylic acid (ASA) was once only considered a pain reliever and was used for menstrual cramps. It seemed to help patients cope with the period but this was assumed to be only because of the pain relief. So it was a placebo for coping, a therapy for pain. Then, because it was later discovered to be an anti-prostaglandin –which is a chemical mediator of inflammation and has a direct effect on the flow through blood vessels (and hence one cause for increased bleeding and cramping with periods because of dilated blood vessels in the area)- ASA, or at least more modern analogues of antiprostaglandins such as ibuprofen, was reassigned to a new function. A new, non-placebo job, as it were. So, although it did one job at first, was it an unsuspecting placebo that actually did two jobs? Is that a temporal placebo? An interesting philosophical conundrum –but I suspect I am stretching the concept beyond any useful application.

Maybe we’re looking at the whole idea of placebos the wrong way. In our data-glutted age where information is conflated with knowledge perhaps we need a concept that defies mere illumination and transcends erudition. Something that is so embedded in the weft of context that it disappears in the very act of searching for it –an unsolvable Where’s Waldo. Sometimes our need for elucidation of every aspect of the world we live in is self-defeating. Maybe –just maybe- we don’t need to know where the geese go when they disappear through clouds that gird the mountain tops. Just that they come back every year. ..Somehow.