Drug-Drug Interactions With Over-The-Counter Medicines: Mind the Unprescribed.

BACKGROUND: This review provides a summary of the currently available clinical data on drug-drug interactions (DDIs) involving over-the-counter (OTC) medicines. It aims to educate and increase awareness among health care providers and to support decisions in daily practice. METHODS: An extensive literature search was performed using bibliographic databases available through PubMed.gov. An initial structured search was performed using the keywords "drug-drug-interaction AND (over-the-counter OR OTC)," without further restrictions except for the language. The initial results were screened for all described DDIs involving OTC drugs, and further information was gathered specifically on these drugs using dedicated database searches and references found in the bibliography from the initial hits. RESULTS: From more than 1200 initial hits (1972-June 2021), 408 relevant publications were screened for DDIs involving OTC drugs, leading to 2 major findings: first, certain types of drug regimens are more prone to DDIs or have more serious DDI-related consequences, such as antiretroviral, anti-infective, and oral anticancer therapies. Second, although most DDIs involve OTC drugs as the perpetrators, some prescription drugs (statins or phosphodiesterase-5 inhibitors) that currently have OTC status can be identified as the victims in DDIs. The following groups were identified to be frequently involved in DDIs: nonsteroidal anti-inflammatory drugs, food supplements, antacids, proton-pump inhibitors, H2 antihistamines, laxatives, antidiarrheal drugs, and herbal drugs. CONCLUSIONS: The most significant finding was the lack of high-quality evidence for commonly acknowledged interactions. High-quality interaction studies involving different phenotypes in drug metabolism (cytochrome P450) and distribution (transporters) are urgently needed. This should include modern and critical drugs, such as oral anticancer medications and direct oral anticoagulants.

A meta-analysis of randomized controlled trials of a traditional Chinese medicine prescription, modified RunChang-Tang, in treating functional constipation.

BACKGROUND: Modified Runchang-Tang (MRCT), a Chinese herbal medicine, is widely used to treat functional constipation (FC), which is a common digestive system disease. However, its efficacy has not been evaluated systematically and objectively. Thus, a meta-analysis was conducted to assess the efficacy and safety of MRCT for treating functional constipation. METHODS: We searched for relevant publications from Embase, Medline, The Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Data for relevant literature. The timeframe of retrieval was set from the founding date of each database to July 15, 2020. RESULT: A total of 26 randomized controlled trials with 2103 individuals were included in this meta-analysis. All trials were conducted in mainland China and were written in Chinese. The results showed that MRCT monotherapy provided better symptom relief in FC patients compared to prokinetic agent monotherapy (odds ratio, [OR] = 4.06), osmotic laxatives (OR = 4.39) and stimulant laxatives (OR = 2.99). Additionally, there were no obvious adverse effects in MRCT group compared with control group. CONCLUSION: MRCT treatment is an efficient and safe treatment for FC. However, considering the limitations of this study, further well-designed randomized controlled trials are required to validate this conclusion.

[Study on the Safety of Perinatal Medication].

We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarified that prescriptions of antihypertensive drugs for pregnant women increased during the second half of pregnancy, while prescriptions of anti-epileptic and anti-anxiety drugs decreased after pregnancy using a claims database. A survey of pharmacists and pharmacy students revealed a lack of awareness of effective folic acid intake to reduce the risk of neural tube defects in infants. The percentage of pre-pregnancy folic acid supplementation among pregnant women participating in the Babies and their Parents' Longitudinal Observation in Suzuki Memorial Hospital on Intrauterine Period (BOSHI) study, the JECS, and the Tohoku Medical Megabank (TMM) Birth and Three-Generation (BirThree) cohort study was 6.3-18.0%. As a result of close examination of the records of inquiries to the Drug Information Office of our hospital, and of cases in which our lactation plan sheet was applied, it was found that there were discrepancies between the information on the drug package insert and the information on Medications & Mother's Milk, etc. in Japan. The results obtained have been clinically applied in daily practice and we are continuing our research while taking measures.

Unveiling the comparative efficacy and tolerability of comprehensive treatments for migraine: A protocol of systematic review and Bayesian network meta-analysis.

