On- and Off-Label Atypical Antipsychotic Prescription Trends Across a Nine-Year Period Among Adolescents Pre- to Post-COVID-19.

OBJECTIVE: This study examined atypical antipsychotic prescribing by Food and Drug Administration (FDA) approved-use (on-label) status for adolescents before and during the COVID-19 pandemic. METHODS: Retrospective data were collected from electronic health records (EHRs) of adolescents aged 10-17 years in Kaiser Permanente Northern California. New outpatient atypical antipsychotic prescription orders during 2013-2021 were evaluated. Prescriptions were categorized as on-label if linked in EHRs to autism, psychosis, bipolar disorder, or Tourette's diagnoses; otherwise, they were potentially off-label (herein, off-label). Trend analysis of monthly prescribing rates assessed slope change at pandemic onset for the cohort and by sex and age groups. RESULTS: Among 5828 patients, 74.5% of new antipsychotic orders were off-label in 2021. Overall prescribing decreased significantly until early 2020 (slope = -0.045, P < .01) but then significantly increased through 2021 (post-March 2020 slope change = 0.211, P = .01). Off-label prescriptions increased at a similar rate during the COVID-19 time period, but on-label prescriptions did not change significantly. Males and younger adolescents (ages 10-14 years) showed significant decreases until early 2020, while females and older adolescents (ages 15-17 years) did not. Females and younger adolescents exhibited significant increases in overall and off-label prescribing rates following pandemic onset; older adolescents exhibited increases in overall prescriptions while males had no detectable changes. CONCLUSIONS: Antipsychotic prescribing declined slightly but then increased significantly following COVID-19 onset for overall and off-label prescriptions. Pandemic onset differentially impacted antipsychotic prescribing by sex and age, with overall and off-label prescribing driven by increases among female and younger adolescents.

Incident mental health episodes after initiation of gabapentinoids vs. dopamine agonists for early-onset idiopathic restless legs syndrome.

Limited long-term safety information exists for gabapentinoid treatment of idiopathic restless legs syndrome (RLS). We estimated incident mental health-related emergency department visits and hospitalizations with a primary mental health diagnosis (primary outcome) among early-onset idiopathic RLS patients following first-line treatment initiation and examined outcome risk with gabapentinoids compared with dopamine agonists (DAs). A retrospective cohort study was conducted using administrative claims data from 2012 to 2019. Adults with early-onset (18-44 years) idiopathic RLS initiating either gabapentinoids or DAs within 60 days of new diagnosis were followed up to two years. Incidence rates were calculated and a log-binomial regression model with propensity score weighting estimated relative risk of the outcome and of substance use disorders (SUDs) as a secondary analysis with gabapentinoids. Among a cohort of 6,672 patients, 4,986 (74.7%) initiated DAs and 1,686 (25.3%) gabapentinoids. Incidence of the primary outcome (49.8 [95% CI 40.8-69.3] per 1,000 person-years) and SUDs (49.5 [95% CI 40.6-59.9] per 1,000 person-years) were higher in the gabapentinoid group compared with the DA group. A statistically significant risk of mental health diagnoses with gabapentinoids was not detected, but SUD risk was significant after covariate adjustment. High-risk mental health comorbidities (i.e., SUDs) should be considered when initiating RLS treatments.

Treatment initiation and utilization patterns of pharmacotherapies for early-onset idiopathic restless legs syndrome.

