Kathleen A. Fairman

Diagnosis and Treatment of ADHD in the United States: Update by Gender and Race

Objective: The aim of this article is to update ADHD diagnosis/treatment trends by age, gender, and race. Method: National Ambulatory Medical Care Survey data were obtained for 2008-2009 to 2012-2013. Physician office visits including ADHD diagnosis and pharmacotherapy were measured per 1,000 population and per 1,000 office visits overall, and by demographic group. Logistic regression models controlled for demographics, psychiatric comorbidities, insurance type, and time period. Interactions of time, demographics, comorbidities, and insurance type were tested. Results: Diagnoses of ADHD increased by 36% in adults and 18% in youth, and diagnosis + drug by 29% in female and 10% in male youths. ADHD diagnosis was 77% less likely among Black than White adults but 24% more likely among Black than White youths in 2012-2013. Conduct disorder (CD) in youths multiplied odds of diagnosis + drug by 3.31; interaction of Black race × CD by 3.78. Conclusion: Upward trends in ADHD diagnosis and treatment have continued but vary markedly by group. Studies of undertreatment/overtreatment are needed.

Policies to mitigate nonmedical use of prescription medications: how should emerging evidence of gabapentin misuse be addressed?

ABSTRACT Introduction: Over the past decade, increased prescription supply has facilitated an epidemic of nonmedical use of controlled substances, including predominantly opioids, as well as benzodiazepines, z-hypnotics, and stimulants. Areas covered: More recently, misuse of noncontrolled prescriptions, such as gabapentin, has been detected. Gabapentin misuse has been associated with drug-related harm and increased healthcare service utilization in a few studies, including a recent large-sample analysis of commercially insured enrollees in the United States (U.S.) Responding to this emerging base of evidence, a small number of U.S. states have acted to prevent or detect gabapentin misuse by requiring the inclusion of gabapentin utilization in reporting to local Prescription Drug Monitoring Programs (PDMPs) and/or imposing other restrictions on gabapentin prescribing (e.g., classification as a controlled substance, quantity limits). These efforts may result in unintentional harm by (1) encouraging ‘doctor shopping’ across state lines to seek lenient regulatory policies and (2) placing the burden for mitigating misuse on individual practitioners. Expert opinion: We call for a unified national approach, comprising federal regulation and enhanced PDMP reporting to address gabapentin misuse, while laying the groundwork for management of new medications of abuse that the healthcare industry may encounter in the future.

Predictors of gabapentin overuse with or without concomitant opioids ina commercially-insured US population

Research suggests the medical consequences of gabapentin overuse depend on whether gabapentin is abused alone or with opioids to potentiate an opioid “high.” The objective of this study was to assess predictors of gabapentin overuse with or without concomitant opioids.

Real-world use of PCSK-9 inhibitors by early adopters: cardiovascular risk factors, statin co-treatment, and short-term adherence in routine clinical practice

Background Inconsistency of real-world medication use with labeled indications may affect cost and clinical value of pharmacotherapy. PCSK-9 inhibitors are labeled in the US for use with statins to reduce low-density lipoprotein cholesterol in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). Objective To assess consistency with labeled indications and treatment persistency for early (first 5 post-launch months) adopters of PCSK-9 inhibitor pharmacotherapy. Methods Retrospective analysis of commercially insured cohorts derived from the Truven Health MarketScan® database was performed. Subjects were aged 18–64 years, initiated PCSK-9 inhibitor or highest-intensity statin (rosuvastatin 40 mg/day or atorvastatin 80 mg/day) pharmacotherapy from August to December 2015, and were enrolled throughout 2015 and during separate baseline (pre-treatment) periods of 6 and 18 months. Baseline ASCVD, FH, and ASCVD events (myocardial infarction, transient ischemic attack, and cerebrovascular occlusion) were measured. Persistency was measured through December 2015 for subcohorts of patients initiating treatment from August to September 2015. Results Baseline disease rates were higher for patients treated with PCSK-9 inhibitors (n=390) compared with highest-intensity statins (n=26,306): ASCVD (68.5% vs 33.4%, respectively); FH (39.7% vs 15.5%); both P<0.001. In 18 months pre-treatment, 35.6% of PCSK-9 inhibitor-treated patients had ≥1 ASCVD event, and 87.9% had a labeled indication. Rates of 60-day nonpersistency for PCSK-9 inhibitors and highest-intensity statins were 33.3% and 39.8%, respectively (P=0.207). During PCSK-9 inhibitor pharmacotherapy, 33.8% of patients had evidence of statin supply and, of those initiating treatment from August to September, 40.9% filled ≥1 statin prescription. Of those with sustained pre-treatment statin use, 34.8% had no statin supply during PCSK-9 inhibitor pharmacotherapy. Conclusion Among early-adopting PCSK-9 inhibitor-treated patients, the off-label diagnosis rate was 12%; a majority lacked statin co-treatment; and one third filled prescriptions for ≤60 days. Inconsistency with labeled uses may reflect prescriber/patient decisions, health-insurance coverage determinations, or statin intolerance not reported on claims.