BACKGROUND: Migraine is a chronic paroxysmal incapacitating neurological disorder, which endangers the health of human worldwide ranking as the third most prevalent medical condition. There are no comprehensive estimates of treatments for migraine. We will conduct this systematic review and Bayesian network meta-analysis (NMA) to synthesis quantitative and comparative evidence on the efficacy and tolerability of all the known pharmacological and non-pharmacological interventions for migraine. METHOD: We will perform the systematic electronic search of the literature utilizing MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing & Allied Health (CINAHL), and PsycINFO. We will only include randomized controlled trials (RCTs) of high quality which appraise the efficacy or safety of any potential pharmacological or non-pharmacological interventions in the treatment of patients with migraine. The traditional pairwise meta-analyses will be performed to anticipate the heterogeneities and publication bias and the NMA will be conducted within a Bayesian hierarchical model framework to obtain estimates for all valuable treatments for migraine. The entire heterogeneity will be quantified by Q statistic and I2 index. Other analyses included sensitivity analyses, meta-regression, and subgroup analyses will also be conducted. The whole process will be conducted using in R-3.6.0 software. RESULTS: This study will obtain the efficacy and tolerability of all potential treatments for migraine, aiming at providing consolidated evidence to help make the best choice of interventions. The results will be published in a peer-reviewed journal. DISCUSSION: This Bayesian network meta-analysis may be the first attempt to quantitatively synthesize the efficacy and tolerability of all potential treatments for migraine. And this method can ensure us to fully utilize both the direct and indirect evidence as well as gain the comparative estimates displayed in the derived hierarchies. Besides, we have registered this protocol on the international prospective register of systematic review (PROSPERO) (CRD42020157278).

Prevalence of potential interactions of medications, including herbs and supplements, before, during, and after chemotherapy in patients with breast and prostate cancer.

BACKGROUND: The use of herbs and supplements (HS) is common among patients with cancer, yet limited information exists about potential medication interactions (PMIs) with HS use around chemotherapy. METHODS: Patients with breast or prostate cancer who had recently finished chemotherapy at 2 academic medical centers were surveyed by telephone. Interviewers inquired about all medications, including HS, before, during, and after chemotherapy. Micromedex, Lexicomp, and Natural Medicines Comprehensive Database interaction software programs were used to determine PMIs. RESULTS: A total of 67 subjects (age range, 39-77 years) were evaluated in this study. Participants were primarily White patients (73%) with breast cancer (87%). The median number of medications was 11 (range, 2-28) during the entire study and was highest during chemotherapy (7; range, 2-22). Approximately four-fifths (84%) used HS. A total of 1747 PMIs were identified, and they represented 635 unique PMIs across all 3 timeframes, with most occurring during chemotherapy. Prescription-related PMIs (70%) were the most common type, and they were followed by HS-related (56%) and anticancer treatment-related PMIs (22%). Approximately half of the PMIs (54%) were categorized as moderate interactions, and more than one-third (38%) were categorized as major interactions. Patient use of HS increased from 51% during chemotherapy to 66% after chemotherapy, and this correlated with an increased prevalence of HS PMIs (46% to 60%). HS users were more likely to be at risk for a major PMI than non-HS users (92% vs 70%; P = .038). CONCLUSIONS: The use of HS remains prevalent among patients with cancer and may place them at risk for PMIs both during chemotherapy and after the completion of treatment. LAY SUMMARY: This study evaluates the risk of potential medication interactions for patients with breast or prostate cancer undergoing chemotherapy. The results show that patients often use herbs and supplements during treatment. Prescription medications are most often associated with medication interactions, which are followed by herb and supplement-related interactions. More than one-third of potential medication interactions are considered major. Patients should be educated about the risk of herb and supplement-related medication interactions during treatment.

Blood donor exposome and impact of common drugs on red blood cell metabolism.

