Der Placeboeffekt in der Schmerztherapie – für den klinischen Alltag nutzbar? Ja, unbedingt!

Zusammenfassung

Als Placeboeffekte bezeichnet man positive physiologische oder psychologische Veränderungen, die nach einer Einnahme von Medikamenten ohne spezifischen Wirkstoff oder Scheineingriffen auftreten und durch Erwartungs- und Konditionierungsprozesse induziert werden. Die mit Placeboeffekten einhergehenden neurobiologischen und peripher-physiologischen Vorgänge können auch bei der Vergabe von wirkstoffhaltigen Medikamenten eine wichtige Rolle spielen und sind somit nicht zwingend an die Gabe eines Scheinmedikamentes gebunden. Die Darreichung von „traditionellen“ Placebos ist im klinischen Alltag aus juristischen und ethischen Gründen höchst problematisch. Dieser Beitrag zeigt neben neuen Erkenntnissen zu offenen Placebo-Anwendungen (Open-Label Placebos) Wege auf, wie die zugrundeliegenden Mechanismen von Placeboantworten dennoch gezielt im schmerztherapeutischen Alltag genutzt werden können, um die Wirksamkeit, Verträglichkeit und Compliance bestehender pharmakologischer und anderer Therapien zum Wohle des Patienten zu optimieren.

Abstract

Placebo effects are defined as positive physiological or psychological changes that occur after either taking pills without a specific active ingredient or after receiving sham interventions. The underlying mechanisms are based on expectation and conditioning effects. The neurobiological and peripheral physiological processes associated with placebo effects can also play an important role in pharmacological treatments and are therefore not necessarily linked to the use of a sham drug or intervention. In clinical settings, the use of “traditional” placebos is highly problematic for both legal and ethical reasons. In addition to recent scientific findings on open-label placebo applications, this article offers suggestions on how to harness analgesic placebo effects by utilising their underlying mechanisms to optimise the effectiveness, tolerability and compliance of existing pharmacological and non-pharmacological treatments for the patient’s benefit.

