Symptom-network dynamics in irritable bowel syndrome with comorbid panic disorder using electronic momentary assessment: A randomized controlled trial of escitalopram vs. placebo.

INTRODUCTION: Momentary ecological assessment indicated alleviated abdominal pain in escitalopram treatment of irritable bowel syndrome (IBS) with comorbid panic disorder. Hitherto, little is known about symptom formation, i.e., how psychological impact physical symptoms, and vice versa, and about the effect of SSRI-treatment on symptom formation. OBJECTIVE: To investigate how psychological and somatic symptoms co-vary over time in IBS patients with comorbid panic disorder and how they are affected by escitalopram treatment. METHODS: Experience sampling data from 14 IBS patients with panic disorder were obtained from a single-centre, double-blind, parallel-group, randomized controlled trial on escitalopram versus placebo. At baseline, after three and six months, multilevel time-lagged linear regression analysis was used to construct symptom networks. Network connections represented coefficients between various affect and gastrointestinal items. RESULTS: Connectivity increased up to 3 months in both groups. Between 3 and 6 months, connectivity decreased for placebo and further increased in the escitalopram group. Additionally, a steep increase in node strength for negative affect nodes was observed in the escitalopram network and the opposite for positive affect nodes. Over time, group symptom networks became increasingly different from each other. Anxious-anxious and enthusiastic-relaxed became significantly different between groups at 6 months. The connection that changed significantly in all analyses was anxious-anxious. CONCLUSIONS: Escitalopram treatment was associated with changes in the symptom networks in IBS patients with panic disorder. While mood and physical symptoms improve over time, mainly connectivity between mood nodes changed, possibly pointing towards a healthier emotion regulation resulting in alleviation of physical symptoms.

Generic escitalopram initiation and substitution among Medicare beneficiaries: A new user cohort study.

OBJECTIVES: To examine patterns of generic escitalopram initiation and substitution among Medicare beneficiaries. METHODS: This retrospective new user cohort used a 5% random sample of 2013-2015 Medicare administrative claims data. Fee-for-service Medicare beneficiaries continuously enrolled in Parts A, B, and D during a 6-month washout period prior to their initial generic or brand oral escitalopram prescriptions were included (n = 12,351). The primary outcomes were generic escitalopram treatment initiation, and among brand escitalopram initiators, generic substitution within 12 months. Patient demographics, health service utilization, and prescription level factors were measured and assessed. RESULTS: Among all escitalopram initiators, about 88.2% Medicare beneficiaries initiated generic escitalopram. Beneficiaries who were younger age, male, residing in non-Northeast regions or urban area, in the Part D plan deductible benefit phase, and filling prescriptions at community/retail pharmacies were more likely to initiate generic treatment. Among brand escitalopram initiators (n = 1,464), about 20.7% switched to generic escitalopram, 31.2% switched to another alternative antidepressant, 25.1% discontinued treatment, and 8.7% were lost to follow up or passed away within 12 months after brand initiation. Factors associated with generic escitalopram substitution included region (Midwest vs. Northeast, adjusted hazard ratio (HR) = 1.46, 95% CI = 1.04-2.05), pre-index hospitalization (HR = 1.31; 95% CI = 1.16-1.48) and lower escitalopram average daily dosage (HR = 0.97; 95% CI = 0.95-0.99). CONCLUSIONS: In 2013-2015, almost 90% Medicare beneficiaries initiated generic escitalopram treatment. Among brand escitalopram initiators, about 1 in 5 patients switched to generic escitalopram within 1 year, as compared to 1 in 4 or 1 in 3 who discontinued current or switched to alternative treatment, respectively. Medicare beneficiary's geographic region was independently associated with generic escitalopram initiation and substitution. Findings from this study not only provide up-to-date evidence in generic escitalopram use patterns among Medicare population, but also can guide educational and practice interventions to further increase generic escitalopram use.

