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For example, a recent study of patients aged 15—64 years receiving opioids for chronic noncancer pain and followed for up to 13 years revealed that one in patients died from opioid-related overdose at a median of 2. This guideline provides recommendations for the prescribing of opioid pain medication by primary care clinicians for chronic pain i. Although the guideline does not focus broadly on pain management, appropriate use of long-term opioid therapy must be considered within the context of all pain management strategies including nonopioid pain medications and nonpharmacologic treatments.

The guideline is intended to ensure that clinicians and patients consider safer and more effective treatment, improve patient outcomes such as reduced pain and improved function, and reduce the number of persons who develop opioid use disorder, overdose, or experience other adverse events related to these drugs. The recommendations in the guideline are voluntary, rather than prescriptive standards. They are based on emerging evidence, including observational studies or randomized clinical trials with notable limitations. Clinicians should consider the circumstances and unique needs of each patient when providing care.

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Primary care clinicians report having concerns about opioid pain medication misuse, find managing patients with chronic pain stressful, express concern about patient addiction, and report insufficient training in prescribing opioids Across specialties, physicians believe that opioid pain medication can be effective in controlling pain, that addiction is a common consequence of prolonged use, and that long-term opioid therapy often is overprescribed for patients with chronic noncancer pain These attitudes and beliefs, combined with increasing trends in opioid-related overdose, underscore the need for better clinician guidance on opioid prescribing.

Clinical practice guidelines focused on prescribing can improve clinician knowledge, change prescribing practices 28 , and ultimately benefit patient health. Professional organizations, states, and federal agencies e. Existing guidelines share some common elements, including dosing thresholds, cautious titration, and risk mitigation strategies such as using risk assessment tools, treatment agreements, and urine drug testing.

However, there is considerable variability in the specific recommendations e. Most guidelines, especially those that are not based on evidence from scientific studies published in or later, also do not reflect the most recent scientific evidence about risks related to opioid dosage. This CDC guideline offers clarity on recommendations based on the most recent scientific evidence, informed by expert opinion and stakeholder and public input.

Scientific research has identified high-risk prescribing practices that have contributed to the overdose epidemic e. Using guidelines to address problematic prescribing has the potential to optimize care and improve patient safety based on evidence-based practice 28 , as well as reverse the cycle of opioid pain medication misuse that contributes to the opioid overdose epidemic. This guideline is intended for primary care clinicians e. Prescriptions by primary care clinicians account for nearly half of all dispensed opioid prescriptions, and the growth in prescribing rates among these clinicians has been above average 3.

Primary care clinicians include physicians as well as nurse practitioners and physician assistants. Although the focus is on primary care clinicians, because clinicians work within team-based care, the recommendations refer to and promote integrated pain management and collaborative working relationships with other providers e. Although the transition from use of opioid therapy for acute pain to use for chronic pain is hard to predict and identify, the guideline is intended to inform clinicians who are considering prescribing opioid pain medication for painful conditions that can or have become chronic.

For this guideline, palliative care is defined in a manner consistent with that of the Institute of Medicine as care that provides relief from pain and other symptoms, supports quality of life, and is focused on patients with serious advanced illness. Palliative care can begin early in the course of treatment for any serious illness that requires excellent management of pain or other distressing symptoms End-of-life care is defined as care for persons with a terminal illness or at high risk for dying in the near future in hospice care, hospitals, long-term care settings, or at home.

Patients within the scope of this guideline include cancer survivors with chronic pain who have completed cancer treatment, are in clinical remission, and are under cancer surveillance only. The guideline is not intended for patients undergoing active cancer treatment, palliative care, or end-of-life care because of the unique therapeutic goals, ethical considerations, opportunities for medical supervision, and balance of risks and benefits with opioid therapy in such care. The recommendations address the use of opioid pain medication in certain special populations e.

The available evidence concerning the benefits and harms of long-term opioid therapy in children and adolescents is limited, and few opioid medications provide information on the label regarding safety and effectiveness in pediatric patients. However, observational research shows significant increases in opioid prescriptions for pediatric populations from to 36 , and a large proportion of adolescents are commonly prescribed opioid pain medications for conditions such as headache and sports injuries e.

Misuse of opioid pain medications in adolescence strongly predicts later onset of heroin use Thus, risk of opioid medication use in pediatric populations is of great concern. Additional clinical trial and observational research is needed, and encouraged, to inform development of future guidelines for this critical population.

The recommendations are not intended to provide guidance on use of opioids as part of medication-assisted treatment for opioid use disorder. Some of the recommendations might be relevant for acute care settings or other specialists, such as emergency physicians or dentists, but use in these settings or by other specialists is not the focus of this guideline.

