Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in adolescents, adults, and older adults: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania.

BACKGROUND: A panel convened by the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania conducted systematic reviews and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after simple and surgical tooth extraction(s) and for the temporary management (ie, definitive dental treatment not immediately available) of toothache associated with pulp and periapical diseases in adolescents, adults, and older adults. TYPES OF STUDIES REVIEWED: The panel conducted 4 systematic reviews to determine the effect of opioid and nonopioid analgesics, local anesthetics, corticosteroids, and topical anesthetics on acute dental pain. The panel used the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations, Assessment, Development and Evaluation Evidence-to-Decision Framework to formulate recommendations. RESULTS: The panel formulated recommendations and good practice statements using the best available evidence. There is a beneficial net balance favoring the use of nonopioid medications compared with opioid medications. In particular, nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen likely provide superior pain relief with a more favorable safety profile than opioids. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications are first-line therapy for managing acute dental pain after tooth extraction(s) and the temporary management of toothache. The use of opioids should be reserved for clinical situations when the first-line therapy is insufficient to reduce pain or there is contraindication of nonsteroidal anti-inflammatory drugs. Clinicians should avoid the routine use of just-in-case prescribing of opioids and should exert extreme caution when prescribing opioids to adolescents and young adults.

Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in children: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania.

BACKGROUND: A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years). TYPES OF STUDIES REVIEWED: The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations. RESULTS: The panel formulated 7 recommendations and 5 good practice statements across conditions. There is a small beneficial net balance favoring the use of nonsteroidal anti-inflammatory drugs alone or in combination with acetaminophen compared with not providing analgesic therapy. There is no available evidence regarding the effect of corticosteroids on acute pain after surgical tooth extractions in children. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Nonopioid medications, specifically nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen alone or in combination with acetaminophen, are recommended for managing acute dental pain after 1 or more tooth extractions (that is, simple and surgical) and the temporary management of toothache in children (conditional recommendation, very low certainty). According to the US Food and Drug Administration, the use of codeine and tramadol in children for managing acute pain is contraindicated.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

Measures That Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: ACTTION Critique and Recommended Considerations.

Accurate assessment of inappropriate medication use events (ie, misuse, abuse, and related events) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions. Only 2 approaches have been reported that are specifically designed to identify and classify misuse, abuse, and related events occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion (SR-MAD) instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS). The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of MADDERS as well as SR-MAD. PERSPECTIVE: Identifying a medication's abuse potential requires assessing inappropriate medication use events in clinical trials on the basis of a standardized event classification system. The strengths and limitations of the 2 published methods designed to evaluate inappropriate medication use events are reviewed, with recommended considerations for further development and current implementation.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.

Proposed Guideline Revisions for Dental Sedation and General Anesthesia: Why Target the Safest Level of Sedation?

Recently proposed revisions to the American Dental Association's Guidelines for the Use of Sedation and General Anesthesia by Dentists, aimed at improving safety in dental offices, differentiate between levels of sedation based on drug-induced changes in physiologic and behavioral states. However, the author of this op-ed is concerned the proposed revisions may have far-reaching and unintended consequences.

Medication Treatment Efficacy and Chronic Orofacial Pain.

Chronic pain in the orofacial region has always been a vexing problem for dentists to diagnose and treat effectively. For trigeminal neuropathic pain, there are 3 medications (gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors) to use plus topical anesthetics that have therapeutic efficacy. For chronic daily headaches (often migraine in origin), 3 prophylactic medications have reasonable therapeutic efficacy (ß-blockers, tricyclic antidepressants, and antiepileptic drugs). The 3 Food and Drug Administration-approved drugs for fibromyalgia (pregabalin, duloxetine, and milnacipran) are not robust, with poor efficacy. For osteroarthritis, nonsteroidal anti-inflammatory drugs have therapeutic efficacy and when gastritis contraindicates them, corticosteriod injections are helpful.

Prescribing Opioid Analgesics for Acute Dental Pain: Time to Change Clinical Practices in Response to Evidence and Misperceptions.