Depressive Symptoms in Stroke Patients: Are There Sex Differences?

BACKGROUND: We aimed to examine sex differences in symptom characteristics and pharmacological responses in post-stroke depressive (PSD) symptoms. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram for 3 months on depression in patients with acute stroke. Depressive symptoms were evaluated using the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Baseline characteristics, clinical variables, and treatment responses to escitalopram were compared between male and female patients. Treatment responses were defined as changes in MADRS (total score and its components) between baseline and 3 months and were compared between the escitalopram and placebo groups within each sex group. The least square mean was calculated to determine the independent effect of escitalopram, of which interaction was evaluated with patient sex. RESULTS: Of the 478 patients (intention-to-treat population), 187 (39%) were female. Female patients were significantly older than male patients and demonstrated more severe depressive symptoms at baseline (male vs. female, MADRS score, mean [SD]: 9.7 ± 8.0 vs. 12.2 ± 8.4, p = 0.001), especially in apparent sadness, reported sadness, and reduced appetite items. These differences were significant after adjustment for age and the severity of neurologic deficits. The female escitalopram group showed a significant 3-month improvement in MADRS scores (placebo [n = 86] vs. escitalopram [n = 101], least square mean [95% CI] -2.7 [-4.1 to -1.2] vs. -5.0 [-6.4 to -3.6], p = 0.007), and this efficacy was prominent in apparent sadness, reported sadness, and pessimistic thoughts items. However, there was no significant effect of escitalopram on depressive symptoms in the male group. The treatment responses of escitalopram tended to be more pronounced in the female group, particularly in alleviating a subset of depressive symptoms such as apparent sadness (p for interaction = 0.009). CONCLUSION: PSD may differ according to sex in its symptom characteristics and treatment responses to escitalopram, and tailored treatment strategies for PSD may therefore be needed.

Escitalopram para trastornos psiquiátricos / Escitalopram for psychiatric disorders

INTRODUCCIÓN: Los trastornos psiquiátricos representan el 22.8% de la carga global de enfermedades. A. Cuadro clínico: Un estudio de carga de enfermedad en Perú estima que en el 2012 los transtornos mentales y de comportamiento en el Perú́ concentraron el 17% del total de años saludables perdidos por discapacidad y muerte prematura siendo responsables de la pérdida de 1 millón 10 mil 594 años saludables, representando la primera carga de años saludables perdidos en el país. La familia de los inhibidores selectivos de la recaptación de serotonina (ISRS) es una de las más usadas en psiquiatría. El mecanismo de acción principal de los ISRS generalmente se explica simplemente por su inhibición selectiva del transportador de serotonina. B. Tecnologia: Escitalopram es un fármaco de la familia de los ISRS. Se trata del enantiómero levógiro (S) puro del citalopram. Como todos los ISRS actúa inhibiendo selectivamente la recaptación de serotonina en la hendidura sináptica interneuronal, incrementa la concentración sináptica de serotonina y activa las vías serotonérgicas neurales. Sobre la base de sus características farmacológicas únicas, el escitalopram se clasifica además como un inhibidor de la recaptación de serotonina alostérico. Se postula que el escitalopram podría ser una opción de tratamiento eficaz y asociada a menos eventos adversos comparado con sertalina y fluoxetina. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura de escitalopram en trastornos psiquiátricos comparado con fluoxetina y sertralina. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE, LILACS, COCHRANE, así como en buscadores genéricos de Internet incluyendo Google Scholar y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales de manejo de heridas y agencias de tecnologías sanitárias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se identificaron 3 RS. Además, se identificó tres GPC que mencionaban a la tecnología. No se encontraron ETS, ni EE de la región. CONCLUSIONES: La evidencia con respecto a escitalopram en trastornos psiquiátricos es abundante. Para depresión y ansiedad generalizada en adultos, se evidencia una adecuada respuesta a tratamiento de escitalopram versus placebo. En comparaciones indirectas se evidencia un beneficio de escitalopram por sobre fluoxetina para depresión, pero no se evidencia diferencia con sertralina. Basado también em comparaciones indirectas, en el caso de ansiedad generalizada no hay diferencias entre la tecnologia de interés y los comparadores. En el caso de efectividad en niños con diagnóstico de depresión, se identifica escitalopram y fluoxetina como los medicamentos con mayor evidencia y que mostraron beneficio, sin embargo, no se tiene disponibilidad de estudios comparativos de escitalopram vs fluoxetina o sertralina. Las guías de práctica clínica recabadas, en general, recomiendan el uso de inhibidores de la recaptación de serotonina indistintamente como primera línea mencionando que la decisión entre estos medicamentos depende de las características del paciente, interacciones com drogas y criterio clínico.

