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Page 264 Arroyo Seguí et al. J Transl Genet Genom 2020;4:263-77 I http://dx.doi.org/10.20517/jtgg.2020.35

Nevertheless, the development of pharmacogenomic-guided strategies has the potential to reduce opioid misuse,
improve clinical outcomes, and save healthcare resources.

Keywords: Pharmacogenomics, pharmacogenetics, buprenorphine, opioid use disorder, opioids, personalized
medicine, medication-assisted treatment, buprenorphine/naloxone

INTRODUCTION
The United States (US) has seen a surge in prescription and illicit use of opioids in the last twenty years,
creating an unprecedented healthcare and socioeconomic crisis. Approximately 2 million people in the US
[1]
have opioid use disorders (OUD) resulting from prescription usage alone . This life-threatening chronic
brain disease is associated with a significant increase in early death, resulting from overdose, trauma,
[2]
suicide or infectious diseases (e.g., Hepatitis C, HIV/AIDS) . From 1999 to 2018, approximately 450,000
[3]
people died in the US due to opioid overdoses . Healthcare costs, loss of productivity, and criminal
[4]
involvement creates substantial socioeconomic burden . The Centers for Disease Control and Prevention
estimate costs of more than $78 billion per year in the US from prescription opioid misuse, and others have
estimated an additional loss of $50 billion from heroin use .
[5,6]

The prolonged and repeated administration of opioids over time causes lasting effects on neuronal structure
[4]
and function . The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders defines OUD
[7]
as a problematic pattern of misuse resulting in clinically significant impairment or distress . OUD can be
effectively managed using medication-assisted treatment (MAT), a combination of pharmacological and
behavior-based interventions such as, cognitive-behavioral therapy, contingency plans, 12-step programs
[2]
and support groups . Evidence strongly recommends the use of medications in all patient groups,
including adolescents, pregnant women and older adults [4,8-14] . Pharmacotherapy can reduce morbidity
and mortality by restoring brain function, supporting opioid abstinence and reducing risk for overdose
death [4,15,16] . OUD treatment can also lower the risk of blood-borne infections and help patients recover
social functionality, easing reintegration into their communities [17-19] .

After initial detoxification (i.e., opioid withdrawal management), patients should be introduced to
maintenance therapy with MAT. FDA-approved medications for maintenance therapy include methadone,
[2,4]
buprenorphine and extended-release naltrexone . All three medications target receptors within the opioid
[4]
system and work by reducing opioid cravings and/or decreasing the response to future drug use . Due to
their direct agonistic effect on opioid μ-receptors, methadone and buprenorphine are also indicated for
[2]
symptomatic relief of acute opioid withdrawal . Despite the availability of these life-saving medications,
[4]
most patients do not receive adequate treatment . Social barriers and policy regulations limit the number
of patients who receive pharmacotherapy, especially in underserved communities (e.g., African Americans,
Hispanics). Methadone can only be dispensed in federally approved clinics [i.e., opioid treatment programs
(OTPs)], restricting access for many patients . Buprenorphine can be prescribed in office-based settings,
[2]
but providers require completion of an 8-hour training course, and obtain a waiver from the Drug
[20]
Enforcement Administration . About 2%-3% of providers in the US have such waivers [4,21] .
Furthermore, patient-specific factors can alter the response to these medications, which may lead to
treatment failure in some patients [4,22,23] . Clinical characteristics such as sex, concurrent medications,
and mental health comorbidities have all been shown to affect patient variability in response to
pharmacotherapy [24-26] . Social determinants of health such as housing status, involvement with the criminal
justice system, and socioeconomic status may also impact treatment outcomes [4,27,28] . Lastly, genetic
variations can alter pharmacological effects and influence therapeutic response [29-31] . Pharmacogenomic