The Placebo Effect. Homeopathy In the late 1700s a German doctor named Samuel Hahnemann invented a new form of treatment, homeopathy.

The Placebo Effect

Homeopathy

In the late 1700’s a German doctor named Samuel Hahnemann invented a new form of treatment, homeopathy.

Made up Medicine

This was about 100 years before the germ theory of disease was discovered, so we didn’t really know why people got sick or how to treat them.Treatments were just made up, and often they were worse than no treatment at all.

The Plague

The Plague

• First pandemic: caused 50% drop in the population of Europe between 550 and 700.

• Black death: China lost 50% of its population, Europe 1/3. This was between 1347 and 1351.

• Third pandemic: Killed about 12 million people in just India and China.

• From 1894 to 1901, 8,600 people died of the plague in Hong Kong, 95% of everyone infected.

Nutmeg for the Plague

Many people in the west believed that nutmeg could cure or prevent the plague.

England and Holland went to war over control of the Banda Islands, the only source for the spice.

Smoking!

“For personal disinfections nothing enjoyed such favour as tobacco; the belief in it was widespread, and even children were made to light up a reaf in pipes. Thomas Hearnes remembers one Tom Rogers telling him that when he was a scholar at Eton in the year that the great plague raged, all the boys smoked in school by order, and that he was never whipped so much in his life as he was one morning for not smoking.” A J Bell, 1700

Dead Pigeons!

Another “cure” for the plague was applying a dead pigeon to the sores it caused.

Bloodletting

A common treatment in the past was bloodletting. People thought that whatever was making you sick, must be in your blood, so draining your blood would help. But this just weakens you and opens you up to an infection.

Harmful Medicine

All medicine was made up at the time, and most of it was pretty harmful.

Other examples include trepanning (drilling into the head) and ingesting mercury (a highly toxic liquid metal).

Chiropractic

Some more recent non-scientific medicine is still practiced in the west.

This includes chiropractic, a view that holds that all diseases are caused by disorders of the spine and can be treated by spinal manipulation.

Chiropractic

Chiropractic was invented in the 1890’s by DD Palmer. He claimed he learned it from a dead healer’s spirit. It’s name comes from Chi + Rho, the Greek letters used to represent Christ, because Palmer likened it to Christ’s healing hands.

Law of Similars

So what is homeopathy? It’s first principle is that like cures like. If you have a disease with certain symptoms, like vomiting, and you know that ipecac induces vomiting, then you assume ipecac cures the disease.

In other contexts this idea is often called “sympathetic magic.”

Less is More

The second principle was that a substance is more powerful at curing a disease when you have less of it.

So you dilute your ipecac in water, and now it’s even better at curing your disease. Most contemporary homeopathic remedies are so diluted, it’s almost statistically impossible that they contain anything except water.

Succussion

The final principle is that the remedy has to be shaken in a specific way.

The bottle containing the water has to be struck ten times (not more or less) against a hard-but-not-too-hard surface. Hahnemann used a leather board filled with horse hair.

It Still Exists Today

In France, your health insurance covers homeopathic treatment.

In Britain, there are homeopathic hospitals.

People in the US spend $3 billion USD a year on homeopathy.

Why?

People think homeopathy works.

Why? It’s extremely silly.

Why?

Is it regression to the mean? Do they naturally get better after taking homeopathy, and attribute that to the medicine?

Is it confirmation bias? Do they notice the times they get better after drinking the water but not the times where they don’t?

THE PLACEBO EFFECT

Placebo

‘Placebo’ is a Latin word that means “I will please.”

In a medical context, it is used to refer to pill or treatment that a doctor knows don’t do anything.

The treatment pleases the patient, even though it does not actually treat his symptoms.

History of Placebos

Common placebos are sugar pills and saltwater injections.

Until the 20th Century, the placebo was a commonly used medical treatment. Patients wanted treatment, there was no treatment, so doctors gave them “dummy” pills and told them they would help.

Ethics of Placebos

Now it’s considered unethical to lie to patients and give them fake treatment.

In fact, if you pay a doctor for real treatment, and she gives you a placebo, you can sue the doctor and get your money back.

The Placebo in Modern Medicine

But the placebo still has a role to play in modern medicine.

If we are running an experiment to test a new drug, we can give participants in the control group placebos.

