Commentary on Lin et al.: Saving lives during the opioid crisis-widening the focus from opioid use disorder to polysubstance use disorder and to multimorbidity.

Abstract

Polysubstance use and multimorbidity are the norm instead of exception with opioid and other substance use disorders. We must widen the focus of treatment, research, and policy from single substances to the full tapestry of polysubstance use and multimorbidity to help develop interdisciplinary approaches that mitigate their adverse consequences. Amid the persistent opioid addiction crisis in United States (US), Lin et al. [1] highlight the often under recognized fact that most patients who seek treatment for opioid use disorder (OUD) present with polysubstance use disorder (PSUD). In addition, PSUD is associated with a higher burden of psychiatric and medical comorbidity, transforming OUD and other substance use disorders (SUDs) into a “multimorbidity” state (multiple comorbidities interacting with each other in complex ways), exacerbating dysfunction and posing hydra-like treatment challenges [1-4]. Population-based studies from the United States and elsewhere have also shown a similarly high prevalence of PSUD among individuals with OUD and comorbidities among those with PSUD [3, 5]. The high prevalence of multimorbidity and PSUD among patients with OUD has several adverse implications, but its most tragic consequence is an increased risk of overdose deaths. Darke [6, 7] has pointed out that most heroin “overdose” deaths during the pre-fentanyl era were “underdose” deaths (low heroin metabolite levels on autopsy) fueled by high prevalence of polysubstance use and medical comorbidities. This pattern appears to continue even in the current fentanyl era [8] and with overdose deaths associated with prescribed opioids [9]. Case & Deaton [10] have also highlighted the synergistic role of drug and alcohol addictions and medical and psychiatric comorbidity in the sharp rise of excess suicide, cardiovascular, and overall mortality experienced by non-college educated Caucasian adults in the United States after 1990. In summary, multimorbidity (with PSUD at its foundation) appears to be a key factor that drives mortality risk among individuals with OUD (and other SUDs). It is well established that sustained buprenorphine and methadone treatment are associated with decreased overdose and overall mortality and better health outcomes [11]. Patients with PSUD have more severe clinical course of OUD and other SUDs [12], use treatment at higher rates than those with a single SUD [2], and PSUD has minimal adverse impact on buprenorphine treatment retention [13]. However, data provided by Lin et al. [1] illustrate that PSUD is associated with lower rate of initiation of buprenorphine treatment for OUD despite also being associated with a higher rate of engagement in SUD care. Long-acting injectable naltrexone, a seemingly less risky OUD medication treatment (albeit with poorer retention and without demonstrable association with decreased mortality) is used more among those with PSUD and multimorbidity [14-16]. Overdose prevention intervention efforts (such as naloxone) also appear to be deployed at a lower rate among patients with PSUD, despite the higher risk of overdose mortality among them [17]. The alarming treatment paradox of underutilization of life saving OUD treatments despite higher risk of mortality among those with OUD and multimorbidity might have several explanations. SUD has complex relationships with comorbidities that often create complicated clinical scenarios that are bewildering in their complexity to patients and providers [4]. For example, although SUD paradoxically predisposes individuals to chronic pain and worsens its clinical and treatment course rather than alleviating it, chronic pain has a reciprocal adverse exacerbating effect on SUD [4, 18]. The accompanying PSUD and multimorbidity then infuses an even greater relentlessness into the already fierce reciprocal relationship [4]. As Lin et al. point out [1], no treatment framework has emerged to guide management of complex clinical conditions involving OUD, PSUD, pain, psychiatric comorbidities, and its exacerbating functional consequences such as homelessness, incarceration, and suicide attempts. It has been suggested than an integrative approach to the management of multimorbidity by an interdisciplinary team may be more effective than one-by-one treatment of each individual SUD and each comorbidity by an independent specialist [4]. However, beyond the basic descriptive data, there is limited research to help guide such integrated treatment [2, 4]. The need for research on integrative treatment of multimorbidity in OUD (and other SUDs) care has become critical, because polysubstance use has become the norm instead of the exception, and the substance use patterns among patients with OUD have shifted from an exclusive addiction to prescription opioids to its concomitant use with heroin, much riskier opioid forms like fentanyl analogues and multiple other substances [19]. Hence, it is imperative that treatment development efforts, as well as research and policy interventions, widen their focus from multiple single substances to the full tapestry of polysubstance use and multimorbidity that underlies the current crisis in which opioids are just the tip of a much larger and intricately creviced iceberg. None.