Methadone is a synthetic opioid with unique pharmacokinetic and pharmacodynamic properties that distinguish it from other commonly used opioids. Originally developed as an analgesic and later adopted for opioid use disorder (OUD) treatment, methadone’s duration of action plays a central role in both its therapeutic benefits and its risks. Understanding the distinction between its analgesic duration and elimination half-life is essential for safe and effective clinical use.

Methadone acts primarily as a μ-opioid receptor agonist but also exhibits N-methyl-D-aspartate (NMDA) receptor antagonism and inhibits serotonin and norepinephrine reuptake. These additional mechanisms contribute to its efficacy in chronic pain, neuropathic pain, and opioid tolerance. Clinically, methadone’s analgesic duration of action is relatively short, typically lasting 4 to 8 hours after a single dose. This duration is comparable to that of other short-acting opioids and explains why methadone, when used for pain management, often requires divided dosing throughout the day.

In contrast, methadone’s elimination half-life is prolonged and highly variable, ranging from approximately 8 hours to more than 50, with reports of even longer half-lives in some individuals. This disparity between analgesic duration and elimination half-life is one of methadone’s most clinically significant features. While analgesia may wane within hours, the drug continues to accumulate in tissues and plasma with repeated dosing. As a result, steady-state concentrations may not be achieved for several days, increasing the risk of delayed toxicity if doses are escalated too rapidly.

The prolonged and variable half-life of methadone is largely explained by its pharmacokinetics. Methadone is highly lipophilic, leading to extensive tissue distribution and slow release back into circulation. It is metabolized primarily by hepatic cytochrome P450 enzymes, including CYP3A4, CYP2B6, and CYP2D6, which exhibit significant interindividual variability. Genetic polymorphisms, drug–drug interactions, and hepatic function can therefore markedly influence methadone clearance and duration of action.

In the treatment of opioid use disorder, methadone’s long duration of action is therapeutically advantageous. Once-daily dosing suppresses opioid withdrawal symptoms and cravings for 24 hours or longer, while also attenuating the euphoric effects of shorter-acting opioids. This pharmacologic profile supports treatment adherence and reduces illicit opioid use. However, the same properties necessitate careful induction and titration, particularly during the first one to two weeks of therapy, when accumulation can lead to oversedation or respiratory depression.

Methadone’s extended duration of action also has important safety implications. Respiratory depression may occur late after dosing, especially during initiation or dose increases. Additionally, methadone is associated with QT interval prolongation, a risk that may increase with higher plasma concentrations and prolonged exposure. These factors underscore the need for cautious dosing, patient education, and, in selected cases, electrocardiographic monitoring.

Methadone’s duration of action is characterized by a short analgesic effect and a long, variable elimination half-life. This unique pharmacologic profile underlies its effectiveness in chronic pain and opioid use disorder while also contributing to its narrow therapeutic margin. Clinicians must account for these properties to maximize benefit and minimize harm when prescribing methadone.

References

1. Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet. 2002;41(14):1153-1193. DOI: 10.2165/00003088-200241140-00003
2. Kreek MJ. Methadone-related opioid agonist pharmacotherapy for heroin addiction. Ann N Y Acad Sci. 2000;909:186-216. DOI: 10.1111/j.1749-6632.2000.tb06683.x
3. Inturrisi CE. Pharmacology of methadone and its isomers. Minerva Anestesiol. 2005;71(7-8):435-437.
4. Chou R, Cruciani RA, Fiellin DA, et al. Methadone safety: a clinical practice guideline from the American Pain Society. J Pain. 2014;15(4):321-337. DOI: 10.1016/j.jpain.2014.01.494
5. Ferrari A, Coccia CP, Bertolini A, Sternieri E. Methadone—metabolism, pharmacokinetics and interactions. Pharmacol Res. 2004;50(6):551-559. DOI: 10.1016/j.phrs.2004.05.002

Withdrawal due to preoperative medication stoppage refers to the physiological and psychological disturbances that occur when chronic medications are abruptly stopped before surgery. While the cessation of certain drugs before surgery is necessary to reduce risks such as bleeding or intraoperative hemodynamic instability, abrupt stoppage can result in rebound syndromes, physiological dysregulation, and poorer surgical outcomes. Balancing the competing risks of medication continuation versus stoppage is an ongoing challenge for anesthesiologists.

Preoperative medication management involves evaluating each patient’s chronic therapy for potential interactions with anesthetic agents, the surgical stress response, and hemodynamic stability and implementing a stoppage plan when necessary, ideally one that minimizes withdrawal. However, this is often difficult in practice, whether due to the urgency of the procedure, variation in how individual patients respond to medication, or other factors.

