Opioid Use Disorder: Difference between revisions

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<div class="editorbox">'''Original Editors '''- [[Pathophysiology of Complex Patient Problems|Students from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]] '''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp; </div>
<div class="noeditbox">Welcome to [[Pathophysiology of Complex Patient Problems|PT 635 Pathophysiology of Complex Patient Problems]] This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!</div><div class="editorbox">
'''Original Editors '''- [[Pathophysiology of Complex Patient Problems|Students from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  
 
'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp;  
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== Definition/Description  ==
== Definition/Description  ==


[[Image:CDC prescription opioids.png|right|250x250px]]  
[[Image:CDC prescription opioids.png|right|250x250px]]  


Opioid use disorder is a condition characterized by identifying the consequences associated with repeated opioid use, reflective compulsive use, and prolonged self-administration of opioid substances that includes non-prescription or prescription for a medical condition <ref name="1">American Psychiatric Association. Opioid Use Disorder Diagnostic Criteria. http://pcssmat.org/wp-content/uploads/2014/02/5B-DSM-5-Opioid-Use-Disorder-Diagnostic-Criteria.pdf Accessed 07 April 2016.</ref>. Prescribed opioid misuse can lead to addiction and occurs by taking the prescription in greater quantities other than specified, prolonged use past the intended prescribed time period, and use of prescription for other medical conditions that was not identify by the prescribing physician <ref name="1" />.<br>
Opioid use disorder is the chronic use of opioids that causes clinically significant distress or impairment. Opioid use disorders affect over 16 million people worldwide and there are over 120,000 deaths worldwide annually attributed to opioids.<ref name=":1">Dydyk AM, Jain NK, Gupta M. [https://www.ncbi.nlm.nih.gov/books/NBK553166/ Opioid use disorder.] InStatPearls [Internet] 2021 Jul 12. StatPearls Publishing. Available:https://www.ncbi.nlm.nih.gov/books/NBK553166/ (accessed 9.4.2022)</ref> The opioid crisis was declared a nationwide Public Health Emergency in USA on Oct. 27, 2017<ref name=":0">APA Opioid use disorder Available: https://www.psychiatry.org/patients-families/addiction/opioid-use-disorder<nowiki/>(accessed 9.4.20220</ref>.  
<div>
Opioids work by binding to specific receptors found throughout the body’s nervous and immune system <ref name="2">Substance Use Disorders. Substance Abuse and Mental Health Services Administration. 2015. Available at: http://www.samhsa.gov/disorders/substance-use. Accessed April 8, 2016.</ref>. The receptors are responsible for several functions that include pain, stress, temperature, respiration, endocrine activity, gastrointestinal activity, mood, and motivation. The main intended use is to reduce pain perception, but is associated with causing euphoria, drowsiness, mental confusion, nausea, constipation, and depress respiration (high doses) <ref name="2" />.<br>
<div>
Commonly used opioids identified in the healthcare setting include:&nbsp;<br>
 
[[Image:Morphine.png|left|250x200px]][[Image:Codeine.png|right|250x200px]]
 
*Codeine
*Fentanyl (patch)
*Hydrocodone (Hysingla ER, Zohydro ER)
*Hydrocodone/Acetaminophen (Lorcet, Lortabe, Norco, Vicodin)
*Hydromorphone (Dilaudid)&nbsp;
*Methadone (Dolophine)
*Morphine (Avinza, Kadian)
*Oxycodone (OxyContin, Roxicodone)
*Oxycodone
*<span>&nbsp;</span>Naloxone <ref name="1" />.
</div></div>
== Prevalence<br>  ==
 
<span>&nbsp;</span>Drug overdose deaths are on the rise in the United States. The CDC reported that in 2014 overdose deaths increased 6.5% from the previous year <ref name="3">Rudd R, Aleshire N, Zibbell J, Gladden M. Increases in Drug and Opioid Overdose Deaths — United States, 2000–2014. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm?s_cid=mm6450a3_w (accessed 04 April 2016).</ref>. The report also stated that since 2000, overdose death rate had risen 137% <ref name="3" />. Of this rise in overdose deaths 61% was attributed to some type of opioid, with synthetic opioid being the leading of categories examined <ref name="3" />. 78 people die per day due to opioid drug abuse <ref name="4">Center for Disease Control and Prevention. Understanding the Epidemic. http://www.cdc.gov/drugoverdose/epidemic/index.html (accessed 04 April 2016).</ref>.
 
[[Image:NID Opioid Deaths.png|center|300x200px]]<br>Results of the 2014 National Survey on Drug Use and Health reported the impact of opioid use disorders among varying demographics. When examining age, the survey found that roughly 586,000 Americans age 12 or older had a heroin use disorder, with average first use age being 28 <ref name="5">Substance Abuse and Mental Health Services Administration. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. http://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf (accessed 04 April 2016).</ref>. An estimated 1.9 million Americans age 12 or older reported a pain reliever use disorder <ref name="5" />. Opioid use disorder is more common with males than females with the highest abuse rates among the Native American population <ref name="6">American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. http://dsm.psychiatryonline.org/doi/book/10.1176/appi.books.9780890425596 (accessed 06 April 2016).</ref>.
 
<br>A recent study performed by the Substance Abuse and Mental Health Services Administration found a trend in among non-medical pain reliever use and its initiation of heroin use <ref name="7">Muhuri P, Gfroerer J, Davies M. Associations of Nonmedical Pain Reliever Use and Initiation of Heroin Use in the United States.  http://archive.samhsa.gov/data/2k13/DataReview/DR006/nonmedical-pain-reliever-use-2013.htm (accessed 04 April 2016).</ref>. More research is being done in this area to examine the relationship among these topics.<br><br>
 
== Characteristics/Clinical Presentation  ==


Literature suggests that pain and addiction commonly co-exists. There are two theories on how this develops: (1) Individuals with pain are prescribed opioids as part of pain management and develop an opioid use disorder; (2) Individuals with a history of substance use disorder develop subsequent pain syndromes <ref name="8">Wachholtz, A, Foster, S, Cheatle, M. Psychophysiology of pain and opioid use: Implications for managing pain in patients with an opioid use disorder. Drug and Alcohol Dependence. 2015;146:1–6. doi:10.1016/j.drugalcdep.2014.10.023.</ref>.<br>
Opioid use disorder consists of an overpowering desire to use opioids, increased opioid tolerance, and withdrawal syndrome when discontinued.  


