Assessment of psychotropic medications prescribing pattern in Gebretsadik Shawo General Hospital, South West Ethiopia.

Introduction: due to the widespread prescription of antipsychotic medications, their usage is cumulative. Evidence on the trends of medication use in Ethiopia and other parts of the world is lacking. The scant information on prescription trends and medication usage suggests that drug use is generally not sensible in both industrialized and emerging nations. So, the aim of this study was to assess the psychotropic medications prescribing pattern in Gebretsadik Shawo General Hospital, South West Ethiopia. Methods: from June 1st to July 31st, 2019, a cross-sectional study on prescriptions for psychiatric drugs was conducted at Gebretsadik Shawo General Hospital. Using systematic random sampling, prescription records were obtained from the pharmacy dispensing book. Version 21 of the statistical program for social science was used to code and analyze the data. Results: the study included 355 prescription records containing psychotropic drugs in total. The bulk of those taking the psychotropic medication were aged 20 to 49. The most often administered classes of drugs remained antipsychotic, followed by tricyclic antidepressants, antiepileptics, anxiolytics/sedatives, anticholinergic and selective serotonin reuptake inhibitors. The most often ordered antipsychotic medication, which included 102 (23.18%) medications, was chlorpromazine. Tricyclic antidepressants, which included 56 medicines (12.73%) and 24 medications (5.45%), included amitriptyline and imipramine. Conclusion: the results of this investigation showed that psychiatrists preferred traditional psychotropic medications, such as Antipsychotic tricyclic, antidepressants (TCAs) and phenothiazines, in high amounts possibly because these medications were readily available in this hospital and their prices suited patients' needs. Health care workers' interdisciplinary relationships and coherence would improve for the benefit of patients and services of higher quality.

Monitoramento do horizonte tecnológico: Medicamentos para o tratamento do transtorno depressivo maior / Monitoring the technological horizon: Drugs for the treatment of major depressive disorder