Beta-adrenergic antagonists (β-blockers) are among the most well-documented examples of adverse symptoms upon cessation; stopping them preoperatively can cause rebound hypertension, tachycardia, and ischemia due to the upregulation of adrenergic receptors during chronic therapy (1). Multiple studies have demonstrated that continuing β-blockers throughout the perioperative period reduces cardiovascular morbidity and mortality in high-risk patients (2). Consequently, current anesthesia guidelines strongly recommend maintaining β-blockade throughout the perioperative period, except in cases of severe bradycardia or hypotension.

Similar concerns apply to centrally acting antihypertensives, such as clonidine. Abruptly stopping them may cause rebound hypertension and sympathetic overactivity, which can lead to myocardial ischemia during induction or emergence from anesthesia (3). For this reason, clonidine is usually continued until the day of surgery, and if oral administration is not possible, intravenous administration becomes an available option.

Psychotropic medications, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), introduce another layer of complexity. Stoppage of these agents in the preoperative period may cause withdrawal symptoms such as dizziness, insomnia, sensory disturbances, agitation, or anxiety for 24 to 72 hours. These symptoms can mimic or exacerbate postoperative delirium and complicate anesthetic emergence. Evidence from perioperative reviews indicates that antidepressant withdrawal syndromes are clinically relevant and that these medications are best continued through the surgical period, unless there are specific contraindications, such as the potential for serotonin syndrome with monoamine oxidase inhibitors (4).

Benzodiazepine withdrawal syndromes also present significant perioperative risks. Sudden discontinuation may cause tremors, agitation, autonomic instability, or seizures. The aforementioned symptoms can overlap with postoperative delirium and complicate anesthetic recovery. Current perioperative guidelines recommend continuing benzodiazepine therapy for dependent patients or gradually tapering off if discontinuation is unavoidable. Cross-tolerant substitutes (e.g., long-acting benzodiazepines) may be used when necessary to prevent withdrawal during the perioperative period (5).

The broader issue beyond individual drug classes lies in polypharmacy and communication failures among care teams. Patients often don’t know which medications to continue or withhold before surgery, and perioperative teams may not have full medication histories. Studies show that up to 60% of surgical inpatients have at least one medication discrepancy upon admission, which increases the likelihood of inappropriate withdrawal and drug duplication (5). Therefore, medication reconciliation, multidisciplinary coordination, and patient education are crucial components of preoperative safety.

For anesthesiologists, awareness of withdrawal phenomena related to preoperative medication stoppage has practical implications for intraoperative management. Patients in withdrawal states may exhibit elevated catecholamine levels, resistance to anesthetic agents, or altered responses to opioids and sedatives. Inadequately recognized withdrawal can also confound hemodynamic monitoring and lead to misattribution of symptoms (e.g., tachycardia from β-blocker withdrawal mistakenly attributed to inadequate anesthesia). Anticipating and mitigating these effects through preoperative planning and postoperative vigilance can significantly improve surgical safety.

References

1. Pass SE, Simpson RW. Discontinuation and reinstitution of medications during the perioperative period. Am J Health Syst Pharm. 2004 May 1;61(9):899-912; quiz 913-4. PMID: 15156966.

2. Doak GJ. Discontinuing drugs before surgery. Can J Anaesth. 1997 May;44(5 Pt 2):R112-23. English, French. doi: 10.1007/BF03022270. PMID: 9196845.

3. Spell NO 3rd. Stopping and restarting medications in the perioperative period. Med Clin North Am. 2001 Sep;85(5):1117-28. doi: 10.1016/s0025-7125(05)70367-9. PMID: 11565489.

4. Zafirova Z, Vázquez-Narváez KG, Borunda D. Preoperative Management of Medications. Anesthesiol Clin. 2018;36(4):663-675. doi:10.1016/j.anclin.2018.07.012

5. Mercado DL, Petty BG. Perioperative medication management. Med Clin North Am. 2003;87(1):41-57. doi:10.1016/s0025-7125(02)00146-3

Telehealth, sometimes referred to as telemedicine, is the virtual delivery of health care, which can include virtually meeting with a care provider, checking results from labs or x-rays, physical or occupational therapy, and looking at skin problems.¹ Compared with traditional medical appointments, telehealth appointments typically have shorter wait times and can be scheduled more flexibly, making it beneficial for some patients. A 2024 survey estimated that 54% of Americans have had a telehealth visit, with 89% feeling satisfied with their experience, signaling its status as a key component of US healthcare.²

