Changes in medical use of central nervous system stimulants among US adults, 2013 and 2018: a cross-sectional study.

OBJECTIVE: To assess the 5-year changes in the adult medical use of central nervous system (CNS) stimulants with higher risk of dependence and evaluate the population characteristics of users and their medical and/or neurological conditions. DESIGN: Cross-sectional study. SETTING: Annual US Medical Expenditure Panel Survey, a stratified random sample of approximately 30 000 persons designed to produce national population estimates. It focuses on reported medical spending, medical services used, health status and prescription medications. PARTICIPANTS: Adults age 19 years and older who reported obtaining one or more prescriptions for amphetamine or methylphenidate products during two survey years, 2013 and 2018. MAIN OUTCOMES MEASURES: Prescriptions obtained, the specific stimulant product and annual treatment days of drug supplied. RESULTS: In 2018, an estimated 4.1 million US adults (95% CI 3.4 million to 4.8 million) reported prescriptions for CNS stimulants, having filled a mean of 7.3 (95% CI 6.8 to 7.8) prescriptions with a mean of 226 (95% CI 210 to 242) days' supply. Compared with 2013, the estimated number of adults reporting using CNS stimulants in 2018 increased by 1.8 million (95% CI 1.0 million to 2.7 million) or 79.8%. Most 2018 adult stimulant users reported taking psychoactive medication for one or more mental, behavioural or neurodevelopment disorders. Overall, 77.8% (95% CI 72.6% to 83.0%) reported some medication for adult attention deficit disorder, 26.8% (95% CI 22.2% to 31.5%) took medication for anxiety, 25.1% (95% CI 19.9% to 30.3%) for depression and 15.3% (95% CI 9.8% to 20.8%) indicated drug treatment for other mental or neurological disorders. Adult CNS stimulant use was higher in females, in younger age cohorts and among individuals of white race/ethnicity. CONCLUSIONS: Adult medical use of prescription stimulants increased markedly in 5 years and occurred in a population often reporting multiple mental or neurological disorders. Further action is needed to understand and manage this new resurgence in drugs with high risks of dependence.

Primary Care Physicians' Knowledge and Attitudes Regarding Prescription Opioid Abuse and Diversion.

OBJECTIVES: Physicians are a key stakeholder in the epidemic of prescription opioid abuse. Therefore, we assessed their knowledge of opioid abuse and diversion, as well as their support for clinical and regulatory interventions to reduce opioid-related morbidity and mortality. MATERIALS AND METHODS: We conducted a nationally representative postal mail survey of 1000 practicing internists, family physicians, and general practitioners in the United States between February and May 2014. RESULTS: The adjusted response rate was 58%, and all physicians (100%) believed that prescription drug abuse was a problem in their communities. However, only two-thirds (66%) correctly reported that the most common route of abuse was swallowing pills whole, and nearly one-half (46%) erroneously reported that abuse-deterrent formulations were less addictive than their counterparts. In addition, a notable minority of physicians (25%) reported being "not at all" or "only slightly concerned" about the potential for opioid diversion from the licit to the illicit market when this practice is common at all levels of the pharmaceutical supply chain. Most physicians supported clinical and regulatory interventions to reduce prescription opioid abuse, including the use of patient contracts (98%), urine drug testing (90%), requiring prescribers to check a centralized database before prescribing opioids (88%), and instituting greater restrictions on the marketing and promotion of opioids (77% to 82%). Despite this, only one-third of physicians (33%) believed that interventions to reduce prescription opioid abuse had a moderate or large effect on preventing patients' clinically appropriate access to pain treatment. DISCUSSION: Although physicians are unaware of some facets of prescription opioid-related morbidity, most support a variety of clinical and regulatory interventions to improve the risk-benefit balance of these therapies.

Trends in the use of buprenorphine by office-based physicians in the United States, 2003-2013.