A DOENÇA: O transtorno depressivo maior (TDM) é considerado um grave problema de saúde pública que afeta mais de 264 milhões de pessoas em todo o mundo (1). No Brasil, a prevalência nacional da depressão estimada pelo Global Burden of Disease 2017 foi de 3,3% e esta condição está entre as quatro principais causas de invalidez, afetando a produtividade e qualidade de vida dos pacientes. Nas populações vulneráveis como os idosos, esse número é significativamente maior, uma revisão sistemática publicada em 2019 estimou uma prevalência de 21,9% em idosos brasileiros residentes na comunidade. Segundo projeções da Organização Mundial da Saúde (OMS) para 2030, a depressão ocuparia o primeiro lugar entre as principais doenças incapacitantes. TRATAMENTO RECOMENDADO: Atualmente não existem Protocolos Clínicos e Diretrizes Terapêuticas (PCDT) do Ministério da Saúde, bem como avaliações da Conitec sobre esse tema. O tratamento da TDM depende da gravidade da doença, nos indivíduos com depressão grave, em que há risco de suicídio, o encaminhamento para o especialista deve ser imediato e a hospitalização pode ser um recurso necessário. Nos casos moderados, em geral, se sugere a combinação de psicoterapia e medicamentos antidepressivos, sendo que diversas classes são consideradas opções terapêuticas, como Inibidores seletivos da recaptação da serotonina; Inibidores seletivos da recaptação da noradrenalina; Antidepressivos atípicos; Moduladores da serotonina; Antidepressivos tricíclicos; Inibidores da monoaminoxidase. ESTRATÉGIA DE BUSCA: Uma busca no repositório de protocolos de estudos clínicos ClinicalTrials.gov foi realizada com o objetivo de localizar os medicamentos em fase de pesquisa clínica e/ou recentemente aprovados para TDM. Foram excluídos medicamentos com registro na Anvisa superior a dois anos para a indicação de depressão maior, assim como procedimentos, produtos da medicina tradicional chinesa, vitaminas e testes diagnósticos. MEDICAMENTOS APROVADOS RECENTEMENTE: ESCETAMINA SPRAY NASAL: A escetamina, o enantiômero "S" da cetamina racêmica, é um antagonista não seletivo, não competitivo do receptor N-metil-D-aspartato (NMDA), que atua como um modulador do receptor de glutamato, o que parece aumentar a sinalização entre as células, restaurando a função normal nas regiões cerebrais. Embora a ligação da escetamina ao receptor NMDA aumente o glutamato do sistema nervoso central (SNC), o mecanismo de ação exato como antidepressivo permanece incerto. Esse medicamento possui registro nas agências norte-americana e europeia (FDA e EMA) e, em dezembro de 2020, foi aprovado pela Anvisa para tratamento do TDM em pacientes com ideação suicida e de depressão resistente ao tratamento. Depressão resistente ao tratamento: MEDICAMENTOS EM FASE DE PESQUISA CLÍNICA: RAPASTINEL: O rapastinel (GLYX-13) é um anticorpo monoclonal com apresentação para administração endovenosa, que atua como agonista parcial funcional do receptor de N-metil-D-aspartato (NMDA) com ação no sistema glutamatérgico. INFORMAÇÕES ADICIONAIS: Atualmente existem diferentes tecnologias sendo estudadas para o tratamento de TDM, sendo que neste informe, foram descritas as tecnologias que estão em um horizonte mais próximo para aprovação por agências regulatórias ou foram aprovadas pela Anvisa recentemente. A escetamina spray nasal e brexpiprazol foram aprovados pela Anvisa em 2020, com o objetivo de avaliar a incorporação dessas tecnologias no mundo, uma busca foi realizada em novembro de 2021 nos websites das agências de ATS do Reino Unido, Canadá e Austrália. CONSIDERAÇÕES FINAIS O TDM: é um grave problema de saúde pública por afetar milhões de pessoas em todo o mundo. Apesar de haver muitos estudos em andamento para o tratamento dessa condição clínica, em geral os resultados dos estudos demonstraram que não há diferença significativa na eficácia dos medicamentos quando comparados ao placebo. O rapastinel, que recebeu designação Breakthough Therapy pela FDA em 2016, caracterizando-o como medicamento inovador para uma necessidade médica não atendida e que teria prioridade para avaliação na FDA, apresentou resultados promissores para estudo de fase 2, entretanto eles não foram confirmados nos ECR fase 3, duplo-cego, controlados por placebo, tanto em monoterapia como tratamento adjuvante para TDM. O medicamento REL-1017 (ou d-metadona), também é um inibidor do receptor NMDA e recebeu designação FastTrack pela FDA em 2017 para o tratamento adjuvante de TDM. Apesar dos dados do estudo de fase 2 mostrarem resultados promissores, o estudo de fase 3 ainda está em andamento. Também, esperam-se os dados das diversas pesquisas fase 3, realizadas em diferentes cenários (adjuvante ou monoterapia, por exemplo), e que avaliaram o medicamento SAGE-217, um modulador do receptor GABA que mostrou resultados positivos no estudo fase 2. O brexpiprazol foi aprovado pela Anvisa em 2020, indicado para o tratamento de depressão maior em adultos em associação a um antidepressivo, em caso de inefetividade da monoterapia com antidepressivo anterior. Os ensaios clínicos randomizados fase 3 avaliaram que o uso do medicamento reduziu o escore basal de MADRS na semana 6. O brexipiprazol para tratamento de depressão não foi avaliado por nenhuma agência de ATS até o momento. A escetamina spray nasal teve registro sanitário aprovado pela Anvisa em novembro de 2020 para pacientes com ideação suicida e de depressão resistente ao tratamento - a partir da avaliação da redução do escore basal de MADRS em 24h e após 28 dias. Mas esse medicamento não foi recomendado para incorporação pelas agências de ATS do Reino Unido e Canadá. Os medicamentos em desenvolvimento para depressão incluem populações específicas e frequentemente são usados em associação a outros antidepressivos. O tratamento da depressão grave e não responsiva a tratamentos prévios ainda é uma necessidade médica não atendida, assim como tratamentos específicos para populações vulneráveis como idosos. Também é importante destacar que todos os resultados descritos neste documento são dados precoces e devem ser avaliados com cautela. Dessa maneira, considerando os estudos de fase 3 citados neste documento, conclui-se que ainda são poucas as opções promissoras em estudo para um horizonte de curto a médio prazo.

Benefit-Risk Assessment of Psychotropic Drugs in Older Patients with Chronic Obstructive Pulmonary Disease.

Depression, anxiety, and other mental health disorders, including bipolar disorder and schizophrenia, occur commonly in older adults with chronic obstructive pulmonary disease (COPD), and they are often inadequately treated. We review the available evidence for benefits and risks of pharmacologic treatments (e.g. selective serotonin reuptake inhibitors [SSRIs], serotonin-noradrenaline reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], antipsychotic drugs, and benzodiazepines) for common mental illnesses in older persons with COPD. Evidence to use both SSRIs/SNRIs and TCAs from randomized controlled trials is uncertain for treating major depression in patients with COPD. However, population-based findings indicate that they are widely used, and this valuable intervention (preferably SSRIs/SNRIs) should not be denied for selected patients after evaluating potential risks and benefits, especially patients presenting with major depression and suicidal ideation, when a collaborative-care approach is being used. Although there is some evidence for the short-term use of benzodiazepines for treating insomnia, breathlessness, and anxiety in patients with COPD, their long-term use should be closely monitored or avoided to reduce the increased rate of major adverse events. Currently, there are only limited data on the use of antipsychotic drugs for managing schizophrenia or bipolar disorder in older patients with COPD. Hence, clinicians should use extra caution when prescribing antipsychotic agents and be vigilant for symptoms of acute respiratory failure and other adverse effects. Psychotropic medications are clearly beneficial for younger, healthy persons with depression and anxiety; however, the risk-benefit calculation is not so clear for treating psychological problems, schizophrenia, and bipolar disorder in older adults with COPD, given older-adult sensitivity to medications and the mixed findings of relatively few controlled trials.