Computational models based on recent maps of the RBC proteome suggest that mature erythrocytes may harbor targets for common drugs. This prediction is relevant to RBC storage in the blood bank, in which the impact of small molecule drugs or other xenometabolites deriving from dietary, iatrogenic, or environmental exposures ("exposome") may alter erythrocyte energy and redox metabolism and, in so doing, affect red cell storage quality and posttransfusion efficacy. To test this prediction, here we provide a comprehensive characterization of the blood donor exposome, including the detection of common prescription and over-the-counter drugs in blood units donated by 250 healthy volunteers in the Recipient Epidemiology and Donor Evaluation Study III Red Blood Cell-Omics (REDS-III RBC-Omics) Study. Based on high-throughput drug screenings of 1366 FDA-approved drugs, we report that approximately 65% of the tested drugs had an impact on erythrocyte metabolism. Machine learning models built using metabolites as predictors were able to accurately predict drugs for several drug classes/targets (bisphosphonates, anticholinergics, calcium channel blockers, adrenergics, proton pump inhibitors, antimetabolites, selective serotonin reuptake inhibitors, and mTOR), suggesting that these drugs have a direct, conserved, and substantial impact on erythrocyte metabolism. As a proof of principle, here we show that the antacid ranitidine - though rarely detected in the blood donor population - has a strong effect on RBC markers of storage quality in vitro. We thus show that supplementation of blood units stored in bags with ranitidine could - through mechanisms involving sphingosine 1-phosphate-dependent modulation of erythrocyte glycolysis and/or direct binding to hemoglobin - improve erythrocyte metabolism and storage quality.

The Changes in Medication Prescribing Among the Older People with Cognitive Impairment in the Acute Care Setting.

PURPOSE: Most older people with cognitive impairment usually have multiple comorbidities. In the last decade, the guidelines for the management of chronic diseases have been changed, leading to changes in the patterns of medication prescribing and in the prevalence of drug-related problems (DRPs). The main objectives were to explore the changes in medication use and in the prevalence of polypharmacy (PP), the use of potentially inappropriate medications (PIMs) and drug-drug interactions (DDIs) among older hospitalized adults with cognitive impairment in a 5-year period. PATIENTS AND METHODS: Older hospitalized patients with cognitive impairment diagnosed by cognitive performance scale (CPS) score of 2 or more at tertiary hospital in Brisbane, Australia in 2009 and 2015 to 2016 were enrolled. Prescribed medication use, and exposures to PP, PIM and/or DDI were evaluated at two time points. The associated factors with patients exposed to >1 criteria of PP, PIM or DDI were analyzed by using logistic regression analyses. RESULTS: The median number of prescribed medications was not significantly different between the two periods. The number of medications use as dermatological agents and analgesics substantially increased over 5 years. In contrast, there was a decrease in prescription of drugs for acid-related disorders, drugs used in diabetes, and mineral supplements. Most of the participants were exposed to at least one of PP, PIM or DDI. In multivariate regression analysis, the presence of diabetes diagnosis was a risk factor associated with increased exposure to >1 criteria of PP, PIM or DDI. CONCLUSION: The patterns of many prescribed medications use have altered in a 5-year period. The present study confirms that the majority of older adults with cognitive impairment admitted in an acute care setting are prone to PP, PIM and DDI. Comprehensive medication reviews should be undertaken in clinical care of older patients with cognitive impairment.

Anatomical and physiological alterations of pregnancy.

The extensive metabolic demands of pregnancy require specific physiological and anatomical changes. These changes affect almost all organ systems, including the cardiovascular, respiratory, renal, gastrointestinal, and hematologic system. The placenta adds another layer of complexity. These changes make it challenging for clinicians to understand presenting signs and symptoms, or to interpret laboratory and radiological tests. Furthermore, these physiological alterations can affect the pharmacokinetics and pharmacodynamics of drugs. Drug safety in lactation is only supported by limited evidence. In addition, the teratogenic effects of medications are often extrapolated from animals, which further adds uncertainties. Unfortunately, pregnant women are only rarely included in clinical drug trials, while doses, regimens, and side effects are often extrapolated from studies conducted in non-pregnant populations. In this comprehensive review, we present the changes occurring in each system with its effects on the pharmacokinetic variables. Understanding these physiological changes throughout normal pregnancy helps clinicians to optimize the health of pregnant women and their fetuses. Furthermore, the information on pregnancy-related physiology is also critical to guide study design in this vulnerable 'orphan' population, and provides a framework to explore pregnancy-related pathophysiology such as pre-eclampsia.

[Use of medication, supplements and natural products during pregnancy].

