Clinical Review

Words to the wise: 4 secrets of successful pharmacotherapy

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Put these all to good use: the placebo effect, conditioned responses, the power of suggestion, and participatory pharmacotherapy



The author reports no financial relationships relevant to this article.

The therapeutic success of any medication depends on the interaction between its specific biochemical effects and nonspecific factors.1 Therefore, clinical trial designers may view the placebo effect as undesirable, but it can be a valuable response that improves outcomes in medical practice. As Freud stated: “Expectation colored by hope and faith is an effective force with which we have to reckon…in all our attempts at treatment and cure.”2

This article describes how experienced clinicians make use of the placebo effect and three other powerful, nonspecific elements of successful pharmacotherapy.

The placebo effect

Any effect attributable to a pill or potion that does not originate from its specific pharmaceutical properties is known as the placebo effect.3 Its clinical value has been trivialized, in part because of misconceptions (TABLE 1). For example, the placebo effect is commonly believed to be short-lived; in fact, it can last a long time.4

In practice, our goal is to enhance the placebo effect to maximize a desirable therapeutic outcome (TABLE 2).5 Therefore, before I prescribe a medication, I tell my patient that I have selected a particular medication because I have had good results with it in many other patients and I believe it will work well for her, too.

Too often, physicians feel pessimistic about a medication’s potential therapeutic result, and communicate that pessimism. What the patient hears is: “There’s nothing else I can do for you; why not try this medication, even though I don’t believe it’s going to work.” This may create a negative placebo effect6—termed the “nocebo” effect— which gives the patient a negative expectation about the treatment’s outcome. The patient internalizes the physician’s statement and belief, and lives out this negative expectation.


Correcting misconceptions about the placebo effect4

MisconceptionWhat the evidence shows
Placebo effects are short-livedThe placebo effect has been documented to last for a long time
Only complaints of psychological origin respond to placeboChanges after placebo have been documented for most symptoms, including those originating from somatic disease
Placebo responders and nonresponders are distinctly differentThere is no difference between placebo responders and nonresponders
The placebo effect is only about one third of the total therapeutic effectThe placebo effect can be as much as 100% of the total therapeutic effect
Only about one third of the population responds to placeboThe placebo response is context-dependent, and may include more than 90% of the patient population

Strategies to enhance the placebo effect5

Develop a sustained therapeutic partnership with the patient
Listen effectively and verify that she feels listened to
Provide comprehensible explanations of health problems therapeutically tailored to her needs and personality style
Show empathy, care, and concern for her as a person
Enhance her sense of control and mastery over her predicament

CASE 1: Predicting positive results

Mrs. A. J. is a 38-year-old mother of two. She has symptoms of anxiety and depression, crying spells, poor appetite, and insomnia.

After taking a detailed history and examination, I recommend treatment with a combination of counseling and the antidepressant mirtazapine. I tell Mrs. A. J. that this medication has very good potential to help her recover. I also inform her that improved sleep and appetite may well be the first effects she’ll experience—even accompanied by restored hope and optimism. I then give her an appointment for the following week.

When Mrs. A. J. comes for the follow-up appointment, she reports improvement in appetite, sleep, and mood—as predicted.

Even though studies of antidepressants rarely show mood improvement within the first 7 days, it is not unusual to hear patients report feeling less depressed within days after they start a new antidepressant. The drug’s specific chemical effects on the brain may not be sufficient to explain this phenomenon; the explanation for such improvement probably lies in nonspecific effects, such as the patient expecting that this medication will make her feel better. The placebo effect can occur as soon as a patient starts a medication. Experienced clinicians understand the placebo effect’s power and harness it for their patients.

Conditioned responses

Many biologic responses can be associated with visual, auditory, tactile, olfactory, and gustatory stimuli. Nonconditioned physiologic responses paired with conditioned stimuli induce the same biologic effects as a drug. Evidence supporting this phenomenon includes successful conditioning of the immune system.7-10 Conditioned responses—as demonstrated in glycemia regulation10 and with psychopharmacology11—also can enhance the desirable results of pharmacotherapy.

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