OBJECTIVE/BACKGROUND: Restless legs syndrome (RLS) is a complex condition associated with circadian rhythm that disrupts sleep and can cause multisystemic consequences. This study assesses pharmacotherapy treatment initiation, estimates annual treatment prevalence, and assesses treatment patterns for early-onset idiopathic RLS. METHODS: We used the MarketScan Commercial Claims Database from 2012 to 2019 to conduct a new user retrospective cohort study. Annual treatment prevalence was calculated from a cross-sectional sample. Newly diagnosed adults with early-onset (18-44 years) idiopathic RLS who initiated on and off-label gabapentinoids, dopamine agonists, or levodopa/carbidopa were included. Among monotherapy users who had one year of insurance enrollment, treatment patterns (single fill, continuous use of initiated therapy, switching, and add-on therapy) were examined and mean time on the initial treatment (as a measure of persistence) was calculated. RESULTS: In total, 6, 828 patients were initiated on monotherapy treatment for early-onset idiopathic RLS in which 4,638 met all inclusion criteria. In 2019, annual prevalence of monotherapy treatment of diagnosed patients for ropinirole was 171.3/1,000 patients; 85.0/1,000 patients for pramipexole; and 132.1/1,000 patients for gabapentin. Overall, 22.3% (n = 1,033) of patients maintained their initiated pharmacotherapy for the entire year. Rotigotine had the longest persistence (mean 185.4 [161.4 SD] days) but this user group was the smallest (n = 29). Gabapentin enacarbil, pregabalin, and rotigotine use was low (2.8% total). CONCLUSION: Ropinirole, pramipexole, and gabapentin were initiated most often for early-onset idiopathic RLS. FDA-approved agents for RLS, including gabapentin enacarbil and rotigotine, were used less frequently. In general, persistence was low for all RLS study drugs examined.

A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019.

In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016-2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn's disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson's disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.

Practice Patterns and Training Needs Among Physicians Certifying Patients for Medical Marijuana in Florida.

BACKGROUND: Little is known about the clinical training or practice experiences among physicians who certify patients for medical marijuana. The objective of this study was to determine information sources, factors influencing recommendations, clinical practices in patient assessment, communications, and recommendations, and priority areas for additional training among physicians who certify patients for medical marijuana. METHODS: A cross-sectional state-wide anonymous survey of registered medical marijuana physicians in Florida between June and October 2020 was administered. Numerical responses were quantified using counts and percentages. The frequencies for "often" and "always" responses were aggregated when appropriate. RESULTS: Among 116 respondents, the mean (standard deviation) age was 57 (12) years old, and 70% were male. The most frequently used information sources were research articles (n = 102, 95%), followed by online sources (n = 99, 93%), and discussions with other providers and dispensary staff (n = 84, 90%). Safety concerns were most influential in patient recommendations (n = 39, 39%), followed by specific conditions (n = 30, 30%) and patient preferences (n = 26, 30%). Ninety-three physicians (92%) reported they "often" or "always" perform a patient physical exam. Eighty-four (77%) physicians provided specific administration route recommendations. Half (n = 56) "often" or "always" provided specific recommendations for Δ-9-tetrahydrocannabinol: cannabidiol ratios, while 69 (62%) "often" or "always" provided specific dose recommendations. Online learning/training modules were the most preferred future training mode, with 88 (84%) physicians "likely" or "very likely" to participate. The top 3 desired topics for future training were marijuana-drug interactions (n = 84, 72%), management of specific medical conditions or symptoms (n = 83, 72%), and strategies to reduce opioids or other drugs use (n = 78, 67%). CONCLUSIONS: This survey of over 100 medical marijuana physicians indicates that their clinical practices rely on a blend of research and anecdotal information sources. While physicians report clinical factors as influential during patient recommendation, patient assessment practices and treatment regimen recommendations vary substantially and rely on experimental approaches. More research is needed to inform evidence-based practice and training, especially considering details on drug interactions, risk-benefit of treatment for specific clinical conditions, and strategies to reduce opioid use.

Outpatient Off-Label Gabapentin Use for Psychiatric Indications Among U.S. Adults, 2011-2016.

