Central Nervous System-active Medications Research Articles

Reducing Central Nervous System–Active Medications to Prevent Falls and Injuries Among Older Adults

High-risk medications that contribute to adverse health outcomes are frequently prescribed to older adults. Deprescribing interventions reduce their use, but studies are often not designed to examine effects on patient-relevant health outcomes. To test the effect of a health system-embedded deprescribing intervention targeting older adults and their primary care clinicians for reducing the use of central nervous system-active drugs and preventing medically treated falls. In this cluster randomized, parallel-group, clinical trial, 18 primary care practices from an integrated health care delivery system in Washington state were recruited from April 1, 2021, to June 16, 2022, to participate, along with their eligible patients. Randomization occurred at the clinic level. Patients were community-dwelling adults aged 60 years or older, prescribed at least 1 medication from any of 5 targeted medication classes (opioids, sedative-hypnotics, skeletal muscle relaxants, tricyclic antidepressants, and first-generation antihistamines) for at least 3 consecutive months. Patient education and clinician decision support. Control arm participants received usual care. The primary outcome was medically treated falls. Secondary outcomes included medication discontinuation, sustained medication discontinuation, and dose reduction of any and each target medication. Serious adverse drug withdrawal events involving opioids or sedative-hypnotics were the main safety outcome. Analyses were conducted using intent-to-treat analysis. Among 2367 patient participants (mean [SD] age, 70.6 [7.6] years; 1488 women [63%]), the adjusted cumulative incidence rate of a first medically treated fall at 18 months was 0.33 (95% CI, 0.29-0.37) in the intervention group and 0.30 (95% CI, 0.27-0.34) in the usual care group (estimated adjusted hazard ratio, 1.11 (95% CI, 0.94-1.31) (P = .11). There were significant differences favoring the intervention group in discontinuation, sustained discontinuation, and dose reduction of tricyclic antidepressants at 6 months (discontinuation adjusted rate: intervention group, 0.23 [95% CI, 0.18-0.28] vs usual care group, 0.13 [95% CI, 0.09-0.17]; adjusted relative risk, 1.79 [95% CI, 1.29-2.50]; P = .001) and secondary time points (9, 12, and 15 months). In this randomized clinical trial of a health system-embedded deprescribing intervention targeting community-dwelling older adults prescribed central nervous system-active medications and their primary care clinicians, the intervention was no more effective than usual care in reducing medically treated falls. For health systems that attend to deprescribing as part of routine clinical practice, additional interventions may confer modest benefits on prescribing without a measurable effect on clinical outcomes. ClinicalTrials.gov Identifier: NCT05689554.

Nano Emulsion: The Targeted Drug Delivery in the Therapy of Epilepsy

Around the world, 50 million people suffer with epilepsy; it significantly burdens society in terms of finances, society, and health. Our comprehension of the pathophysiological processes causing the illness and the factors affecting its prognosis has significantly advanced during the last ten years. Around a third of patients are still resistive to medical intervention, despite the fact that the number of antiepileptic drugs has expanded dramatically over the past 20 years. The ability of nanotech-based anti-epileptic drug (AED) administration methods to cross the blood brain barrier, increase specificity, and have the capacity for extended brain administration of drugs have lately attracted interest. Nanotechnology appears to be a promising and innovative development in this area. Nano emulsions have a mean droplet size of 20 to 200 nm and remain kinetically stable dispersions of two incompatible liquids with the assistance of an emulsifier or emulsifiers. The effectiveness of NEs as a delivery system for Central Nervous System-active medications used in effective regimens against difficult-to-treat CNS conditions.

Medication misuse and overuse in community-dwelling persons with dementia.

Persons with dementia (PWD) have high rates of polypharmacy. While previous studies have examined specific types of problematic medication use in PWD, we sought to characterize a broad spectrum of medication misuse and overuse among community-dwelling PWD. We included community-dwelling adults aged ≥66 in the Health and Retirement Study from 2008 to 2018 linked to Medicare and classified as having dementia using a validated algorithm. Medication usage was ascertained over the 1-year prior to an HRS interview date. Potentially problematic medications were identified by: (1) medication overuse including over-aggressive treatment of diabetes/hypertension (e.g., insulin/sulfonylurea with hemoglobin A1c < 7.5%) and medications inappropriate near end of life based on STOPPFrail and (2) medication misuse including medications that negatively affect cognition and medications from 2019 Beers and STOPP Version 2 criteria. To contextualize, we compared medication use to people without dementia through a propensity-matched cohort by age, sex, comorbidities, and interview year. We applied survey weights to make our results nationally representative. Among 1441 PWD, median age was 84 (interquartile range = 78-89), 67% female, and 14% Black. Overall, 73% of PWD were prescribed ≥1 potentially problematic medication with a mean of 2.09 per individual in the prior year. This was notable across several domains, including 41% prescribed ≥1 medication that negatively affects cognition. Frequently problematic medications included proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antihypertensives, and antidiabetic agents. Problematic medication use was higher among PWD compared to those without dementia with 73% versus 67% prescribed ≥1 problematic medication (p = 0.002) and mean of 2.09 versus 1.62 (p < 0.001), respectively. Community-dwelling PWD frequently receive problematic medications across multiple domains and at higher frequencies compared to those without dementia. Deprescribing efforts for PWD should focus not only on potentially harmful central nervous system-active medications but also on other classes such as PPIs and NSAIDs.

