Program- MSc Clinical Pharmacology

GUID- 2954578S

Opioid Crisis in North America

 Introduction: Chronic opioid usage that results in clinically significant

distress or impairment is known as opioid use disorder. An overwhelming
urge to use opioids, an increase in opioid tolerance, and withdrawal
symptoms when opioid usage is stopped are symptoms of this illness. In
the US, it has impacted more than 2.1 million people. Opioids include
morphine, codeine, oxycodone, heroin (diacetylmorphine), and fentanyl
(1,2 (1,2)). To make the diagnosis of opioid use disorder, the patient must
meet the criteria of Diagnostic and Statistical Manual of Mental
Disorders, Fifth edition (DSM-5). As per the DSM-5, OUD is defined as
repeated opioid use within 12 months leading to problems or distress with
2 or more of the following occurring:

1. Continued opioid use despite worsening physical or psychological

health.
2. Continued opioid use despite social and interpersonal consequences.
3. Decreased social or recreational activities.
4. Difficulty fulfilling professional duties at school or work.
5. Excessive time is taken to obtain or recover from taking opioids.
6. More opioids are taken than intended.
7. Opioid cravings occur.
8. Inability to decrease the amount of opioids used.
9. Tolerance to opioids develop.
10.Opioid use continues despite the danger it poses to the users.
11.Withdrawal occurs, or the user continues to take opioids to avoid
withdrawal.
The presence of 6 or more of these diagnostic criteria indicates sevcere
OUD (Opioid Use Disorder). Drug-seeking behavior, the existence of
legal or social repercussions from opioid use, multiple opioid
prescriptions from various prescribers, opioid cravings, increased opioid
usage over time, and withdrawal symptoms upon cessation of opioid use
are among the signs and symptoms of opioid use disorder. When an
 opioid user stops using, physical symptoms that are typical of withdrawal
include chills, diarrhea, muscle pains, and rhinorrhea start appearing
(3,4 (3,4)).

 Background: Roughly 68,500 Americans died in 2018 alone from opioid

overdoses involving heroin, prescription painkillers, and illegal synthetic
opioids like fentanyl. (5 (5)). The abuse and addiction to opioids has
become a nationwide epidemic impacting the public health and economic
prosperity of the United States, with an estimated cost of over $150
billion USD in 2015. (6 (6)). North America as a whole is experiencing
this epidemic, including Canada, where a public health emergency is
currently in effect. Canada has the second-highest per-capita use of
prescription opioids behind the United States, so the rising trend of
opioid-related deaths there is hardly shocking. The Public Health Agency
of Canada reports that there were 3987 opioid-related deaths in 2017 and
that 17 Canadians are hospitalized per day as a result of overdosing on
opioids. What is even more concerning is that 72% of these deaths used
fentanyl or one of its extremely powerful synthetic variants, and 92% of
these deaths were accidental—up from 55% in 2016. (7 (7)).

 Opioid Practice in North America and related Morbidity and

Mortality: Pain management was mostly approached conservatively
before the 1990s. Because of the potential for abuse and addiction,
doctors in North America were very hesitant to prescribe opioid drugs.
Reliability for addiction was identified as a reason for the increased use
of opioids in non-chronic cancer pain therapy by well-known pain
specialists. Two publications corroborated the aforementioned analogy: i)
a one-paragraph letter to the editor of the New England Journal of
Medicine stating low rates of addiction as low as 0.03% in patients
receiving opioids for acute pain, and ii) a retrospective assessment of 38
patients with chronic pain showing that only 2 of them experienced drug
abuse problems after receiving opioids. The notion of using opioid drugs
to treat pain has gained tremendous support from medical professionals,
to the point that they are conflicted over whether treating patients' pain
could improve their quality of life or cause them to develop a substance
dependence problem. (8,9,10 (8–10)). The Federation of State Medical
Boards supported the "war against pain" campaign in their 1998 model
guidelines, which made the use of opioid drugs for the treatment of
 chronic non-cancerous pain the new standard of care. The rise of
widespread opioid abuse began with the release of oxycodone in a
sustained release formulation that could relieve pain for eight to twelve
hours. Due to its strong binding to the μ-opioid receptor, it exhibited great
analgesic and euphoric properties. The continuous release oxycodone,
which was sold under the brand name OxyContin, was especially alluring
since, in contrast to other opioids available at the time, it only needed to
be used once or twice a day to maintain analgesia. The FDA came to the
conclusion that the slow-release formulation would deter abuse by
imposing a delay on reinforcement, based on the justification that instant
rewarding is important to reinforce behavior. Consequently, this led the
producers to assert on the labeling of their products that OxyContin had a
limited risk for abuse. Nevertheless, users soon found that massive doses
of oxycodone could be injected intravenously or used orally by crushing
or dissolving the pills. Following its misrepresentation as an abuse-
resistant medication, OxyContin was later the focus of a $300 million
lawsuit. (11,12,13 (11–13)). Overzealous opioid use in pain management
was made possible by the pharmaceutical industry's advocacy for the use
of opioids and the need to provide appropriate pain control. Prescriptions
for opioids increased dramatically at the turn of the millennium, by more
than 400% between 1999 and 2010. (14 (14)). Between 1997 and 2002,
the number of annual prescriptions for OxyContin in the United States
climbed by nearly ten times, from 670,000 to 6.2 million. (15 (15)).
According to estimates from the National Institute of Drug Abuse (NIDA)
and the International Narcotics Control Board (INCB), prescription
opioid consumption increased three to fourteen times in the United States
and Canada between 1995 and 2015. (16 (16)). Between 1999 and 2015,
the rate of opioid overdose deaths in the United States more than tripled,
from 2.9 to 10.4 deaths per 100,000 people. (17 (17)). Similarly, opioid-
related mortality in Ontario, the most populated province in Canada,
increased by nearly three times between 2000 and 2015, from 1.9 to 5.3
deaths per 100,000 people, respectively. (18 (18)).