INTRODUCTION: Evidence-based information regarding the use of medication during pregnancy is lacking, even though the use of medication during pregnancy is considered common and often neccesary. The aim of this study was to obtain reliable information on the use of medications during the first 20 weeks of pregnancy and the use of vitamins, minerals, fatty acids, herbs and other natural products. Women´s attitude and beliefs towards the use of medications was also examined. MATERIAL AND METHODS: The study was conducted at the Prenatal Diagnosis Unit at Landspitali from January to April 2017. Women who attended routine ultrasound examination at 20 weeks were offered to participate. A questionnaire was submitted to partici-pants in an interview with the researcher following the doctor's appointment. RESULTS: Of the 213 participants, 90% used medication at least once during the first 20 weeks of pregnancy. Approximately 80% of these medications belong to FASS safety classes A and B and are considered safe during pregnancy. The proportion of women who did not use folic acid was 14% which was associated with residence in rural areas (p=0.03) and younger age (p=0.019). Natural products were used by 14% but information about their safety is lacking. The majority (81%) was satisfied with the information they received when a drug was prescribed and 94% said they had sufficient access to information about medication use during pregnancy. The most commonly used sources of information were the internet (51%) and the local midwive (44%). CONCLUSION: The use of medications and supplements during pregnancy is common. Most medications being used are considered safe during pregnancy. The majority of pregnant women take folic acid. Pregnant women have a logical and generally a positive attitude towards medication use during pregnancy.

Prescription of Benzodiazepines and Related Drugs in Patients with Mild Cognitive Deficits and Alzheimer's Disease.

INTRODUCTION: Benzodiazepines and related drugs (BZDR) should be avoided in patients with cognitive impairment. We evaluated the relationship between a BZDR treatment and the health status of patients with Alzheimer's disease (AD). METHODS: Cross-sectional study in 395 AD patients using bivariate and multiple logistic analyses to assess correlations between the prescription of BZDR and patients' characteristics (cognitive and functional capacity, health-related quality of life (HrQoL), neuropsychiatric symptoms). RESULTS: BZDR were used in 12.4% (n=49) of all participants. In bivariate analyses, the prescription was associated with a lower HrQoL, a higher need of care, and the presence of anxiety. Multivariate models revealed a higher risk of BZDR treatment in patients with depression (OR 3.85, 95% CI: 1.45 - 10.27). Community-dwelling participants and those treated by neurologists/psychiatrists had a lower risk of receiving BZDR (OR 0.33, 95% CI: 0.12 - 0.89 and OR 0.16, 95% CI: 0.07 - 0.36). DISCUSSION: The inappropriate use of BZDR conflicts with national and international guidelines. We suggest evaluating indications and treatment duration and improving the knowledge of alternative therapies in healthcare institutions.

Medicated or not medicated hypnotic substance use: strategies in sleep disorders among patients of community pharmacy.

The principal outcome was to identify which hypnotics substances, medicated (benzodiazepines, antihistamine, antidepressant…) or not medicated (herbal medicine, homeopathy, melatonin…), were consumed by community pharmacy patients who reported taking something for sleep disorder, and which factors can influence the consumption of medicated substance rather than nonmedicated substance. Data were collected via a network of 73 partner pharmacies around Nantes, France. Patients who reported taking a substance to sleep completed a questionnaire that collected data relative to the different substances consumed by that person for sleep, and the desired effect. Substances were classified in Hypnotic Drug Substances and nonmedicated hypnotic substances. A logistical regression was done in order to highlight the factors associated with the consumption of Hypnotic Drug Substance rather than nonmedicated hypnotic substances. Six hundred and forty-seven patients were included, with an average age of 58 years and 74% female. The principal strategy employed to combat sleep disorder was the consumption of Hypnotic Drug Substance (54%), followed by herbal medicine (32%) and homeopathy (19%). The factors positively associated with the consumption of a Hypnotic Drug Substance are age, living alone, being out of work, or in the process of looking for a job and being a parent. In our survey, the use of Hypnotic Drug Substance to help patients with sleep is far from systematic. On the other hand, among patients who consume HDS, misuse is still significant, particularly in terms of the duration of consumption.

Psychosocial interventions for chronic pain and comorbid prescription opioid use disorders: A narrative review of the literature.

