Analgesics

Medications for Opioid Use Disorder, Opioid Withdrawal, and Opioid Overdose: A Review

Author/s: 
Miriam T H Harris, Zoe M Weinstein, Alexander Y Walley

Importance: Opioid use disorder (OUD) involves compulsive opioid use that causes substantial distress or impairment at work, school, or home. OUD, which is the third most prevalent substance use disorder worldwide, affected an estimated 3.7% of US adults (9 367 000) in 2022 and caused 53 774 deaths in the US in 2024. Medications for opioid use disorder (MOUD) reduce morbidity and mortality. Individuals with OUD also benefit from medications to treat opioid withdrawal and reverse acute opioid overdose.

Observations: Methadone, buprenorphine, and naltrexone are medications approved by the US Food and Drug Administration (FDA) to reduce unregulated opioid use. Methadone and buprenorphine reduce the risks of overdose and all-cause mortality. However, only 25.1% of people in the US with OUD were treated with these medications in 2022. MOUD should be selected based on shared decision-making that considers availability and convenience of treatment options and patient preferences. Buprenorphine and naltrexone are prescribed in office-based settings and can be taken at home. Outpatients with OUD in the US can only obtain methadone in person at federally regulated clinics. After stopping or substantially reducing use of opioids, individuals with OUD develop symptoms of opioid withdrawal, such as anxiety, insomnia, pain, nausea, vomiting, and diarrhea. Medications for opioid withdrawal include opioid agonists (eg, methadone and buprenorphine), α2-receptor agonists (eg, lofexidine and clonidine), and medications to treat pain (ibuprofen) and nausea (ondansetron). Individuals being treated for acute withdrawal should also be prescribed MOUD to decrease the risk of all-cause mortality (adjusted hazard ratio, 0.52; 95% CI, 0.42-0.63 for MOUD vs no MOUD). Individuals who use opioids may develop opioid overdose, which can cause respiratory depression, stupor, and, if severe, coma and death. Opioid overdose can be treated or can be reversed with naloxone, an opioid antagonist that is FDA approved and should be administered at the lowest dose needed to restore a normal respiratory rate (eg, naloxone 0.4 mg intramuscularly or 2-4 mg intranasally). Community-wide distribution of naloxone to people who use opioids and their social networks has been associated with 25% to 46% lower community opioid overdose rates.

Conclusions and relevance: All individuals with OUD should be offered treatment with MOUD to reduce opioid use. Methadone and buprenorphine decrease opioid-associated and all-cause mortality in patients with OUD. Opioid withdrawal symptoms may be treated with opioid agonists, α2-receptor agonists, and medications for pain and nausea. All individuals with OUD should have access to opioid antagonists, such as naloxone, to treat opioid overdose.

Management of Opioid Use Disorder

Author/s: 
Sarah E. Messmer, Molly M. Perri, Andrew M. Davis

Opioid use disorder is a chronic disease characterized by a maladaptive pattern of opioid use despite negative consequences. In the US, nearly 75 000 overdose deaths occurred in 2023, a 10-fold increase from 1999.1 However, only 1 in 4 US adults eligible for MOUD received it in 2022.2 The 2024 CRISM guideline outlines evidence-based OUD management that can be implemented by clinicians with or without specialized MOUD training for patients aged 18 years or older.3 It does not address withdrawal induction protocols, scheduling of opioid agonist therapies, or urine drug testing.

What Is Diverticulitis?

Author/s: 
Shreya Narayanan, Christopher D. Jackson, MD

Diverticulitis involves inflammation of outpouchings of the intestinal wall, a condition known as diverticulosis.

Risk factors for diverticulosis include being older than 65 years, obesity (body mass index [BMI] of 30 or more), high blood pressure, type 2 diabetes, certain medications (such as opioids, steroids, and nonsteroidal anti-inflammatory drugs [NSAIDs]), connective tissue diseases (such as polycystic kidney disease, Marfan syndrome, and Ehlers-Danlos syndrome), and specific genetic variants.1

By age 60 years, nearly 60% of people have diverticulosis, most often on the left side of the colon. About 1% to 4% of people with diverticulosis develop diverticulitis in their lifetime. Acute diverticulitis affects about 180 per 100 000 people in the US each year, resulting in approximately 200 000 hospitalizations annually.

Adrenal Insufficiency in Adults: A Review

Author/s: 
Anand Vaidya, James Findling, Irina Bancos

Importance: Adrenal insufficiency is a syndrome of cortisol deficiency and is categorized as primary, secondary, or glucocorticoid induced. Although primary and secondary adrenal insufficiency are rare, affecting less than 279 per 1 million individuals, glucocorticoid-induced adrenal insufficiency is common.

