Nocebo Effects

Summary and Comment |
July 16, 2014

Nocebo Effects

  1. Mark V. Dahl, MD

Patients' expectations are important determinants of unwanted adverse effects, and clinicians must be strategic to foster optimal treatment outcomes.

  1. Mark V. Dahl, MD

Nocebo effects are negative effects on treatment efficacy and tolerability induced or driven by psychological factors. Like placebo effects, nocebo effects do not result from bias but are triggered by neurobiological, psychosocial, and contextual factors. In studies, nocebo effects reduced treatment effectiveness and affected adherence.

For example, patients switching from a brand name to a generic of identical medication are prone to report negative effects from the new drug. In a recent study, the 5-HT1 agonist rizatriptan was less effective when falsely labeled placebo. Nocebo effects result from public media coverage, “contagion” in social media, patient-clinician communications, and, I would think, warnings from watchdog agencies like the FDA.

Recently, a “Placebo Competence Team” proposed strategies to minimize nocebo effects. Recommendations include:

  • Optimize expectations of treatment and adverse effects.

  • Balance presentation of adverse and desired effects.

  • Use Web-based and other sources to provide evidence-based information.

  • Improve design, layout, and content of drug leaflets.

  • After informing patients that a drug dose will be modified if necessary, hide taper or withdrawal so patients are unaware of pace and timing.

  • Use “pretreatments” with low adverse effect rates.

  • Use observational learning (e.g., video clips) to show patients coping well with adverse effects.

  • Adapt an authentic and empathetic communication style.

  • Provide adequate information regarding disease, diagnosis, treatments, and adverse effects.

  • Ask proactive check-back questions (ask patients to summarize information).

  • Assess and address patient concerns, anxieties, and expectations.


I'm not sure how useful, practical, and effective these recommendations might be. I do think that patients suffer lower quality of life when they are afraid of their treatments and are more likely to abandon useful treatments when warned of rare, unlikely side effects. What's a harried practitioner to do? The golden rule may provide some guidance, but I recommend also spiking discussions with optimism, transparency, and compassion.

Editor Disclosures at Time of Publication

  • Disclosures for Mark V. Dahl, MD at time of publication Consultant / Advisory board Makucell, Inc.; Castle Diagnostics, Inc.; Up To Date; Ulthera, Inc.; Biohealth, Inc. Equity Elorac, Inc.; Makucell, Inc. Editorial boards UpToDate


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