OBJECTIVE: Opioid misuse in the context of chronic noncancer pain (CNCP) is a multifaceted and complex issue. As opioid misuse and corresponding rates of addiction and overdose deaths exceed epidemic proportions, there is an urgent need for research in this area. The objective of this review is to evaluate the literature addressing psychosocial interventions targeting CNCP and prescription opioid misuse. DESIGN: A systematic search of PubMed, MEDLINE, PsychINFO, ClinicalTrials.gov was conducted to identify studies evaluating psychosocial interventions targeting CNCP and prescription opioid misuse. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: 56 peer-reviewed research articles from 1993 to July, 2016, which included studies of psychosocial interventions for CNCP and opioid use disorders. Studies that examined psychosocial interventions for CNCP, treatment modalities included: cognitive behavioral therapy (CBT), acceptance and commitment therapy, mindfulness-based cognitive therapy and mindfulness-based stress reduction, and chronic pain self-management programs. The psychosocial interventions for opioid misuse included: CBT and relapse prevention, motivational enhancement therapy and stages of change, contingency management, and self-help and peer support-based groups. CONCLUSIONS: The findings of this review offer clinical insight and reinforce the importance of psychosocial interventions in CNCP and opioid use disorders. However, little empirical data are available to guide practitioners in treating patients with CNCP who misuse opioid medications, and thus future research on integrated approaches, is needed.

Opioid Prescribing Patterns and Patient Outcomes by Prescriber Type in the Oregon Prescription Drug Monitoring Program.

Objective: Prescription drug monitoring programs (PDMPs) were created to facilitate responsible use of controlled substances. In Oregon, physicians, physician's assistants (MDs/DOs/PAs), dentists, nurse practitioners (NPs), and naturopathic physicians (NDs) may prescribe opioids, but differences in prescribing practices, patient mix, and patient outcomes among prescriber types have not been characterized. Methods: De-identified Oregon PDMP data from October 2011 through October 2014 were linked with vital records and a statewide hospital discharge registry. The disciplines of registered prescribers were identified by board affiliations. Prescription profiles associated with opioid overdose risk were tabulated for patients with at least one registered prescriber. Opioid-related hospitalizations and deaths were identified using ICD-9 and ICD-10 codes. Results: There were 5,935 prescribers registered during the study period. Patients of NPs or NDs received more high-risk opioid prescriptions than patients of MDs/DOs/PAs. For example, they received greater proportions of high-dose prescriptions (NP 12.9%, ND 15%, MD/DO/PA 11.1%), and had greater opioid-related hospitalization (NP 1.7%, ND 3.1%, MD/DO/PA 1.2%; P < 0.005 for all). However, patients of NPs or NDs were also more likely to have four or more prescribers (NP 45.3%, ND 58.5%, MD/DO/PA 27.1%), and most of their patients' high-risk opioid prescriptions came from prescribers in other disciplines. Conclusion: Our analysis suggests significant differences in opioid prescription profiles and opioid-related hospitalization and mortality among patients receiving opioid prescriptions from nurse practitioners, naturopathic physicians, or medical clinicians in Oregon. However, these differences appear largely due to differences in patient mix between provider types rather than discipline-specific prescribing practices.

Pregnancy, prescription medicines and the potential risk of herb-drug interactions: a cross-sectional survey.

BACKGROUND: Pregnant women are routinely prescribed medicines while self-medicating with herbal natural products to treat predominantly pregnancy related conditions. The aim of this study was to assess the potential for herb-drug interactions (HDIs) in pregnant women and to explore possible herb-drug interactions and their potential clinical significance. METHODS: A cross-sectional survey of women during early pregnancy or immediately postpartum in North-East Scotland. Outcome measures included; Prescription medicines use excluding vitamins and potential HDIs assessed using Natural Medicines Comprehensive Database. RESULTS: The survey was completed by 889 respondents (73% response rate). 45.3% (403) reported the use of at least one prescription medicine, excluding vitamins. Of those taking prescription medicines, 44.9% (181) also reported concurrent use of at least one HNP (Range 1-12). A total of 91 different prescription medicines were reported by respondents using HNPs. Of those taking prescription medicines, 44.9% (181) also reported concurrent use of at least one HNP (Range 1-12). Thirty-four herb-drug interactions were identified in 23 (12.7%) women with the potential to increase the risk of postpartum haemorrhage, alter maternal haemodynamics, and enhance maternal/fetal CNS depression. Almost all were rated as moderate (93.9%), one as a potentially major (ginger and nifedipine) and only one minor (ondansetron and chamomile). CONCLUSION: Almost half of pregnant women in this study were prescribed medicines excluding vitamins and minerals and almost half of these used HNPs. Potential moderate to severe HDIs were identified in an eighth of the study cohort. Healthcare professionals should be aware that the concurrent use of HNPs and prescription medicines during pregnancy is common and carries potential risks.

