Any medication’s therapeutic success depends on the interaction between its specific biochemical effects and nonspecific factors.1 Thus, clinical trial designers may view the placebo effect as undesirable, but it can be a valuable response that improves treatment outcomes in clinical 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 3 other powerful, nonspecific elements of successful pharmacotherapy.
The placebo effect
The placebo effect is any effect attributable to a pill or potion that does not originate from its specific pharmacologic properties.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, whereas in fact it can last a long time.4
In clinical 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 him or her, too.
Too often, doctors feel pessimistic about a medication’s potential therapeutic result and communicate this 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 doctor’s words and lives out this negative expectation.
Table 1
Correcting misconceptions about the placebo effect
Misconception | What the evidence shows |
---|---|
Placebo effects are short-lived | The placebo effect has been documented to last for a long time |
Only complaints that are psychologically originated respond to placebo | Changes after placebo have been documented for most symptoms, including those originating from somatic diseases |
Placebo responders are distinctly different from nonresponders | There is no difference between placebo responders and nonresponders |
The placebo effect is only about one-third of the total therapeutic effect | The placebo effect can be up to 100% of the total therapeutic effect |
Only about one-third of the population responds to placebo | The placebo response is context-dependent and may include >90% of the patient population |
Source: Reference 4 |
Clinical strategies to enhance the placebo effect
| |
Source: Reference 5 |
CASE REPORT: Predicting positive results
Mr. B, age 42, has a history of recurrent depression associated with severe insomnia, poor appetite, significant weight loss, and psychosocial withdrawal with feelings of hopelessness. After I take a detailed history and do a mental status examination, I suggest that he be treated with cognitive-behavioral therapy (CBT) and mirtazapine.
Even though studies of antidepressants rarely show mood improvements within the first 7 days, it is not unusual to hear patients report feeling less depressed within days after they start a new antidepressant. Although the drug’s specific chemical effects on the brain may not be sufficient to explain this phenomenon, the explanation probably lies in nonspecific effects—such as the patient expecting that this medication will make him 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 to benefit their patients.
Conditioned responses
Many biological responses can be associated with visual, auditory, tactile, olfactory, or gustatory stimuli. Nonconditioned physiologic responses paired with conditioned stimuli induce the same biological effects of 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.
CASE REPORT: A soothing drink
Ms. L, a 22-year-old college student, suffers from obsessive-compulsive disorder associated with anxiety and depression. She arrives at the appointment hurried and worried that she might be late. She is short of breath and looks stressed. The nurse offers Ms. L a cup of tea or water. She chooses a glass of water and is asked to bring it into her session.