Engagement is a necessary condition to test audit and feedback design features: results of a pragmatic, factorial, cluster-randomized trial with an embedded process evaluation

BackgroundWhile audit & feedback (A&F) is an effective implementation intervention, the design elements which maximize effectiveness are unclear. Partnering with a healthcare quality advisory organization already delivering feedback, we conducted a pragmatic, 2 × 2 factorial, cluster-randomized trial to test the impact of variations in two factors: (A) the benchmark used for comparison and (B) information framing. An embedded process evaluation explored hypothesized mechanisms of effect.MethodsEligible physicians worked in nursing homes in Ontario, Canada, and had voluntarily signed up to receive the report. Groups of nursing homes sharing physicians were randomized to (A) physicians’ individual prescribing rates compared to top-performing peers (the top quartile) or the provincial median and (B) risk-framed information (reporting the number of patients prescribed high-risk medication) or benefit-framed information (reporting the number of patients not prescribed). We hypothesized that the top quartile comparator and risk-framing would lead to greater practice improvements. The primary outcome was the mean number of central nervous system-active medications per resident per month. Primary analyses compared the four arms at 6 months post-intervention. Factorial analyses were secondary. The process evaluation comprised a follow-up questionnaire and semi-structured interviews.ResultsTwo hundred sixty-seven physicians (152 clusters) were randomized: 67 to arm 1 (median benchmark, benefit framing), 65 to arm 2 (top quartile benchmark, benefit framing), 75 to arm 3 (median benchmark, risk framing), and 60 to arm 4 (top quartile benchmark, risk framing). There were no significant differences in the primary outcome across arms or for each factor. However, engagement was low (27–31% of physicians across arms downloaded the report). The process evaluation indicated that both factors minimally impacted the proposed mechanisms. However, risk-framed feedback was perceived as more actionable and more compatible with current workflows, whilst a higher target might encourage behaviour change when physicians identified with the comparator.ConclusionsRisk framing and a top quartile comparator have the potential to achieve change. Further work to establish the strategies most likely to enhance A&F engagement, particularly with physicians who may be most likely to benefit from feedback, is required to support meaningfully addressing intricate research questions concerning the design of A&F.Trial registrationClinicalTrials.gov, NCT02979964. Registered 29 November 2016.

High opioid doses, naloxone, and central nervous system active medications received by Medicare-enrolled adults.

A limited number of studies have analyzed prescribing among Medicare-enrolled adults at risk for opioid overdoses. The objectives of this study were to evaluate prescribing for naloxone and central nervous system (CNS) active medications and to determine the relationships of patient characteristics with exposure to these medications. This was a retrospective cross-sectional analysis of a Medicare-enrolled medication therapy management eligible cohort. Patients were stratified into two cohorts, individuals with a mean daily morphine milligram equivalent (MME) dose <50 and individuals with MME ≥50. Medications assessed included benzodiazepines, skeletal muscle relaxants (SMR), hypnotics, gabapentanoids, selective-serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), antipsychotics, barbiturates, other antiepileptics, hydroxyzine, and naloxone. Chi-square with odds ratios and logistic regressions determined the relationships of medications and patient characteristics with mean daily MME ≥50. Relationship between medications and opioid dose was adjusted for age and sex. There were 3452 patients with a daily MME <50 and 1116 with a daily MME ≥50. After adjusting for age and sex, patients with a daily MME ≥50 were more likely to be prescribed hypnotics (OR: 1.41, 95% CI 1.17-1.70), SNRIs (OR: 1.39, 95% CI 1.17-1.64), and naloxone (OR: 3.21, 95% CI 2.49-4.12) (p < 0.001). Nine percent of eligible patients received naloxone. Age groups of persons <85 years of age had 1.58-4.04 (p ≤ 0.004) times the odds of being prescribed a mean daily MME ≥50. Nearly one-fourth of patients were prescribed a mean daily opioid therapy of MME ≥50. These patients were more likely to be prescribed hypnotics, SNRIs, and naloxone. Patients receiving chronic high-dose opioid therapy were more likely to be in age groups of persons <85 years. Naloxone may be underprescribed among eligible adults. Targeted medication services may ensure optimal prescribing among Medicare patients with chronic opioid therapies.