Antidepressant drug use and regional prescribing patterns in Germany: results from a large population-based study.

OBJECTIVE: To consider antidepressant prescribing on a population level with a focus on regional prescribing patterns in Germany. BASIC METHODS: Based on data from about 70 million individuals covered by all statutory health insurance funds in Germany in 2010, the prevalence of antidepressant use (overall, for drug classes and individual drugs) was calculated stratified by age and sex. Regional analyses were performed on a state and also on a district level. MAIN RESULTS: The study population comprised 68 427 464 (female: 53.0%) persons, of which 5 052 293 (7.4%) were prescribed at least one antidepressant. The most frequently prescribed drug class was tricyclic antidepressants whereas on a substance level citalopram was most commonly used. Antidepressant prescribing was lowest in children and adolescents (0.2%) and most common in persons aged 70 years and older (13.4%). Women more often received antidepressants than men (9.7% vs. 4.8%). Prevalence of antidepressant use varied between 8.7% (Saarland) and 6.3% (Saxony-Anhalt) and was generally highest in the southwestern and lowest in the eastern states. Accordingly, districts with the highest prevalence were located in the southwestern states. PRINCIPAL CONCLUSIONS: Antidepressant use in Germany varied considerably by age and sex and also on a state and district level.

Use of tricyclic antidepressants and other anticholinergic medicines by older Aboriginal Australians: association with negative health outcomes.

BACKGROUND: Aboriginal and Torres Strait Islander Australians have a relatively high prevalence of multimorbidity requiring treatment with medications. This study examines medication use and anticholinergic burden (ACB) among a cohort of older Aboriginal and Torres Strait Island people. METHOD: This cross-sectional study involving five Aboriginal communities (two in metropolitan Sydney and three on the mid-north coast of New South Wales) used a structured interview process to assess cognition, depression, and activities of daily living for a cohort of older adults (aged 60 years and over). Participants also reported on their health status, medical history, and prescription medications during the interview. ACB was calculated, and its association with adverse health outcomes including cognitive impairment, falls, hospitalization, and depressive symptoms were examined. RESULTS: Most participants (95%) were taking at least one regular medication with polypharmacy (≥5 medications) observed in 43% of participants; 12.2% had a significant ACB (≥3) with antidepressants being a major contributor. Anticholinergic medication use was associated with cognitive impairment, recent hospitalization (past 12 months), and depressive symptoms. After controlling for age, sex, and comorbidity, only the presence of depressive symptoms remained significantly associated with the use of anticholinergic medication (odds ratio 2.86; 95% confidence interval 1.48-5.51). CONCLUSIONS: Clinically significant ACB was common in older Aboriginal Australians and was largely attributable to inappropriate use of tricyclic antidepressants. Greater awareness of medication-related risk factors among both health care professionals and Aboriginal communities can play an important role in improving health and quality of life outcomes.

Switches and early discontinuations of antidepressant medication in young adults with depression.

BACKGROUND: Receiving treatment for depression is increasingly common among young adults. Antidepressants (AD) are important in depression treatment and modification of medication is common. We examined switches and discontinuations of ADs among young Finnish adults aged 18-29 years. METHODS: All persons diagnosed with depression in inpatient or specialized outpatient care or having received sickness absence or disability pension due to depression at age of 18-29 years during 2004-17 were included (N = 110761). Among them, we focused on incident AD users (N = 52855, 47.7%) who were identified with a 6 month washout before AD initiation. The follow-up was 2 years. RESULTS: The majority (76.3%) initiated with selective serotonin reuptake inhibitors (SSRIs). The initial AD was switched in 17.4% of cases. Switching was most common when treatment was initiated with tricyclic antidepressants (TCA) or polytherapy, and least common when initiated with SSRIs or serotonin-noradrenaline reuptake inhibitors. Factors associated with switch included initiation with polytherapy, TCA or mirtazapine, and use of benzodiazepines or Z-drugs at baseline. During the first 3 months, 27.6% discontinued AD use, and only 14.1% used AD for 2 years. Factors associated with discontinuation included substance abuse, ADHD, previous suicide attempt and initiation with mirtazapine. SSRIs had the longest time to discontinuation (median 144 days, IQR 64-302). LIMITATIONS: Our data sources lack those treated in primary care only, without receiving a sick leave of ≥2 weeks. In addition, we do not have data on severity of depression, social factors or psychotherapy. CONCLUSIONS: Special emphasis should be paid to persons with increased risk of discontinuation, including those with previous self-harm/suicide attempt or substance abuse.

