"We not only know placebos work," Dr. Harriet Hall explains in a fascinating, well-researched article inSkeptic, "we know there is a hierarchy of effectiveness":
* Placebo surgery works better than placebo injections
* Placebo injections work better than placebo pills
* Sham acupuncture treatment works better than a placebo pill
* Capsules work better than tablets
* Big pills work better than small
* The more doses a day, the better
* The more expensive, the better
* The color of the pill makes a difference
* Telling the patient, "This will relieve your pain" works better than saying "This might help.
To help convey the power of persuasion that doctors routinely wield, Dr. Hall's article opens with a treatment anecdote that gives a flavor of the article to come:
"Jane D. was a regular visitor to our ER," she recalls, "usually showing up late at night demanding an injection of the narcotic Demerol, the only thing that worked for her severe headaches. One night the staff psychiatrist had the nurse give her an injection of saline instead. It worked! He told Jane she had responded to a placebo, discussed the implications, and thought he'd helped her understand that her problem was psychological. But as he was leaving the room, Jane asked, "Can I get that new medicine again next time instead of the Demerol? It really worked great!"
In short, when we think something will work, its chances of doing so increase dramatically. Dr. Hall then refines that idea by giving it a sharper explanation: "What’s effective is not the placebo," meaning the benefit patients derive from a "dummy" pill, "but the meaning of the treatment." She hypothesizes that the power of the effect depends on four variables: patient expectancy; motivation (the desire to improve one's health); a certain amount of conditioning, including from advertising; and endogenous opiates, or pain-relieving chemicals produced in the brain, which copy the effect of pain-relievers such as opiates.
To that end, it isn't so surprising to hear her claim: "A substantial percentage of the effects from antidepressants may be placebo effects." Her assertion jibes with one that PT blogger Dr. Philip Newton made on this site last December: "In some controversial cases, such as selective serotonin reuptake inhibitor (SSRI) anti-depressants," he wrote, "placebo effects are thought to account for a major proportion of the positive effects of a drug."
Researchers have of course long-known and long-studied the effect of placebos, and just as obviously try to minimize the effect by controlling for it. In "Listening to Prozac but Hearing Placebo," however, a significant meta-analysis of SSRI antidepressants given to 2,318 patients with depression, Drs. Irving Kirsch and Guy Sapirstein found in 1998 that "the placebo response is a predictor of the drug response," which is rather telling, and a relation they chart quite dramatically on the following graph:
Not only that, but "the placebo response was constant across different types of medication (75%), and the correlation between placebo effect and drug effect was .90." As they put it, "These data indicate that virtually all of the variation in drug effect size was due to the placebo characteristics of the studies," which calculated placebo as the single largest factor, accounting for 50.97% of SSRI efficacy.
"Our results are in agreement with those of other meta-analyses," Kirsch and Sapirstein explained, "revealing a substantial placebo effect in antidepressant medication." "They also indicate that the placebo component of the response to medication is considerably greater than the pharmacological effect."
Kirsch and Sapirstein's study never got the airtime it deserved. A serious, well-executed meta-analysis, it was quickly drowned out by a litany of other studies that assessed the efficacy of antidepressants in comparative terms with each other, rather than as a base-level investigation of efficacy, with each drug studied relative to placebo alone. The shift in emphasis played a big role in tilting interest more toward comparative pharmacology, shunting the effect of placebos aside.
Still, Dr. Hall's striking article hopefully will return our attention to the exciting opportunities and real quandaries (medical and ethical) that the placebo effect poses, in so far as it can have a documented, substantial, and lasting impact on patients without costs or side effects. Hence the pun in my title: placebos do work—which is to say, they have effects that are part of the treatment process and should not be discounted as such.
The placebo indicates that the mind and its sometimes unconscious effects are incredibly powerful instruments in treatment, and that we're getting but half the story in focusing so relentlessly on biology and genes, to the expense of so much else.
Granted, offering placebo alone to patients (something I'm not advocating) would raise charges of quackery and suspicions that the doctor or psychiatrist is inherently against medication, a position viewed with great skepticism today. To put that another way, patients so often expect medication that if the doctor or psychiatrist doesn't prescribe any the patient can view that outcome (and physician) negatively, as minimizing their problem and even as hinting that they've wasted time.
With that level of expectancy, however, the placebo effect is doubtless ramped up even more, accounting for still-greater pharmaceutical effects, something that's worth taking into consideration, not least because it adds a benefit or a wrinkle—depending on perspective—to the treatment options available.
I am suggesting that we pay a lot more attention to how those forms of persuasion influence medical and psychiatric practice across the board.
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Social entrepreneur Daniel Jacobs raised US$50,000 to develop a “placebo” iPhone app that he says will help people make positive changes in their lives for health, joy and love.
No deception is involved. And the user will get to choose their type of placebo, such as (an image of) a pill, a magic wand, or a communion wafer.