Prescription characteristics associated with fall-related injury risk among older adults prescribed benzodiazepines: a cohort study

BackgroundBenzodiazepines (BZD) are widely prescribed to older adults despite their association with increased fall injury. Our aim is to better characterize risk-elevating factors among those prescribed BZD.MethodsA retrospective cohort study using a 20% sample of Medicare beneficiaries with Part D prescription drug coverage. Patients with a BZD prescription (“index”) between 1 April 2016 and 31 December 2017 contributed to incident (n=379,273) and continuing (n=509,634) cohorts based on prescriptions during a 6-month pre-index baseline. Exposures were index BZD average daily dose and days prescribed; baseline BZD medication possession ratio (MPR) (for the continuing cohort); and co-prescribed central nervous system-active medications. Outcome was a treated fall-related injury within 30 days post-index BZD, examined using Cox proportional hazards adjusting for demographic and clinical covariates and the dose prescribed.ResultsAmong incident and continuing cohorts, 0.9% and 0.7% experienced fall injury within 30 days of index. In both cohorts, injury risk was elevated immediately post-index among those prescribed the lowest quantity: e.g., for <14-day fill (ref: 14-30 days) in the incident cohort, risk was 37% higher the 10 days post-fill (adjusted hazard ratio [HR] 1.37 [95% confidence interval [CI] 1.19-1.59]). Risk was elevated immediately post-index for continuing users with low baseline BZD exposure (e.g., for MPR <0.5 [ref: MPR 0.5-1], HR during days 1-10 was 1.23 [CI 1.08-1.39]). Concurrent antipsychotics and opioids were associated with elevated injury risk in both cohorts (e.g., incident HRs 1.21 [CI 1.03-1.40] and 1.22 [CI 1.07-1.40], respectively; continuing HRs 1.23 [1.10-1.37] and 1.21 [1.11-1.33]).ConclusionsLow baseline BZD exposure and a small index prescription were associated with higher fall injury risk immediately after a BZD fill. Concurrent exposure to antipsychotics and opioids were associated with elevated short-term risk for both incident and continuing cohorts.

Co-prescribing of Central Nervous System-Active Medications for COPD Patients: Impact on Emergency Room Visits and Hospitalization.

Anxiety and chronic pain are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which are frequently managed with benzodiazepines (BZDs) and opioids, respectively. The purpose of this study was to determine whether different combinations of opioids, BZD, and their substitutes-gabapentinoids (GABA) and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs)-are associated with lower risk of acute respiratory events in COPD patients with co-occurring chronic pain and anxiety. This retrospective cohort study used a nationally representative sample of Medicare beneficiaries with COPD, chronic pain, and anxiety. Patients were grouped based on drug combination (opioid + BZD/Z-hypnotics, opioid + GABA, opioid + SSRI/SNRI, BZD/Z-hypnotics + GABA, BZD/Z-hypnotics + SSRI/SNRI, GABA + SSRI/SNRI, or ≥3 drugs). The primary outcome was emergency room (ER) visit or hospitalization due to acute respiratory events assessed up to 180 days following initiation of drug combination. Overdose secondary to central nervous system (CNS)-related drugs was also assessed up to 180 days following initiation of drug combination. The drug combination opioid + GABA was associated with decreased risk for ER visit (hazard ratio [HR] = 0.73; 95% CI = 0.61-0.87) and hospitalization (HR = 0.69; 95% CI = 0.55-0.85). Opioid + SSRI/SNRI also showed decreased risk for ER visit (HR = 0.84; 95% CI = 0.71-0.99). There was no significant difference in risk for CNS-related drug overdose among different drug combinations compared with opioid + BZD/Z-hypnotics. Opioids in combination with GABA and SSRI/SNRI demonstrate relatively lower risk for acute respiratory events among patients with COPD and comorbid chronic pain and anxiety. The findings emphasize the need for multimodal management in this vulnerable population.

Management of hypoactive sexual desire disorder in transgender women: a guide for clinicians.