Impact of Antidepressant Prescriptions on Suicidal Behavior in Times of Severe Financial Strain.

ABSTRACT: This descriptive study observes the relationship between antidepressant prescriptions and the suicide rate in Italy in the 2000s to the mid-2010s, which includes a period of severe economic crisis. The observation period was from 2000 to 2015. Suicide and unemployment rates disaggregated by age and sex were collected from the Italian Institute of Statistics. Statistical analyses were performed using correlations between suicide rates and the defined daily dose, with reference to selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other types of antidepressants. Fixed-effects panel regressions were also run. Increases in SSRIs prescriptions were associated with decreases in suicide rates among both men and women. However, when the analyses were adjusted for the rate of growth of the unemployment rate and for gross domestic product, the associations were weaker. The potential protective factor of SSRIs with respect to suicidal behavior may be reduced by severe recessions, especially when unemployment increases.

The Impact of Failed Antidepressant Trials on Outcomes in Children and Adolescents with Anxiety and Depression: A Systematic Review and Meta-Analysis.

Objective: To identify predictors of medication-placebo differences in double-blind placebo-controlled antidepressant trials in children and adolescents with anxiety and depression. Methods: Clinical trials in patients <18 years of age with major depressive disorder or generalized, separation or social anxiety disorders were obtained from PubMed, the Cochrane Database and clinicaltrials.gov searches from inception through 2019. Forty-nine trials (43 published and 6 unpublished) of anxiety (κ = 13) and depression (κ = 36) evaluated 19 antidepressants in 8642 child and adolescent patients; placebo and medication response rates, trial characteristics, disorder, medication class, and funding source were extracted. Antidepressant-placebo differences were examined using Bayesian hierarchical models and estimates of response were determined for trial design, disorder, and medication class variables. Using meta-regression, correlates of antidepressant-placebo difference and placebo response were examined. Results: Funding source differentiated medication-placebo differences regardless of disorder. Industry trials had larger placebo response rates (mean difference: 0.189 ± 0.066, credible interval [CrI]: 0.067 to 0.33, p = 0.0008) and smaller medication-placebo differences (-0.235 ± 0.078, CrI: -0.397 to -0.086, p = 0.005) compared with federally funded trials. However, medication response was similar for industry- and federally-funded studies (-0.046 ± 0.042, CrI: -0.130 to 0.038, p = 0.252). Conclusions: The impact of study sponsorship on trial outcome supports the assertion that industry-funded trials with high placebo response rates and small drug-placebo differences are "failed trials" and should not be described as "negative trials" or used to determine public health estimates of antidepressant efficacy in children and adolescents with anxiety and depression. Identifying the proper role and value of industry-funded trials is critical to establishing the evidence base for antidepressants in youth.

Understanding the migraine treatment landscape prior to the introduction of calcitonin gene-related peptide inhibitors: Results from the Assessment of TolerabiliTy and Effectiveness in MigrAINe Patients using Preventive Treatment (ATTAIN) study.