Placebo Controlled Trials

A clinical trial (experiment) where the control group gets placebos is called a placebo controlled trial.

Best Practices

Normally, we don’t use placebo controlled trials. Instead, the control group gets the best treatment there is.

This is because we don’t want to know whether a new treatment is better than a placebo, we want to know if it’s better than the treatment we already have. (Also, it’s unethical not to give patients treatment when it’s available.)

Reasons for Placebo Controls

However, when we’re testing a new treatment for a condition where there is no other treatment, or where the other treatments are ineffective for many patients, then we use placebo controls.

The Placebo Effect

But why placebo controls instead of no treatment controls? Why do we give the control group fake pills rather than no pills at all.

Because fake pills make you get better. The act of undergoing treatment– even if it is fake treatment– improves patient health.

The Placebo Effect

In fact, the truth is even stranger than that. The anthropologist Daniel Moerman looked at several placebo controlled studies of gastric ulcer medication.

A gastric ulcer is a painful sore spot in the inside of the stomach. Looking at these studies is clever, because you can count people’s ulcers.

More is Better

What Moerman found is crazy.He found that placebo controls in experiments where the placebo was four sugar pills had fewer ulcers than placebo controls in experiments where the placebo was two sugar pills.

Blackwell (1972)

Blackwell (1972) did a study where students were given one of two pills: a pink one and a blue one.

They were told that one pill was a stimulant, which made you more alert, and the other was a sedative, that made you more sleepy.

Color Matters

Both pills were actually placebos– just sugar pills.

When Blackwell measured alertness at the end of class, he found that pink pills made you more alert than blue pills.

Why is Prozac Blue?

Drug companies know about the effects of color on how you feel.

So if you buy a stimulant, it will be red, orange, or yellow, and an anti-depressant will be blue, green, or purple.

Capsules Better than Pills

One study of a sedative in 1970 of a sedative found that the same dosage of the drug was more effective in capsule form than in pill form.At the time capsules were new and they seemed more “sciencey” to people.

Injection Better than Pill

Several other studies have found that saltwater injections are better than sugar pills—

For headaches, blood pressure, and pain after an operation!

Flashy Packaging Better than Dull

Studies have also found that medicine is more effective if it comes in flashy brand-name packaging, rather than generic packaging.

Placebos work better in flashy packaging too.

Expensive Better than Cheap

If you take the same pain medication– the very same pills– and charge people more for it, the medication works better. People feel less pain when they’ve paid more.

Fake Surgery

The placebo effect isn’t just restricted to pills and injections.

Sham surgery, where the doctor pretends to operate on you but does not, has been shown to reduce knee pain!

Surgery for Angina

In the 1950’s there was a belief that you could promote artery growth (in people that needed it) by tying off a not-too-important artery in the heart and “tricking” the body into growing other arteries more.And the surgery did work, in the sense that people who underwent the surgery improved, though only a little bit.

More Fake Surgery

But was it the procedure that helped or just the fact that they were performing surgery?In 1959, there was a placebo controlled test of this idea. The controls underwent heart surgery, but the surgeons didn’t tie off any arteries.The people who underwent the real surgery got a little better, as before. But the placebo controls improved just as much!

Pacemakers

A Swedish study found that patients who had pacemakers installed to maintain a regular heart rate improved even if the pacemaker was not turned on.

Good Exercise

In another study, 84 female hotel attendants were split into two groups.

The experimental group was told that cleaning hotel rooms is “good exercise” and that it “satisfies the Surgeon General’s recommendations for an active lifestyle.” The other group was not told anything.

Good Exercise

Four weeks later, both groups were measured.

The group that was told that cleaning hotel rooms was “good exercise” had lost weight and had less body fat.

Both groups reported that they were doing the same amount of activity!

Placebo Sleep

One recent study found that people did better on mathematical and verbal tests when they were falsely told they had a good night’s sleep.

The scientists pretended to measure how well they slept (but did not) and then either lied to them saying they got good sleep or bad sleep.

Known Placebos

In 1965, a study was done on “neurotic” patients (people with anxiety, stress, irrational fears, etc.).

The patients were told that they were being given “a pill with no medicine in it at all.” And they showed improvement after taking it!

Important!

The placebo effect does not mean that all diseases are in the head or can be cured by changing our beliefs!

Important!