Hypoactive sexual desire disorder (HSDD) represents a common condition among transgender women. However, to date no specific guidelines for the management of HSDD in transgender persons are available. The aim of the present narrative Review is to evaluate evidence-based treatment for HSDD and to suggest treatment options for HSDD in transgender women. Clinically relevant publications on the management of HSDD (from 1985 to 2020) were searched in PubMed and Medline databases, using the following terms: "sexual desire", "sexual health", "HSDD", "transgender", "gender-affirming treatment", "sexual therapy", "testosterone treatment", "Central nervous system-active medications", and variants. Since sexual desire could be affected by several factors, a comprehensive assessment of HSDD- exploring biological, psychological, and social domains- is recommended, in order to identify possible predisposing, precipitating and maintaining factors. Among treatment options, transgender women may benefit of different sex therapy strategies and/or central nervous system-active medications-such as flibanserin, bremelanotide, bupropion and buspirone-and transdermal testosterone, bearing in mind that this option could be poorly accepted by patients due to the risk of virilizing effects. The lack of data regarding the efficacy of HSDD treatment options in transgender women emphasize the need for literature to focus more on this topic in the future.

The influence of opioids and nonopioid central nervous system active medications on central sleep apnea: a case-control study.

Opioids are known to contribute to central sleep apnea (CSA), but the influence of nonopioid central nervous system active medications (CNSAMs) on CSA remains unclear. In light of the hypothesized impact of nonopioid CNSAMs on respiration, we examined the relationships between the use of opioids only, nonopioid CNSAMs alone, and their combination with CSA. Among all adults who underwent polysomnography testing at the University of Michigan's sleep laboratory between 2013 and 2018 (n = 10,606), we identified 212 CSA cases and randomly selected 300 controls. Participants were classified into four groups based on their medication use: opioids alone, nonopioid CNSAMs only, their combination, and a reference group, including those who did not use any of these medications. We defined CSA as a binary outcome and as a continuous variable using central apnea index data. Logistic and linear regression were used to examine associations between medication use, CSA diagnosis, and central apnea index. Study participants included 58% men, and mean age was 50 (± 14 standard deviation years. Nearly half of the study participants did not use opioids or nonopioid CNSAMs, 6% used opioids alone, 27% nonopioid CNSAMs alone, and 16% used a combination of these medications. In adjusted analyses, opioids-only users had a nearly twofold increase in CSA odds, whereas those who used a combination of opioids and nonopioid CNSAMs had fivefold higher odds of CSA relative to the reference group. In contrast, the use of nonopioid CNSAMs alone had protective associations with CSA. This report showed increased odds of CSA, particularly among patients with sleep complaints who were prescribed opioids in combination with nonopioid CNSAMs compared with those who did not use any of these medications.

Concurrent Use of Opioids with Other Central Nervous System-Active Medications Among Older Adults.

The primary objective was to determine the prevalence and characteristics of older adults concurrently using opioids and other central nervous system (CNS)-active medications, and the specialties of providers who ordered the medications. A secondary objective was to document medication-related adverse effects associated with such concurrent drug use. Study populations were identified as older adults aged ≥65 years with 1 year continuous medical and drug plan enrollment during 2017 and opioid use of ≥2 prescriptions for ≥15 days' supply. CNS-active medications included benzodiazepines, non-benzodiazepine hypnotics, muscle relaxants, antipsychotics, and gabapentinoids. Provider specialties were identified from the National Provider Identification database. Characteristics associated with opioids only, opioids plus 1, and opioids plus ≥2 additional CNS-active medications were determined using multinomial logistic regression. Outcome measures during 2017 included injurious falls/fractures and ≥3 emergency room (ER) visits. Among eligible insureds (N = 209,947), 57% used opioids only, 28% used opioids plus 1 additional CNS medication, and 15% used ≥2 additional medications. About 60% of opioids and other concurrent CNS medications were prescribed by the same provider, generally a primary care provider. Benzodiazepines and gabapentinoids were most often used concurrently with opioids. Health status, insomnia, anxiety, depression, and low back pain had the strongest associations with concurrent medication use. Overall, concurrent use with ≥2 CNS medications increased the likelihood of injurious falls/fractures or ≥3 ER visits in this population by about 18% and 21%, respectively. Both patients and providers may benefit from an awareness of adverse outcomes associated with concurrent opioid and other CNS-active medication use.

Prevalence and temporal trends of prescription drug use in cancer survivors: A population study, 2001 to 2016.