A detailed and pertinent history should be obtained not only by the individual, but from the family, caregiver, and/or friends to identify ingestion time, quantity and any co-ingestants of substances <ref name="8" />.  
While opioid use disorder is similar to other substance use disorders in many respects, it has several unique features. Opioids can lead to physical dependence within a short time, as little as 4-8 weeks. In chronic users, the abruptly stopping use of opioids leads to severe symptoms, including generalized pain, chills, cramps, diarrhea, dilated pupils, restlessness, anxiety, nausea, vomiting, insomnia, and very intense cravings. Because these symptoms are severe it creates significant motivation to continue using opioids to prevent withdrawal.<ref name=":1" /> <div>
== Opioids ==
[[Image:Drowsiness_opioids.jpg|350x300px|alt=|thumb|Drowsy]][[Opioids]] are natural or synthetic (made in laboratories to mimic the properties of natural opioids) chemicals that interact with opioid receptors on the nerve cells in the body and brain and reduce feelings of [[Pain Behaviours|pain.]] They are a class of drugs that include prescription [[Pain Medications|pain relievers]], synthetic opioids and heroin. Prescription opioids are meant to be used to treat acute pain (such as recovering from injury or post-surgery), [[Chronic Pain and the Brain|chronic pain]], active-phase [[Cancer pain|cancer]] treatment, [[Palliative Care Competence Framework for Physiotherapists|palliative care]] and end-of-life care. The main intended use is to reduce pain perception, but is associated with causing euphoria, drowsiness, mental confusion, nausea, constipation, and depress respiration (high doses) <ref name=":0" /><ref name="p2">Substance Use Disorders. Substance Abuse and Mental Health Services Administration. 2015. Available at: http://www.samhsa.gov/disorders/substance-use. Accessed April 8, 2016.</ref>.<div>
Commonly used opioids identified in the healthcare setting include:&nbsp;


Symptoms associated with opioid use disorder include:  
*Codeine
*Fentanyl (patch)
*Hydrocodone (Hysingla ER, Zohydro ER)
*Hydrocodone/Acetaminophen (Lorcet, Lortabe, Norco, Vicodin)
*Hydromorphone (Dilaudid)&nbsp;
*Methadone (Dolophine)
*Morphine (Avinza, Kadian)
*Oxycodone (OxyContin, Roxicodone)
*Oxycodone
*Naloxone <ref name="p1">American Psychiatric Association. Opioid Use Disorder Diagnostic Criteria. http://pcssmat.org/wp-content/uploads/2014/02/5B-DSM-5-Opioid-Use-Disorder-Diagnostic-Criteria.pdf Accessed 07 April 2016.</ref>


*Strong desire of opioids
== Epidemiology ==
*Inability to control or reduce use  
[[File:NID Opioid Deaths.png|thumb|Opioid Deaths]]Over 16 million people worldwide are opioid-dependent and would meet the criteria for opioid use disorder, three million in the USA. Opioid use disorder results in over 120000 and 47000 deaths per year worldwide and in the U.S., respectively<ref name=":1" />.
*Continued use despite interference with major obligations or social functioning
*Use of larger amounts over time
*Development of tolerance
*Spending a great deal of time to obtain and use opioids
*Withdrawal symptoms that occur after stopping or reducing use


Ex: negative mood, nausea or vomiting, muscle aches, diarrhea, fever and insomnia&nbsp;<ref name="2" />  
== Etiology ==
There is not one single cause that will lead someone to develop an opioid use disorder. Although, there are several factors that can increase the risk for developing an addiction including both individual and environmental <ref name="p1" />. [[Genetic Conditions and Inheritance|Genetic]] factors have been found to play an important role for predisposition tendencies that can respond to the environment <ref name="p1" />.


<br>  
Opioids are known to activate the [[Limbic System|mesolimbic]] reward system which signals the release of dopamine causing feelings of pleasure. Our [[Brain Anatomy|brain]]<nowiki/>s ability to establish this conditioned association is responsible for the desire to repeatedly use the drug <ref name="p9">Goodman, CC, Snyder, TEK. Differential Diagnosis for Physical Therapists: Screening for Referral. 5th ed. St. Louis, MO: Saunders/Elsevier; 2013. (Pg 49-51)</ref>. However, the body is highly specialized to make adaptations to the presence of the drug and will transition from compulsion of seeking pleasure to depending on the drug existence entirely. Therefore, the increased compulsion is related to an individual tolerance and dependence of the drug <ref name="p9" />.


[[Image:Miosis.jpg|right|275x150px]]
== Clinical Presentation ==
 
[[File:Opioid addict.jpeg|thumb|Giving up or reducing activities because of opioid use]]Opioids produce high levels of positive reinforcement, increasing the odds that people will continue using them despite negative resulting consequences. Opioid use disorder is a chronic lifelong disorder, with serious potential consequences including disability, relapses, and death. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition describes opioid use disorder as a problematic pattern of opioid use leading to problems or distress, with at least two of the following occurring within a 12-month period:
Another issue associated with the presences of opioid use is the risk of toxicity which characteristically present with decreased level of consciousness. Signs and symptoms include:&nbsp;<br>
 
*Altered mental status – confusion or delirium
*Respiratory depression – low respiratory rate
*Extreme sleepiness
*Nausea and vomiting
*Pupillary miosis (constriction)
 
Respiratory depression is the most significant sign and not all cases present with pupillary miosis <ref name="1" />.  
 
