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