BACKGROUND: Calcitonin gene-related peptide (CGRP) inhibitors were introduced in the United States (US) in 2018. To understand the changing patterns of preventive treatment following the introduction of these new agents, we must first characterize the patterns which preceded their introduction. OBJECTIVE: To characterize the burden, unmet need, and treatment patterns in patients with migraine initiating preventive migraine medications before the introduction of CGRP inhibitors in the US. METHODS: Between March 2016 and October 2017, we enrolled episodic (EM) and chronic migraine (CM) patients initiating or changing preventive treatment at primary care or neurology clinic visits in the US, in a real-world observational study using a prospective cohort design. At baseline and monthly thereafter for 6 months, we collected data from study sites and patients on migraine frequency, treatment modifications, migraine impact on functioning, and work productivity for a descriptive analysis of migraine patient experience and treatment patterns. RESULTS: From the sample of 234 completers, 118 had EM (50.4%) and 116 had CM (49.6%). Mean age at enrollment was 41 years (SD = 12) and mean age at first migraine diagnosis was 22 years (SD = 11). Most participants were females (n = 204/234; 87.2%) and white (n = 178/234; 76.1%). The majority (n = 164/234; 70.1%) had not used preventive migraine treatment in the 5 years prior to enrollment (treatment naïve). At baseline, mean monthly migraine days were 9.6 days (SD = 5.0) for the preventive treatment naïve group and 12.4 days (SD = 7.0) for treatment experienced patients. The majority had severe Migraine Disability Assessment (Grade IV, total score ≥21), including 67.1% (n = 110/164) of the preventive treatment naïve and 77.1% (n = 54/70) of the preventive treatment experienced patients. Headache Impact Test total scores indicating severe impairment (score >59) occurred in 88.4% (n = 145/164) of the treatment naïve and 88.6% (n = 62/70) of treatment experienced patients. Mean work productivity loss as measured by the Work Productivity and Activity Impairment questionnaire in the subsample of employed patients was 53.3% loss. The most used acute medications at baseline were nonsteroidal anti-inflammatory agents (n = 124/234; 53.0%), acetaminophen-based products (n = 112/234; 47.9%), and triptans (n = 105/234; 44.9%). The most commonly initiated preventive treatments were topiramate (n = 100/234; 42.7%), tricyclic antidepressants (n = 39/234; 16.7%), beta-blockers (n = 26/234; 11.1%), and onabotulinumtoxinA (n = 24/234; 10.3%). Over the 6-month follow-up period, almost half of patients (n = 116/234, 49.6%) modified their preventive treatment and discontinued treatment (n = 88/312 total modifications; 28.2%) or modified their pattern of use by increasing, decreasing, or skipping doses (n = 224/312 total modifications; 71.8%), often without seeking medical advice. Avoiding side effects was the main reason reported among patients who discontinued (n = 52/88; 59.1%), decreased frequency or dose (n = 37/89; 41.6%), and skipped doses (n = 29/86; 33.7%). Perceived lack of efficacy was another frequent reason reported among those who discontinued (n = 20/88; 22.7%), decreased frequency or dose (n = 15/89; 16.9%), and skipped doses (n = 18/86; 20.9%). Despite initiation of preventive treatment and improvements observed in number of headache and migraine days, migraine patients continued to experience substantial disability, headache impact, and reduced productivity throughout the 6-month follow-up period. CONCLUSIONS: Prior to 2018, the burden of migraine was high for patients initiating preventive treatments. Despite having more than 9 days of migraine per month on average, the majority (70.1%) of patients initiating prevention had been treatment naïve, indicating underuse of preventive treatments. The preventive treatments used in this study were poorly tolerated and were reported by patients to lack efficacy, resulting in suboptimal adherence. The high discontinuation rates suggest that the preventive medications being offered during the period of the study did not meet the treatment needs of patients. In addition, the decisions by about half of patients to alter their prescribed treatment plan without consulting their provider can pose substantial health risks. These findings pertain to the broad set of preventive treatments initiated in this study and do not support inferences about individual preventive treatments, due to limitations in sample size. These findings suggest the need for more effective and better tolerated preventive treatment options.

Estimating the Use of Potentially Inappropriate Medications Among Older Adults in the United States.

OBJECTIVES: Inappropriate prescribing of medications is common in health care, and is an important safety concern, especially for older adults, who have a high burden of comorbidity and are at greater risk for medication-related adverse events. This study aims to estimate the extent and cost of potentially inappropriate prescribing of medications to older adults in the United States. DESIGN: A cross-sectional study. SETTING: Medicare Part D Prescription Drug Program data set (2014-2018). PARTICIPANTS: Older adults who were enrolled in Medicare Part D Prescription Drug Program between 2014 and 2018. MEASUREMENTS: Potentially inappropriate medications were identified using the 2019 American Geriatrics Society Beers Criteria®. RESULTS: In 2018, 7.3 billion doses of potentially inappropriate medications were dispensed. The most common medications by number of doses dispensed were proton pump inhibitors, benzodiazepines, and tricyclic antidepressants, and the top five unique medications by reported spending were dexlansoprazole, esomeprazole, omeprazole, dronedarone, and conjugated estrogens. From 2014 to 2018, 43 billion doses of potentially inappropriate medications were dispensed, with a reported spending of $25.2 billion. CONCLUSION: Potentially inappropriate medication use among older adults is both common and costly. Careful attention to potentially inappropriate medication use and deprescribing when clinically appropriate could reduce costs and potentially improve outcomes among older adults.

Association of Formulary Exclusions and Restrictions for Opioid Alternatives With Opioid Prescribing Among Medicare Beneficiaries.