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This method specifies the systematic review of scientific evidence and offers a transparent approach to grading quality of evidence and strength of recommendations. This hierarchy reflects degree of confidence in the effect of a clinical action on health outcomes. The categories include type 1 evidence randomized clinical trials or overwhelming evidence from observational studies , type 2 evidence randomized clinical trials with important limitations, or exceptionally strong evidence from observational studies , type 3 evidence observational studies or randomized clinical trials with notable limitations , and type 4 evidence clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations.

Type of evidence is categorized by study design as well as limitations in study design or implementation, imprecision of estimates, variability in findings, indirectness of evidence, publication bias, magnitude of treatment effects, dose-response gradient, and a constellation of plausible biases that could change observations of effects. Type 1 evidence indicates that one can be very confident that the true effect lies close to that of the estimate of the effect; type 2 evidence means that the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different; type 3 evidence means that confidence in the effect estimate is limited and the true effect might be substantially different from the estimate of the effect; and type 4 evidence indicates that one has very little confidence in the effect estimate, and the true effect is likely to be substantially different from the estimate of the effect 47 , When no studies are present, evidence is considered to be insufficient.

Four major factors determine the category of the recommendation: the quality of evidence, the balance between desirable and undesirable effects, values and preferences, and resource allocation cost. Category A recommendations apply to all persons in a specified group and indicate that most patients should receive the recommended course of action. Category B recommendations indicate that there should be individual decision making; different choices will be appropriate for different patients, so clinicians must help patients arrive at a decision consistent with patient values and preferences, and specific clinical situations According to the GRADE methodology, a particular quality of evidence does not necessarily imply a particular strength of recommendation 48 — Category A recommendations can be made based on type 3 or type 4 evidence when the advantages of a clinical action greatly outweigh the disadvantages based on a consideration of benefits and harms, values and preferences, and costs.

Category B recommendations are made when the advantages and disadvantages of a clinical action are more balanced. GRADE methodology is discussed extensively elsewhere 47 , The U. The coverage requirements went into effect September 23, Similar requirements are in place for vaccinations recommended by ACIP, but do not exist for other recommendations made by CDC, including recommendations within this guideline. A previously published systematic review sponsored by the Agency for Healthcare Research and Quality AHRQ on the effectiveness and risks of long-term opioid treatment of chronic pain 14 , 52 initially served to directly inform the recommendation statements.

This systematic clinical evidence review addressed the effectiveness of long-term opioid therapy for outcomes related to pain, function, and quality of life; the comparative effectiveness of different methods for initiating and titrating opioids; the harms and adverse events associated with opioids; and the accuracy of risk-prediction instruments and effectiveness of risk mitigation strategies on outcomes related to overdose, addiction, abuse, or misuse.

For the current guideline development, CDC conducted additional literature searches to update the evidence review to include more recently available publications and to answer an additional clinical question about the effect of opioid therapy for acute pain on long-term use. As identified in the AHRQ-sponsored clinical evidence review, the overall evidence base for the effectiveness and risks of long-term opioid therapy is low in quality per the GRADE criteria.

Thus, contextual evidence is needed to provide information about the benefits and harms of nonpharmacologic and nonopioid pharmacologic therapy and the epidemiology of opioid pain medication overdose and inform the recommendations. Further, as elucidated by the GRADE Working Group, supplemental information on clinician and patient values and preferences and resource allocation can inform judgments of benefits and harms and be helpful for translating the evidence into recommendations. CDC conducted a contextual evidence review to supplement the clinical evidence review based on systematic searches of the literature.

CDC constructed narrative summaries of this contextual evidence and used the information to support the clinical recommendations. On the basis of a review of the clinical and contextual evidence review methods are described in more detail in subsequent sections of this report , CDC drafted recommendation statements focused on determining when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use.

CDC sought the input of experts to assist in reviewing the evidence and providing perspective on how CDC used the evidence to develop the draft recommendations. CDC identified representatives from leading primary care professional organizations to represent the audience for this guideline. Finally, CDC identified state agency officials and representatives based on their experience with state guidelines for opioid prescribing that were developed with multiple agency stakeholders and informed by scientific literature and existing evidence-based guidelines.

Prior to their participation, CDC asked potential experts to reveal possible conflicts of interest such as financial relationships with industry, intellectual preconceptions, or previously stated public positions. Experts could not serve if they had conflicts that might have a direct and predictable effect on the recommendations. CDC excluded experts who had a financial or promotional relationship with a company that makes a product that might be affected by the guideline.

CDC reviewed potential nonfinancial conflicts carefully e. CDC determined the risk of these types of activities to be minimal for the identified experts. All experts completed a statement certifying that there was no potential or actual conflict of interest. Activities that did not pose a conflict e. Experts provided individual ratings for each draft recommendation statement based on the balance of benefits and harms, evidence strength, certainty of values and preferences, cost, recommendation strength, rationale, importance, clarity, and ease of implementation. CDC hosted an in-person meeting of the experts that was held on June 23—24, , in Atlanta, Georgia, to seek their views on the evidence and draft recommendations and to better understand their premeeting ratings.

