1. 2017;20;E1091-E1105Philosophical Issues and Psychological Variables that Influence the Determination of Opioid Effectiveness: A Narrative Review
   Narrative Review
   Daniel Michael Doleys, PhD.

BACKGROUND: The prescribing of opioids in the chronic pain setting is often based on the pharmacodynamics, pharmacokinetics, and pharmacogenetics of the drug obtained during development and clinical trials. However, the effectiveness of opioids varies widely and often appears to bear no relationship to the aforementioned variables. The impact of philosophical issues and psychological factors on determining how clinically effective opioid therapy is has often been over looked.

OBJECTIVES: This manuscript provides a selective review and narrative summary of the philosophical issues 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 factors on the effectiveness of opioids were extracted from the literature. Studies in which psychological factors were used as an independent variable were given preference.

RESULTS: The philosophical issues reviewed include: (a) one’s understanding of the nature of chronic pain, (b) the meaning of the score on the pain numerical rating scale (NRS), and (c) the selection of outcome measures. The psychological factors found to influence the effectiveness of opioids include: (a) role conditioning and learning, especially as they relate to conditioned analgesia, non-associative tolerance, and the nocebo effect, (b) dosing pattern, (c) patient specific factors, 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 its relationship to various psychological disorders.

LIMITATIONS: This is a selective review of the literature. Some of the hypotheses presented have not been experimentally validated. The review includes animal, human, experimental, and clinical studies.

CONCLUSIONS: In general, the effectiveness of opioids may be influenced as much by the overall context in which they are used, including the physician-patient relationship as well as their pharmacological properties. Data obtained from short-term and well-controlled trials may not generalize to the clinical setting, which is often more complex and dynamic. Appreciating the impact of psychological factors may assist the clinician in proper patient selection, monitoring, and improved outcomes.

KEY WORDS: Psychological factors, philosophical issues, chronic pain, opioid therapy, effectiveness, conditioning, placebo, cognitive dysfunction