Importance: Although there are many pharmacologic alternatives to opioids, it is unclear whether the structure of Medicare Part D formularies discourages use of the alternatives. Objectives: To quantify the coverage of opioid alternatives and prevalence of prior authorization, step therapy, quantity limits, and tier placement for these drugs, and test whether these formulary exclusions and restrictions are associated with increased opioid prescribing to older adults at the county level. Design, Setting, and Participants: County fixed-effect models were estimated using a panel of counties across the 50 US states and the District of Columbia over calendar years 2015 and 2016. Data analysis was conducted from July 1 to September 23, 2019. The sample included 2721 counties in 2015 and 2671 counties in 2016 with sufficient data on Medicare Part D formulary design and opioid prescribing. Main Outcomes and Measures: County-level opioid prescribing rate (number of opioid claims divided by the number of overall claims) and counts of excluded opioid alternatives and opioid alternatives with prior authorization, step therapy, quantity limits, and high-tier placements. Results: A total of 30 nonopioid analgesics were examined across 28 997 Medicare plans in 2015 and 30 390 plans in 2016. Medicare plans did not cover a mean of 7% of these drugs (interquartile range, 10%; lower to upper limit, 0%-23%). Among covered nonopioids, prior authorization and step therapy were uncommon, with fewer than 5% affected by prior authorization and 0% by step therapy. However, 13% of covered nonopioids had quantity limits (interquartile range, 10%; lower to upper limit, 0%-31%) and 22% were in high-cost tiers (interquartile range, 38%; lower to upper limit, 0%-50%). Increases in the number of nonopioids excluded on Medicare plans in a county were associated with increased opioid prescribing (effect size relative to mean, 2.2%-3.7%; P = .004). Conversely, increases in the number of opioids not covered on Medicare plans in a county was found to be associated with decreased opioid prescribing (effect size relative to mean, 0.8%-1.5%; P = .02). None of the utilization management strategies (prior authorization, step therapy, and quantity limits) examined or high-cost tier placements of nonopioids were associated with increased opioid prescribing. Conclusions and Relevance: Lack of Medicare coverage for pharmacologic alternatives to opioids may be associated with increased opioid prescribing.

Pharmacogenomics: An evolving clinical tool for precision medicine.

Pharmacogenomics, ie, the study of how an individual's genomic profile influences his or her response to drugs, has emerged as a clinical tool to optimize drug therapy. Certain variants in some genes increase the risk of severe, life-threatening adverse effects from certain drugs. Integrating pharmacogenomics into clinical practice to assist in drug selection and dosing has the potential to improve the outcomes of treatment, reduce the risk of drug-induced morbidity and death, and be cost-effective.

Treatment patterns and sequences of pharmacotherapy for patients diagnosed with depression in the United States: 2014 through 2019.

BACKGROUND: Understanding how patients are treated in the real-world is vital to identifying potential gaps in care. We describe the current pharmacologic treatment patterns for the treatment of depression. METHODS: Patients with depression were identified from four large national claims databases during 1/1/2014-1/31/2019. Patients had ≥2 diagnoses for depression or an inpatient hospitalization with a diagnosis of depression. Patients were required to have enrollment in the database ≥1 year prior to and 3 years following their first depression diagnosis. Treatment patterns were captured at the class level and included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, and antipsychotics. Treatment patterns were captured during all available follow-up. RESULTS: We identified 269,668 patients diagnosed with depression. The proportion not receiving any pharmacological treatment during follow-up ranged from 29 to 52%. Of the treated, approximately half received ≥2 different classes of therapy, a quarter received ≥3 classes and more than 10% received 4 or more. SSRIs were the most common first-line treatment; however, many patients received an anxiolytic, hypnotic/sedative, or antipsychotic prior to any antidepressive treatment. Treatment with a combination of classes ranged from approximately 20% of first-line therapies to 40% of fourth-line. CONCLUSIONS: Many patients diagnosed with depression go untreated and many others receive a non-antidepressant medication class as their first treatment. More than half of patients received more than one type of treatment class during the study follow up, suggesting that the first treatment received may not be optimal for most patients.

Effects of antidepressant treatments on health service utilization and medical costs among patients with depression: a nationwide population-based retrospective cohort study in Taiwan.

This study aimed to assess the associations between the use of different types of antidepressants and health service utilization and costs among depressed patients. Data used in this study were retrieved from the Taiwan National Health Insurance Research Database. We identified 447 411 new antidepressant users during the study period (2011-2015) and they were individually followed for a 1-year period. Two-part generalized estimating equation models were conducted. Results demonstrated that there was a substantial decrease in outpatient service utilized by patients undertaking serotonin antagonists and reuptake inhibitors (ß = -0.2074), serotonin-norepinephrine reuptake inhibitors (ß = -0.0452), tricyclic antidepressants (ß = -0.1308), or other antidepressants (ß = -0.0637), compared with their counterparts in the selective serotonin reuptake inhibitors group (all P < 0.05). Compared with patients who were treated with selective serotonin reuptake inhibitors, those who were prescribed serotonin antagonists and reuptake inhibitors (ß = -0.4934, P < 0.05) or tricyclic antidepressants (ß = -0.4194, P < 0.05) had incurred lower costs pertaining to outpatient service, while considerably higher costs were borne by those patients embarked on the treatment of serotonin-norepinephrine reuptake inhibitors (ß = 0.3228, P < 0.05) or other antidepressants (ß = 0.1118, P < 0.05). We concluded that the initiation of various classes of antidepressants led to significant variations in health service utilization and costs among depressed patients.