<br>
 
Potential behavioral aspects can be indicated for individuals that should be screen for any type of substance use/abuse can include:
 
*Consistently missing appointments/ being extremely late
*Noncompliance with home exercise program or poor attention to self-care
*Shifting mood patterns (especially the presences of depression)
*Excessive daytime sleepiness or unusually excessive energy
*Deterioration of physical appearance and personal hygiene&nbsp;<ref name="2" />
 
<br>
 
The older adult population may be harder to identify causative signs and symptoms due to mimicking typical aging characteristics including memory loss, cognitive problems, tremors, falls, weight loss, and muscle wasting <ref name="9">Goodman, CC, Snyder, TEK. Differential Diagnosis for Physical Therapists: Screening for Referral. 5th ed. St. Louis, MO: Saunders/Elsevier; 2013. (Pg 49-51)</ref>.<br><br>


# Taking larger amounts or taking drugs over a longer period than intended.
# Persistent desire or unsuccessful efforts to cut down or control opioid use.
# Spending a great deal of time obtaining or using the opioid or recovering from its effects.
# Craving, or a strong desire or urge to use opioids
# Problems fulfilling obligations at work, school or home.
# Continued opioid use despite having recurring social or interpersonal problems.
# Giving up or reducing activities because of opioid use.
# Using opioids in physically hazardous situations.
# Continued opioid use despite ongoing physical or psychological problem likely to have been caused or worsened by opioids.
# Tolerance (i.e., need for increased amounts or diminished effect with continued use of the same amount)
# Experiencing withdrawal (opioid withdrawal syndrome) or taking opioids (or a closely related substance) to relieve or avoid withdrawal symptoms<ref name=":0" />
</div></div>
== Associated Co-morbidities  ==
== Associated Co-morbidities  ==


As research has shown, there is a high correlation between drug abuse and mental disorders. The National Institute on Drug Abuse has seen this association through national surveys dating back to the 1980s <ref name="10">National Institute on Drug Abuse. Comorbidity: Addiction and Other Mental Illnesses. https://www.drugabuse.gov/sites/default/files/rrcomorbidity.pdf (accessed 06 April 2016).</ref>. People that are “diagnosed with mood or anxiety disorders are twice as likely to suffer from a drug use disorder” and vice versa <ref name="10" />. While different mental disorders can bring about opioid use disorder, the most common comorbidities associated with opioid use are anxiety and depression <ref name="11">Gordon A. Australian Government: Department of Health and Aging. Comorbidity of mental disorders and substance use: A brief guide for the primary care clinician. http://www.nationaldrugstrategy.gov.au/internet/drugstrategy/publishing.nsf/Content/FE16C454A782A8AFCA2575BE002044D0/$File/mono71.pdf (accessed 06 April 2016).</ref>.  
[[Image:Depression_opioid.JPG|350x300px|alt=|thumb|Depression]]As research has shown, there is a high correlation between drug abuse and [[Mental Health Challenges of Health Professionals in Times of COVID-19|mental disorders]]. <ref name="p0">National Institute on Drug Abuse. Comorbidity: Addiction and Other Mental Illnesses. https://www.drugabuse.gov/sites/default/files/rrcomorbidity.pdf (accessed 06 April 2016).</ref> The most common comorbidities associated with opioid use are anxiety and [[depression]] <ref name="p1" />.<br>Another frequent comorbidity associated with opioid use disorder is [[Chronic Pain|chronic pain]] <ref name="p2" />. The importance of screening an individual with chronic pain for substance use disorder is crucial; this way it can prevent any relapses with previously abused drugs like opioids or set up a strict plan for the individual using the drug <ref name="p2" />.  


[[Image:Depression_opioid.JPG|center|350x300px]]<br>Another frequent comorbidity associated with opioid use disorder is chronic pain. Both opioid use disorder and chronic pain are driven by neurophysiological changes that can lead to altered or dysfunctional neural patterns <ref name="12">Substance Abuse and Mental Health Services Administration. A Treatment Improvement Protocol: Managing Chronic Pain in Adults With or in Recovery from Substance Use Disorders. http://store.samhsa.gov/shin/content/SMA12-4671/TIP54.pdf (accessed 06 April 2016).</ref>. Opioids are a common treatment option for those who have recently experienced trauma, surgery, and with chronic pain <ref name="12" />. Opioid use disorder is increasing in chronic pain patients due to the risk of noncompliance with drug use <ref name="13">Sullivan M, Edlund M, Fan M, DeVries A, Braden J, Martin B. Risks for Possible and Probable Opioid Misuse Among Recipients of Chronic Opioid Therapy in Commercial and Medicaid Insurance Plans: the TROUP Study. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897915/ (accessed 06 April 2016).</ref>. The importance of screening an individual with chronic pain for substance use disorder is crucial; this way it can prevent any relapses with previously abused drugs like opioids or set up a strict plan for the individual using the drug <ref name="12" />.
== Treatment ==
Effective treatments are available, however, only about one in four people with opioid use disorder receive specialty treatment. Medication-assisted treatment is an effective treatment for individuals with an opioid use disorder. It involves use of medication along with counseling and behavioral therapies. Brain chemistry may contribute to an individual's mental illness as well as to their treatment. For this reason medications might be prescribed to help modify one's brain chemistry. Medications are also used to relieve cravings, relieve withdrawal symptoms and block the euphoric effects of opioids.<ref name=":0" />


[[Image:Pain.jpg|center]]
# The disease is treated with opioid replacement therapy using buprenorphine or methadone, which reduces the risk of morbidity and mortality.
# Naltrexone may be useful to prevent relapse. Naloxone is used to treat opioid overdose. Nonpharmacologic behavioral therapy is also beneficial.
# Patients with opioid use disorder often benefit from twelve-step programs, peer support, and mental health professionals, individual and group therapy<ref name=":1" />