12023 Background: The burden of prescription drug use is higher in cancer survivors than the general population. We examined the prevalence and temporal trends of prescription drug use among cancer survivors, with an emphasis on central nervous system (CNS) active medications used to manage long-term cancer sequelae. Methods: Adult respondents with (n=3207) and without (n=40,440) a prior cancer diagnosis from 8 cycles (2001-2016) of the National Health and Nutritional Examinational Survey (NHANES) were evaluated for prescription drug usage. Cross-sectional analyses and temporal trends across cycles were evaluated and weighted to represent the US adult population. Results: Cancer survivors report higher rates of prescription drug usage (85.1% vs 54.3%, p&lt;0.001, and 75.8%, p&lt;0.001) and polypharmacy (27.8% vs 10.7%, p&lt;0.001, and 22.7%, p&lt;0.001) than both unadjusted and age-adjusted controls. Younger survivors report greater usage of CNS (36.8% vs 13.1%, p&lt;0.001), psychotherapeutic (18.4% vs 7.7%, p&lt;0.001), hormonal agents (19.1% vs 10.1%, p=0.003), and gastrointestinal (10.7% vs 4.7%, p=0.02) than controls, while differences are attenuated in older cohorts. Among broad drug categories, the usage of cardiovascular (p-trend&lt;0.001), metabolic (p-trend&lt;0.001), and immunologic agents (p-trend=0.01) has increased. Among CNS active subclasses, the usage of anticonvulsants (p-trend&lt;0.001), anxiolytics (p-trend =0.02), narcotics (p-trend=0.02) and GABA analogs (p-trend&lt;0.001) has increased. When comparing respondents with and without a history of cancer, the increased usage of anti-depressant prescription medications (18.3% vs 1.5% p&lt;0.001), including SSRIs (11.2% vs 1.0%, p&lt;0.001), SSNRIs (3.5% vs 0.3%, p&lt;0.001), tricyclics (2.8% vs 0.1%, p&lt;0.001), among cancer survivors was disproportionate compared to the increased proportion of positive depression screens (9.2% vs 7.0%, p=0.006). Conclusions: Cancer survivors report higher prescription drug use for both chronic conditions and late effects of cancer. The usage of CNS active medications, many of which are used on and off label for their pain management properties, has increased. The higher rates of pharmaceutical use may result in unanticipated long-term toxicities and financial burdens.

Psychiatric adverse events and effects on mood with prolonged-release naltrexone/bupropion combination therapy: a pooled analysis

Background/objectivesProlonged-release (PR) naltrexone 32 mg/bupropion 360 mg (NB) is approved for chronic weight management as an adjunct to reduced-calorie diet and increased physical activity. Central nervous system-active medications have the potential to affect mood; therefore, post hoc analysis of clinical trial data was conducted to evaluate psychiatric adverse events (PAEs) and effects on mood of NB therapy versus placebo.Subjects/methodsData were pooled from 5 prospective, double-blind, randomized, placebo-controlled clinical trials (duration range, 24–56 weeks) of NB in subjects with overweight or obesity. PAEs were collected via AE preferred terms, organized into major subtopics (e.g., anxiety, depression, sleep disorders), and divided into category terms (e.g., anxiety, potential anxiety symptoms). Additionally, the Inventory of Depressive Symptomatology Self Report (IDS-SR; score range 0–84) and the Columbia Classification Algorithm of Suicide Assessment (C-CASA) evaluated treatment-emergent depressive/anxiety symptoms and suicidal behavior/ideation, respectively.ResultsBaseline characteristics and comorbidities were comparable for placebo (n = 1515) and NB (n = 2545). Most common PAEs in the NB group (using category grouping; NB vs placebo) were sleep disorders (12.7 vs 7.9%, P < 0.001), anxiety (5.4 vs 3.3%, P = 0.029), and depression (1.8 vs 2.7%, P = 0.014); PAEs were more frequent during dose escalation and generally mild or moderate. Mean (SD) changes in IDS-SR total score from baseline to endpoint were small in both groups: 0.13 (5.83) for NB and −0.45 (5.65) for placebo. Retrospective AE categorization via C-CASA confirmed no completed suicides, suicide attempts, or preparatory acts toward imminent suicidal behavior.ConclusionsThis large pooled analysis of 5 clinical trials provides additional safety information about the NB PAE profile. Anxiety and sleep disorder-related PAEs were more frequent with NB versus placebo but were mostly mild to moderate and generally occurred early. Depression-related PAEs were less common with NB than placebo, and NB was not associated with suicidal ideation or behavior in this patient population.

