Physiological opioid dependence in LTOT may be functionally adaptive or maladaptive
The opioid induced allostatic opponent adaptations are the primary drivers of the biological process and the clinical expression of physiological opioid dependence and tolerance.52,65-69Physiological opioid dependence is an expected and unavoidable response accompanying long term opioid use that is characterized by self-limiting acute withdrawal symptoms (7-10 days) following opioid cessation or dose reduction.69 Physiological opioid dependence in LTOT may be accompanied by sustained functional improvement without significant adverse effects and thus can be considered adaptive or helpful. In our clinical experience, this window of benefit tends to close after a few months of regular opioid use. The opposite effect can also occur where physiological opioid dependence can be considered maladaptive or unhelpful when associated with worsening pain and function. In maladaptive LTOT dependence, the ill effects of allostatic opponent adaptations overwhelm the benefits. This maladaptive LTOT dependence can sometimes be associated with OUD and addiction characterized by a pattern of compulsive opioid use despite harms.52,66
Maladaptive LTOT dependence without OUD and addiction has been recently characterized as complex persistent opioid dependence (CPOD),52,66 a condition that should not be confused with “opioid dependence” as per International Classification of Diseases-10 (ICD-10) criteria, nor OUD per Diagnostic and Statistical Manual-5 (DSM-5) and/or addiction.52,66 Opioid Induced Chronic Pain syndrome (OICP) was put forward recently as a diagnostic term to describe the clinical phenomenology related to CPOD (which in turn is conceptualized as the pathological process underlying OICP) with the hope that such a pain specific diagnostic term would be more clinically appropriate and perhaps mitigate the common confounding of CPOD (used as a diagnostic term) with related diagnoses like OUD, ICD-10 opioid dependence, and opioid addiction, or the physiological state of opioid dependence.45 More details on the distinct characteristics of CPOD and OICP are provided elsewhere.45,52,66