== Medications  ==
== Physical Therapy Management  ==


Medication use in this population is indicated mostly for management of withdrawal symptoms and/or overdose. The purpose of the medication is to reduce the side effects of the opioid substance and/or the body’s dependence for the substance <ref name="14">Opioid Abuse Clinical Presentation. Opioid Abuse Clinical Presentation: History, Physical, Causes. 2015. Available at: http://emedicine.medscape.com/article/287790-clinical#b1. Accessed April 10, 2016.</ref>. Treatment/management for opioid withdrawal is discussed in Medical Management. The medications that may be used as a form of treatment include <ref name="14" />:  
Physical therapists are not qualified to manage opioid use disorders. Physical therapists should be able to recognize signs and symptoms of this disorder, but need to refer patients out for treatment. Physical therapists need to advocate for their patients to get them the treatment and help they deserve <ref name="p1" />. A recent review suggests physical therapy may promote use of nonpharmacological treatment model for musculoskeletal pain management thus indirectly helping  reduce cases of opioid use disorders.<ref>George SZ, Goode AP. Physical therapy and opioid use for musculoskeletal pain management: competitors or companions?. Pain reports. 2020 Sep;5(5).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808685/ (Accessed on 18th October 2022)</ref>A retrospective study recommends early physical therapy for patients of  low back pain, who are at risk of  long term opioid use or misuse with avoidance of opioid prescription<ref>Fritz JM, King JB, McAdams-Marx C. Associations between early care decisions and the risk for long-term opioid use for patients with low back pain with a new physician consultation and initiation of opioid therapy. The Clinical journal of pain. 2018 Jun 1;34(6):552-8.https://pubmed.ncbi.nlm.nih.gov/29135698/<nowiki/>(Last accessed on 18th October 2022)</ref>. The attitude of physical therapists in managing patients with prescription opioid medication misuse (POMM) is related to how often they are engaged in treating them.<ref>Magel J, Cochran G, West N, Fritz JM, Bishop MD, Gordon AJ. Physical therapists’ attitudes are associated with their confidence in and the frequency with which they engage in prescription opioid medication misuse management practices with their patients. A cross–sectional study. Substance Abuse. 2022 Dec 1;43(1):433-41.https://pubmed.ncbi.nlm.nih.gov/34283690/<nowiki/>(Accessed on 18th October 2022)</ref> This will help not only to treat musculoskeletal issues like low back pain in such individuals but assist in early detection of opioid use disorder in many cases. Physical therapy interventions focusing on aerobic exercise in Opioid maintenance therapy (OMT) patients were found to be both feasible and beneficial<ref>ake-Schoffman DE, Berry MS, Donahue ML, Christou DD, Dallery J, Rung JM. Aerobic exercise interventions for patients in opioid maintenance treatment: a systematic review. Substance abuse: research and treatment. 2020 May;14:1178221820918885.https://pubmed.ncbi.nlm.nih.gov/35153484/<nowiki/>(Accessed on 18th  October 2022)</ref>.<br>On March 15, 2016 the CDC released “Guideline for Prescribing Opioids for Chronic Pain” <ref name="p2" />. In these guidelines it promotes “nonpharmacological therapy and non opioid therapy as preferred treatment for chronic pain” <ref name="p2" />. The CDC found that physical therapy and exercise therapy had a high-quality of evidence to reduce pain and improve function <ref name="p2" />. In recent times the scope of physical therapy as a profession has grown for this disorder. Physical therapy now is included in the multidisciplinary team for prevention & management of opioid use disorder at community level<ref>Davenport TE, DeVoght AC, Sisneros H, Bezruchka S. Navigating the intersection between persistent pain and the opioid crisis: population health perspectives for physical therapy. Physical Therapy. 2020 Jun 23;100(6):995-1007.https://pubmed.ncbi.nlm.nih.gov/32115638/<nowiki/>(Accessed on 18th October 2022)</ref>.


*Naloxone (opioid reversal agent) -&nbsp;Pure opioid antagonist – reverse opioid intoxication
*Methadone (opioid analgesic) -&nbsp;Reduces craving and withdrawal symptoms,&nbsp;Preferred agent for opioid agonist maintenance,&nbsp;Benefits – good treatment retention, psychosocial adjustment, and reduced criminal activity
*Buprenorphine (opioid analgesic) -&nbsp;Produces agonist/antagonist effects,&nbsp;Potent analgesic - can be administered once a day to block withdrawal symptom,&nbsp;Agonist effect is limited by ceiling effect (higher doses do not have additive effect),&nbsp;Abuse potential is low (compared to other opioids)
*Naltrexone (antidote) - Long-acting opioid antagonist, Blocks receptor sites, Indicated for prevention of relapse following detox<br>
*Clonidine (alpha 2 adrenergic agonists) -&nbsp;May reduce norepinephrine release,&nbsp;Most effective in suppressing autonomic signs/symptoms (withdrawal),&nbsp;Less effective for subjective symptoms&nbsp;<ref name="14" />


“Medication-assisted treatment with methadone, buprenorphine, or extended-release injectable naltrexone plays a critical role in the treatment of opioid use disorders. According to the latest survey of opioid treatment providers more than 300,000 people received some form of medication-assisted treatment for an opioid use disorder in 2011” <ref name="2" />. <br><br>
<br>
 
== Case Reports ==
== Diagnostic Tests/Lab Tests/Lab Values  ==
#Sullivan M, Edlund M, Fan M, DeVries A, Braden J, Martin B. Risks for Possible and Probable Opioid Misuse Among Recipients of Chronic Opioid Therapy in Commercial and Medicaid Insurance Plans: the TROUP Study. Pain. 2010 Aug; 150(2): 332–339. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897915/ www.ncbi.nlm.nih.gov/pmc/articles/PMC2897915/]  
 
&nbsp;The following are screening tools that can be used to test for opioid use disorder.
 