A randomised controlled trial assessing the use of citalopram, sertraline, fluoxetine and mirtazapine in preventing relapse in primary care patients who are taking long-term maintenance antidepressants (ANTLER: ANTidepressants to prevent reLapse in dEpRession): study protocol for a randomised controlled trial.

BACKGROUND: Antidepressants are used both for treating acute episodes and for prophylaxis to prevent future episodes of depression, also called maintenance treatment. This article describes the protocol for a randomised controlled trial (ANTLER: ANTidepressants to prevent reLapse in dEpRession) to investigate the clinical effectiveness and cost-effectiveness in UK primary care of continuing on long-term maintenance antidepressants compared with a placebo in preventing relapse of depression in those who have taken antidepressants for more than 9 months and who are currently well enough to consider stopping maintenance treatment. METHODS/DESIGN: The ANTLER trial is an individually randomised, double-blind, placebo-controlled trial in which participants are randomised to remain on active medication or to take an identical placebo after a tapering period of 2 months. Eligible participants are those who: are between the ages of 18 and 74 years; have had at least two episodes of depression; and have been taking antidepressants for 9 months or more and are currently taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg but are well enough to consider stopping their medication. The participants will be followed up at 6, 12, 26, 39 and 52 weeks. The primary outcome will be the time in weeks to the beginning of the first episode of depression after randomisation. This will be measured using a retrospective version of the Clinical Interview Schedule-Revised administered at 12, 26, 39 and 52 weeks. Secondary outcomes will include depressive and anxiety symptoms, adverse effects, withdrawal symptoms, emotional processing tasks, quality of life and the resources and costs used. We will also perform a cost-effectiveness analysis based on results of the trial. DISCUSSION: The ANTLER trial findings will inform primary care prescribing practice by providing a valid and generalisable estimate of the clinical effectiveness and cost-effectiveness of long-term maintenance treatment with antidepressants in UK primary care. TRIAL REGISTRATION: Controlled Trials ISRCTN Registry, ISRCTN15969819. Registered on 21 September 2015.

Comparative effectiveness of generic and brand-name medication use: A database study of US health insurance claims.

BACKGROUND: To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications. METHODS AND FINDINGS: For commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004-2013) and (2) Truven MarketScan (years: 2003-2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88-0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84-0.99] and 0.84 [0.76-0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01-1.10] and 1.07 [1.01-1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98-1.13] and 1.11 [1.05-1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by either residual confounding or generic perception bias. Limitations of this study include potential residual confounding due to the unavailability of certain clinical parameters in administrative claims data and the inability to evaluate surrogate outcomes, such as immediate changes in blood pressure, upon switching from brand products to generics. CONCLUSIONS: In this study, we observed that use of generics was associated with comparable clinical outcomes to use of brand-name products. These results could help in promoting educational interventions aimed at increasing patient and provider confidence in the ability of generic medicines to manage chronic diseases.

Switching Selective Serotonin Reuptake Inhibitors in Adolescents with Selective Serotonin Reuptake Inhibitor-Resistant Major Depressive Disorder: Balancing Tolerability and Efficacy.