Call for increased pharmacovigilance of gabapentin

Huybrechts and colleagues find increased risk of neonatal drug withdrawal when gabapentin and opioids are co-prescribed.1 We conducted the first large scale assessment of the prevalence and clinical consequences of gabapentin misuse.23 The top 1% of gabapentin users consumed or diverted 19% of total gabapentin supply at mean (median) 11 274 (9534) mg/day; nearly 25% of these users exceeded 12 822 mg/day.2 Additionally, 24% …

Concomitant use of opioid medications with triptans or serotonergic antidepressants in US office-based physician visits

Background Opioids are not recommended for routine treatment of migraine because their benefits are outweighed by risks of medication overuse headache and abuse/dependence. A March 2016 US Food and Drug Administration (FDA) safety communication warned of the risk of serotonin syndrome from using opioids concomitantly with 5-hydroxytryptamine receptor agonists (triptans) or serotonergic antidepressants: selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs). Epidemiological information about co-prescribing of these medications is limited. The objective of this study was to estimate the nationwide prevalence of co-prescribing of an opioid with a serotonergic antidepressant and/or triptan in US office-based physician visits made by 1) all patients and 2) patients diagnosed with migraine. Methods National Ambulatory Medical Care Survey (NAMCS) data were obtained for 2013 and 2014. Physician office visits that included the new or continued prescribing of ≥1 opioid medication with a triptan or an SSRI/SNRI were identified. Co-prescribed opioids were stratified by agent to determine the proportion of co-prescriptions with opioids posing a higher risk of serotonergic agonism (meperidine, tapentadol, and tramadol). Results Of an annualized mean 903.6 million office-based physician visits in 2013–2014, 17.7 million (2.0% of all US visits) resulted in the prescribing of ≥1 opioid medication with a triptan or an SSRI/SNRI. Opioid–SSRI/SNRI was co-prescribed in 16,044,721 visits, while opioid–triptan was co-prescribed in 1,622,827 visits. One-fifth of opioid co-prescribing was attributable to higher-risk opioids, predominantly tramadol (18.6% of opioid–SSRI/SNRI, 21.8% of opioid–triptan). Of 7,672,193 visits for patients diagnosed with migraine, 16.3% included opioid prescribing and 2.0% included co-prescribed opioid–triptan. Conclusion During a period approximately 2 years prior to an FDA warning about the risk of serotonin syndrome from opioid–SSRI/SNRI or opioid–triptan co-prescribing, use of these combinations was common in the USA. Studies on prescribing patterns following the March 2016 warning, and on the risk of serotonin syndrome associated with these co-prescriptions, are needed.

Cardiovascular Risk Factors and Provision of Lifestyle Counseling for Diabetes or Prediabetes With Comorbid Obesity: Analysis of Office-Based Physician Visits Made by Patients 20 Years of Age or Older

Obesity, defined as a BMI ≥30 kg/m2, is one of the most common and costly preventable causes of death in the United States (1–3). Increased prevalence of obesity, which affects an estimated 36.5% of U.S. adults (1), has been linked to a growing risk of morbidity from several medical conditions, including diabetes and heart disease (4). In parallel with increases in obesity rates (4), the age-adjusted percentage of adults with diagnosed diabetes increased from 3.6% in 1990 to 8.7% in 2010 (5), and an estimated 9.3% of U.S. adults had diagnosed diabetes in 2015 (6). Prediabetes, another consequence of obesity, affects ∼34% of U.S. adults, placing them at increased risk of developing diabetes and cardiovascular complications (5,7). Of those with prediabetes, only about 12% report having been told by a health care professional that they had the condition (5). A previous analysis of office-based physician visits made by U.S. patients with diabetes in 2005, conducted by Neumiller et al. with data reported in the National Ambulatory Medical Care Survey (NAMCS), found that comorbid obesity increased the likelihood of presenting with concomitant disease states such as heart failure (6.1% for obesity/diabetes visits vs. 4.0% for all diabetes visits), depression (21.2 vs. 10.8%), hyperlipidemia (62.2 vs. 46.3%), and hypertension (71.4 vs. 64.1%) (8). Obesity was also associated with increases in the ordering or provision of lifestyle counseling (e.g., diet/nutrition counseling in 58.8% of obesity/diabetes visits vs. 36.6% of all diabetes visits) (8). Since the time of the study by Neumiller et al., attention to obesity-related health risks has increased, with a focus on the potential for early screening and intervention to prevent disease progression, such as from prediabetes to diabetes or from diabetes to cardiovascular disease (9,10). These trends make it important …