*Drug Abuse Screening Tool (DAST-10): assesses drug use in the past 12 months. 10-item yes-no questions; high scores indicate drug abuse.&nbsp;<ref name="15">National Institute on Drug Abuse. DAST-10. https://www.drugabuse.gov/sites/default/files/files/DAST-10.pdf (accessed 06 April 2016).</ref>
*Diagnostic and Statistical Manual of Mental Disorders (DSM-5): assesses a 12 month period. Can indicate opioid use disorder if the patient fits in the criteria of 2 or more of the 11 criteria examined (ex. craving the substance).&nbsp;<ref name="6" />
*CAGE-AID Questionnaire: 4 yes-no question tool about drug use. Answering yes to 1 or more questions is a positive test <ref name="16">Agency Medical Directors’ Group. Interagency Guideline on Prescribing Opioids for Pain. http://www.agencymeddirectors.wa.gov/Files/cageover.pdf (accessed 07 April 2016).</ref>.
*RAFFT: Relaxed, Alone, Friends, Family, Trouble. 5 yes-no questionnaire targeting adolescent drug abuse. 2 or more yes answers results in a positive test <ref name="17">Addiction Technology Transfer Center Network. Screening Tools for Adolescent Populations. http://www.nattc.org/topics/RxAbuse/docs/Adolescentscreeningtools.pdf (accessed 07 April 2016).</ref>.
*COMM: Current Opioid Misuse Measurement. 17 item, self-reported questionnaire. The higher the score, the increased likelihood of current opioid related deviant behavior <ref name="18">Opioid Risk. COMM. http://www.opioidrisk.com/node/1208 (accessed 07 April 2016).</ref>.
 
<br>  
 
The following are lab tests to test for opioid use disorder.
 
*Urine/blood toxicology tests: opioids can elicit positive test results 12-36 hours after ingestion <ref name="1" />.
*Screening for Hepatitis A, B, and C, and HIV: opioid abusers have an increased risk for acquiring these diseases from injection or sharing needles <ref name="1" />.
*Liver function tests: increase in ALT and AST can represent signs of acute liver damage; which could be a result from drug use <ref name="1" />. <br>
 
== Etiology/Causes  ==
 
There is not one single cause that will lead someone to develop an opioid use disorder. Although, there are several factors that can increase the risk for developing an addiction including both individual and environmental <ref name="1" />. Genetic factors have been found to play an important role for predisposition tendencies that can respond to the environment <ref name="1" />.
 
Opioids are known to activate the mesolimbic reward system which signals the release of dopamine causing feelings of pleasure. Our brains ability to establish this conditioned association is responsible for the desire to repeatedly use the drug <ref name="19">Kosten TR, George TP. The Neurobiology of Opioid Dependence: Implications for Treatment. Science &amp; Practice Perspectives. 2002;1(1):13-20.</ref>. However, the body is highly specialized to make adaptations to the presence of the drug and will transition from compulsion of seeking pleasure to depending on the drug existence entirely. Therefore, the increased compulsion is related to an individual tolerance and dependence of the drug <ref name="19" />.<br><br>
 
== Systemic Involvement  ==
 
Opioids reduce the perception of pain by attaching to proteins called opioid receptors that are located in the brain, spinal cord, gastrointestinal tract, and other organs <ref name="20">Volkow N. National Institute on Drug Abuse. America’s Addiction to Opioids: Heroin and Prescription Drug Abuse. https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2015/prescription-opioid-heroin-abuse (accessed 04 April 2016).</ref>. Opioids also affect brain regions involved in reward so they produce a sense of well-being and pleasure <ref name="20" />.<br>
 
Common side effects associated with taking opioid include the following <ref name="11" />:
 
*Drowsiness &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;&nbsp;[[Image:Drowsiness_opioids.jpg|right|350x300px]]
*Confusion
*Nausea and vomiting
*Constipation
*Sweating
*Pruritus <br>
 
For those that inject opioids, the following complications can be seen <ref name="11" />:
 
*Scarred/collapsed veins
*Abscesses
*Bacterial infections
*Blood borne viruses
*Thrombophlebitis
*Intravascular sepsis
*Endocarditis
*Accidental arterial injection
*Peripheral ischemia <br>
 
For those with long-term opioid abuse, the following can be seen <ref name="11" />:
 
*Gonadal suppression
*Reduced bone density
*Increase risk of osteoporotic fractures
*Decreased decision making ability &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;&nbsp;[[Image:Decision_making_opioids.jpg|right|300x300px]]
*Decreased ability to regulate behaviors
*Decreased management of stressful situations
*Addiction/dependence <br>
 
Signs of opioid overdose include <ref name="11" />, <ref name="20" />:
 
*Respiratory depression
*Cardiovascular depression
*Loss of consciousness/coma
*Hypoxia <br>
 
Signs of patients having withdraw symptoms include <ref name="11" />, <ref name="20" />:
 
*Restlessness
*Muscle and bone pain
*Insomnia
*Vomiting
*Diarrhea
*Cold flashes
*Involuntary leg movements
*Agitation
*Flu-like symptoms <br><br>
 
== Medical Management (current best evidence)  ==
 
Medical management for individuals with opioid use disorder begins treatment with detoxification followed by pharmaceutical maintenance therapy, psychotherapy, and treatment of acute pain in patients already on maintenance therapy <ref name="14" />.
 
Pharmacologic methods of detoxification typically include the use of methadone, burprenorphine, and alpha-2 agonists <ref name="14" />. Other medications (listed in Medication section) are used for treating associated signs/symptoms from opioid intoxication, opioid overdose, and/or opioid withdrawal. Cognitive behavior psychotherapy works by focusing on the individual’s thoughts/behaviors and establishes techniques used to resist substance abuse and reduce factors related to drug use <ref name="14" />. Treatment of acute pain in these individuals should include education on how to aggressively treat their pain with conventional opioid analgesics and reassurance of previous addiction history not hindering from adequate pain management <ref name="14" />.<br><br>
 
== Physical Therapy Management (current best evidence)  ==
 
Physical therapists are not qualified to manage opioid use disorders. Physical therapists should be able to recognize signs and symptoms of this disorder, but need to refer patients out for treatment. Physical therapists need to advocate for their patients to get them the treatment and help they deserve. Once treatment plans for the opioid use disorder are in place with a physician and patients began receiving medical treatment, if physical therapy treatment is needed, it would be utilized to help recover functional deficits. The physical therapy role mainly applies in opioid use disorders to get patients the appropriate care and begin advocating for nonopioid therapy through research in order to help decrease the prevalence of opioid abuse. The APTA has called to action for physical therapists and physical therapist assistances to focus on their role in pain management with the use of fewer or no drugs, such as opioids <ref name="21">PT in Motion News. APTA's Role in Opioid Abuse Initiative Reflects Wide Scope of White House Efforts. http://www.apta.org/PTinMotion/News/2015/10/23/OpioidInitiative/ (accessed 07 April 2016).</ref>. <br>
 