Pitfalls of using the risk ratio in meta-analysis.

For meta-analysis of studies that report outcomes as binomial proportions, the most popular measure of effect is the odds ratio (OR), usually analyzed as log(OR). Many meta-analyses use the risk ratio (RR) and its logarithm because of its simpler interpretation. Although log(OR) and log(RR) are both unbounded, use of log(RR) must ensure that estimates are compatible with study-level event rates in the interval (0, 1). These complications pose a particular challenge for random-effects models, both in applications and in generating data for simulations. As background, we review the conventional random-effects model and then binomial generalized linear mixed models (GLMMs) with the logit link function, which do not have these complications. We then focus on log-binomial models and explore implications of using them; theoretical calculations and simulation show evidence of biases. The main competitors to the binomial GLMMs use the beta-binomial (BB) distribution, either in BB regression or by maximizing a BB likelihood; a simulation produces mixed results. Two examples and an examination of Cochrane meta-analyses that used RR suggest bias in the results from the conventional inverse-variance-weighted approach. Finally, we comment on other measures of effect that have range restrictions, including risk difference, and outline further research.

Value-based Pricing for Rifaximin Increases Access of Patients With Irritable Bowel Syndrome With Diarrhea to Therapy.

BACKGROUND & AIMS: Increasing drug prices lead to payer coverage restrictions, which limit access to therapy. We assessed the cost effectiveness of rifaximin in management of patients with irritable bowel syndrome with diarrhea (IBS-D) under common payer coverage restrictions and determined the maximum price at which rifaximin would be cost effective using contemporary cost-effectiveness thresholds. METHODS: A decision analytic model was constructed to evaluate quality of life, cost, and cost effectiveness of rifaximin for patients with IBS-D and complete noncoverage (insurer pays none of the drug cost), unrestricted access (insurer pays 100% of the drug cost), and formulary-restricted access (insurer pays 100% of the drug cost after for patients failed by initial therapy). The maximum cost-effective drug price was determined for each level of drug coverage using threshold analysis adjusted for willingness to pay thresholds from $50,000 to $150,000 per quality-adjusted life year (QALY). Analysis was performed from a payer perspective with a 1-year time horizon. RESULTS: Unrestricted and formulary-restricted access were more effective than complete non-coverage, resulting in additional 0.03 and 0.05 QALYs gained over noncoverage. However, unrestricted and formulary-restricted coverage were more expensive. At current drug prices, unrestricted or formulary-restricted coverage would cost an additional $1,207,136 or $171,850/QALY gained, compared to complete non-coverage. A 12% to 62% price reduction ($18.46 to $26.34/pill) for formulary-restricted access and 84% to 88% price reduction ($3.53 to $4.71/pill) for unrestricted access would be needed for rifaximin to be a cost-effective treatment strategy. Rifaximin retreatment intervals, response rates, and adverse events were important factors in sensitivity analysis. CONCLUSION: Using a decision analytic model, we show that payer coverage for rifaximin for patients with IBS-D exceeds generally accepted cost-effectiveness thresholds at current drug prices. Improved payer coverage could be justified using value-based pricing methods.

Tricyclic Antidepressant and/or γ-Aminobutyric Acid-Analog Use Is Associated With Fall Risk in Diabetic Peripheral Neuropathy.

BACKGROUND/OBJECTIVES: Peripheral neuropathy is a common diabetes complication that can increase fall risk. Regarding fall risk, the impact of pain management using tricyclic antidepressants (TCAs) or γ-aminobutyric acid (GABA) analogs is unclear because these medications can also cause falls. This study investigates the impact of these drugs on fall and fracture risk in older diabetic peripheral neuropathy (DPN) patients. DESIGN: Historical cohort study with 1-to-1 propensity matching of TCA/GABA-analog users and nonusers. SETTING: Nationally representative 5% Medicare sample between the years 2008 and 2010. PARTICIPANTS: After applying all selection criteria, 5,550 patients with prescription and 22,200 patients without prescription of TCAs/GABA-analogs were identified. Both patient groups were then stratified for fall history and matched based on propensity of receiving TCAs/GABA-analogs within each group. MEASUREMENTS: Patients were followed until the first incidence of fall or the first incidence of fracture during the follow-up period (for up to 5 years). RESULTS: After matching, users and nonusers were largely similar. After covariate adjustment, TCA/GABA-analog use was associated with a statistically significant increase in fall risk (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 1.03-1.20), but was not associated with fracture risk (adjusted HR = 1.09; 95% CI = 0.99-1.19) in the conventional analysis. Treating TCA/GABA-analog use as a time-dependent covariate resulted in statistically significant associations of TCA/GABA-analog use with both fall and fracture risk (HR = 1.26 [95% CI = 1.17-1.36]; and HR = 1.12 [95% CI = 1.02-1.24], respectively). CONCLUSION: Among older patients with DPN, GABA-analogs or TCAs increase fall risk and possibly fracture risk. Use of these medications is therefore a potentially modifiable risk factor for falls and fractures in this population.