Prescription Medication Use Among Community-Based U.S. Adults With Chronic Low Back Pain: A Cross-Sectional Population Based Study

Many classes of medications have been evaluated in chronic low back pain (cLBP), however their utilization in the community remains unclear. We examined patterns of prescription medication use among Americans with cLBP in a nationally representative, community-based sample. The Back Pain Survey was administered to a representative sample of U.S. adults aged 20 to 69 years (N = 5,103) during the 2009 to 2010 cycle of the National Health and Nutrition Examination Survey. cLBP was defined as self-reported pain in the area between the lower posterior margin of the ribcage and the horizontal gluteal fold on most days for at least 3 months (N = 700). Home-based interviews with pill bottle verification were used to capture commonly prescribed medications for chronic pain. Among the sample of U.S. adults with cLBP aged 20 to 69 years, 36.9% took at least 1 prescription pain medication in the past 30 days; of them, 18.8% used opioids, 9.7% nonsteroidal anti-inflammatory drugs, 8.5% muscle relaxants, and 6.9% gabapentin or pregabalin. Nonpain antidepressants and hypnotics were used by 17.8% and 4.7%, respectively. Opioids were used long-term in 76.9% of cases (median = 2 years) and were frequently coadministered with antidepressants, benzodiazepines, or hypnotics. Ninety-four percent of prescription opioids in the cLBP population were used by individuals with less than a college education. Opioids were the most widely used prescription analgesic class in community-based U.S. adults with cLBP and were often coadministered with other central nervous system-active medications. Opioid use was highly prevalent among less educated Americans with cLBP. PerspectiveBecause prescription opioid use is an issue of national concern, we examined pain-related prescription medication use in community-dwelling U.S. adults with cLBP. Opioids were the most common prescription pain medication, typically used long-term, in combination with other central nervous system-active agents, and disproportionately among individuals with less than a college education.

Reducing Cost by Reducing Polypharmacy: The Polypharmacy Outcomes Project

To examine the effect of intervention by geriatric medicine fellows and a geriatrician on medication cost among long term care residents with polypharmacy. Interventional study. A single hospital-affiliated long term care facility. Long term care residents with polypharmacy, defined as being on 9 or more medications. Medication lists of all nursing home residents were reviewed in October 2007 by geriatric medicine fellows and a faculty geriatrician using the 2003 Beers Criteria and the Epocrates online drug-drug interaction program. Recommendations for each resident were prepared and discussed directly with their primary physicians, who made the final decisions regarding medication discontinuation or taper. Mean monthly costs (derived from current retail prices) for overall as well as scheduled and pro re nata (PRN) medications were compared before and after the intervention. Estimated reduction in nursing administration time and cost were calculated based on published literature on medication administration time and nursing labor costs. Seventy-four (46.3%) of 160 residents were on 9 or more medications. Four residents died or were discharged before the intervention, leaving a final sample of 70 residents for the intervention. After the intervention, mean monthly medication costs per resident significantly decreased; overall medications, from $874.27 to $843.56 (P < .0001); scheduled medications, from $814.05 to $801.14 (P= .007); PRN medications, from $60.22 to $42.43 (P < .0001). Gastrointestinal medications demonstrated the highest cost savings of all medication categories (eg, promethazine and proton pump inhibitors), followed by central nervous system-active medications (including benzodiazepines and fluoxetine), then analgesics and diabetes medications. This polypharmacy reduction intervention by physicians used readily available tools, demonstrated a significant decrease in medication-related costs, and provided training in the core competencies of practice-based learning and improvement and systems-based practice to geriatric medicine fellows in long term care.

The impact of acute care medications on rehabilitation outcome after traumatic brain injury

Objectives: To examine the impact of medications with known central nervous system (CNS) mechanisms of action, given during the acute care stages after traumatic brain injury (TBI), on the extent of cognitive and motor recovery during inpatient rehabilitation.Design: Retrospective extraction of data utilizing an inception cohort of moderate and severe TBI survivors.Methods: The records of 182 consecutive moderate and severe TBI survivors admitted to a single, large, Midwestern level I trauma centre and subsequently transferred for acute inpatient rehabilitation were abstracted for the presence of 11 categories of medication, three measures of injury severity (worst 24 hour Glasgow Coma Scale, worst pupillary response, intra-cranial hypertension), three measures of outcome (Function Independence Measure (FIM) Motor and Cognitive scores at both rehabilitation admission and discharge and duration of post-traumatic amnesia (PTA)).Main outcome and results: The narcotics, benzodiazepines and neuroleptics were the most common categories of CNS active medications (92%, 67% and 43%, respectively). The three categories of medications appeared to have no significant outcome on the FIM outcome variables. The neuroleptics affected cognitive recovery with almost 7 more days required to clear PTA in the neuroleptic treated group. The presence of benzodiazepines did tend to obscure the impact of neuroleptics on PTA duration but the negative impact of neuroleptics on PTA duration remained significant.Conclusions: The results suggest that the use of neuroleptics during the acute care stage of recovery has a negative impact on recovery of cognitive function at discharge from inpatient rehabilitation. Due to the paucity of subjects with hemiplegia in this cohort, conclusions could not be drawn as to the impact of acute care medications on motor recovery.