As the epidemic of opioid overuse has increased, the CDC has been working on guidelines to decrease risks of abuse and deaths in the United States. On March 15, 2016 the CDC released “Guideline for Prescribing Opioids for Chronic Pain” <ref name="22">Move Forward: Physical Therapy Brings Motion to Life. Health Center on Opioid Use for Pain Management.  http://www.moveforwardpt.com/Opioids (accessed 07 April 2016).</ref>. In these guidelines it promotes “nonpharmacological therapy and nonopioid therapy as preferred treatment for chronic pain” <ref name="22" />. The CDC found that physical therapy and exercise therapy had a high-quality of evidence to reduce pain and improve function <ref name="22" />. The CDC also states that the risks are much lower with nonopioid treatment plans, but in situations that opioids are prescribed they should always be combined with nonopioid therapies, such as physical therapy <ref name="22" />. The movement is toward physical therapy affects in pain management to prevent opioid use disorder. <br><br>
 
== Differential Diagnosis  ==
 
In the healthcare profession, the importance to accurately identify the diagnosis is key for the effectiveness of treatment. There are several different diagnoses that present with similar signs and symptoms as opioid use disorder and must be considered with each individual. The list presented is not a limitation to possible diagnosis and proceeds as follows:
 
*Acute Pancreatitis
*Bacterial Gastroenteritis
*Barbiturate Toxicity
*Benzodiazepine Toxicity
*Chronic Pancreatitis
*Influenza
*Peptic Ulcer Disease
*Sepsis
*Antisocial Personality
*Panic Attack
*Pontine Infarct or hemorrhage
*Depressed Mood
*Viral Gastroenteritis&nbsp;<ref name="14" />
 
Physical therapists work directly with individuals that experience pain and are prescribed opioid medications. Therefore, screening for the presence of substance abuse needs to be included in the physical therapy assessment. The Trauma Scale Questionnaire consists of four questions that are based on an established correlation between trauma and substance use (alcohol and other) for individuals 18 years old and older <ref name="9" />. Answering “Yes” to two are more of the questions is an indication to discuss with the physician and/or generate a referral for further evaluation of substance use <ref name="9" />. The questions included are:
 
#Have you had any fractures or dislocation to your bones or joints?
#Have you been injured in a road traffic accident?
#Have you injured your head?
#Have you been in a fight or assault?&nbsp;<ref name="9" /><br><br>
 
== Case Reports/ Case Studies  ==
 
#Sullivan M, Edlund M, Fan M, DeVries A, Braden J, Martin B. Risks for Possible and Probable Opioid Misuse Among Recipients of Chronic Opioid Therapy in Commercial and Medicaid Insurance Plans: the TROUP Study. Pain. 2010 Aug; 150(2): 332–339. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897915/ www.ncbi.nlm.nih.gov/pmc/articles/PMC2897915/]<br>
#Niesters M, Overdyk F, Smith T, Aarts L, Dahan A. Opiod-induced respiratory depression in paediatrics: a review of case reports. Br. J. Anaesth. (2013) 110 (2): 175-182. [http://bja.oxfordjournals.org/content/110/2/175.short bja.oxfordjournals.org/content/110/2/175.short]  
#Niesters M, Overdyk F, Smith T, Aarts L, Dahan A. Opiod-induced respiratory depression in paediatrics: a review of case reports. Br. J. Anaesth. (2013) 110 (2): 175-182. [http://bja.oxfordjournals.org/content/110/2/175.short bja.oxfordjournals.org/content/110/2/175.short]  
#5. Maloney E, Degenhardt L, Darke S, Mattick R, Nelson E. Suicidal behaviour and associated risk factors among opioid-dependent individuals: a case–control study. Addiction. December (2007) 102 (12) 1933–1941.&nbsp;[Http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2007.01971.x/full onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2007.01971.x/full ]  
#Maloney E, Degenhardt L, Darke S, Mattick R, Nelson E. Suicidal behaviour and associated risk factors among opioid-dependent individuals: a case–control study. Addiction. December (2007) 102 (12) 1933–1941.&nbsp;[Http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2007.01971.x/full onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2007.01971.x/full]
#4. Ives T, Chelminski P, Hammett-Stabler C, Malone R, Perhac J, Potisek N, Shilliday B, DeWalt D, Pignone M. Predictors of opioid misuse in patients with chronic pain: a prospective cohort study. BMC Health Services Research 2006, 6:46.&nbsp;[http://bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-6-46 bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-6-46 ]
 
#Muhuri P, Gfroerer J, Davies M. Associations of Nonmedical Pain Reliever Use and Initiation of Heroin Use in the United States. CBASQ Data Review. 2013 August.&nbsp;[http://archive.samhsa.gov/data/2k13/DataReview/DR006/nonmedical-pain-reliever-use-2013.htm archive.samhsa.gov/data/2k13/DataReview/DR006/nonmedical-pain-reliever-use-2013.htm ]
<div class="researchbox"> </div>  
 
== Resources <br>  ==
 
National Institute on Drug abuse:&nbsp;[https://www.drugabuse.gov/ www.drugabuse.gov/]
 
Substance Abuse and Mental Health Services Administration:&nbsp;[http://www.samhsa.gov/ www.samhsa.gov/]
 
<br>
 
[http://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf SAMHSA:&nbsp;Results from the 2014 National Survey on Drug Use and Health]&nbsp;
 
[https://www.drugabuse.gov/sites/default/files/rrcomorbidity.pdf NIDA: Comorbidity- Addiction and Other Mental Illnesses]&nbsp;
 
== Recent Related Research (from [http://www.ncbi.nlm.nih.gov/pubmed/ Pubmed])<br>  ==
<div class="researchbox">
<rss>http://www.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1DmWOa7abSbbDLZH6S9n59gsrTL0xT_4GK75X9NQ7ldfqGPkuM</rss>
</div>  
== References  ==
== References  ==
see [[Adding References|adding references tutorial]].