Variables Associated With the Use of Prophylactic Amitriptyline Treatment in Patients With Tension-type Headache.

OBJECTIVE: The objective of this study was to investigate differences in clinical, psychological, and psychophysical outcomes according to use of prophylactic medication (amitriptyline) in tension-type headache (TTH). METHODS: In total, 173 individuals with TTH participated. Headache features and symptomatic medication intake were collected with a 4-weeks headache diary at baseline and at 6-months. Burden of headache (Headache Disability Inventory-HDI), sleep quality (Pittsburgh Sleep Quality Index-PSQI), anxiety/depression (Hospital Anxiety and Depression Scale-HADS), and trait/state anxiety levels (State-Trait Anxiety Inventory-STAI) were also assessed at baseline. Pressure pain thresholds (PPT) were assessed over the temporalis, C5-C6 joint, second metacarpal, and tibialis anterior at baseline. Differences between participants taking or not taking prophylactic medication based on self-perceived effectiveness of the medication on headache characteristics were assessed. RESULTS: In total, 49 (28%) reported taking prophylactic medication for the headaches (amitriptyline: 100%). From these, 11 (23%) reported no effect, 25 (51%) reported moderate effect, and 13 (26%) reported positive effect with medication. Patients taking prophylactic medication had longer headache history, higher frequency of headaches (61% CTTH), higher headache burden, worse quality of sleep, and higher depression than those not taking medication. Prophylactic medication was less effective in patients with generalized pressure pain hyperalgesia. No other significant differences were found. CONCLUSIONS: Prophylactic medication is used by TTH patients with higher headache frequency, higher headache burden, worse sleep quality, and higher depression. Lower effectiveness of prophylactic amitriptyline was associated with widespread pain hyperalgesia.

Self-harm in a primary care cohort of older people: incidence, clinical management, and risk of suicide and other causes of death.

BACKGROUND: Self-harm is a major risk factor for suicide, with older adults (older than 65 years) having reportedly greater suicidal intent than any other age group. With the aging population rising and paucity of research focus in this age group, the extent of the problem of self-harm needs to be established. In a primary care cohort of older adults we aimed to investigate the incidence of self-harm, subsequent clinical management, prevalence of mental and physical diagnoses, and unnatural-cause mortality risk, including suicide. METHODS: The UK Clinical Practice Research Datalink contains anonymised patient records from general practice that routinely capture clinical information pertaining to both primary and secondary care services. We identified 4124 adults aged 65 years and older with a self-harm episode ascertained from Read codes recorded during 2001-14. We calculated standardised incidence and in 2854 adults with at least 12 months follow-up examined the frequency of psychiatric referrals and prescription of psychotropic medication after self-harm. We estimated prevalence of mental and physical illness diagnoses before and after self-harm and, using Cox regression in a matched cohort, we examined cause-specific mortality risks. FINDINGS: Overall incidence of self-harm in older adults aged 65 years and older was 4·1 per 10 000 person-years with stable gender-specific rates observed over the 13-year period. After self-harm, 335 (11·7%) of 2854 adults were referred to mental health services, 1692 (59·3%) were prescribed an antidepressant, and 336 (11·8%) were prescribed a tricyclic antidepressant (TCA). Having a diagnosed previous mental illness was twice as prevalent in the self-harm cohort as in the comparison cohort (prevalence ratio 2·10 [95% CI 2·03-2·17]) and with a previous physical health condition prevalence was 20% higher in the self-harm cohort compared to the comparison cohort (1·20 [1·17-1·23]). Adults from the self-harm cohort (n=2454) died from unnatural causes an estimated 20 times more frequently than the comparison cohort (n=48 921) during the first year. A markedly elevated risk of suicide (hazard ratio 145·4 [95% CI 53·9-392·3]) was observed in the self-harm cohort. INTERPRETATION: Within primary care, we have identified a group of older adults at high risk from unnatural death, particularly within the first year of self-harm. We have highlighted a high frequency of prescription of TCAs, known to be potentially fatally toxic in overdose. We emphasise the need for early intervention, careful alternative prescribing, and increased support when older adults consult after an episode of self-harm and with other health conditions. FUNDING: National Institute for Health Research Greater Manchester Patient Safety Translational Research Centre.