• Real medicine has the placebo effect too. It also has real effects on top of that effect.

• Science based medicine is the stuff that’s proven to work better than a placebo.

• For lots of things, placebos make no difference: they won’t cure your cancer or make your AIDS go away.

THE NOCEBO EFFECT

If it works, it doesn’t matter how

A common defense of “placebo medicine” (medicine that was no better than a placebo) is that it didn’t matter whether the treatment caused the improvement or our beliefs about the treatment caused the improvement—

The improvement is all that matters!

The Nocebo Effect

‘Placebo’ is Latin for “I will please,” and the placebo effect is when a treatment that doesn’t by itself cause any improvement leads to positive expectations in the patient that cause improvement.

‘Nocebo’ means “I will harm,” and the nocebo effect is when an inactive treatment causes harm, because we believe that it will.

Basic Tastes

In the early 20th Century, Western scientists thought that there were 4 basic tastes:

• Sweet: peach, strawberry, honey• Sour: lemon, grape, tamarind, kimchi• Salty: salt • Bitter: lime, chocolate, coffee, dark greens

Spicy!

Asian scientists actually recognized another taste: spicy!

Umami

In 1908 Kikunae Ikeda proposed another basic taste: umami (savory, meaty). He isolated the chemical that caused it (glutamate) and found a way to powerfully increase the flavor (MSG).

Umami: Cheese, soy sauce, tomatoes, beans, mushrooms, seaweed.

“Chinese Restaurant Syndrome”

In 1986, Dr. Robert Ho Man Kwok wrote a letter to the New England Journal of Medicine, describing the symptoms he seemed to experience after eating Northern Chinese food in America: “numbness at the back of the neck, gradually radiating to both arms and the back, general weakness and palpitation.” He speculated that MSG was the cause.

CRS and MSG

In 1987, an article was published in the prestigious journal Science blaming MSG.

Since then, a large number of Americans have come to believe that they are allergic to MSG and experience CRS.

Even in Hong Kong, I see restaurants all the time that advertise “No MSG!”

Silliness

But this is ridiculous!

1. MSG is delicious.2. Glutamate is in everything with an umami

flavor. There’s lots of it in tomatoes.3. All the science says that CRS is a nocebo

effect.

And the Science Says…

In fact, in multiple double-blind placebo-controlled trials conducted by Geha et. al. (2000), where all the participants believed they were sensitive to/ allergic to MSG, it was found that there was no difference in reaction between the MSG group (experimental) and the placebo control group. Other similar studies have had similar results.

Why?

Where did this belief come from? Well, it probably began with normal accidental correlations, confirmation bias (only noticing the times when you felt less than perfect after eating Chinese) and “goalpost shifting”: http://www.saynotomsg.com/basics_symptoms.php lists 62 different symptoms of MSG. How likely is it that you experience one by accident every time you eat Chinese?

And Racism

You also can never rule out the fact that some Americans are racially prejudiced against Chinese. They perceive the food as alien and different and thus judge it as wrong and unhealthy, not suited for “civilized” people. (I’m sure a lot of this is unconscious.)

The Point

Something is wrong with the argument “if it works, it doesn’t matter how it works” for placebos.

The same argument could be given for nocebos: “if it hurts, it doesn’t matter how it hurts: so stop using MSG!”

ACTIVE PLACEBOS AND ANTIDEPRESSANTS

Active Placebos

Sometimes placebos are pharmacologically active– they just don’t do anything anyone would want.

So, for example, atropine blocks certain nerve receptors and causes dry mouth and other symptoms.

Active Placebos

What’s the point of an active placebo? Well, they work better than regular placebos.

If I pretend to be investigating pain, and give one group of people regular placebos and the other group active placebos, the active placebo group will experience less pain, on average.

Active Placebos

The explanation for this phenomenon is something like this:

When people take the active placebos, they experience the side effects. This makes them believe that the drugs are powerful and really work, and the power of their belief then influences what they experience.

Antidepressants

Recently, it has been argued by a number of scientists that antidepressant drugs, especially SSRIs, are just active placebos.

This is pretty serious, if true. 1 in 10 Americans are on antidepressants, and they have serious side effects (insomnia, sexual dysfunction, appetite loss), can cause sever withdrawal, and are very expensive.

Meta-Analysis

A meta-analysis is a study that looks at lots of clinical trials and uses data from all of them.