BACKGROUND AND OBJECTIVES: Despite buprenorphine's promise as a novel therapy for opioid dependence, little is known about its clinical adoption. We characterized trends in ambulatory use of buprenorphine in the United States. METHODS: Cross-sectional, descriptive analyses of buprenorphine utilization from 2003 to 2013 using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory care. The primary unit of analysis was an office visit where buprenorphine was used for opioid dependence (treatment visit). RESULTS: Between 2003 and 2013, there was significant uptake of buprenorphine in ambulatory treatment visits, from 0.16 million [M] (95% confidence interval [CI] 0.10-0.20) visits in 2003 to 2.1M (CI 1.9-2.3M) treatment visits during 2013. Approximately 90% involved the use of brand name combination buprenorphine/naloxone (Suboxone), although this percentage decreased modestly to 80% by the last quarter of 2013. Buprenorphine prescribing increased among all specialties, but the proportion accounted for by primary care physicians increased significantly from 6.0% in 2003 to 63.5% in 2013 and decreased among psychiatrists from 92.2% to 32.8% over the same time period. CONCLUSIONS: The use of buprenorphine products to treat opioid dependence has increased significantly in the past 10 years and has shifted to greater use by primary care physicians, indicating a rapidly changing face of opioid maintenance therapy in the United States.

Prevalence and treatment of pain in EDs in the United States, 2000 to 2010.

OBJECTIVES: To describe changes in the prevalence and severity of pain and prescribing of non-opioid analgesics in US emergency departments (EDs) from 2000 to 2010. METHODS: Analysis of serial cross-sectional data regarding ED visits from the National Hospital Ambulatory Medical Care Survey. Visits were limited to patients ≥18 years old without malignancy. Outcome measures included annual volume of visits among adults with a primary symptom or diagnosis of pain, annual rates of patient-reported pain severity, and predictors of non-opioid receipt for non-malignant pain. RESULTS: Rates of pain remained stable, representing approximately 45% of visits from 2000 through 2010. Patients reported pain as their primary symptom twice as often as providers reported a primary pain diagnosis (40% vs 20%). The percentage of patients reporting severe pain increased from 25% (95% confidence intervals [CI] 22%-27%) in 2003 to 40% (CI 37%-42%) in 2008. From 2000 to 2010, the proportion of pain visits treated with pharmacotherapies increased from 56% (CI 53%-58%) to 71% (CI 69%-72%), although visits treated exclusively with non-opioids decreased 21% from 28% (CI 27%-30%) to 22% (CI 20%-23%). The adjusted odds of non-opioid rather than opioid receipt were greater among visits for patients 18 to 24 years old (odds ratio [OR] 1.35, CI 1.24-1.46), receiving fewer medicines (OR 2.91, CI 2.70-3.15) and those with a diagnosis of mental illness (OR 2.24, CI 1.99-2.52). CONCLUSIONS: Large increases in opioid utilization in EDs have coincided with reductions in the use of non-opioid analgesics and an unchanging prevalence of pain among patients.

Serum biochemical parameters following heroin withdrawal: an exploratory study.

BACKGROUND: Long-term consumption of opioid compounds, even after withdrawal, affects serum biochemical parameters. Investigating these alterations is a new approach in substance abuse studies. METHOD: This study investigated clinical laboratory results in men who are currently active, recently abstinent and non-heroin users. Participants (N = 240) of this matched cohort study included heroin dependent men referred for abstinence treatment, volunteer men who did not abuse opioids matched for age, sex, body mass index, and educational level (control group). The groups were further sub-divided for analysis into (a) continuous heroin users for more than 2 years (N = 70), the dependent group; (b) heroin abusers with 1 month abstinence period (N = 70), identified as ex-heroin dependents; and (c) a matched, non-dependent control group (N = 100). All participants were tested for fasting blood sugar (FBS), sodium, potassium, calcium, uric acid (UA), blood urea nitrogen (BUN), creatinine, total cholesterol, triglycerides (TGs), total protein, fibrinogen, and prothrombin. RESULTS: Compared to the control group, ex-heroin dependents showed decreased FBS and significantly higher sodium, creatinine, and cholesterol levels. Compared to the heroin dependent group, the ex-heroin dependents showed significant differences in FBS, sodium, calcium, creatinine, UA, and thrombin time. No significant differences were noted between ex-heroin dependents and controls in potassium, calcium, UA, BUN, TGs, total protein, and thrombin time. CONCLUSION: These results demonstrate altered laboratory markers in long-term heroin dependents as well as ex-heroin dependents and suggest the need for further identification, population distribution, and etiological understanding of these biomarkers in individuals who have abused heroin.