Objective: To guide clinicians in selecting the "next line" selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. Methods: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study. Using a joint bivariate normal likelihood for response and tolerability (based on the maximum implied variance from the 95% credible intervals previously reported for the three SSRIs), a Monte Carlo pseudorandom sample (100,000 draws) was obtained, from which credible intervals, means, posterior tail probabilities, etc. were determined. Joint null hypotheses of no difference in efficacy and tolerability were then evaluated with regard to superiority of each SSRI over the others. Results: No significant differences in response were observed for citalopram compared with fluoxetine (p = 0.247) or for fluoxetine compared with paroxetine (p = 0.110), although citalopram trended toward being superior to paroxetine (mean difference: 0.2, p = 0.055). For efficacy-tolerability models, citalopram and fluoxetine were superior to paroxetine (p = 0.029 and p = 0.022, respectively) but did not differ between each other (p = 0.146). Conclusions: Joint efficacy-tolerability models suggest that citalopram and fluoxetine were statistically significantly superior to paroxetine while citalopram trended toward superiority over paroxetine in the efficacy model. These findings provide a more granular and practical evidence base for clinicians faced with treatment sequencing decisions in adolescents with SSRI-resistant depression.

The Concise Health Risk Tracking Self-Report (CHRT-SR) assessment of suicidality in depressed outpatients: A psychometric evaluation.

BACKGROUND: The 12-item Concise Health Risk Tracking Self-Report (CHRT-SR12 ) is a brief, self-report measure that systematically assesses both suicidal thinking and associated thoughts that may indicate the propensity for suicidal acts. It can be used as a tool to both assess risk and guide treatment interventions targeting associated cognitions. METHODS: This report used acute treatment data from a clinically representative sample of outpatients with nonpsychotic major depressive disorder (N = 665) participating in the Combining Medications to Enhance Depression Outcomes trial, who received up to 12 weeks of escitalopram, escitalopram plus bupropion SR, or venlafaxine XR plus mirtazapine. Outcome assessors and patients were masked to treatment. RESULTS: Factor analysis of CHRT-SR12 confirmed that the 12 items have higher order structure with two subscales (Propensity, Suicidal Thoughts) and a total score. Internal consistencies were acceptable for both subscales and total score. All three scales were modestly correlated with overall depression severity (r = 0.54 to r = 0.21) and highly discriminating among patients grouped by suicide item ratings on three different depressive symptom ratings. The three scales also distinguished change over the acute phase treatment for those with different levels of baseline suicidal ideation (measured by 30-item Inventory of Depressive Symptomatology (item 18) and for those with change in suicidal ideation (baseline to last visit). CONCLUSIONS: The CHRT-SR12 has good to excellent psychometric properties and is sensitive to change in suicidal thinking and propensity toward suicidal behavior in outpatients with major depressive disorder. It allows for the monitoring of thoughts and feelings associated with increased suicidal risk as well as levels of thoughts about suicide.

Validation of the University of California San Diego Performance-based Skills Assessment (UPSA) in major depressive disorder: Replication and extension of initial findings.

