Philosophical Issues and Psychological Variables that Influence the Determination of Opioid Effectiveness: A Narrative Review

Background: The prescribing of opioids in the chronic pain setting is often based on thepharmacodynamics, pharmacokinetics, and pharmacogenetics of the drug obtained duringdevelopment and clinical trials. However, the effectiveness of opioids varies widely and oftenappears to bear no relationship to the aforementioned variables. The impact of philosophical issuesand psychological factors on determining how clinically effective opioid therapy is has often beenover looked.Objectives: This manuscript provides a selective review and narrative summary of the philosophicalissues and psychological factors which can influence opioid effectiveness.Study Design: A selective review and narrative analysis of the literature.Methods: Experimental and clinical-based studies examining the impact of psychological factorson the effectiveness of opioids were extracted from the literature. Studies in which psychologicalfactors were used as an independent variable were given preference.Results: The philosophical issues reviewed include: (a) one’s understanding of the nature ofchronic pain, (b) the meaning of the score on the pain numerical rating scale (NRS), and (c) theselection of outcome measures. The psychological factors found to influence the effectivenessof opioids include: (a) role conditioning and learning, especially as they relate to conditionedanalgesia, non-associative tolerance, and the nocebo effect, (b) dosing pattern, (c) patient specificfactors, e.g., mood, overall psychological and neurocognitive status, (d) social variables, e.g.,personal environment and the media, and (e) the dysfunctional endogenous opioid system and itsrelationship to various psychological disorders.Limitations: This is a selective review of the literature. Some of the hypotheses presented havenot been experimentally validated. The review includes animal, human, experimental, and clinicalstudies.Conclusions: In general, the effectiveness of opioids may be influenced as much by the overallcontext in which they are used, including the physician-patient relationship as well as theirpharmacological properties. Data obtained from short-term and well-controlled trials may notgeneralize to the clinical setting, which is often more complex and dynamic. Appreciating theimpact of psychological factors may assist the clinician in proper patient selection, monitoring, andimproved outcomes.Key words: Psychological factors, philosophical issues, chronic pain, opioid therapy, effectiveness,conditioning, placebo, cognitive dysfunction