Placebo Use Today
Physicians regularly prescribe pharmaceuticals without knowing exactly how they work. There is not enough time to read up on the literature and for most drugs only the major affected bio-molecular pathways are understood. In any case, a detailed mechanistic understanding of each drug is simply not necessary for clinical practice. Doctors can trust that approved drugs are safe within limitations and work for large groups of patients with the same diagnosis.
At the same time, there is no guarantee that a specific drug will work for an individual patient, even when the given diagnosis is correct and the selected drug’s indication matches the diagnosis. Initial trust and continuing observation are necessary to ensure effective care. Frankly, the uncertainty and the need for an observational approach to treat one patient with a pharmaceutical drug are not much different from how one would administer a placebo.
In fact, it happens frequently that doctors use prescription drugs as placebos.
Unwittingly or not, it is not rare that drugs get prescribed in doses that are ineffective or for diagnoses the drug was not approved for. In these cases prescription drugs are in fact frequently used as 2.0 placebo.
The good news is that patients still benefit from the drug’s placebo effect. The not so good news: side-effects from the drug’s active ingredient still apply.
A Language to Talk about Placebos
We need a common language to talk about placebos. There are different types of placebos, yet we usually only use the same term to catch them all. This can cause confusion and misunderstanding. In this chapter I am proposing a simple system that I set up to classify placebos. I’ll then use this classification to describe the most common examples of placebos today.
P – Pure Placebo
A pure placebo contains no biochemically active ingredient. Historically sugar has often been used as a filler for placebos. However, sugar is somewhat of an active ingredient. It can affect a person’s energy level and can cause problems for people with diabetes. When preparing a pure placebo it is better to use fillers that are inert. Such fillers contain no active ingredient and pass through the body without any biochemical interaction. Pure placebos are 100% free of active ingredients.
O – Open Placebo
Open placebos, also called honest placebos, are a new concept that was explored only recently in placebo studies. A person who takes an open placebo knows it is a placebo. There is no deceit involved. An open placebo is given in a situation where all participants, including the patient, know that a placebo is used. For example, in the open placebo studies described here, the patients would receive a pill container labeled “Placebo”.
B – Branded Placebo
Today, brands play a tremendous role. They convey meaning that reaches the subconscious. Brands create trust and confidence. It makes sense and studies confirmed this, that branded placebos solicit a stronger response than mere sugar pills. Branded placebos harvest the marketing power of modern medicine.
Examples
The placebo terms I just proposed bring clarity into the unfolding placebo discussion. Now, here is a list of placebos that you will find in real life. Some of these placebos may come as a surprise or appear weird, at first glance. Yet looking at the medical world form a placebo perspective can be helpful and can deepen our understanding of how medicine works.
| Placebo Examples | Pure | Open | Branded |
| Sugar Pill | + | ‒ | ‒ |
| Drug Off-Label | ‒ | ‒ | + |
| Drug On-Label | ‒ | + | + |
| 3rd Gen Placebo | + | + | + |
p[‒] o[‒] b[‒]: Ancient remedies
Many historical pharmacological compounds were placebo-like. There are not many traditional remedies that contain active ingredients that benefit the patient. At the same time ancient remedies usually were not pure placebos either. They often contained ingredients that could actually harm the patient.
p[+] o[‒] b[‒]: The classical sugar pill
In the 19th century doctors would sometimes knowingly give generic sugar pills – just to “please the patient”. The deceitful use of sugar pills became increasingly controversial in the US, mainly for ethical reasons. Its use had very much ended by about 1950.
p[‒] o[‒] b[+]: Drugs used off-label
This may come as a surprise, but regular drugs are sometimes prescribed as placebo. If we apply today’s gold standard of evidence-based medicine, then a drug used off-label is in fact administered only as a placebo. Patients usually do not know when a drug is given for some other purpose than what the FDA approved it for. Doctors are sometimes aware of their off-label use but often are not. This is problematic. Drugs used as placebo are not pure placebo and still contain active ingredients that can cause harmful side effects, or can reduce the therapeutic benefit of a drug. E.g., bacterial antibiotics given for viral infections.
p[‒] o[+] b[+]: Drugs used on-label
Most drugs when used as approved deliver a combination of biochemical and placebo effect. Patient and doctor usually know that the patient benefits from the combination of both effects. In some special cases, e.g., some antidepressants, the placebo effect can make up 80% of the overall treatment effect. Instead of thinking about such drugs as ‘also having also a placebo effect’, would it not rather make sense to describe these as “biochemically enhanced placebos”?
p[+] o[‒] b[+]: Placebos in FDA trials
These placebos are pure, but they are not open. Patient and, if it is a double blind study, also the doctor do not know if the patient gets a placebo or the drug. These placebos are branded; the patient usually knows that a powerful pharmaceutical brand is sponsoring the study. The patient benefits from the brand’s placebo effect. Even when the patient does not know which specific company is the sponsor of a trial, I suggest there is something like a “mega” brand that comprises all the leading pharmaceutical companies.
By design, these placebos are not available for regular care. It would be problematic if a placebo pill looked exactly like the active drug with patient and doctor not being able to distinguish the two. The ethical use of these often custom made Generation 2.0 placebos is limited to large clinical trials which are reviewed by the FDA for drug approval.
p[+] o[+] b[+]: Pure, open, branded placebo
Generation 3.0 placebos are pure and are taken in an honest way. Their effect is enhanced by strong product and brand design. I introduced Zeebo in 2014 to lead and shape 3rd generation placebos. Zeebo is an integrated solution that consists of Zeebo pills, a Zeebo pill-taking experience, and the Zeebo tracking app.