Although there was widespread agreement on some of the recommendations, there was disagreement on others.

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Experts did not vote on the recommendations or seek to come to a consensus. Decisions about recommendations to be included in the guideline, and their rationale, were made by CDC. After revising the guideline, CDC sent written copies of it to each of the experts for review and asked for any additional comments; CDC reviewed these written comments and considered them when making further revisions to the draft guideline. The experts have not reviewed the final version of the guideline. Interagency collaboration will be critical for translating these recommendations into clinical practice. Department of Veterans Affairs, the U.

The SRG included representatives from professional organizations that represent specialties that commonly prescribe opioids e. Each of these representatives provided written comments. Once input was received from the full SRG, CDC reviewed all comments and carefully considered them when revising the draft guideline. To obtain initial perspectives from constituents on the recommendation statements, including clinicians and prospective patients, CDC convened a constituent engagement webinar and circulated information about the webinar in advance through announcements to partners.

CDC hosted the webinar on September 16 and 17, , provided information about the methodology for developing the guideline, and presented the key recommendations. CDC received comments during and for 2 days following the first webinar. Over 1, constituent comments were received. Comments were reviewed and carefully considered when revising the draft guideline. Three experts independently reviewed the guideline to determine the reasonableness and strength of recommendations; the clarity with which scientific uncertainties were clearly identified; and the rationale, importance, clarity, and ease of implementation of the recommendations.

CDC assessed and managed potential conflicts of interest using a process similar to the one as described for solicitation of expert opinion. No financial interests were identified in the disclosure and review process, and nonfinancial activities were determined to be of minimal risk; thus, no significant conflict of interest concerns were identified.

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CDC reviewed peer review comments and revised the draft guideline accordingly. To obtain comments from the public on the full guideline, CDC published a notice in the Federal Register 80 FR announcing the availability of the guideline and the supporting clinical and contextual evidence reviews for public comment.

The comment period closed January 13, CDC received more than 4, comments from the general public, including patients with chronic pain, clinicians, families who have lost loved ones to overdose, medical associations, professional organizations, academic institutions, state and local governments, and industry.

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CDC reviewed each of the comments and carefully considered them when revising the draft guideline. BSC members are special government employees appointed as CDC advisory committee members; as such, all members completed an OGE Form to disclose relevant interests. BSC members also reported on their disclosures during meetings. Disclosures for the BSC are reported in the guideline. CDC provided the BSC with the draft guideline as well as summaries of comments provided to CDC by stakeholders, constituents, and peer reviewers, and edits made to the draft guideline in response.

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  • The OGW included a balance of perspectives from audiences directly affected by the guideline, audiences that would be directly involved with implementing the recommendations, and audiences qualified to provide representation. The OGW comprised clinicians, subject matter experts, and a patient representative, with the following perspectives represented: primary care, pain medicine, public health, behavioral health, substance abuse treatment, pharmacy, patients, and research.

    The professional credentials and interests of OGW members were carefully reviewed to identify possible conflicts of interest such as financial relationships with industry, intellectual preconceptions, or previously stated public positions. Only OGW members whose interests were determined to be minimal were selected. When an activity was perceived as having the potential to affect a specific aspect of the recommendations, the activity was disclosed, and the OGW member was recused from discussions related to that specific aspect of the recommendations e.

    Disclosures for the OGW are reported. CDC and the OGW identified ad-hoc consultants to supplement the workgroup expertise, when needed, in the areas of pediatrics, occupational medicine, obstetrics and gynecology, medical ethics, addiction psychiatry, physical medicine and rehabilitation, guideline development methodology, and the perspective of a family member who lost a loved one to opioid use disorder or overdose. The BSC charged the OGW with reviewing the quality of the clinical and contextual evidence reviews and reviewing each of the recommendation statements and accompanying rationales.

    For each recommendation statement, the OGW considered the quality of the evidence, the balance of benefits and risks, the values and preferences of clinicians and patients, the cost feasibility, and the category designation of the recommendation A or B. Members of the public provided comments at this meeting. CDC conducted a clinical systematic review of the scientific evidence to identify the effectiveness, benefits, and harms of long-term opioid therapy for chronic pain, consistent with the GRADE approach 47 , A previously published AHRQ-funded systematic review on the effectiveness and risks of long-term opioid therapy for chronic pain comprehensively addressed four clinical questions 14 , CDC, with the assistance of a methodology expert, searched the literature to identify newly published studies on these four original questions.

    Because long-term opioid use might be affected by use of opioids for acute pain, CDC subsequently developed a fifth clinical question last in the series below , and in collaboration with a methodologist conducted a systematic review of the scientific evidence to address it. In brief, five clinical questions were addressed:.