The COVID-19 pandemic led to an expansion of telehealth services in the US. A study of over 36 million individuals in the US found that, from March to June of 2019, only 0.3% of outpatient visits were conducted via telehealth, compared to 23.6% from March to June of 2020—a staggering 766% increase within a year.³ Telehealth’s increased usage has lasted beyond the pandemic: According to the American Hospital Association, the percentage of US hospitals offering telehealth services in 2022 was 86.9%, up from 78.3% in 2019 and slightly higher than 2020 and 2021 levels.⁴

Doximity, an online networking service for medical professionals that also provides telehealth services, publishes an annual “State of Telemedicine Report” that provides information on the current state of telehealth in the US based on an analysis of the service usage and physician surveys. According to the most recent report, 50% of physicians who used telehealth in 2023 are 39 years old or younger.⁵ The most common use cases were for follow-up visits and medication management, and the specialties with the highest rates of telehealth adoption were endocrinology, urology, and gastroenterology.

The COVID-19 pandemic spurred new legislation to ease and expand access to telehealth services. For instance, the CARES Act, the $2.2 trillion stimulus package signed into law at the beginning of the pandemic, included updates to Centers for Medicaid & Medicare Services telehealth regulations that lifted restrictions on the use of telehealth. With the changes, patients in all settings, not just rural ones, could receive telehealth under Medicare. Additionally, federally qualified health centers could offer telehealth, and more telehealth services became available.⁶ One change expanded Medicare coverage for audio-only services, which are important for those with limited Internet access.

Various pieces of congressional legislation extended the Medicare flexibilities beyond the pandemic, but the benefits were ultimately set to expire on September 30, 2025—the same day congressional funding expired and the government shut down. As of October 26, 2025, the government remains shut down, and until it reopens, Congress cannot vote to extend the flexibilities. Kyle Zebley, senior vice president of public policy at the American Telehealth Association, noted that older and disabled Americans will be most impacted.⁷

In a statement on the shutdown, the Association also noted that commercial insurers often model their coverage based on Medicare coverage, so in the absence of Medicare coverage for expanded telehealth, there is “growing uncertainty in the marketplace, and concern that commercial payers could soon follow suit if Congress and the Administration do not act quickly.”⁸ For the millions of Americans for whom adequate health care depends on broad insurance coverage of telehealth, these circumstances could be disastrous.

References

1. What can be treated through telehealth? | Telehealth.HHS.gov. https://telehealth.hhs.gov/patients/what-can-be-treated-through-telehealth.
2. Legere, D. 2024 National Telehealth Survey – Public Opinion Strategies. https://pos.org/2024-national-telehealth-survey/ (2024).
3. Weiner, J. P. et al. In-Person and Telehealth Ambulatory Contacts and Costs in a Large US Insured Cohort Before and During the COVID-19 Pandemic. JAMA Netw Open 4, e212618 (2021), DOI: 10.1001/jamanetworkopen.2021.2618
4. Fact Sheet: Telehealth | AHA. https://www.aha.org/fact-sheets/2025-02-07-fact-sheet-telehealth (2025).
5. Doximity. Doximity 2024 State of Telemedicine Report. https://www.doximity.com/reports/state-of-telemedicine-report/2024.
6. CARES Act: AMA COVID-19 pandemic telehealth fact sheet. American Medical Association https://www.ama-assn.org/health-care-advocacy/federal-advocacy/cares-act-ama-covid-19-pandemic-telehealth-fact-sheet (2020).
7. Cuevas, -Karina Cuevas Karina. Millions of seniors lose access to telehealth services in wake of shutdown. PBS News https://www.pbs.org/newshour/show/millions-of-seniors-lose-access-to-telehealth-services-in-wake-of-shutdown (2025).
8. Cardillo, B. DAY 14 OF THE TELEHEALTH SHUTDOWN: THE “RIPPLE EFFECT” ON TELEHEALTH REIMBURSEMENT – ATA ACTION CALLS FOR SHORT-TERM SOLUTION TO GROWING PATIENT CARE DISRUPTIONS. ATA https://www.americantelemed.org/press-releases/day-14-of-the-telehealth-shutdown-the-ripple-effect-on-telehealth-reimbursement-ata-action-calls-for-short-term-solution-to-growing-patient-care-disruptions/ (2025).

Signed into law by President Donald Trump on July 4, 2025, the One Big Beautiful Bill Act (OBBB) introduces major changes to the US healthcare system (1). The bill includes measures to cut federal healthcare spending, with significant implications for healthcare delivery. Officially known as H.R.1, the bill was narrowly approved by the Senate (51-50) and the House (218-214) and has been the subject of much controversy over reallocating funds, limiting federal program eligibility, and reversing Affordable Care Act (ACA or “Obamacare”) provisions (1). In the early stages of implementation, two main changes from the One Big Beautiful Bill have begun to reduce federal spending—but some critics argue that these savings come at a cost to Americans and healthcare providers.