Observations: Primary adrenal insufficiency, which involves deficiency of all adrenocortical hormones, is caused by autoimmune destruction, congenital adrenal hyperplasia, pharmacological inhibition (eg, high doses of azole antifungal therapy), infection (eg, tuberculosis, fungal infections), or surgical removal of adrenal cortical tissue. Secondary adrenal insufficiency is caused by disorders affecting the pituitary gland, such as tumors, hemorrhage, inflammatory or infiltrative conditions (eg, hypophysitis, sarcoidosis, hemochromatosis), surgery, radiation therapy, or medications that suppress corticotropin production, such as opioids. Glucocorticoid-induced adrenal insufficiency is caused by administration of supraphysiological doses of glucocorticoids. Patients with adrenal insufficiency typically present with nonspecific symptoms, including fatigue (50%-95%), nausea and vomiting (20%-62%), and anorexia and weight loss (43%-73%). Glucocorticoid-induced adrenal insufficiency should be suspected in patients who have recently tapered or discontinued a supraphysiological dose of glucocorticoids. Early-morning (approximately 8 am) measurements of serum cortisol, corticotropin, and dehydroepiandrosterone sulfate (DHEAS) are used to diagnose adrenal insufficiency. Primary adrenal insufficiency is typically characterized by low morning cortisol levels (<5 µg/dL), high corticotropin levels, and low DHEAS levels. Patients with secondary and glucocorticoid-induced adrenal insufficiency typically have low or intermediate morning cortisol levels (5-10 µg/dL) and low or low-normal corticotropin and DHEAS levels. Patients with intermediate early-morning cortisol levels should undergo repeat early-morning cortisol testing or corticotropin stimulation testing (measurement of cortisol before and 60 minutes after administration of cosyntropin, 250 µg). Treatment of adrenal insufficiency involves supplemental glucocorticoids (eg, hydrocortisone, 15-25 mg daily, or prednisone, 3-5 mg daily). Mineralocorticoids (eg, fludrocortisone, 0.05-0.3 mg daily) should be added for patients with primary adrenal insufficiency. Adrenal crisis, a syndrome that can cause hypotension and shock, hyponatremia, altered mental status, and death if untreated, can occur in patients with adrenal insufficiency who have inadequate glucocorticoid therapy, acute illness, and physical stress. Therefore, all patients with adrenal insufficiency should be instructed how to increase glucocorticoids during acute illness and prescribed injectable glucocorticoids (eg, hydrocortisone, 100 mg intramuscular injection) to prevent or treat adrenal crisis.

Conclusions and relevance: Although primary and secondary adrenal insufficiency are rare, glucocorticoid-induced adrenal insufficiency is a common condition. Diagnosis of adrenal insufficiency involves early-morning measurement of cortisol, corticotropin, and DHEAS. All patients with adrenal insufficiency should be treated with glucocorticoids and instructed how to prevent and treat adrenal crisis.

The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update

The American Society of Addiction Medicine (ASAM) developed this National Practice Guideline for the Treatment of Opioid Use Disorder to provide information on evidence-based treatment of opioid use disorder. This guideline is an update and replacement of the 2015 ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use.

Nurse Standing Orders for Buprenorphine Follow-Up Care in a Community Health Center Network

Author/s: 
Richard C. Waters, Meaghan Mugleston, Anina Terry, Carrie Reinhart, Megan Wilson

Background: Less than 20% of individuals with opioid use disorder (OUD) are receiving a medication treatment for OUD in the United States. Though nurses can assume critical roles in outpatient models of OUD care, there are no published reports of buprenorphine standing orders for nurses that guide a nuanced response for patients returning as expected versus those re-engaging after a treatment lapse, without requiring real-time prescriber consultation.

Methods: Standing orders for buprenorphine were created with multiple stakeholders within an urban community health center that includes traditional clinics as well as non-traditional homeless care sites. After more than two years of use, an anonymous survey assessed staff perception of usability and safety of the standing orders using the validated system usability scale (SUS) and a 5-item Likert scale. Patient retention rates at 12 and 18 months were compared for sites that were early- and late-adopters of the standing orders.

Results: Of 24 clinicians and 7 nurses who responded to the survey, 46% had used the standing orders. More than 85% reported a perception that the standing orders improved team-based care and increased access to buprenorphine refills. None reported any safety concerns. The median SUS score was 75.0 (SD 15.4), rated as “excellent”. There was no statistically significant difference in 12- or 18-month retention rates between early- and late-adopter sites of the standing orders.