<references />  
<references />  


[[Category:Bellarmine_Student_Project]]
[[Category:Bellarmine_Student_Project]]
[[Category:Pharmacology]]
[[Category:Pain]]
[[Category:Older People/Geriatrics]]
[[Category:Pharmacology for Older People]]

Latest revision as of 08:00, 19 October 2022

Original Editors - Students from Bellarmine University's Pathophysiology of Complex Patient Problems project. Top Contributors - Lucinda hampton, Kim Jackson, Lauren Lopez, Sonal Joshi, 127.0.0.1, Ginny Zimlich, WikiSysop, Elaine Lonnemann and Jeanette Lanoire  

Definition/Description[edit | edit source]

CDC prescription opioids.png

Opioid use disorder is the chronic use of opioids that causes clinically significant distress or impairment. Opioid use disorders affect over 16 million people worldwide and there are over 120,000 deaths worldwide annually attributed to opioids.[1] The opioid crisis was declared a nationwide Public Health Emergency in USA on Oct. 27, 2017[2].

Opioid use disorder consists of an overpowering desire to use opioids, increased opioid tolerance, and withdrawal syndrome when discontinued.

While opioid use disorder is similar to other substance use disorders in many respects, it has several unique features. Opioids can lead to physical dependence within a short time, as little as 4-8 weeks. In chronic users, the abruptly stopping use of opioids leads to severe symptoms, including generalized pain, chills, cramps, diarrhea, dilated pupils, restlessness, anxiety, nausea, vomiting, insomnia, and very intense cravings. Because these symptoms are severe it creates significant motivation to continue using opioids to prevent withdrawal.[1]

Opioids[edit | edit source]

Drowsy
Opioids are natural or synthetic (made in laboratories to mimic the properties of natural opioids) chemicals that interact with opioid receptors on the nerve cells in the body and brain and reduce feelings of pain. They are a class of drugs that include prescription pain relievers, synthetic opioids and heroin. Prescription opioids are meant to be used to treat acute pain (such as recovering from injury or post-surgery), chronic pain, active-phase cancer treatment, palliative care and end-of-life care. The main intended use is to reduce pain perception, but is associated with causing euphoria, drowsiness, mental confusion, nausea, constipation, and depress respiration (high doses) [2][3].

Commonly used opioids identified in the healthcare setting include: 

  • Codeine
  • Fentanyl (patch)
  • Hydrocodone (Hysingla ER, Zohydro ER)
  • Hydrocodone/Acetaminophen (Lorcet, Lortabe, Norco, Vicodin)
  • Hydromorphone (Dilaudid) 
  • Methadone (Dolophine)
  • Morphine (Avinza, Kadian)
  • Oxycodone (OxyContin, Roxicodone)
  • Oxycodone
  • Naloxone [4]

Epidemiology[edit | edit source]

Opioid Deaths
Over 16 million people worldwide are opioid-dependent and would meet the criteria for opioid use disorder, three million in the USA. Opioid use disorder results in over 120000 and 47000 deaths per year worldwide and in the U.S., respectively[1].

Etiology[edit | edit source]

There is not one single cause that will lead someone to develop an opioid use disorder. Although, there are several factors that can increase the risk for developing an addiction including both individual and environmental [4]. Genetic factors have been found to play an important role for predisposition tendencies that can respond to the environment [4].

Opioids are known to activate the mesolimbic reward system which signals the release of dopamine causing feelings of pleasure. Our brains ability to establish this conditioned association is responsible for the desire to repeatedly use the drug [5]. However, the body is highly specialized to make adaptations to the presence of the drug and will transition from compulsion of seeking pleasure to depending on the drug existence entirely. Therefore, the increased compulsion is related to an individual tolerance and dependence of the drug [5].

Clinical Presentation[edit | edit source]

Giving up or reducing activities because of opioid use
Opioids produce high levels of positive reinforcement, increasing the odds that people will continue using them despite negative resulting consequences. Opioid use disorder is a chronic lifelong disorder, with serious potential consequences including disability, relapses, and death. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition describes opioid use disorder as a problematic pattern of opioid use leading to problems or distress, with at least two of the following occurring within a 12-month period:
  1. Taking larger amounts or taking drugs over a longer period than intended.
  2. Persistent desire or unsuccessful efforts to cut down or control opioid use.
  3. Spending a great deal of time obtaining or using the opioid or recovering from its effects.
  4. Craving, or a strong desire or urge to use opioids
  5. Problems fulfilling obligations at work, school or home.
  6. Continued opioid use despite having recurring social or interpersonal problems.
  7. Giving up or reducing activities because of opioid use.
  8. Using opioids in physically hazardous situations.
  9. Continued opioid use despite ongoing physical or psychological problem likely to have been caused or worsened by opioids.
  10. Tolerance (i.e., need for increased amounts or diminished effect with continued use of the same amount)
  11. Experiencing withdrawal (opioid withdrawal syndrome) or taking opioids (or a closely related substance) to relieve or avoid withdrawal symptoms[2]

Associated Co-morbidities[edit | edit source]

Depression

As research has shown, there is a high correlation between drug abuse and mental disorders. [6] The most common comorbidities associated with opioid use are anxiety and depression [4].
Another frequent comorbidity associated with opioid use disorder is chronic pain [3]. The importance of screening an individual with chronic pain for substance use disorder is crucial; this way it can prevent any relapses with previously abused drugs like opioids or set up a strict plan for the individual using the drug [3].