Ambulatory diagnosis and treatment of nonmalignant pain in the United States, 2000-2010.

BACKGROUND: Escalating rates of prescription opioid use and abuse have occurred in the context of efforts to improve the treatment of nonmalignant pain. OBJECTIVE: The aim of the study was to characterize the diagnosis and management of nonmalignant pain in ambulatory, office-based settings in the United States between 2000 and 2010. DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional and multivariate regression analyses of the National Ambulatory Medical Care Survey (NAMCS), a nationally representative audit of office-based physician visits, were conducted. MEASURES: (1) Annual visit volume among adults with primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3) receipt of prescription opioid or nonopioid pharmacologic therapy in visits for new musculoskeletal pain. RESULTS: Primary symptoms or diagnoses of pain consistently represented one-fifth of visits, varying little from 2000 to 2010. Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%, whereas nonopioid analgesic prescribing remained unchanged (26%-29% of visits). One-half of new musculoskeletal pain visits resulted in pharmacologic treatment, although the prescribing of nonopioid pharmacotherapies decreased from 38% of visits (2000) to 29% of visits (2010). After adjusting for potentially confounding covariates, few patient, physician, or practice characteristics were associated with a prescription opioid rather than a nonopioid analgesic for new musculoskeletal pain, and increases in opioid prescribing generally occurred nonselectively over time. CONCLUSIONS: Increased opioid prescribing has not been accompanied by similar increases in nonopioid analgesics or the proportion of ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives to prescription opioids may be underutilized as a means of treating ambulatory nonmalignant pain.

Quality of evidence in drug compendia supporting off-label use of typical and atypical antipsychotic medications.

Public and private payers use drug compendia to make coverage determinations, yet the quality of evidence they contain has received little scrutiny. We examined compendia citations regarding antipsychotic drugs, an important drug class given their substantial costs and widespread use. Nearly three-fold as many off-label indications were recommended for atypical as for typical agents, a difference that did not appear to be due to differences in quality of evidence for typical and atypical off-label indications. Given the important role that compendia play in evidence synthesis, coverage decisions, and ultimately, prescription utilization, these data suggest greater efforts are needed to improve the quality of evidence and transparency of evidence evaluations compendia contain.

Gabapentin-induced delirium and dependence.

Gabapentin (Neurontin) is approved by the US Food and Drug Administration for treatment of epilepsy and post-herpetic neuralgia. Despite lack of strong evidence, gabapentin is also often prescribed off-label for psychiatric conditions. The case described here involved a 38-year-old male physician with substance intoxication delirium and psychoactive substance dependence due to high self-administered doses of gabapentin, which had been prescribed at lower doses in combination with buspirone and bupropion for depression and anxiety. This unusual case of gabapentin dependence and abuse involved toxic delirium, intense cravings, and a prolonged post-withdrawal confusional state reminiscent of benzodiazepine withdrawal. Gabapentin is a central nervous system inhibitory agent with likely gamma-aminobutyric acid (GABA)-ergic and non-GABAergic mechanisms of action. The similarity between benzodiazepine withdrawal and what this patient experienced with gabapentin suggests a common role for GABA-related effects. The case reported here suggests the need for heightened concern regarding the off-label prescription of this drug to vulnerable individuals with psychiatric conditions.