Prescription drug use during pregnancy in France: a study from the national health insurance permanent sample.

PURPOSE: To provide an up-to-date account of drug prescription during pregnancy in France from 2011 to 2014 using the permanent sample of the French national computerized healthcare database and with a focus on recommended supplementations, fetotoxic drugs and teratogenic drugs. METHODS: All pregnancies identified by the International Classification of Diseases, 10th Revision codes list in the hospitalization database, lasting more than 9 weeks of amenorrhea and whose delivery occurred between 01/01/2011 and 12/31/2014, were included. Drugs delivered between the trimester before and until the end of the pregnancy were included. Drug exposure prevalence was calculated for each year and according to pregnancy trimesters. RESULTS: The study included 28,491 pregnancies with a median number of 9 [5-13] (median [IQ range]) drugs delivered. The most prescribed drug class was antianemia (in 72.5% of exposed). The prescription rate of recommended vitamins (B9 and D) increased over the study period (+10%). Influenza vaccination also increased but remained at a low rate (1%). Exposure to fetotoxic drugs decreased as pregnancy advanced. Exposure to the main teratogenic antiepileptics was stable over the study period. Low-income pregnant women had a higher average drug consumption except for recommended vitamins. CONCLUSION: Pregnant French women are among the largest consumers of prescription medications worldwide. Overall, the dispensation trends observed in this study are in line with the recommendations of the French National College of Gynecologists and Obstetricians. Nevertheless, while being low, exposure to fetotoxic drugs, teratogenic drugs or those under safety alerts still occurred. Supplementations and vaccines in low-income pregnant women should also be increased.

Health and Public Policy to Facilitate Effective Prevention and Treatment of Substance Use Disorders Involving Illicit and Prescription Drugs: An American College of Physicians Position Paper.

Substance use disorders involving illicit and prescription drugs are a serious public health issue. In the United States, millions of individuals need treatment for substance use disorders but few receive it. The rising number of drug overdose deaths and the changing legal status of marijuana pose new challenges. In this position paper, the American College of Physicians maintains that substance use disorder is a treatable chronic medical condition and offers recommendations on expanding treatment options, the legal status of marijuana, addressing the opioid epidemic, insurance coverage of substance use disorders treatment, education and workforce, and public health interventions.

Higher Prescription Opioid Dose is Associated With Worse Patient-Reported Pain Outcomes and More Health Care Utilization.

Some previous research has examined pain-related variables on the basis of prescription opioid dose, but data from studies involving patient-reported outcomes have been limited. This study examined the relationships between prescription opioid dose and self-reported pain intensity, function, quality of life, and mental health. Participants were recruited from 2 large integrated health systems, Kaiser Permanente Northwest (n = 331) and VA Portland Health Care System (n = 186). To be included, participants had to have musculoskeletal pain diagnoses and be receiving stable doses of long-term opioid therapy. We divided participants into 3 groups on the basis of current prescription opioid dose in daily morphine equivalent dose (MED): low dose (5-20 mg MED), moderate dose (20.1-50 mg MED), and higher dose (50.1-120 mg MED) groups. A statistically significant trend emerged where higher prescription opioid dose was associated with moderately sized effects including greater pain intensity, more impairments in functioning and quality of life, poorer self-efficacy for managing pain, greater fear avoidance, and more health care utilization. Rates of potential alcohol and substance use disorders also differed among groups. Findings from this evaluation reveal significant differences in pain-related and substance-related factors on the basis of prescription opioid dose. PERSPECTIVE: This study included 517 patients who were prescribed long-term opioid therapy and compared differences on pain- and mental health-related variables on the basis of prescription opioid dose. Findings reveal small- to medium-sized differences on pain-related variables, alcohol and substance use, and health care utilization on the basis of the dose of opioid prescribed.