    The effectiveness of short-term opioid therapy has already been established However, opioids have unique effects such as tolerance and physical dependence that might influence assessments of benefit over time. These effects raise questions about whether findings on short-term effectiveness of opioid therapy can be extrapolated to estimate benefits of long-term therapy for chronic pain. Thus, it is important to consider studies that provide data on long-term benefit. For certain opioid-related harms overdose, fractures, falls, motor vehicle crashes , observational studies were included with outcomes measured at shorter intervals because such outcomes can occur early during opioid therapy, and such harms are not captured well in short-term clinical trials.

    Complete methods and data for the AHRQ report, upon which this updated systematic review is based, have been published previously 14 , Study authors developed the protocol using a standardized process 53 with input from experts and the public and registered the protocol in the PROSPERO database Also included were relevant studies from an earlier review 10 in which searches were conducted without a date restriction, reference lists were reviewed, and ClinicalTrials. CDC updated the AHRQ literature search using the same search strategies as in the original review including studies published before April, Seven additional studies met inclusion criteria and were added to the review.

    Evidence was categorized into the following types: type 1 randomized clinical trials or overwhelming evidence from observational studies , type 2 randomized clinical trials with important limitations, or exceptionally strong evidence from observational studies , type 3 observational studies, or randomized clinical trials with notable limitations , or type 4 clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations.

    When no studies were present, evidence was considered to be insufficient. Per GRADE methods, type of evidence was categorized by study design as well as a function of limitations in study design or implementation, imprecision of estimates, variability in findings, indirectness of evidence, publication bias, magnitude of treatment effects, dose-response gradient, and constellation of plausible biases that could change effects. Results were synthesized qualitatively, highlighting new evidence identified during the update process.

    Meta-analysis was not attempted due to the small numbers of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of the studies. The main findings of this updated review are consistent with the findings of the AHRQ report In summary, evidence on long-term opioid therapy for chronic pain outside of end-of-life care remains limited, with insufficient evidence to determine long-term benefits versus no opioid therapy, though evidence suggests risk for serious harms that appears to be dose-dependent.

    These findings supplement findings from a previous review of the effectiveness of opioids for adults with chronic noncancer pain. The GRADE evidence summary with type of evidence ratings for the five clinical questions for the current evidence review are outlined Table 1. This summary is based on studies included in the AHRQ review 35 studies plus additional studies identified in the updated search seven studies. Additional details on findings from the original review are provided in the full AHRQ report 14 , Thus, the body of evidence for KQ1 is rated as insufficient 0 studies contributing For KQ2, the body of evidence is rated as type 3 12 studies contributing; 11 from the original review plus one new study.

    One fair-quality cohort study found that long-term opioid therapy is associated with increased risk for an opioid abuse or dependence diagnosis as defined by ICDCM codes versus no opioid prescription Rates of opioid abuse or dependence diagnosis ranged from 0. Ten fair-quality uncontrolled studies reported estimates of opioid abuse, addiction, and related outcomes 55 — Factors associated with increased risk for misuse included history of substance use disorder, younger age, major depression, and use of psychotropic medications 55 , Two studies reported on the association between opioid use and risk for overdose 66 , One large fair-quality retrospective cohort study found that recent opioid use was associated with increased risk for any overdose events and serious overdose events versus nonuse It also found higher doses associated with increased risk.

    A similar pattern was observed for serious overdose. A good-quality population-based, nested case-control study also found a dose-dependent association with risk for overdose death Findings of increased fracture risk for current opioid use, versus nonuse, were mixed in two studies 68 , Two studies found an association between opioid use and increased risk for cardiovascular events 70 , Indirect evidence was found for endocrinologic harms increased use of medications for erectile dysfunction or testosterone from one previously included study; laboratory-defined androgen deficiency from one newly reviewed study 72 , For KQ3, the body of evidence is rated as type 4 14 studies contributing; 12 from the original review plus two new studies.

    A fair-quality retrospective cohort study based on national Veterans Health Administration system pharmacy data found that methadone was associated with lower overall risk for all-cause mortality versus morphine 81 , and a fair-quality retrospective cohort study based on Oregon Medicaid data found no statistically significant differences between methadone and long-acting morphine in risk for death or overdose symptoms However, a new observational study 83 found methadone associated with increased risk for overdose versus sustained-release morphine among Tennessee Medicaid patients.

    The observed inconsistency in study findings suggests that risks of methadone might vary in different settings as a function of different monitoring and management protocols, though more research is needed to understand factors associated with safer methadone prescribing. For dose escalation, the AHRQ report included one fair-quality randomized trial that found no differences between more liberal dose escalation and maintenance of current doses after 12 months in pain, function, all-cause withdrawals, or withdrawals due to opioid misuse For example, evidence on the comparative effectiveness of opioid tapering or discontinuation versus maintenance, and of different opioid tapering strategies, was limited to small, poor-quality studies 85 — For KQ4, the body of evidence is rated as type 3 for the accuracy of risk assessment tools and insufficient for the effectiveness of use of risk assessment tools and mitigation strategies in reducing harms six studies contributing; four from the original review plus two new studies.