Bone mineral density in subjects using central nervous system-active medications

Purpose Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample. Subjects and methods We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index. Results In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm 2; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm 2; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm 2; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs—benzodiazepines or antidepressants—were not associated with significantly reduced bone mineral density. Conclusion In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.

Eye movements in neurodevelopmental disorders.

The aim of this paper is to review the literature on eye-movement abnormalities associated with neurodevelopmental disorders. Eye-movement testing is a non-invasive quantitative approach for evaluating brain systems across the age spectrum. It thus provides a promising methodology for characterizing and documenting maturational abnormalities in brain systems associated with neurodevelopmental disorders. Recent oculomotor studies have made significant contributions to the understanding of neurodevelopmental disorders, most notably in autism, attention-deficit/hyperactivity disorder, and Tourette's syndrome. Notably different patterns of deficits have been found in these disorders and have helped to clarify their pathophysiology. Eye-movement studies have begun to serve as a useful approach for studying cognitive and neurophysiological aspects of neurodevelopmental disorders. They also have potential as a strategy for establishing quantitative endophenotypes for genetic research, and for monitoring beneficial and adverse effects of pharmacotherapies. Studies are needed that involve larger patient populations, longitudinal characterization of developmental failures, patients free from central nervous system-active medications, and that use functional imaging, as patients perform eye-movement tasks, for direct identification of clinically relevant abnormalities in brain systems.

Link Between Psychiatric Drugs, Fractures More Complex Than Thought

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessLink Between Psychiatric Drugs, Fractures More Complex Than ThoughtJim RosackJim RosackSearch for more papers by this authorPublished Online:4 Jul 2003https://doi.org/10.1176/pn.38.13.0021aOlder women who take serotonin reuptake inhibitors or tricyclic antidepressants in combination with narcotics have a significantly elevated risk of sustaining a nonspinal fracture.Previous research had indicated that, at least in the case of narcotics, the medications alter the patients' gait and steadiness, directly increasing the patients' risk of falling and, as such, indirectly increasing the rate of fractures sustained during those falls.Now a new report suggests that for SSRIs and TCAs, the relationship may be more complicated. That report appeared in the April 28 issue of Archives of Internal Medicine."We know that antidepressants do increase the rate of falls in elderly women; we had confirmed that in an earlier study from our group," said Kristine Ensrud, M.D., a professor of medicine at the Minneapolis Veterans Affairs Medical Center and the University of Minnesota, and the lead author of the new report."But in this new study," Ensrud told Psychiatric News, "even controlling for the diagnosis of depression, controlling for depressive symptoms, and controlling for the patients' rate of fall over the prior 12 months, we see that rate of fall does not account for the increased rate of fractures. I think there's something else going on here."Ensrud and her colleagues examined the use of four classes of CNS active medications -benzodiazepines, anticonvulsants, antidepressants, and narcotics-in more than 8,000 women who were at least 65 years of age. The women were interviewed to determine medication use, which was then verified through examining prescription- medication bottles during two periods: 1992 to 1994, and 1995 to 1996. Fractures were assessed through history and verified through radiographic reports.Ensrud's team found that, during an average of 4.8 years of follow-up, 1,256 women (15 percent) had at least one nonspinal fracture, including 288 (4 percent) with a first hip fracture. Compared with women not taking any of the four classes of medications studied, women taking narcotics had almost a 40 percent increase in risk of a nonspinal fracture, and women taking an antidepressant were 25 percent more likely to experience a nonspinal fracture.Of those women taking an antidepressant, fracture rates were not statistically significantly different between the women taking an SSRI and those taking a TCA. However, Ensrud's group had previously reported that rate of fall was higher in those taking an SSRI than in those taking a TCA."Even more important," Ensrud added, "women taking antidepressants were 70 percent more likely to have a hip fracture while taking the medication. Hip fractures are especially devastating and are often significantly debilitating over the long term."Ensrud and her colleagues believe that the link between antidepressant use and increased incident fractures, especially the more serious hip fractures, is a more direct medication effect. Prior studies, she said, have linked clinical depression or depressive symptoms to lowered bone density. But other studies have not found this association, and in the current study cohort, Ensrud said, they did not see any significant difference in bone density in elderly women taking antidepressants. And even adjusting for any small difference that was present in bone density, there was no substantial difference in the association between medication use and fracture.The current study also attempted to control for any "confounding by diagnosis," and "confounding by indication," Ensrud said. When the team analyzed the data, controlling for factors such as functional impairment, cognitive function, depressive symptoms, weight change, and neuromuscular performance, Ensrud added, "antidepressant use appeared to be a more robust predictor of fracture than other potentially confounding factors."Obviously, she noted, "the association here is not simple, and we don't really know what the link is yet." But, she added, "In this particular case, some might have expected the risk of fracture to be higher with TCAs than SSRIs because of their side-effect profiles. We didn't find that. One sort of takehome lesson, then, is that we cannot simply assume that newer medications, such as SSRIs, are safer compared with older drugs, such as TCAs, simply because they are new."An abstract of the study, "Central Nervous System Active Medications and Risk for Fractures in Older Women," is posted on the Web at <http://archinte.ama-assn.org/cgi/content/abstract/163/8/949>. ▪ Archives of Internal Medicine 2003 163 949 ISSUES NewArchived

