Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management

Abstract

What is known and objective Opioid use in the United States has reached unprecedented—some would even say crisis—levels. Although many individuals use opioid drugs as part of legitimate pain management plans, a significant number misuse prescription or illicit opioids. With regular opioid use, individuals develop tolerance and physical dependence; both are predictable, physiologic responses to repeated opioid exposure. However, a substantial number of individuals who misuse opioids will develop opioid use disorder (OUD), a complex, primary, chronic, neurobiological disease rooted in genetic, environmental and psychosocial factors. This article discusses OUD, opioid receptor physiology, and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to reduce opioid withdrawal symptoms in individuals with physical dependence and/or OUD. Methods The research articles regarding OUD and its management have been reviewed thoroughly based on a PubMed literature search using keywords related to opioid dependence, its pathophysiology and current treatment strategies. Results and discussion Tolerance/physical dependence and the behavioural characteristics associated with OUD reflect complex neurobiologic adaptations in several major systems of the brain, including the locus ceruleus and mesolimbic systems. Physical dependence is responsible for the distressing withdrawal symptoms individuals experience upon abrupt cessation or rapid dose reduction of exogenous opioids. Opioid withdrawal symptoms are a key driver behind continued opioid use, and a barrier to opioid discontinuation. Several opioid‐based medications are available to treat patients with OUD; these treatments can diminish opioid withdrawal symptoms and cravings as well as block opioid effects in the event of relapse. Additionally, non‐opioid drugs may be used during acute detoxification to help alleviate opioid withdrawal symptoms. What is new and conclusion The opioid crisis has produced many challenges for physicians, one being the need to determine which patients would benefit most from maintenance therapy and which may be candidates for opioid discontinuation. In addition to summarizing current understanding of OUD, we provide a new algorithm for determining the need for continued opioid use as well as examples of situations where management of opioid withdrawal symptoms is indicated.

Neural bases for attenuation of morphine withdrawal by Heantos-4: role of l-tetrahydropalmatine

“…Opioid detoxification is a critical first step in transitioning to long-term management of OUD. The cessation of use, however, triggers debilitating affective and somatic withdrawal signs that can last for several days to weeks and difficulty enduring this period may contribute to relapse 2 , 3 . Even the anticipation of these negative states serves as a major deterrent against seeking clinical treatment.…”

Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents

“…Our findings in this study were limited to the effects of S1PR1 signaling had on the physical manifestation of withdrawal in rodent models. These physical symptoms parallel the somatic withdrawal symptoms in humans that include myalgia, hyperalgesia, chills, and stomach cramping [ 60 ]. However, opioid withdrawal syndrome also has negative affective aspects that include stress, malaise, emotional pain, anxiety, and depression [ 60 , 61 ].…”

“…These physical symptoms parallel the somatic withdrawal symptoms in humans that include myalgia, hyperalgesia, chills, and stomach cramping [ 60 ]. However, opioid withdrawal syndrome also has negative affective aspects that include stress, malaise, emotional pain, anxiety, and depression [ 60 , 61 ]. Collectively, the physical and affective components provide a negative reinforcement that can motivate opioid seeking behaviors [ 61 ].…”

“…The affective aspects of opioid withdrawal are quite complex and will require extensive studies to understand how S1PR1 signaling may impact their development. Moreover, our studies focused on the effects in male mice as they have been reported to exhibit greater physical withdrawal symptoms and sensitivity to naloxone (i.e., less naloxone to induce withdrawal) than females [ 60 , 61 ]. Future studies will need to include the effects in females to parse out any potential sex-dependent difference.…”

Concordance between high antibiotic prescribing and high opioid prescribing among primary care physicians: a cross-sectional study

“…In fact, abrupt discontinuation of opioids represents inappropriate prescribing, as this can lead to withdrawal symptoms. 27 It is also important to note that, although we selected 6 separate metrics of antibiotic and opioid prescribing as proxy measures of appropriateness, this does not equate to a definitive assessment of appropriateness. This is important since opioid and antibiotic stewardship efforts aim to optimize the appropriate use of these medications rather than indiscriminately reduce their use.…”