BACKGROUND: The University of California San Diego Performance-based Skills Assessment (UPSA) has been validated as a functional measure in patients with major depressive disorder (MDD). The study herein aims to both replicate and extend the initial validation incorporating data sets from two additional studies. METHODS: NCT02279966 and NCT02272517 were multinational, double-blind, placebo-controlled studies in adult outpatients with moderate-to-severe MDD and a current major depressive episode of ≥3 months and less than 1 year, respectively. Subjects were randomized to vortioxetine (10 or 20 mg), placebo or active reference drug (paroxetine [20 mg], or escitalopram [10 or 20 mg]) for 8 weeks. Pearson correlation coefficients were estimated for baseline UPSA-Brief (UPSA-B), demographic/disease characteristics, Montgomery-Åsberg Depression Rating Scale (MADRS), Perceived Deficit Questionnaire-20 items (PDQ-20), and Digit Symbol Substitution Test (DSST), to examine construct validity. Distribution- and anchor-based methods examined clinically important difference (CID) threshold. A pooled analysis with data from NCT01564862 (initial validation study) was performed to increase the statistical power of the estimations. RESULTS: In pooled analysis of the two new studies, UPSA-B score correlated with the DSST (r = 0.32, P < 0.0001), but not the MADRS (r = -0.07, p = 0.302) or the PDQ-20 (r = -0.10, p = 0.109), replicating initial validation results. Estimated CID range was 7.1-11.2 and 5.5-6.1 points for anchor- and distribution-based methods, respectively. In pooled analyses of all three studies, the CID was 7.0 and 6.4 for anchor- and distribution-based methods, respectively. CONCLUSIONS: These results confirm the construct validity of UPSA for assessing functional capacity in patients with MDD. Estimated CID using UPSA is approximately 6-7 points. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01564862; NCT02272517; NCT02279966.

Escitalopram para trastornos psiquiátricos / Escitalopram for psychiatric disorders

En el Perú se estima que en el 2012 los trastornos mentales y de comportamiento en el Perú́ concentraron el 17% del total de años saludables perdidos por discapacidad y muerte prematura siendo responsables de la pérdida de 1 millón 10 mil 594 años saludables, representando la primera carga de años saludables perdidos en el país. La familia de los inhibidores selectivos de la recaptación de serotonina (ISRS) es una de las más usadas en psiquiatría. El mecanismo de acción principal de los ISRS generalmente se explica simplemente por su inhibición selectiva del transportador de serotonina. - Escitalopram es un fármaco de la familia de los ISRS. Se trata del enantiómero levógiro (S) puro del citalopram. Como todos los ISRS actúa inhibiendo selectivamente la recaptación de serotonina en la hendidura sináptica interneuronal, incrementa la concentración sináptica de serotonina y activa las vías serotonérgicas neurales. Se postula que el escitalopram podría ser una opción de tratamiento eficaz y asociada a menos eventos adversos comparado con sertalina y fluoxetina. - Se identificaron 3 RS. Además, se identificó tres GPC que mencionaban a la tecnología. No se encontraron ETS, ni EE de la región. - La evidencia con respecto a escitalopram en trastornos psiquiátricos es abundante. Para depresión y ansiedad generalizada en adultos, se evidencia una adecuada respuesta a tratamiento de escitalopram versus placebo. En comparaciones indirectas se evidencia un beneficio de escitalopram por sobre fluoxetina para depresión, pero no se evidencia diferencia con sertralina. Basado también en comparaciones indirectas, en el caso de ansiedad generalizada no hay diferencias entre la tecnología de interés y los comparadores. En el caso de efectividad en niños con diagnóstico de depresión, se identifica escitalopram y fluoxetina como los medicamentos con mayor evidencia y que mostraron beneficio, sin embargo, no se tiene disponibilidad de estudios comparativos de escitalopram vs fluoxetina o sertralina. - Las guías de práctica clínica recabadas, en general, recomiendan el uso de inhibidores de la recaptación de serotonina indistintamente como primera línea mencionando que la decisión entre estos medicamentos depende de las características del paciente, interacciones con drogas y criterio clínico.

Patterns and predictors of off-label prescription of psychiatric drugs.