    The AHRQ report included four studies 88 — 91 on the accuracy of risk assessment instruments, administered prior to opioid therapy initiation, for predicting opioid abuse or misuse. Results for the Opioid Risk Tool ORT 89 — 91 were extremely inconsistent; evidence for other risk assessment instruments was very sparse, and studies had serious methodological shortcomings. For the ORT, sensitivity was 0.

    No study evaluated the effectiveness of risk mitigation strategies use of risk assessment instruments, opioid management plans, patient education, urine drug testing, use of PDMP data, use of monitoring instruments, more frequent monitoring intervals, pill counts, or use of abuse-deterrent formulations for improving outcomes related to overdose, addiction, abuse, or misuse. For KQ5, the body of evidence is rated as type 3 two new studies contributing. Two fair-quality retrospective cohort studies found opioid therapy prescribed for acute pain associated with greater likelihood of long-term use.

    Use of opioids within 7 days of surgery was associated with increased risk for use at 1 year. Versus no early opioid use, the adjusted OR was 2. Contextual evidence is complementary information that assists in translating the clinical research findings into recommendations. CDC conducted contextual evidence reviews on four topics to supplement the clinical evidence review findings:. CDC also reviewed clinical guidelines that were relevant to opioid prescribing and could inform or complement the CDC recommendations under development e.

    CDC conducted a contextual evidence review to assist in developing the recommendations by providing an assessment of the balance of benefits and harms, values and preferences, and cost, consistent with the GRADE approach. Given the public health urgency for developing opioid prescribing recommendations, a rapid review was required for the contextual evidence review for the current guideline.

    Rapid reviews are used when there is a need to streamline the systematic review process to obtain evidence quickly Methods used to streamline the process include limiting searches by databases, years, and languages considered, and truncating quality assessment and data abstraction protocols. In brief, CDC conducted systematic literature searches to identify original studies, systematic reviews, and clinical guidelines, depending on the topic being searched.

    CDC also solicited publication referrals from subject matter experts. Given the need for a rapid review process, grey literature e. Multiple reviewers scanned study abstracts identified through the database searches and extracted relevant studies for review. Findings from the contextual reviews provide indirect evidence and should be interpreted accordingly. The studies that addressed benefits and harms, values and preferences, and resource allocation most often employed observational methods, used short follow-up periods, and evaluated selected samples.

    Therefore the strength of the evidence from these contextual review areas was considered to be low, comparable to type 3 or type 4 evidence. The quality of evidence for nonopioid pharmacologic and nonpharmacologic pain treatments was generally rated as moderate, comparable to type 2 evidence, in systematic reviews and clinical guidelines e. Similarly, the quality of evidence on pharmacologic and psychosocial opioid use disorder treatment was generally rated as moderate, comparable to type 2 evidence, in systematic reviews and clinical guidelines.

    Several nonpharmacologic and nonopioid pharmacologic treatments have been shown to be effective in managing chronic pain in studies ranging in duration from 2 weeks to 6 months. For example, CBT that trains patients in behavioral techniques and helps patients modify situational factors and cognitive processes that exacerbate pain has small positive effects on disability and catastrophic thinking Exercise therapy can help reduce pain and improve function in chronic low back pain 98 , improve function and reduce pain in osteoarthritis of the knee 99 and hip , and improve well-being, fibromyalgia symptoms, and physical function in fibromyalgia Multimodal and multidisciplinary therapies e.

    Nonopioid pharmacologic approaches used for pain include analgesics such as acetaminophen, NSAIDs, and cyclooxygenase 2 COX-2 inhibitors; selected anticonvulsants; and selected antidepressants particularly tricyclics and serotonin and norepinephrine reuptake inhibitors [SNRIs]. Multiple guidelines recommend acetaminophen as first-line pharmacotherapy for osteoarthritis — or for low back pain but note that it should be avoided in liver failure and that dosage should be reduced in patients with hepatic insufficiency or a history of alcohol abuse Although guidelines also recommend NSAIDs as first-line treatment for osteoarthritis or low back pain , , NSAIDs and COX-2 inhibitors do have risks, including gastrointestinal bleeding or perforation as well as renal and cardiovascular risks FDA has recently strengthened existing label warnings that NSAIDs increase risks for heart attack and stroke, including that these risks might increase with longer use or at higher doses Several guidelines agree that first- and second-line drugs for neuropathic pain include anticonvulsants gabapentin or pregabalin , tricyclic antidepressants, and SNRIs — Interventional approaches such as epidural injection for certain conditions e.

    Epidural injection has been associated with rare but serious adverse events, including loss of vision, stroke, paralysis, and death Balance between benefits and harms is a critical factor influencing the strength of clinical recommendations. In particular, CDC considered what is known from the epidemiology research about benefits and harms related to specific opioids and formulations, high dose therapy, co-prescription with other controlled substances, duration of use, special populations, and risk stratification and mitigation approaches. Additional information on benefits and harms of long-term opioid therapy from studies meeting rigorous selection criteria is provided in the clinical evidence review e.