Adverse Events Associated With Antibiotics and Intravenous Therapies for Post–Lyme Disease Syndrome in a Commercially Insured Sample

Background Non-guideline-endorsed posttreatment courses of antibiotics for post-Lyme disease syndrome (PLDS) have been linked to adverse patient outcomes, but these findings have yet to be validated in large systematic evaluations. Methods A retrospective cohort analysis of medical and pharmacy claims derived from the Truven Health Market Scan Commercial Claims and Encounters Database assessed 90-day incidence rates of adverse events (AEs) associated with PLDS treatment (PLDS-Tx). Patients were diagnosed with PLDS ≥6 months after initial diagnosis and standard antibiotic treatment for Lyme disease. Comparison cohorts included intravenous (IV) PLDS-Tx with or without oral antibiotics; oral antibiotic-only PLDS-Tx; or neither. Results Composite AE incidence rates were higher for patients treated with IV or oral PLDS-Tx than for patients not receiving either treatment (18.7%, 16.8%, and 13.4%, respectively; P = .019). Significant between-group differences in AE incidence rates were noted for electrolyte imbalance (4.0%, 1.5%, and 0.7%, respectively; P = .001) and infection (14.0%, 12.7%, and 9.3%; P = .006). Infection prevalence increased by 22.0% in the IV treatment group and 17.7% in the oral group. Incidence rates for all-cause and AE-related hospital stays and emergency department visits were higher for treated than nontreated patients, particularly when treatment was IV (all P < .01). Of IV-treated patients, 7.3% experienced an incident all-cause inpatient stay and 11.3% an incident all-cause emergency department visit, compared with, respectively, 2.2% and 3.4% of those treated with oral antibiotics and 0.9% and 1.9% of nontreated patients. Conclusions Use of IV therapies or oral antibiotics for PLDS was associated with increased patient morbidity within 90 days.

Use of power-law analysis to predict abuse or diversion of prescribed medications: proof-of-concept mathematical exploration

ObjectiveTo conduct a proof-of-concept study comparing Lorenz-curve analysis (LCA) with power-law (exponential function) analysis (PLA), by applying segmented regression modeling to 1-year prescription claims data for three medications—alprazolam, opioids, and gabapentin—to predict abuse and/or diversion using power-law zone (PLZ) classification.ResultsIn 1-year baseline observation, patients classified into the top PLZ groups (PLGs) were demographically and diagnostically similar to those in Lorenz-1 (top 1% of utilizers) and Lorenz-25 (top 25%). For prediction of follow-up (6-month post-baseline) Lorenz-1 use of alprazolam and opioids (i.e., potential abuse/diversion), PLA had somewhat lower sensitivity compared with LCA (83.5–95.4% vs. 99.5–99.9%, respectively) but better specificity (98.2–98.8% vs. 75.5%) and much better positive predictive value (PPV; 34.5–45.3% vs. 4.0–4.6%). Of top-PLG alprazolam- and opioid-treated patients, respectively, 20.7 and 9.9% developed incident (new) Lorenz-1 in followup, compared with < 3% of Lorenz-25 patients. For gabapentin, neither PLA nor LCA predicted incident Lorenz-1 (PPV = 0.0–1.4%). For all three medications, PLA sensitivity for follow-up hospitalization was < 5%, but specificity was better for PLA (97.3–99.2%) than for LCA (74.3–75.4%). PLA better identified patients at risk of future controlled substance abuse/diversion than did LCA, but the technique needs refinement before widespread use.

Prevalence of depression and receipt of antidepressant pharmacotherapy among patients with Parkinson’s disease: a national assessment of US office-based physician visits

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