Rise of escitalopram and the fall of citalopram.

Introduction: Citalopram and escitalopram are among the most used medications and are key treatments for many psychiatric disorders. Previous findings suggest citalopram and escitalopram prescription rates are changing because of the patent for citalopram ending as opposed to evidence of a clear therapeutic advantage, which is called evergreening. This retrospective study focuses on characterizing the chronologic and geographic variation in the use of citalopram and escitalopram among US Medicaid and Medicare patients. We hypothesized that prescription rates of citalopram will decrease with a concurrent increase in escitalopram, consistent with evergreening. Methods: Citalopram and escitalopram prescription rates and costs per state were obtained from the Medicaid State Drug Utilization Database and Medicare Provider Utilization and Payment Data. Annual prescription rates outside a 95% confidence interval were considered significantly different from the average. Results: Overall, a decreasing trend for citalopram and an increasing trend for escitalopram prescription rates were noted in both Medicare and Medicaid patients. Cost differences between generic and brand were noted for both drugs, with generic forms being cheaper compared to the brand-name version. Discussion: Despite limited evidence suggesting that citalopram and escitalopram have any meaningful differences in therapeutic or adverse effects, there exists a noticeable decline in the use of citalopram that cooccurred with an increase in escitalopram prescribing, consistent with our hypothesis. Moreover, among these general pharmacoepidemiologic trends exists significant geographic variability. There was disproportionate spending (relative to their use) on the brand versions of these medicines compared to their generic forms.

Specialty-type and state-level variation in paroxetine use among older adult patients.

Introduction: Paroxetine is an older "selective" serotonin reuptake inhibitor (SSRI) that is notable for its lack of selectivity, resulting in a cholinergic adverse-effect profile, especially among older adults (65+). Methods: Paroxetine prescription rates and costs per state were ascertained from the Medicare Specialty Utilization and Payment Data. States' annual prescription rate, corrected per thousand Part D enrollees, outside 95% confidence interval were considered significantly different from the average. Results: There was a steady decrease in paroxetine prescriptions (-34.52%) and spending (-16.69%) from 2015-2020 but a consistent, five-fold state-level difference. From 2015-2020, Kentucky (194.9, 195.3, 182.7, 165.1, 143.3, 132.5) showed significantly higher prescriptions rates relative to the national average, and Hawaii (42.1, 37.9, 34.3, 31.7, 27.7, 26.6) showed significantly lower prescription rates. North Dakota was often a frequent elevated prescriber of paroxetine (2016: 170.7, 2018: 143.3), relative to the average. Neuropsychiatry and geriatric medicine frequently prescribed the largest amount of paroxetine prescriptions, relative to the number of providers in that specialty, from 2015-2020. Discussion: Despite the American Geriatrics Society prohibition against paroxetine use in the older adults and many effective treatment alternatives, paroxetine was still commonly used in this population, especially in Kentucky and North Dakota and by neuropsychiatry and geriatric medicine. These findings provide information on the specialty types and states where education and policy reform would likely have the greatest impact on improving adherence to the paroxetine prescription recommendations.

Occurrence of Z-drugs, benzodiazepines, and ketamine in wastewater in the United States and Mexico during the Covid-19 pandemic.

Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including an elevated risk of addiction and substance misuse. These drugs have a strong potential for misuse, which has escalated over the years and was hypothesized here to have been exacerbated during the COVID-19 pandemic. Wastewater-based epidemiology (WBE) constitutes a fast, easy, and relatively inexpensive approach to epidemiological surveys for understanding the incidence and frequency of uses of these drugs. In this study, we analyzed wastewater (n = 376) from 50 cities across the United States and Mexico from July to October 2020 to estimate drug use rates during a pandemic event. Both time and flow proportional composite and grab samples of untreated municipal wastewater were analyzed using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry to determine loadings of alprazolam, clonazepam, diazepam, ketamine, lorazepam, nordiazepam, temazepam, zolpidem, and zaleplon in raw wastewater. Simultaneously, prescription data of the aforementioned drugs were extracted from the Medicaid database from 2019 to 2021. Results showed high detection frequencies of ketamine (90 %), lorazepam (87 %), clonazepam (76 %) and temazepam (73 %) across both Mexico and United States and comparatively lower detection frequencies for zaleplon (22 %), zolpidem (9 %), nordiazepam (<1 %), diazepam (<1 %), and alprazolam (<1 %) during the pandemic. Average mass consumption rates, estimated using WBE and reported in units of mg/day/1000 persons, ranged between 62 (temazepam) and 1100 (clonazepam) in the United States. Results obtained from the Medicaid database also showed a significant change (p < 0.05) in the prescription volume between the first quarter of 2019 (before the pandemic) and the first quarter of 2021 (pandemic event) for alprazolam, clonazepam and lorazepam. Study results include the first detections of zaleplon and zolpidem in wastewater from North America.

Situation Awareness Performance in Healthy Young Adults Is Associated With a Serotonin Transporter Gene Polymorphism.