    CDC also considered the number of persons experiencing chronic pain, numbers potentially benefiting from opioids, and numbers affected by opioid-related harms. Finally, CDC considered the effectiveness of treatments that addressed potential harms of opioid therapy opioid use disorder. Time-scheduled opioid use was associated with substantially higher average daily opioid dosage than as-needed opioid use in one study Methadone has been associated with disproportionate numbers of overdose deaths relative to the frequency with which it is prescribed for pain. Regarding high-dose therapy, several epidemiologic studies that were excluded from the clinical evidence review because patient samples were not restricted to patients with chronic pain also examined the association between opioid dosage and overdose risk 23 , 24 , — Consistent with the clinical evidence review, the contextual review found that opioid-related overdose risk is dose-dependent, with higher opioid dosages associated with increased overdose risk.

    A listing of common opioid medications and their MME equivalents is provided Table 2. Regarding coprescription of opioids with benzodiazepines, epidemiologic studies suggest that concurrent use of benzodiazepines and opioids might put patients at greater risk for potentially fatal overdose. In one of these studies 67 , among decedents who received an opioid prescription, those whose deaths were related to opioids were more likely to have obtained opioids from multiple physicians and pharmacies than decedents whose deaths were not related to opioids.

    Regarding duration of use, patients can experience tolerance and loss of effectiveness of opioids over time Patients who do not experience clinically meaningful pain relief early in treatment i. Regarding populations potentially at greater risk for harm, risk is greater for patients with sleep apnea or other causes of sleep-disordered breathing, patients with renal or hepatic insufficiency, older adults, pregnant women, patients with depression or other mental health conditions, and patients with alcohol or other substance use disorders.

    Interpretation of clinical data on the effects of opioids on sleep-disordered breathing is difficult because of the types of study designs and methods employed, and there is no clear consensus regarding association with risk for developing obstructive sleep apnea syndrome However, opioid therapy can decrease respiratory drive, a high percentage of patients on long-term opioid therapy have been reported to have an abnormal apnea-hypopnea index , opioid therapy can worsen central sleep apnea in obstructive sleep apnea patients, and it can cause further desaturation in obstructive sleep apnea patients not on continuous positive airway pressure CPAP Reduced renal or hepatic function can result in greater peak effect and longer duration of action and reduce the dose at which respiratory depression and overdose occurs Older adults might also be at increased risk for falls and fractures related to opioids — Opioids used in pregnancy can be associated with additional risks to both mother and fetus.

    Some studies have shown an association of opioid use in pregnancy with birth defects, including neural tube defects , , congenital heart defects , and gastroschisis ; preterm delivery , poor fetal growth , and stillbirth Importantly, in some cases, opioid use during pregnancy leads to neonatal opioid withdrawal syndrome Patients with mental health comorbidities and patients with histories of substance use disorders might be at higher risk than other patients for opioid use disorder 62 , , Recent analyses found that depressed patients were at higher risk for drug overdose than patients without depression, particularly at higher opioid dosages, although investigators were unable to distinguish unintentional overdose from suicide attempts Regarding risk stratification approaches, limited evidence was found regarding benefits and harms.

    Potential benefits of PDMPs and urine drug testing include the ability to identify patients who might be at higher risk for opioid overdose or opioid use disorder, and help determine which patients will benefit from greater caution and increased monitoring or interventions when risk factors are present. For example, one study found that most fatal overdoses could be identified retrospectively on the basis of two pieces of information, multiple prescribers and high total daily opioid dosage, both important risk factors for overdose , that are available to prescribers in the PDMP However, limited evaluation of PDMPs at the state level has revealed mixed effects on changes in prescribing and mortality outcomes Potential harms of risk stratification include underestimation of risks of opioid therapy when screening tools are not adequately sensitive, as well as potential overestimation of risk, which could lead to inappropriate clinical decisions.

    Regarding risk mitigation approaches, limited evidence was found regarding benefits and harms. Although no studies were found to examine prescribing of naloxone with opioid pain medication in primary care settings, naloxone distribution through community-based programs providing prevention services for substance users has been demonstrated to be associated with decreased risk for opioid overdose death at the community level Concerns have been raised that prescribing changes such as dose reduction might be associated with unintended negative consequences, such as patients seeking heroin or other illicitly obtained opioids or interference with appropriate pain treatment With the exception of a study noting an association between an abuse-deterrent formulation of OxyContin and heroin use, showing that some patients in qualitative interviews reported switching to another opioid, including heroin, for many reasons, including cost and availability as well as ease of use , CDC did not identify studies evaluating these potential outcomes.