As the nation comes to terms with a prescription opioid epidemic, dentistry is beginning to understand its own unintentional contribution and seek ways to address it. The article urges dental providers to reexamine entrenched prescribing habits and thought patterns regarding treatment of acute dental pain. It points to evidence suggesting that nonsteroidal anti-inflammatory drugs are nonaddictive and usually more effective for managing many cases of acute dental pain. The authors provide therapeutic recommendations to help dental providers change prescribing patterns.

Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations.

There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for "precision medicine" or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

Opioid Prescribing in Dentistry: Keys for Safe and Proper Usage.

Although dentists typically prescribe opioids for pain control in lower doses and for shorter periods of time than other healthcare providers, they need to be mindful of potential unintended consequences, such as dependency by the patients for whom they are prescribed and diversion of the unused pills to others, including drug dealers and substance abusers. Due to public health issues related to the misuse or abuse of prescription drugs, dentists must be aware of which drugs are most commonly misused or abused; be able to identify individuals who may be at risk for prescription drug abuse; and be prepared to manage patients at risk in the dental setting. They should also be cognizant of alternatives or modified approaches to using opioids--including long-acting anesthetics, NSAIDs, and combining non-opioid drugs with differing mechanisms of action to enhance their ability to control pain due to an additive effect.

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

Prescription of opioid analgesics for nontraumatic dental conditions in emergency departments.

BACKGROUND: Opioid analgesics prescribed for nontraumatic dental conditions (NTDCs) by emergency physicians continue to receive attention because of the associated potential for misuse, abuse and addiction. This study examined rates of prescription of opioid analgesics and types of opioid analgesics prescribed for NTDC visits in U.S. emergency departments. METHODS: Data from the National Hospital Ambulatory Medical Care Survey from 2007 to 2010 were analyzed. Descriptive statistics and logistic regression analysis were performed and adjusted for the survey design. RESULTS: NTDCs made up 1.7% of all ED visits from 2007 to 2010. The prescription of opioid analgesics was 50.3% for NTDC and 14.8% for non-NTDC visits. The overall rate of opioid analgesics prescribed for NTDCs remained fairly stable from 2007 through 2010. Prescription of opioids was highest among patients aged 19-33 years (56.8%), self-paying (57.1%), and non-Hispanic Whites (53.2%). The probability of being prescribed hydrocodone was highest among uninsured patients (68.7%) and for oxycodone, it was highest among private insurance patients (33.6%). Compared to 34-52 year olds, children 0-4 years were significantly more likely to be prescribed codeine and less likely to be prescribed oxycodone. Compared to non-Hispanic Whites, non-Hispanic Blacks had significantly higher odds of been prescribed codeine and somewhat lower odds of been prescribed oxycodone, but it was not statistically significant. CONCLUSIONS: There was no significant change in the rates of opioid analgesics prescribed over time for NTDC visits to EDs. Age, payer type and race/ethnicity were significant predictors for the prescription of different opioid analgesics by emergency physicians for NTDC visits.

Changing Paradigms for Acute Dental Pain: Prevention Is Better Than PRN.

A B S T R A C T The drugs available for the management of acute orofacial pain have changed very little since the introduction of ibuprofen into practice 40 years ago. Orally effective opioids, acetaminophen, aspirin and NSAIDs remain the mainstay of analgesic therapy. Increased recognition of the societal and personal impact of opioid diversion and abuse requires re-examination of the traditional approach of prescribing an opioid-containing analgesic combination to be administered by the patient "as needed" (PRN) starting postoperatively.

Research designs for proof-of-concept chronic pain clinical trials: IMMPACT recommendations.

Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.

Genomic methods for clinical and translational pain research.

Pain is a complex sensory experience for which the molecular mechanisms are yet to be fully elucidated. Individual differences in pain sensitivity are mediated by a complex network of multiple gene polymorphisms, physiological and psychological processes, and environmental factors. Here, we present the methods for applying unbiased molecular-genetic approaches, genome-wide association study (GWAS), and global gene expression analysis, to help better understand the molecular basis of pain sensitivity in humans and variable responses to analgesic drugs.