Central nervous system-active medications and risk for falls in older women.

To determine whether current use of central nervous system (CNS)-active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases the risk for subsequent falls. Prospective cohort study. Four clinical centers in Baltimore, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. Eight thousand one hundred twenty-seven women aged 65 and older participating in the fourth examination of the Study of Osteoporotic Fractures between 1992 and 1994. Current use of CNS-active medications was assessed with an interviewer-administered questionnaire with verification of use from medication containers. A computerized dictionary was used to categorize type of medication from product brand and generic names. Incident falls were reported every 4 months for 1 year after the fourth examination. During an average follow-up of 12 months, 2,241 women (28%) reported falling at least once, including 917 women (11%) who experienced two or more (frequent) falls. Compared with nonusers, women using benzodiazepines (multivariate odds ratio (MOR) = 1.51, 95% confidence interval (CI) = 1.14-2.01), those taking antidepressants (MOR = 1.54, 95% CI = 1.14-2.07), and those using anticonvulsants (MOR = 2.56, 95% CI = 1.49-4.41) were at increased risk of experiencing frequent falls during the subsequent year. We found no evidence of an independent association between narcotic use and falls (MOR = 0.99 for frequent falling, 95% CI = 0.68-1.43). Among benzodiazepine users, both women using short-acting benzodiazepines (MOR = 1.42, 95% CI = 0.98-2.04) and those using long-acting benzodiazepines (MOR = 1.56, 95% CI = 1.00-2.43) appeared to be at greater risk of frequent falls than nonusers, although the CIs overlapped 1.0. We found no evidence to suggest that women using selective serotonin-reuptake inhibitors (MOR = 3.45, 95% CI = 1.89-6.30) had a lower risk of frequent falls than those using tricyclic antidepressants (MOR 1.28, 95% CI = 0.90-1.84). Community-dwelling older women taking CNS-active medications, including those taking benzodiazepines, antidepressants, and anticonvulsants, are at increased risk of frequent falls. Minimizing use of these CNS-active medications may decrease risk of future falls. Our results suggest that fall risk in women taking benzodiazepines is at best marginally decreased by use of short-acting preparations. Similarly, our findings indicate that preferential use of selective serotonin-reuptake inhibitors is unlikely to reduce fall risk in older women taking antidepressants.

A Perspective on the Primary Care of Patients With Behavior, Mood, and Thought Disturbances: Clinical Applications of Olanzapine.

Primary care practitioners are in an ideal position to initiate treatment for patients with behavior, mood, and thought disturbances. It is believed that early identification and treatment of these symptomatic features of primary or secondary central nervous system disorders may significantly reduce morbidity and benefit the patient, his/her family, and involved caregivers, including the primary care physician. A broad list of central nervous system-active medications are utilized by family physicians to treat patients who exhibit symptoms of agitation, altered mood, and disordered thought. Some medications have demonstrated superiority over placebo or active medicines in reported clinical trials. This article is a brief overview of the safety and efficacy from reported studies of the use of medications frequently used to treat symptoms related to behavior, mood, and thought disturbances, with a specific focus on the clinical applicability of olanzapine.