 Socioeconomic factors contributing to the toll of opioid abuse:

1. Lack of education and opportunity: According to a study published

in 2020, people who attained the highest educational qualifications
accounted for 35.4% of all opioid-related deaths and those who
failed to receive formal education accounted for 23.7% of all
 opioid overdose deaths, which makes evident that individuals with
no formal education or potentially illiterate potentially end up with
limited job opportunities in the market and resort to engaging in
substance abuse that in turn escalates into overdose.
2. Being unmarried or divorced: Those who are single or divorced
have disproportionately higher incidence of opioid-related
mortality. According to the same study, those who had never
married made up 42.9% of all opioid overdose deaths, while
divorced people made up 21.3% of those fatalities. It has been
demonstrated that loneliness, commonly known as the "silent
killer," has detrimental effects on mental health and frequently
results in suicidal thoughts or sadness.
3. Leading cause of accidental death among men: Opioid-related
accidental deaths in the United States account for roughly 70% of
deaths by accident. Men continue to be the most vulnerable group
overall, even while the rate of opioid-related deaths in the US has
climbed more quickly among women than men since 1999,
proportionately at 1608% for women and 1076% for males,
respectively, suggesting the primary cause of death among
homeless white women.
4. Degradation of rural community health services: Since there aren't
enough qualified experts to handle dire circumstances, treating
OUD (opioid use disorder) places rural hospitals in a vulnerable
position. This is especially true given that rural regions were the
US's hub for decades of the opioid crisis. In addition, rural
hospitals struggle to keep staff and run efficient care delivery
systems due to a lack of funding from government grants. Because
slightly over 30% of Medicaid patients in the United States live in
rural areas and receive care from rural hospitals, the federal
government pays less for the care these patients receive than it does
for their actual medical needs. One in five OUD patients are
uninsured, and three out of ten are covered by Medicaid.(19 (18)).

 Mitigative Strategies:
1. Medication-assisted treatment (MAT): This includes using
methadone or buprenorphine in addition to behavioral therapies.
Through a variety of methods, these medicines bind the μ-opioid
receptor and provide protection against overdose and relapse.
While buprenorphine functions as a partial agonist with a
 buffering "ceiling effect," methadone functions as a full agonist
with a lengthy terminal half-life (120 hours). In individuals who
are accustomed to opioids, buprenorphine's decreased efficacy at
the μ-opioid receptor is advantageous as it avoids euphoria and
dose-dependent respiratory depression, in contrast to methadone.
When a complete agonist is present, buprenorphine can be
antagonistic and can hasten withdrawal symptoms. These drugs
prevent withdrawal, lessen cravings, lower the stress response, and
interfere with other opioids' reinforcing effects. MAT shows
improved efficacy in terms of medication adherence, decreased
risk of death and morbidity, and sustained opioid abstinence. The
American Society of Addiction Medicine's national practice
recommendations and Canada's best practice guidelines both
endorse buprenorphine/naloxone as the first-line treatment for
people with moderate-to-severe opioid use disorders. Apart from
its function in aiding addiction recovery, numerous research works
have also indicated a correlation between MAT and a decrease in
the spread of blood-borne illnesses. One such study revealed a
drop of almost 60% in HIV among 552 young adult intravenous
drug users in the San Francisco region (20 (19–21),21,22).
2. Harm reduction strategies: This strategy, in contrast to standard
abstinence techniques, offers treatment to people who are
unwilling or unable to give up taking illegal drugs. By allowing
for what is best for the patient within their radar or what works
well for their best interests, supervised injection facilities (SIFs)
enhance health and well-being. Over 3.6 million people have
utilized Insite, North America's first legal SIF, since its launch in
2003. In the Vancouver area, nearly 6000 overdoses had been
reversed as of 2019; no fatalities had occurred. SIFs offer a secure
setting for the use of opioids in addition to integrating
comprehensive addiction treatment, which was previously
unavailable. The utilization of these facilities is linked to more
people having access to treatments including MAT, addiction
medicine providers, residential treatment or detoxification sites,
social work, and nursing care (23 (22,23),24).
3. When opioids are prescribed, treatment goals should be aimed at a
plan to taper opioids and avoid long-term exposure if treatment
objectives are not met.
4. To lessen the risks associated with opioid use, it is necessary to
monitor for high-risk behaviors like doctor shopping, which is the
 practice of getting prescriptions from several prescribers, or opioid
diversion. Prescription Drug Monitoring Programs (PDMPs),
which can accomplish this, have to be implemented in healthcare
systems more extensively.
5. A coordinated multidisciplinary care team made up of primary
care doctors, nurses, pharmacists, physical therapists, occupational
therapists, and psychiatrists is advised when tapering presents
challenges.
6. Since MAT frequently helps individuals with opioid use disorder
(OUD) continue regular lives, including going back to work, it
should be taken into consideration for these patients. However,
one significant disadvantage of MAT has been medication
diversion. As a result, patients on MAT ought to get routine
counseling, preventative primary care, referrals to appropriate
psychosocial treatments, and monitoring of their substance use
along with routine evaluations that include urine drug testing
(7 (7)).