Off-label prescribing of psychiatric drugs is common, despite lacking strong scientific evidence of efficacy and potentially increasing risk for adverse events. The goal of this study was to characterize prevalence of off-label prescriptions of psychiatric drugs and examine patient and clinician predictors of off-label use. This manuscript presents a retrospective, cross-sectional study using data from the 2012 and 2013 National Ambulatory Medical Care Surveys (NAMCS). The study examined all adult outpatient visits to psychiatric practices for chronic care management with a single listed visit diagnosis in which at least one psychiatric drug was prescribed. The main outcome measure was off-label prescribing of at least one psychiatric drug, defined as prescription for a condition for which it has not been approved for use by the FDA. Among our sample representative of 1.85 billion outpatient visits, 18.5 million (1.3%) visits were to psychiatrists for chronic care management in which at least one psychiatric drug was prescribed. Overall, the rate of off-label use was 12.9% (95% CI: 12.2-15.7). The most common off-label uses were for manic-depressive psychosis treated with citalopram and primary insomnia treated with trazodone. Several patient and clinician characteristics were positively associated with off-label prescribing, including seeing a psychiatrist (OR: 1.06, 95% CI, 1.01-1.12; p = 0.03) instead of another type of clinician, the office visit taking place in the Western region of the country (OR: 1.09, 95% CI, 1.01-1.17; p = 0.02), and the patient having 3 or more chronic conditions (OR: 1.12, 95% CI, 1.02-1.14; p = 0.003). In contrast, having Medicare coverage (OR: 0.93, 95% CI, 0.84-0.97; p = 0.04) and receiving payment assistance from a medical charity (OR: 0.91, 95% CI, 0.88-0.96; p = 0.03) instead of private insurance were negatively associated with off-label prescribing. These results suggest that certain classes of psychiatric medications are being commonly prescribed to treat conditions for which they have not been determined by the FDA to be clinically efficacious and/or safe.

Quality of life and functioning of Hispanic patients with Major Depressive Disorder before and after treatment.

BACKGROUND: Similar rates of remission from Major Depressive Disorder (MDD) have been documented between ethnic groups in response to antidepressant treatment. However, ethnic differences in functional outcomes, including patient-reported quality of life (QOL) and functioning, have not been well-characterized. We compared symptomatic and functional outcomes of antidepressant treatment in Hispanic and non-Hispanic patients with MDD. METHODS: We analyzed 2280 nonpsychotic treatment-seeking adults with MDD who received citalopram monotherapy in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression study. All subjects (239 Hispanic, 2041 non-Hispanic) completed QOL, functioning, and depressive symptom severity measures at entry and exit. RESULTS: Hispanic participants had significantly worse QOL scores at entry and exit (p < 0.01). However, after controlling for baseline QOL, there was no difference between Hispanic and non-Hispanic patients' QOL at exit (p = 0.21). There were no significant between-group differences at entry or at exit for depressive symptom severity or functioning. Both groups had significant improvements in depressive symptom severity, QOL, and functioning from entry to exit (all p values < 0.01). Patients with private insurance had lower depressive symptom severity, greater QOL, and better functioning at exit compared to patients without private insurance. LIMITATIONS: This study was a retrospective data analysis, and the Hispanic group was relatively small compared to the non-Hispanic group. CONCLUSIONS: Hispanic and non-Hispanic participants with MDD had similar responses to antidepressant treatment as measured by depressive symptom severity scores, quality of life, and functioning. Nevertheless, Hispanic patients reported significantly worse quality of life at entry.

Improvements in Quality-Adjusted Life Years and Cost-Utility After Pharmacotherapy for Premenstrual Dysphoric Disorder: A Retrospective Study.

BACKGROUND AND OBJECTIVE: To investigate the cost-effectiveness of pharmacotherapy for premenstrual dysphoric disorder (PMDD), a relatively new classification of depressive disorder that is characterized by recurrent depression during the premenstrual phase of the menstrual cycle. METHODS: We performed a retrospective analysis of data from 49 previously untreated PMDD patients who visited our psychiatric department between October 2013 and February 2016 and received pharmacotherapy for 3 or 6 subsequent menstrual cycles. Quality-adjusted life years (QALYs) were estimated across individual menstrual cycles using mean EuroQoL-5D values. Direct costs per patient were estimated in order to conduct a preliminary cost-effectiveness analysis. RESULTS: Pharmacotherapy produced a 0.190-point increase in mean EuroQoL-5D score per menstrual cycle after 6 menstrual cycles and an improvement of approximately 0.2 QALYs. Based on direct costs of 156,000 yen per patient, the cost-effectiveness of pharmacotherapy was calculated to be 823,000 yen per QALY. A cost-effectiveness acceptability curve analysis indicated that escitalopram tended to be superior to sertraline when willingness to pay per QALY was over 4,000,000 yen, whereas sertraline was superior when willingness to pay was below 2,000,000 yen. CONCLUSIONS: Pharmacotherapy is cost effective for the treatment of PMDD. Moreover, escitalopram is a more cost-effective option than sertraline when willingness to pay is sufficiently high.