In an attempt to cut federal spending, the first change of the bill targets the nation’s largest healthcare expenditure: public healthcare programs (1). In 2012, around 102 million Americans were enrolled in Medicare and Medicaid, which support Americans over the age of 65 and low-income or disabled adults and children, respectively (2, 3). However, due to the aging American population, ACA policies, and COVID-19 expansions, Medicaid and Medicare enrollments surged to roughly 160 million in 2023, raising total costs from about $989 billion in 2012 to $1.9 trillion in 2023 (3-6). In 2023, these programs accounted for nearly 40% of U.S. healthcare spending (5, 7).

Consequently, the OBBB targeted Medicaid, incorporating provisions for implementing employment requirements, reversing simplified Biden-era procedures, and increasing the frequency of eligibility re-determinations (8-11). Additional cost-saving measures include explicitly excluding Americans without proof of citizenship, shortening retroactive coverage periods, reducing federal health center staffing requirements, and removing federal incentives and funding for state Medicaid programs (8-11). According to the House of Representatives, these changes aim to reduce fraud and waste by disqualifying certain groups, primarily able-bodied, childless, unemployed young adults and undocumented immigrants (1, 12). However, evidence demonstrates that Medicaid fraud rarely occurs, and most Medicaid recipients work at least part-time (4, 13). Therefore, critics argue, the OBBB may cause funding issues for states, introduce administrative burdens for Medicaid management organizations, and withdraw healthcare from Americans, for minimal overall benefit (9, 13-16).

The One Big Beautiful Bill’s second change derives significant savings by reducing payments to healthcare providers (1). Historically, states utilized provider payment programs (DPPs) to reimburse Medicaid providers at above-market rates, which incentivized higher-quality, more accessible care (11). However, the OBBB sets a cap on these payments at 100% to 110% of average commercial rates (1, 10, 11). Furthermore, provider taxes—funds imposed by states to finance Medicaid and provider reimbursements—are slated to decline from a maximum of 6% in 2023 to 3.5% by 2032 (1, 10, 11). Beyond fiscal considerations, the OBBB also raises political concerns by eliminating federal funding for reproductive healthcare providers that offer abortion services (1, 16, 17). Overall, while the bill established a safety net for rural hospitals, the reduced payment rates and federal funding may lead to the closure or reduction of services in approximately 300 to 700 hospitals, as well as at least 200 reproductive healthcare clinics (11, 17, 18). Although the OBBB restricts states’ ability to waive or modify these federal adjustments, critics have urged states to counteract these changes to protect the health and livelihood of American providers and patients (8, 17).

As a consequence of these healthcare reforms, the OBBB is projected to reduce federal spending by at least $990 billion over the next decade (1, 11). Yet, these savings come at a substantial cost to American patients and providers, with estimates indicating that around 11 million Americans may lose Medicaid coverage, 839,000 may avoid necessary medical treatment, and 12,600 may suffer medically preventable deaths (11, 19). On the providers’ side, reductions in Medicaid payments, diminished hospital and state funding, and decreased patient volumes could lead to a $24 billion increase in uncompensated care, as well as the loss of 400,000 to 1.2 million healthcare jobs, over the next decade (8, 11, 20). Overall, although the bill is expected to lower income taxes for most American households, it carries profound implications for the future of the U.S. healthcare landscape (21).

References

1: One Big Beautiful Bill Act, H.R. 1, 119th Congress. 2025. https://www.congress.gov/bill/119th-congress/house-bill/1/text

2: Centers for Medicare and Medicaid Services. 2013. 2012 CMS Statistics. CMS Research, Statistics, Data, and Systems. https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/cms-statistics-reference-booklet/downloads/cms_stats_2012.pdf

3: Kaiser Family Foundation. 2024. Health insurance coverage of the total population. KFF State Health Facts. https://www.kff.org/other/state-indicator/total-population/?currentTimeframe=0&sortModel=%7B%22colId%22:%22Location%22,%22sort%22:%22asc%22%7D

4: Desilver, D. 2025. What the data says about Medicaid. Pew Research Center. https://www.pewresearch.org/short-reads/2025/06/24/what-the-data-says-about-medicaid/

5: Centers for Medicare and Medicaid Services. 2024. National health expenditure data: NHE fact sheet. CMS Research, Statistics, Data, and Systems. https://www.cms.gov/data-research/statistics-trends-and-reports/national-health-expenditure-data/nhe-fact-sheet

6:  Kaiser Family Foundation. 2016. National health expenditures 2012 highlights. KFF. https://www.kff.org/wp-content/uploads/sites/2/2012/12/highlights.pdf

7: McGough, M., Wager, E., Winger, A., Panchal, N., and Cotter, L. 2024. How has US healthcare spending changed over time? Peterson-KFF Health Systems Tracker. https://www.healthsystemtracker.org/chart-collection/u-s-spending-healthcare-changed-time/#:~:text=Private%20health%20insurance%20accounted%20for,of%20all%20health%20consumption%20spending.