Schlüsselwörter

Placebo-Effekt - Schmerzmedizin - Placeboanalgesie

Key words

Placebo effect - Pain management - Placeboanalgesia

Publication History

Article published online:
26 August 2020

• Literatur

• 1 Enck P, Bingel U, Schedlowski M. et al. The placebo response in medicine: minimize, maximize or personalize?. Nat Rev Drug Discov 2013; 12: 191-204 Im Internet: http://www.nature.com/articles/nrd3923
• 2 Schedlowski M, Enck P, Rief W. et al. Neuro-bio-behavioral mechanisms of placebo and nocebo responses: Implications for clinical trials and clinical practice. Pharmacol Rev 2015; 67: 697-730 Im Internet: https://www.ncbi.nlm.nih.gov/pubmed/26126649
• 3 Vase L, Petersen GL, Riley JL, et al. Factors contributing to large analgesic effects in placebo mechanism studies conducted between 2002 and 2007. Pain 2009
• 4 Bingel U. Avoiding nocebo effects to optimize treatment outcome. JAMA – J Am Med Assoc 2014; 312: 693-694
• 5 Mitsikostas DD. Nocebo in headaches: Implications for clinical practice and trial design. Curr Neurol Neurosci Rep 2012; 12: 132-137
• 6 Doering BK, Rief W. Utilizing placebo mechanisms for dose reduction in pharmacotherapy. Trends Pharmacol Sci 2012; 33: 165-172
• 7 Bingel U, Wanigasekera V, Wiech K. et al. The Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid Remifentanil. Sci Transl Med 2011; 3: 70 Im Internet: http://www.ncbi.nlm.nih.gov/pubmed/21325618
• 8 Ulrich RS. View through a window may influence recovery from surgery. Science (80- ) 1984; 224: 420-421
• 9 Meissner K, Linde K. Are Blue Pills Better Than Green? How Treatment Features Modulate Placebo Effects. In: International Review of Neurobiology. Academic Press Inc; 2018: 357-378
• 10 Colloca L, Lopiano L, Lanotte M. et al. Overt vs. covert treatment for pain, anxiety, and Parkinson’s disease. Lancet Neurol 2004; 3: 679-684 Im Internet: https://linkinghub.elsevier.com/retrieve/pii/S1474442204009081
• 11 Vase L, Riley JL, Price DD. A comparison of placebo effects in clinical analgesic trials vs. studies of placebo analgesia. Pain 2002; 99: 443-452
• 12 Stewart-Williams S, Podd J. The Placebo Effect: Dissolving the Expectancy vs. Conditioning Debate. Psychol Bull 2004; 130: 324-340 Im Internet: http://doi.apa.org/getdoi.cfm?doi=10.1037/0033-2909.130.2.324
• 13 Jensen K, Kirsch I, Odmalm S. et al. Classical conditioning of analgesic and hyperalgesic pain responses without conscious awareness. Proc Natl Acad Sci U S A 2015; 112: 7863-7867 Im Internet: http://www.ncbi.nlm.nih.gov/pubmed/25979940
• 14 Kirchhof J, Petrakova L, Brinkhoff A. et al. Learned immunosuppressive placebo responses in renal transplant patients. Proc Natl Acad Sci USA 2018; 115: 4223-4227
• 15 Benedetti F, Amanzio M, Rosato R. et al. Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nat Med 2011; 17: 1228-1230
• 16 Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: Expectation- activated opioid systems vs. conditioning-activated specific subsystems. J Neurosci 1999; 19: 484-494
• 17 Wager TD, Atlas LY. The neuroscience of placebo effects: Connecting context, learning and health. Nat Rev Neurosci 2015; 16: 403-418 Im Internet: https://www.ncbi.nlm.nih.gov/pubmed/26087681
• 18 Eippert F, Finsterbusch J, Bingel U. et al. Direct evidence for spinal cord involvement in Placebo Analgesia. Science (80- ) 2009; 326: 404
• 19 Scott DJ, Stohler CS, Egnatuk CM. et al. Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry 2008; 65: 220-231
• 20 Kaptchuk TJ, Miller FG. Placebo effects in medicine. N Engl J Med 2015; 373: 8-9 Im Internet: http://www.nejm.org/doi/10.1056/NEJMp1504023
• 21 Wager TD, Atlas LY, Leotti LA. et al. Predicting individual differences in placebo analgesia: Contributions of brain activity during anticipation and pain experience. J Neurosci 2011; 31: 439-452
• 22 Kam-Hansen S, Jakubowski M, Kelley JM. et al. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med 2014; 6: 218 Im Internet: http://stm.sciencemag.org/cgi/doi/10.1126/scitranslmed.3006175
• 23 Zunhammer M, Ploner M, Engelbrecht C. et al. The effects of treatment failure generalize across different routes of drug administration. Sci Transl Med 2017; 9: 1-8
• 24 Laubenthal H, Neugebauer E. S3-Leitlinie „Behandlung akuter perioperativer und posttraumatischer Schmerzen“. 2009. Im Internet: http://www.awmf.org/uploads/tx_szleitlinien/001-025l_S3_Behandlung_akuter_perioperativer_und_posttraumatischer_Schmerzen_abgelaufen.pdf
• 25 Bodenheimer T. Transforming Practice. N Engl J Med 2008; 359: 2086-2089 Im Internet: http://www.nejm.org/doi/abs/10.1056/NEJMp0805631
• 26 Charlesworth JEG, Petkovic G, Kelley JM. et al. Effects of placebos without deception compared with no treatment: A systematic review and meta-analysis. J Evid Based Med 2017; 10: 97-107 Im Internet: http://doi.wiley.com/10.1111/jebm.12251
• 27 Kleine-Borgmann J, Schmidt K, Hellmann A. et al. Effects of open-label placebo on pain, functional disability, and spine mobility in patients with chronic back pain: A randomized controlled trial. Pain 2019; 160: 2891-2897
• 28 Carvalho C, Caetano JM, Cunha L. et al. Open-label placebo treatment in chronic low back pain: A randomized controlled trial. Pain 2016; 157: 2766-2772. Im Internet: http://dx.doi.org/10.1097/j.pain.0000000000000700
• 29 Kaptchuk TJ, Friedlander E, Kelley JM, et al. Placebos without deception: A randomized controlledtrial in irritable bowel syndrome. PLoS One 2010
• 30 Zhou ES, Hall KT, Michaud AL. et al. Open-label placebo reduces fatigue in cancer survivors: a randomized trial. Support Care Cancer 2019; 27: 2179-2187 Im Internet: https://www.ncbi.nlm.nih.gov/pubmed/30298411
• 31 Sandler AD, Bodfish JW. Open-label use of placebos in the treatment of ADHD: a pilot study. Child Care Health Dev 2007; 34: 104-110 Im Internet: http://doi.wiley.com/10.1111/j.1365-2214.2007.00797.x
• 32 Kelley JM, Kaptchuk TJ, Cusin C. et al. Open-label placebo for major depressive disorder: A pilot randomized controlled trial. Psychother Psychosom 2012; 81: 312-314 Im Internet: http://www.ncbi.nlm.nih.gov/pubmed/22854752
• 33 Schaefer M, Harke R, Denke C. Open-label placebos improve symptoms in allergic rhinitis: A randomized controlled trial. Psychother Psychosom 2016; 85: 373-374
• 34 Belcher AM, Cole TO, Greenblatt AD. et al. Open-label dose-extending placebos for opioid use disorder: A protocol for a randomised controlled clinical trial with methadone treatment. BMJ Open 2019; 9