Irving Kirsch, a psychologist, conducted a meta-analysis of all the drug-company sponsored antidepressant trials sent to the US Food and Drug Administration. (The FDA approves the use of drugs, when companies can show they work.)

Placebos vs. Antidepressants

Kirsch found that placebos are 82% as good as antidepressants. That means that if you take a placebo, you’ll feel about 82% better than someone who takes the real thing.And the difference is small. What’s the extra 18% benefit of the real thing? 1.8 points on the 54 point scale doctors use to measure the severity of depression.(Sleeping better: 6 points, less fidgety: 2 points)

Antidepressants as Active Placebos

That number goes to 100%, he argues, when active placebos are compared with antidepressants.

That is, active placebos cause the exact same improvement in depression symptoms as expensive, habit-forming, government approved, antidepressant drugs. It’s depressing!

BAD MEDICINE

Bad Medicine

So why do so many people turn to medicine that has no scientific basis, like homeopathy?

There are some reasons we’ve discussed before. One is the regression fallacy: they get treatment when they’re feeling worst, they “regress to the mean,” and they attribute their improvement to the treatment.

Bad Medicine

So why do so many people turn to medicine that has no scientific basis, like homeopathy?

Another reason is confirmation bias. They notice the times when they get the treatment and later feel better, but they don’t notice the times when the treatment does not work.

Bad Medicine

So why do so many people turn to medicine that has no scientific basis, like homeopathy?

But another powerful reason is that maybe those treatments do “work”– but only as placebos. We’ve seen that the placebo effect can be very strong, especially for elaborate fakes– and most bad medicine is very elaborate.

“Real” Medicine

And it’s not just “bad” medicine– the silly stuff that no one should believe in.

“Real” medicine is subject to these biases too. As I’ve suggested, even though lots and lots of people believe that antidepressants work, the evidence says they don’t. It’s only because they believe in them that they have any effect at all.

People aren’t necessarily stupid for genuinely believing in treatments that don’t work– because they do get better, from the placebo effect.

Does that mean we shouldn’t correct them? That the government should continue to allow treatments that don’t work?

Ethics of Placebos

This is an interesting question. Sometimes we don’t have treatments that work, and sometimes patients don’t respond to the treatments we have.

It’s very common for people with lower back pain to not respond to evidence-based medicine. Nothing helps them.

Acupuncture

Sometimes these patients turn to alternative, non-evidence-based treatments for pain, like acupuncture. And they get better!But we know that acupuncture is no better than a placebo (sham acupuncture).

Ethics of Placebos

Still, there are lots of reasons that we should discourage treatment that is no better than a placebo. If the treatment is:• Expensive• Harmful• Deceptive• Used instead of effective alternatives

Expensive Interventions

Osteoarthritis is a degenerative disease that can cause people severe joint pain.Knee surgery often reduces that pain, but no better than sham surgery.And knee surgery costs about HKD$77,500.

Harmful Interventions

Sometimes treatments that don’t work can harm patients, even if it otherwise helps them too.

Recall the case of antidepressants. People do get better after taking them, but antidepressants have serious side effects (sexual dysfunction, loss of appetite, insomnia).

Deceptive Treatment

All medicine that is not science-based (proven to work, and proven to work better than a placebo) is in some sense deceptive.

People who administer those treatments present them as if they work or are known to work, when that simply isn’t true. Many of them are known not to work (homeopathy, acupuncture).

Deceptive Treatment

There’s an additional harm in many “alternative” therapies in that along with treatment, they give patients a pre-scientific or anti-scientific worldview (like the law of similars, or qi meridians).

If people don’t trust science, they don’t trust our best way of knowing things.

For example, because of unscientific claims by “alternative” practitioners in the US and Britain, many parents have stopped vaccinating their children. This has led to an increase in vaccine-preventable deaths.

Environmental Harm

Treatments can also harm the environment even if they’re safe for the patient. Traditional Chinese Medicine is driving several species to extinction, like the manta ray, because of its (false) claims about medical benefits.

Opportunity Cost

Treatments that don’t work (no better than placebo) can be extremely dangerous when people use them instead of treatments that do work (much better than placebo).A recent report in Britain showed that two children had died because one needed anti-seizure drugs, and the other needed blood-clotting drugs, but they were given ineffective “alternative” medicine.