OBJECTIVE: Gabapentin is widely prescribed off label in medical practice, including psychiatry. The U.S. Food and Drug Administration (FDA) warned of risks associated with gabapentin combined with central nervous system depressant (CNS-D) drugs, which are commonly prescribed in psychiatric treatment. This study examined off-label outpatient gabapentin use for psychiatric indications and concomitant CNS-D medication use. METHODS: National Ambulatory Care Medical Survey data (2011-2016) were used to identify encounters involving gabapentin (gabapentin visits) for adults (ages ≥18) (N=5,732). FDA-approved uses and off-label psychiatric use indications were identified with ICD-9-CM and ICD-10-CM diagnosis codes. CNS-D drugs examined were opioids, benzodiazepines, sedatives-hypnotics, antidepressants, antipsychotics, first-generation antihistamines, and skeletal muscle relaxants. Concomitance was prescription of one or more CNS-D medications at the same visit. Visits were stratified by provider type and specialty. RESULTS: Between 2011 and 2016, 2.8% of visits listed gabapentin prescriptions (weighted estimate of 129.6 million visits). A small proportion (<1%) listed an FDA-approved indication. Among off-label gabapentin visits, 5.3% listed a depressive disorder, 3.5% an anxiety disorder, and 1.8% bipolar disorder. Over 6 years, 58.4% of off-label gabapentin visits listed one or more concomitant CNS-D medications, most frequently antidepressants (24.3%), opioids (22.9%), and benzodiazepines (17.3%). Most gabapentin visits were with primary care providers (34.9%) and other provider specialties (i.e., not primary care, neurology, or psychiatry) (48.1%). CONCLUSION: In this nationally representative sample, <1% of outpatient gabapentin use was for approved indications. High concomitant use of CNS-D drugs and off-label gabapentin for psychiatric diagnoses underlines the need for improved communication about safety.

Clinical Conditions and Prescription Drug Utilization among Early Medical Marijuana Registrants in Florida.

Initial legalization of medical marijuana (MM) in Florida required providers to submit initial and follow-up treatment plan forms to the University of Florida to support research on MM safety and efficacy. This study retrospectively analyzed all treatment plan forms submitted between program inception (August 2016) through July 2017 and describes early Florida MM registrants by clinical conditions and prescription drug utilization. Among 7,548 unique treatment plans, the initial visit was characterized by registrants who were mostly white (83.7%), 52.3 (SD 16.4) years of age on average, and who were assessed by the provider as at least moderately ill (79.6%). Musculoskeletal and spasticity-related conditions (44.8%), chronic pain (41.9%), and mental health disorders (17.0%) were the most frequent medical complaints for seeking MM treatment with more than one condition per patient possible. One in four (25.9%) patients reported use of prescription opioids and over one-fifth of patients frequently utilized at least one psychotropic medication as well as cardiovascular agents. There were 2,075 unique follow-up plans available which were mostly characterized by clinical improvement and reported reductions in utilization of some drug classes. Further research is needed to guide clinicians on the risks and benefits of MM used concomitantly with prescription drugs.

Characteristics of Older Adults Who Were Early Adopters of Medical Cannabis in the Florida Medical Marijuana Use Registry.

Use of medical marijuana is increasing in the United States and older adults are the fastest growing user group. There is little information about the characteristics and outcomes related to medical marijuana use. This study is a descriptive analysis of older adults (aged ≥50 years old) who were early adopters of a medical marijuana program in the U.S. state of Florida. Per state legislation, initial and follow-up treatment plans were submitted to the University of Florida College of Pharmacy. Data collection included demographics, clinical history, medical conditions, substance use history, prescription history, and health status. Follow-up treatment plans noted changes in the chief complaint and actions taken since the initial visit. Of the state's 7548 registered users between August 2016 and July 2017, N = 4447 (58.9%) were older adults. Patients utilized cannabidiol (CBD)-only preparations (45%), preparations that had both tetrahydrocannabinol (THC) and CBD (33.3%) or were recorded to use both CBD-only and THC + CBD products (21.7%). The chief complaints indicating medical cannabis treatment were musculoskeletal disorders and spasms (48.4%) and chronic pain (45.4%). Among other prescription medications, patients utilized antidepressants (23.8%), anxiolytics and benzodiazepines (23.5%), opioids (28.6%), and cardiovascular agents (27.9%). Among all drug classes with potential sedating effects, 44.8% of the cohort were exposed to at least one. Patients with follow-up visits (27.5%) exhibited marked improvement as assessed by the authorizing physicians. However, the patient registry lacked detailed records and linkable information to other data resources to achieve complete follow up in order to assess safety or efficacy. Future improvements to registries are needed to more adequately capture patient information to fill knowledge gaps related to the safety and effectiveness of medical marijuana, particularly in the older adult population.