8: Galace, A. 2025. State impacts of the One Big Beautiful Bill. National Association of Community Health Centers (NACHC) Newsroom. https://www.nachc.org/state-impacts-of-the-one-big-beautiful-bill/

9: Ortaliza, J., McGough, M., Cox, C., Pestaina, K., Rudowitz, R., and Burns, A. 2025. How will the One Big Beautiful Bill Act affect the ACA, Medicaid, and the uninsured rate? KFF Policy Watch. https://www.kff.org/policy-watch/how-will-the-2025-budget-reconciliation-affect-the-aca-medicaid-and-the-uninsured-rate/

10: Association of State and Territorial Health Officials (ASTHO). 2025. One Big Beautiful Bill Law Summary. ASTHO Legislative Alerts. https://www.astho.org/advocacy/federal-government-affairs/leg-alerts/2025/one-big-beautiful-bill-law-summary/

11: Heuer, T. 2025. The One Big Beautiful Bill: what every PA needs to know. American Academy of Physician Assistants (AAPA) News Central. https://www.aapa.org/news-central/2025/07/the-one-big-beautiful-bill-act-h-r-1-what-every-pa-needs-to-know/

12: The White House. 2025. Myth vs. fact: the One Big Beautiful bill. The White House Articles. https://www.whitehouse.gov/articles/2025/06/myth-vs-fact-the-one-big-beautiful-bill/

13: Hinton, E. and Rudowitz, R. 2025. 5 key facts about Medicaid work requirements. KFF Medicaid issue briefs.

https://www.kff.org/medicaid/issue-brief/5-key-facts-about-medicaid-work-requirements/

14: National Academy for State Health Policy (NASHP). 2025. What health care provisions of the One Big Beautiful Bill Act mean for states. NASHP Health Coverage. https://nashp.org/what-health-care-provisions-of-the-one-big-beautiful-bill-act-mean-for-states/

15: Galewitz, P., Appleby, J., Rayasam, R., and Wolfson, B. 2025. 5 ways Trump’s megabill will limit healthcare access. Shots: Health News, National Public Radio. https://www.npr.org/sections/shots-health-news/2025/07/02/nx-s1-5453870/senate-republicans-tax-bill-medicaid-health-care

16: Lee, C. 2025. Abortion is legal in Maine, but Trump’s Big Beautiful Bill could gut much of the state’s reproductive health care access. Reproductive Health, TIME. https://time.com/7299743/trump-big-beautiful-bill-reproductive-health-care-maine/

17: Goldman, R. 2025. What is the One Big Beautiful Bill and its impact? League of Women Voters. https://www.lwv.org/blog/what-one-big-beautiful-bill-and-its-impact#:~:text=Federal%20funding%2C%20including%20Medicaid%2C%20is,filed%20lawsuits%20challenging%20the%20law.

18: Cruz-Martinez, G. 2025. What to know about new Medicaid cuts: is your local hospital closing soon? Kiplinger Today. https://www.kiplinger.com/taxes/medicaid-cuts-and-your-local-hospital

19: Gaffney, A., Himmelstein, D. and Woolhandler, S. 2025. Projected effects of proposed cuts in federal Medicaid expenditures on Medicaid enrollment, uninsurance, health care, and health. Annals of Internal Medicine, vol. 25. https://doi.org/10.7326/ANNALS-25-00716

20: Ku, L., Kwon, K., Krips, M., Gorak, T. and Cordes, J. 2025. How Medicaid and SNAP cutbacks in the One Big Beautiful Bill would trigger big and bigger job losses across states. The Commonwealth Fund Issue Briefs.

https://www.commonwealthfund.org/publications/issue-briefs/2025/jun/how-medicaid-snap-cutbacks-one-big-beautiful-bill-trigger-job-losses-states

21: Watson, G., Li, H., York, E., Muresianu, A., Cole, A., Van Ness, P. and Durante. A. 2025. One Big Beautiful Bill Act tax policies: details and analysis. Tax Foundation. https://taxfoundation.org/research/all/federal/big-beautiful-bill-senate-gop-tax-plan/