Treatment[edit | edit source]

Effective treatments are available, however, only about one in four people with opioid use disorder receive specialty treatment. Medication-assisted treatment is an effective treatment for individuals with an opioid use disorder. It involves use of medication along with counseling and behavioral therapies. Brain chemistry may contribute to an individual's mental illness as well as to their treatment. For this reason medications might be prescribed to help modify one's brain chemistry. Medications are also used to relieve cravings, relieve withdrawal symptoms and block the euphoric effects of opioids.[2]

  1. The disease is treated with opioid replacement therapy using buprenorphine or methadone, which reduces the risk of morbidity and mortality.
  2. Naltrexone may be useful to prevent relapse. Naloxone is used to treat opioid overdose. Nonpharmacologic behavioral therapy is also beneficial.
  3. Patients with opioid use disorder often benefit from twelve-step programs, peer support, and mental health professionals, individual and group therapy[1]

Physical Therapy Management[edit | edit source]

Physical therapists are not qualified to manage opioid use disorders. Physical therapists should be able to recognize signs and symptoms of this disorder, but need to refer patients out for treatment. Physical therapists need to advocate for their patients to get them the treatment and help they deserve [4]. A recent review suggests physical therapy may promote use of nonpharmacological treatment model for musculoskeletal pain management thus indirectly helping reduce cases of opioid use disorders.[7]A retrospective study recommends early physical therapy for patients of low back pain, who are at risk of long term opioid use or misuse with avoidance of opioid prescription[8]. The attitude of physical therapists in managing patients with prescription opioid medication misuse (POMM) is related to how often they are engaged in treating them.[9] This will help not only to treat musculoskeletal issues like low back pain in such individuals but assist in early detection of opioid use disorder in many cases. Physical therapy interventions focusing on aerobic exercise in Opioid maintenance therapy (OMT) patients were found to be both feasible and beneficial[10].
On March 15, 2016 the CDC released “Guideline for Prescribing Opioids for Chronic Pain” [3]. In these guidelines it promotes “nonpharmacological therapy and non opioid therapy as preferred treatment for chronic pain” [3]. The CDC found that physical therapy and exercise therapy had a high-quality of evidence to reduce pain and improve function [3]. In recent times the scope of physical therapy as a profession has grown for this disorder. Physical therapy now is included in the multidisciplinary team for prevention & management of opioid use disorder at community level[11].



Case Reports[edit | edit source]

  1. Sullivan M, Edlund M, Fan M, DeVries A, Braden J, Martin B. Risks for Possible and Probable Opioid Misuse Among Recipients of Chronic Opioid Therapy in Commercial and Medicaid Insurance Plans: the TROUP Study. Pain. 2010 Aug; 150(2): 332–339. www.ncbi.nlm.nih.gov/pmc/articles/PMC2897915/
  2. Niesters M, Overdyk F, Smith T, Aarts L, Dahan A. Opiod-induced respiratory depression in paediatrics: a review of case reports. Br. J. Anaesth. (2013) 110 (2): 175-182. bja.oxfordjournals.org/content/110/2/175.short
  3. Maloney E, Degenhardt L, Darke S, Mattick R, Nelson E. Suicidal behaviour and associated risk factors among opioid-dependent individuals: a case–control study. Addiction. December (2007) 102 (12) 1933–1941. onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2007.01971.x/full

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 1.3 Dydyk AM, Jain NK, Gupta M. Opioid use disorder. InStatPearls [Internet] 2021 Jul 12. StatPearls Publishing. Available:https://www.ncbi.nlm.nih.gov/books/NBK553166/ (accessed 9.4.2022)
  2. ↑ 2.0 2.1 2.2 2.3 APA Opioid use disorder Available: https://www.psychiatry.org/patients-families/addiction/opioid-use-disorder(accessed 9.4.20220
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Substance Use Disorders. Substance Abuse and Mental Health Services Administration. 2015. Available at: http://www.samhsa.gov/disorders/substance-use. Accessed April 8, 2016.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 American Psychiatric Association. Opioid Use Disorder Diagnostic Criteria. http://pcssmat.org/wp-content/uploads/2014/02/5B-DSM-5-Opioid-Use-Disorder-Diagnostic-Criteria.pdf Accessed 07 April 2016.
  5. ↑ 5.0 5.1 Goodman, CC, Snyder, TEK. Differential Diagnosis for Physical Therapists: Screening for Referral. 5th ed. St. Louis, MO: Saunders/Elsevier; 2013. (Pg 49-51)
  6. ↑ National Institute on Drug Abuse. Comorbidity: Addiction and Other Mental Illnesses. https://www.drugabuse.gov/sites/default/files/rrcomorbidity.pdf (accessed 06 April 2016).
  7. ↑ George SZ, Goode AP. Physical therapy and opioid use for musculoskeletal pain management: competitors or companions?. Pain reports. 2020 Sep;5(5).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808685/ (Accessed on 18th October 2022)
  8. ↑ Fritz JM, King JB, McAdams-Marx C. Associations between early care decisions and the risk for long-term opioid use for patients with low back pain with a new physician consultation and initiation of opioid therapy. The Clinical journal of pain. 2018 Jun 1;34(6):552-8.https://pubmed.ncbi.nlm.nih.gov/29135698/(Last accessed on 18th October 2022)
  9. ↑ Magel J, Cochran G, West N, Fritz JM, Bishop MD, Gordon AJ. Physical therapists’ attitudes are associated with their confidence in and the frequency with which they engage in prescription opioid medication misuse management practices with their patients. A cross–sectional study. Substance Abuse. 2022 Dec 1;43(1):433-41.https://pubmed.ncbi.nlm.nih.gov/34283690/(Accessed on 18th October 2022)
  10. ↑ ake-Schoffman DE, Berry MS, Donahue ML, Christou DD, Dallery J, Rung JM. Aerobic exercise interventions for patients in opioid maintenance treatment: a systematic review. Substance abuse: research and treatment. 2020 May;14:1178221820918885.https://pubmed.ncbi.nlm.nih.gov/35153484/(Accessed on 18th October 2022)
  11. ↑ Davenport TE, DeVoght AC, Sisneros H, Bezruchka S. Navigating the intersection between persistent pain and the opioid crisis: population health perspectives for physical therapy. Physical Therapy. 2020 Jun 23;100(6):995-1007.https://pubmed.ncbi.nlm.nih.gov/32115638/(Accessed on 18th October 2022)
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