    Finally, regarding the effectiveness of opioid use disorder treatments, methadone and buprenorphine for opioid use disorder have been found to increase retention in treatment and to decrease illicit opioid use among patients with opioid use disorder involving heroin — Although findings are mixed, some studies suggest that effectiveness is enhanced when psychosocial treatments e.

    Clinician and patient values and preferences can inform how benefits and harms of long-term opioid therapy are weighted and estimate the effort and resources required to effectively provide implementation support. Many physicians lack confidence in their ability to prescribe opioids safely , to predict or detect prescription drug abuse, and to discuss abuse with their patients Clinicians do not consistently use practices intended to decrease the risk for misuse, such as PDMPs , , urine drug testing , and opioid treatment agreements This is likely due in part to challenges related to registering for PDMP access and logging into the PDMP which can interrupt normal clinical workflow if data are not integrated into electronic health record systems , competing clinical demands, perceived inadequate time to discuss the rationale for urine drug testing and to order confirmatory testing, and feeling unprepared to interpret and address results For example, patients taking hydrocodone for noncancer pain commonly reported side effects including dizziness, headache, fatigue, drowsiness, nausea, vomiting, and constipation Patients with chronic pain in focus groups emphasized effectiveness of goal setting for increasing motivation and functioning Patients taking high dosages report reliance on opioids despite ambivalence about their benefits and regardless of pain reduction, reported problems, concerns, side effects, or perceived helpfulness Resource allocation cost is an important consideration in understanding the feasibility of clinical recommendations.

    CDC searched for evidence on opioid therapy compared with other treatments; costs of misuse, abuse, and overdose from prescription opioids; and costs of specific risk mitigation strategies e. Although there are perceptions that opioid therapy for chronic pain is less expensive than more time-intensive nonpharmacologic management approaches, many pain treatments, including acetaminophen, NSAIDs, tricyclic antidepressants, and massage therapy, are associated with lower mean and median annual costs compared with opioid therapy COX-2 inhibitors, SNRIs, anticonvulsants, topical analgesics, physical therapy, and CBT are also associated with lower median annual costs compared with opioid therapy There are 12 recommendations Box 1.

    Each recommendation is followed by a rationale for the recommendation, with considerations for implementation noted. In accordance with the ACIP GRADE process, CDC based the recommendations on consideration of the clinical evidence, contextual evidence including benefits and harms, values and preferences, resource allocation , and expert opinion.

    For each recommendation statement, CDC notes the recommendation category A or B and the type of the evidence 1, 2, 3, or 4 supporting the statement Box 2. Expert opinion is reflected within each of the recommendation rationales. Where differences in expert opinion emerged for detailed actions within the clinical recommendations or for implementation considerations, CDC notes the differences of opinion in the supporting rationale statements. Category A recommendations indicate that most patients should receive the recommended course of action; category B recommendations indicate that different choices will be appropriate for different patients, requiring clinicians to help patients arrive at a decision consistent with patient values and preferences and specific clinical situations.

    Consistent with the ACIP 47 and GRADE process 48 , category A recommendations were made, even with type 3 and 4 evidence, when there was broad agreement that the advantages of a clinical action greatly outweighed the disadvantages based on a consideration of benefits and harms, values and preferences, and resource allocation. Category B recommendations were made when there was broad agreement that the advantages and disadvantages of a clinical action were more balanced, but advantages were significant enough to warrant a recommendation.

    All recommendations are category A recommendations, with the exception of recommendation 10, which is rated as category B. Recommendations were associated with a range of evidence types, from type 2 to type 4. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate recommendation category: A, evidence type: 3.

    Patients with pain should receive treatment that provides the greatest benefits relative to risks. The contextual evidence review found that many nonpharmacologic therapies, including physical therapy, weight loss for knee osteoarthritis, psychological therapies such as CBT, and certain interventional procedures can ameliorate chronic pain. There is high-quality evidence that exercise therapy a prominent modality in physical therapy for hip or knee 99 osteoarthritis reduces pain and improves function immediately after treatment and that the improvements are sustained for at least 2—6 months.

    Exercise therapy also can help reduce pain and improve function in low back pain and can improve global well-being and physical function in fibromyalgia 98 , Multimodal therapies and multidisciplinary biopsychosocial rehabilitation-combining approaches e. Multimodal therapies are not always available or reimbursed by insurance and can be time-consuming and costly for patients. Interventional approaches such as arthrocentesis and intraarticular glucocorticoid injection for pain associated with rheumatoid arthritis or osteoarthritis and subacromial corticosteroid injection for rotator cuff disease can provide short-term improvement in pain and function.

    Evidence is insufficient to determine the extent to which repeated glucocorticoid injection increases potential risks such as articular cartilage changes in osteoarthritis and sepsis Serious adverse events are rare but have been reported with epidural injection Several nonopioid pharmacologic therapies including acetaminophen, NSAIDs, and selected antidepressants and anticonvulsants are effective for chronic pain.