But how much deception is involved in more conventional forms of placebo used in medical practice?
The placebo effect is caused by an expectation (people taking a placebo may experience something that they expect to happen, such as pain relief) or through classical conditioning, or both.
Classical conditioning is based on the idea that we form an association between a stimulus and a response. In Ivan Pavlov’s famous experiment, dogs were conditioned to salivate when a bell was rung because they had been taught to associate the bell with food.
This kind of conditioning or expectation leads to biochemical reactions in the brain, so placebos involve the same mechanisms and biochemical pathways as drugs, such as activating different neurotransmitters.
Studies show that placebos can alleviate symptoms of illnesses that involve pain, fatigue, nausea, and anxiety and functional disorders in the digestive, pulmonary and urinary systems, among other illnesses.
Many medical doctors use placebos regularly. A UK survey of primary care practitioners published earlier this year, for instance, found that three out of four use placebos at least once a week.
In particular, the use of impure placebos appears to be common. Impure placebos involve substances with pharmacological effect but not on the condition being treated, such as antibiotics for viral infections or vitamins.
Using deception is often considered necessary for a placebo to be effective. Indeed, the use of placebos in clinical practice usually involves deception. But research shows that placebos can be used without deception and still work.
Using deception for the placebo effect violates the ethical principles of respect for patient autonomy and informed consent. It can also undermine trust and damage the patient-physician relationship.
There are arguments both for and against the deceptive use of placebos in peer-reviewed medical literature as well as advice from professional organisations.
An argument for placebo with deception
One of the arguments for the deceptive use of placebos is that, in some situations, they are the best available treatment. In these instances, the principle of beneficence takes priority over patient autonomy, and deception is justified when it serves the patient’s welfare.
From this viewpoint, paternalism is justified.
Medical ethicist Daniel Sokol suggests such deception is justified when:
the reasons include the prevention of great physical or psychological harm (including death), the exercise of kindness or compassion, the emotional or cognitive incapacity of the patient, and the reliable belief that the patient wishes to be deceived.
To help practitioners decide when deception is appropriate, Sokol has published a deception flow chart in the British Medical Journal. He restricts the use of deception to rare occasions when “benignly deceiving patients can be morally acceptable”.
Arguments against placebo with deception
Medical practitioners use placebos sometimes to calm people when they can’t make a firm diagnosis but the patient expects a tangible treatment. In these situations, the American Medical Association cautions against the use of placebo.
placebo must not be given merely to mollify a difficult patient, because doing so serves the convenience of the physician more than it promotes the patient’s welfare.
Another reason against the use of placebos is that it amounts to disease mongering where healthy people are seen as requiring treatment and thus converted into patients.
Impure placebos can be unsafe; antibiotics, sedatives and analgesics can cause serious adverse reactions. And although the risk of adverse reactions might be low, the use of impure placebos without informed consent is problematic.
The unnecessary prescription of antibiotics also carries the risk of leading to antibiotic resistance, affecting not just the person who takes the drugs, but a much broader group of seriously ill people.
Even pure placebos can be unsafe; the sugar in sugar pills is often lactose, for instance, and some people are intolerant to it.
The guidance of medical associations
Some medical associations provide advice on the ethical use of placebos, such as the advice of the American Medical Association mentioned above. It generally guides its members against the use of placebos.
But others, such the Australian Medical Association, are quiet on the topic.
The German medical association, the Bundesärztekammer, advises that placebo treatments outside of clinical trials are ethically justified:
if there is no current proven (drug) intervention for that particular medical condition;
for minor conditions in circumstances where the patient expresses a wish for treatment; and
if it seems likely that a placebo treatment will be successful.
The chairman of the British Medical Association’s Ethics Committee expressed disappointment on learning of the extensive use of placebos by British GPs. He is quoted in a British newspaper as saying, “[P]rescribing something that you know is of no value is not ethical.”
How do patients perceive placebo use?
A recent survey from the United States confirmed what previous surveys (for example, from Switzerland and Hungary) discovered: most people found the use of placebo acceptable and valued honesty and transparency with such treatment.
Medical practitioners may be underestimating the openness of their patients toward the use of placebos.
The clinical use of placebos appears to be fairly well accepted and established by medical practitioners, given the extent of placebo use reported in several surveys. A systematic review of empirical studies found that between 41% and 99% of physicians and nurses had used pure or impure placebos, or both.
But without consensus on ethical use and without international guidelines, the use of placebos that involve deception continues to be an ethical conundrum.
Perhaps we can take guidance from the surveys and the placebo app. If the app proves to be effective and popular with users, it would confirm the open attitudes found by the surveys.
Medical practitioners should feel encouraged to explore their patients’ views on placebo treatments as part of clinical decision making, and be open and transparent about their use of placebo treatments.