Conclusions: Nurse standing orders for buprenorphine follow-up and re-engagement care are feasible, usable and perceived as safe in varied community health center settings.

Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

Author/s: 
McDonagh, M. S., Wagner, J., Ahmed, A. Y., Fu, R., Morasco, B., Kansagara, D., Chou, R.

In an effort to address the opioid epidemic, a prominent goal of current research is to identify alternative treatments with equal or better benefits for pain while avoiding potential unintended consequences that could result in harms.

This 'living' systematic review assesses the effectiveness and harms of cannabis and other plant-based treatments for chronic pain conditions. For the purposes of this review, plant-based compounds (PBCs) included are those that are similar to opioids in effect and that have the potential for addiction, misuse, and serious adverse effects; other PBCs such as herbal treatments are not included. The intended audience includes policy and decision makers, funders and researchers of treatments for chronic pain, and clinicians who treat chronic pain.

The report will be updated on a quarterly basis.

Trajectories of Opioid Use Following First Opioid Prescription in Opioid-Naive Youths and Young Adults

Author/s: 
Wilson, J.D., Zbebe, K.Z., Kraemer, K., Liebschutz, J., Merlin, J., Miller, E., D., Donohue, J.

Importance: Although prescription opioids are the most common way adolescents and young adults initiate opioid use, many studies examine population-level risks following the first opioid prescription. There is currently a lack of understanding regarding how patterns of opioid prescribing following the first opioid exposure may be associated with long-term risks.

Objective: To identify distinct patterns of opioid prescribing following the first prescription using group-based trajectory modeling and examine the patient-, clinician-, and prescription-level factors that may be associated with trajectory membership during the first year.

Design, setting, and participants: This cohort study examined Pennsylvania Medicaid enrollees' claims data from 2010 through 2016. Participants were aged 10 to 21 years at time of first opioid prescription. Data analysis was performed in March 2020.

Main outcomes and measures: This study used group-based trajectory modeling and defined trajectory status by opioid fill.

Results: Among the 189 477 youths who received an initial opioid prescription, 107 562 were female (56.8%), 81 915 were non-Latinx White (59.6%), and the median age was 16.9 (interquartile range [IQR], 14.6-18.8) years. During the subsequent year, 47 477 (25.1%) received at least one additional prescription. Among the models considered, the 2-group trajectory model had the best fit. Of those in the high-risk trajectory, 65.3% (n = 901) filled opioid prescriptions at month 12, in contrast to 13.1% (n = 6031) in the low-risk trajectory. Median age among the high-risk trajectory was 19.0 years (IQR, 17.1-20.0 years) compared with the low-risk trajectory (17.8 years [IQR, 15.8-19.4 years]). The high-risk trajectory received more potent prescriptions compared with the low-risk trajectory (median dosage of the index month for high-risk trajectory group: 10.0 MME/d [IQR, 5.0-21.2 MME/d] vs the low-risk trajectory group: 4.7 MME/d [IQR, 2.5-7.8 MME/d]; P < .001). The trajectories showed persistent differences with more youths in the high-risk trajectory going on to receive a diagnosis of opioid use disorder (30.0%; n = 412) compared with the low-risk group (10.1%; n = 4638) (P < .001).

Conclusions and relevance: This study's results identified 2 trajectories associated with elevated risk for persistent opioid receipt within 12 months following first opioid prescription. The high-risk trajectory was characterized by older age at time of first prescription, and longer and more potent first prescriptions. These findings suggest even short and low-dose opioid prescriptions can be associated with risks of persistent use for youths.

Responding to Unsafe Opioid Use: Abandon the Drug, Not the Patient

Author/s: 
Tobin, Daniel G., Holt, Stephen R., Doolittle, Benjamin R.

Physicians have a legal and ethical duty to protect their patients and support them during times of clinical need; the decision to end a doctor-patient relationship should not be made lightly. However, in a recent survey of 794 primary care practices, 90% reported discharging patients in the previous two years, often for opioid-related issues.1 Disruptive or inappropriate behavior was the most common reason for discharge (81%), but 78% reported dismissing patients for violations of a chronic pain or controlled substance agreement. We find this practice worrisome, particularly since many controlled substance agreements use coercive and stigmatizing language that patients may reluctantly sign or have trouble understanding.2 Although violent, threatening, or disruptive behavior may be a valid reason to discharge patients in certain circumstances, opioid misuse should rarely rise to this threshold

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