    Selected anticonvulsants such as pregabalin and gabapentin can improve pain in diabetic neuropathy and post-herpetic neuralgia contextual evidence review. Pregabalin, gabapentin, and carbamazepine are FDA-approved for treatment of certain neuropathic pain conditions, and pregabalin is FDA approved for fibromyalgia management.

    In patients with or without depression, tricyclic antidepressants and SNRIs provide effective analgesia for neuropathic pain conditions including diabetic neuropathy and post-herpetic neuralgia, often at lower dosages and with a shorter time to onset of effect than for treatment of depression see contextual evidence review. Tricyclics and SNRIs can also relieve fibromyalgia symptoms. Because patients with chronic pain often suffer from concurrent depression , and depression can exacerbate physical symptoms including pain , patients with co-occurring pain and depression are especially likely to benefit from antidepressant medication see Recommendation 8.

    Nonopioid pharmacologic therapies are not generally associated with substance use disorder, and the numbers of fatal overdoses associated with nonopioid medications are a fraction of those associated with opioid medications contextual evidence review. For example, acetaminophen, NSAIDs, and opioid pain medication were involved in , , and 16, pharmaceutical overdose deaths in the United States in However, nonopioid pharmacologic therapies are associated with certain risks, particularly in older patients, pregnant patients, and patients with certain co-morbidities such as cardiovascular, renal, gastrointestinal, and liver disease see contextual evidence review.

    NSAID use has been associated with gastritis, peptic ulcer disease, cardiovascular events , , and fluid retention, and most NSAIDs choline magnesium trilisate and selective COX-2 inhibitors are exceptions interfere with platelet aggregation Clinicians should review FDA-approved labeling including boxed warnings before initiating treatment with any pharmacologic therapy. Although opioids can reduce pain during short-term use, the clinical evidence review found insufficient evidence to determine whether pain relief is sustained and whether function or quality of life improves with long-term opioid therapy KQ1.

    While benefits for pain relief, function, and quality of life with long-term opioid use for chronic pain are uncertain, risks associated with long-term opioid use are clearer and significant. Based on the clinical evidence review, long-term opioid use for chronic pain is associated with serious risks including increased risk for opioid use disorder, overdose, myocardial infarction, and motor vehicle injury KQ2. At a population level, more than , persons in the United States have died from opioid pain-medication-related overdoses since see Contextual Evidence Review.

    Integrated pain management requires coordination of medical, psychological, and social aspects of health care and includes primary care, mental health care, and specialist services when needed Despite this, these therapies are not always or fully covered by insurance, and access and cost can be barriers for patients. For many patients, aspects of these approaches can be used even when there is limited access to specialty care. A randomized trial found no difference in reduced chronic low back pain intensity, frequency or disability between patients assigned to relatively low-cost group aerobics and individual physiotherapy or muscle reconditioning sessions Low-cost options to integrate exercise include brisk walking in public spaces or use of public recreation facilities for group exercise.

    Clicking on the main categories reveals a list of broad questions. Clicking on any of these symptoms questions reveals a list of common disorders that might be at the root cause of the particular symptom. Comprehensive HPI and the rest of the history. Infectious Diseases. All rights reserved.

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    A possible non-specific indicator of problems. Malignancy - many cancers e. Conjunctivitis conunctival redness, itching, painless, no visual change, uni- or bilateral other infectious, allergic. Infection - e. Dental infection , poor chronic care, lack of access to dentists.

    Clinical Practice Guidelines

    GERD heartburn, bad taste in mouth when lie down Cancer hx smoking, etoh, slowly progressive sx Psychogenic. COPD, asthma, other. Hypertenion, hyperlipidemia, congestive heart failure, valvular heart disease, coronary artery disease, peripheral vascular disease, stroke, etc. Cerebral hypo-perfusion from sudden drop in blood pressure, noting that BP is a function of: Cardiac output x systemic vascular resistance; and CO is a function of heart rate x stroke volume; and stroke volume is a function of inotropy and pre-load.

    BPH, cancer, stones, intrinsic renal disease, etc. Erectile Dysfunction ED?

    1. The Deterioration of Articular Cartilage in Osteoarthritis by Corticosteroid Injections;
    2. Adult Review of Systems (ROS)!
    3. A Brief Introduction to the Psychology of Religion.
    4. Introduction.

    Cancer progressive, painless hydrocele painless. Risks as per STIs. Infection Acute - bacterial Localize site by Sx - e. Infertility, endometriosis, infection, cancer, etc. Stroke, seizure, neurodegenerative - Multiple sclerosis, ALS, etc. Suggests sensory abnormality - e. Poorly controlled dm see under Genito-Urinary - Frequency. See under General - Weight loss. See under General - Weight gain. Generalized joint pain or swelling? Infection, inflammatory, other. UCSD's Practical Guide to Clinical Medicine A comprehensive physical examination and clinical education site for medical students and other health care professionals.