References:

1. Vallersnes OM, Jacobsen D, Ekeberg Ø, Brekke M. Mortality, morbidity and follow-up after acute
poisoning by substances of abuse: A prospective observational cohort study. Scand J Public Health.
2019 Jun 1;47(4):452–61.

2. Chang HY, Kharrazi H, Bodycombe D, Weiner JP, Alexander GC. Healthcare costs and utilization
associated with high-risk prescription opioid use: A retrospective cohort study. BMC Med. 2018 May
16;16(1).

3. John WS, Zhu H, Mannelli P, Schwartz RP, Subramaniam GA, Wu LT. Prevalence, patterns, and
correlates of multiple substance use disorders among adult primary care patients. Drug Alcohol
Depend. 2018 Jun 1;187:79–87.

4. Ober AJ, Watkins KE, McCullough CM, Setodji CM, Osilla K, Hunter SB. Patient predictors of substance
use disorder treatment initiation in primary care. J Subst Abuse Treat. 2018 Jul 1;90:64–72.

5. Hall WD, Farrell M. Reducing the opioid overdose death toll in North America. PLoS Med. 2018 Jul
1;15(7).

6. The Council of Economic Advisers The Underestimated Cost of the Opioid Crisis. 2017.

7. Ayoo K, Mikhaeil JS, Huang A, Wąsowicz M. The opioid crisis in North America: Facts and future
lessons for Europe. Anaesthesiol Intensive Ther. 2020;52(2):139–47.

8. Collier R. A short history of pain management. CMAJ. 2018 Jan 8;190(1):E26–7.

9. 9th ref article opioid essay.

10. 2873550.

11. Model Policy for the Use of Controlled Substances for the Treatment of Pain Federation of State
Medical Boards of the United States, Inc.

12. Cicero TJ, Ellis MS. The prescription opioid epidemic: a review of qualitative studies on the
progression from initial use to abuse [Internet]. 2017. Available from: www.dialogues-cns.org

13. Haffajee RL, Mello MM. Drug Companies’ Liability for the Opioid Epidemic. New England Journal of
Medicine. 2017 Dec 14;377(24):2301–5.

14. Frenk SM, Porter KS, Paulozzi LJ. Prescription Opioid Analgesic Use Among Adults: United States,
1999-2012 Key findings Data from the National Health and Nutrition Examination Survey [Internet].
1999. Available from: http://www.cdc.gov/nchs/data/databriefs/db189_table.pdf#3.

15. Jones Omar Viswanath Jacquelin Peck Alan D Kaye Jatinder S Gill Thomas T Simopoulos MR. A Brief
History of the Opioid Epidemic and Strategies for Pain Medicine. Pain Ther [Internet]. 7. Available
from: https://doi.org/10.6084/

16. for Disease Control C, Center for Injury Prevention N, of Health D, Services H. ANNUAL SURVEILLANCE
REPORT OF DRUG-RELATED RISKS AND OUTCOMES [Internet]. Available from: https://www.

17. Gomes T, Greaves S, Tadrous M, Mamdani MM, Paterson JM, Juurlink DN. Measuring the Burden of
Opioid-related Mortality in Ontario, Canada. Vol. 12, Journal of Addiction Medicine. Lippincott
Williams and Wilkins; 2018. p. 418–9.

18. Judd D, King CR, Galke C. The Opioid Epidemic: A Review of the Contributing Factors, Negative
Consequences, and Best Practices. Cureus. 2023 Jul 10;

19. 25747920.

20. Opioid Use Disorder: Diagnosis and Management in Primary Care. 2018.

21. Hagan H, Pouget ER, Des Jarlais DC. A systematic review and meta-analysis of interventions to
prevent hepatitis C virus infection in people who inject drugs. Vol. 204, Journal of Infectious Diseases.
2011. p. 74–83.

22. Kennedy MC, Hayashi K, Milloy MJ, Wood E, Kerr T. Supervised injection facility use and all-cause
mortality among people who inject drugs in Vancouver, Canada: A cohort study. PLoS Med.
2019;16(11).

23. 24th article opioid essay.pdf.