Background Situation awareness (SA) is defined in three levels: SA1 is the perception of the elements in a specific context, SA2 is the comprehension of their meaning, and SA3 is the projection of their status. Purpose To analyze the possible association of a genetic polymorphism in the serotonin transporter ( SLC6A4) gene and performance on the Situational Awareness test (SAtest). Methods SAtest was applied to a sample of 230 healthy Colombian subjects, using the Psychology Experiment Building Language platform and a functional polymorphism in the SLC6A4 gene was genotyped by polymerase chain reaction. Results In the SA1 level, s/s genotype carriers had worse accuracy, in comparison with s/l and l/l genotypes. At SA2 level, l/l genotype carriers had better accuracy than s/s and s/l individuals and that in the SA3 level, l/l carriers also had better accuracy. These associations were significant after correction for multiple testing. Conclusions It is possible that l/l carriers have a better ability to perceive and focus their attention on the elements of their environment and to have the capacity to understand and predict what will happen with those elements. This is the first genetic study of SA performance in healthy participants. Additional investigations of other genes could contribute to the understanding of the molecular correlates of SA in healthy subjects and in neuropsychiatric patients.

BDNF Val66Met is Associated With Performance in a Computerized Visual-Motor Tracking Test In Healthy Adults.

The brain-derived neurotrophic factor gene (BDNF) is known to play an important role in neuroplasticity and cognitive processes. We explored the association of BDNF Val66Met polymorphism with performance in a visual-motor tracking test. One hundred and sixty-seven young, healthy Colombian adults completed a computerized version of the Pursuit Rotor Task, using the Psychology Experiment Building Language (PEBL) platform. DNA genotyping was performed by allele-specific polymerase chain reaction. We found that BDNF Val/Met and Met/Met subjects performed better in the pursuit rotor task (p = .03). Our findings suggest that the BDNF gene is essential to understand differences in motor performance in healthy participants in different populations. This approach could be useful for future fine mapping of genetic modifiers for neuropsychiatric diseases.

Differences in planning performance, a neurocognitive endophenotype, are associated with a functional variant in PER3 gene.

Performance alterations in executive function have been studied as potential endophenotypes for several neuropsychiatric diseases. Planning is an important component of executive function and has been shown to be affected in diseases such as attention deficit hyperactivity disorder, schizophrenia, obsessive-compulsive disorder and Parkinson's disease. Several genes related to dopaminergic systems, such as COMT, have been explored as candidates for influencing planning performance. The circadian clock gene PERIOD3 (PER3) has been shown to be associated with several complex behaviors in humans and could be involved in different signaling mechanisms. In this study, we evaluated the possible association between a functional polymorphism in the PER3 gene (PER3-VNTR, rs57875989) and performance in a commonly used test of planning (Tower of London, TOL) in 229 healthy subjects from Bogotá, Colombia. PER3-VNTR genotyping was carried out with conventional PCR and all participants completed the TOL test using the computerized Psychology Experiment Building Language (PEBL) battery. A linear regression model was used for the analysis of association with the SNPStats program. We found that 4/4 genotype carriers showed a better performance and made fewer moves, in comparison to 4/5 and 5/5 genotype carriers (p = 0.003). These results appear to be independent from effects of this polymorphism on self-reported average hours of sleep during work days in our sample. This is the first evidence of an association between PER3-VNTR and planning performance in a sample of healthy subjects and our results are consistent from previous findings for alterations in other cognitive domains. Future studies examining additional genes could lead to the identification of novel molecular underpinnings of planning in healthy subjects and in patients with neuropsychiatric disorders.

Functional polymorphisms in BDNF and COMT genes are associated with objective differences in arithmetical functioning in a sample of young adults.

BACKGROUND: Understanding the molecular genetics of complex human behaviors and functions remains a substantial challenge for the neurosciences. Previous studies have shown a genetic basis for individual differences in mathematical functioning; however, the specific genes remain to be completely identified. In the present study, we explored the possibility that 2 functional polymorphisms in candidate genes could be associated with differences in arithmetical performance. METHODS: A computerized test to analyze performance in basic arithmetical calculations (additions and subtractions) was applied to 168 healthy young Colombian participants using the PEBL (Psychology Experiment Building Language) battery. DNA samples were genotyped for 2 functional SNPs in candidate genes: brain-derived neurotrophic factor (BDNF)-Val66Met and catechol-O-methyltransferase (COMT)-Val158Met. RESULTS: We found significant differences for arithmetical processing scores between genotypes. For BDNF, Val/Val subjects had a worse performance (p value: 0.025) and for COMT, Val/Val carriers had a better performance (p value: 0.006). A multivariate model, including both BDNF and COMT genes, accounted for 7.1% of the variance in math processing scores. DISCUSSION: To our knowledge, this is the first study finding associations of polymorphisms in BDNF and COMT genes with quantitative measures of numerical aptitude in healthy young participants. A future study of other genes involved in neural plasticity could be helpful to identify genetic correlates of arithmetical functioning, which will be important for the understanding of normal human behaviors and related neuropsychiatric disorders.