Análisis de impacto presupuestal de citalopram, clomipramina escitalopram, paroxetina, fluvoxamina, fluoxetina y sertralina para pacientes con Trastorno Obsesivo Compulsivo en Colombia / Budget impact analysis of citalopram, clomipramine escitalopram, paroxetine, fluvoxamine, fluoxetine and sertraline for patients with Obsessive Compulsive Disorder in Colombia

INTRODUCCIÓN: El análisis de impacto presupuestal (AIP) del citalopram, clomipramina, escitalopram, paroxetina, fluvoxamida, fluoxetina y sertralina para pacientes con trastorno obsesivo compulsivo (TOC) en Colombia, se desarrolló en el marco del mecanismo técnico-científico para la ampliación progresiva del Plan de Beneficios en Salud con cargo a la UPC (PBSUPC) y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015 (1). Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. El TOC es un trastorno de ansiedad que se caracteriza por pensamientos intrusivos, recurrentes (obsesiones) y persistentes, que producen inquietud, temor o preocupación y comportamientos repetitivos (compulsiones) dirigidos a reducir la ansiedad asociada. Afectan el rendimiento laboral, académico y las relaciones interpersonales, generando un deterioro en la calidad de vida de los pacientes, así como el desarrollo de ideas o comportamientos suicidas. Se estima que la prevalencia del TOC en la población general a nivel mundial es de 1,6%, siendo uno de los principales trastornos que afecta a niños y adolescentes (3). La prevalencia de TOC en Colombia oscila entre el 0,9% y el 2,4% (4); se ha observado una mayor incidencia de este trastorno en las mujeres que en los hombres, en quienes se evidencia una fuerte relación de episodios psicóticos con otros tipos de trastornos como la esquizofrenia (5,6).Según los reportes del Sistema Integral de Información de la Protección Social (SISPRO), entre los años 2009 y 2013, se diagnosticaron en promedio 1194 casos nuevos de pacientes con TOC en Colombia. Adicionalmente, se ha encontrado que el 55 % de los casos reportados han sido en pacientes entre los 27 a 59 años de edad. El DSM-IV establece como criterio para el diagnóstico de TOC, que las obsesiones y compulsiones resulten excesivas o irracionales para el paciente, aunque aclara que este criterio no es aplicable a los menores, ya que es frecuente que estos síntomas sean ego sintónicos para los niños e incluso para algunos adolescentes (8). En la actualidad, el TOC es entendido como un único trastorno sea cual sea la edad en el que aparezca, aunque en el 80% de los casos el inicio del trastorno ocurre antes de los 18 años. Este documento describe la metodología desarrollada para realizar el análisis de impacto presupuestal de citalopram y clomipramina para pacientes con TOC que requieren manejo farmacológico en Colombia. Este informe, sigue los lineamientos propuestos en el Manual para la Elaboración de Análisis de Impacto Presupuestal y en el Manual de Participación y Deliberación publicados por IETS. TECNOLOGÍAS EVALUADAS: En el escenario actual se incluyeron las tecnologías que se encuentran cubiertas por el Plan de Beneficios en Salud con cargo a la UPC (PBSUPC) para el TOC. Así mismo, se definieron los tratamientos farmacológicos para primera y segunda línea del TOC a partir de consideraciones clínicas expuestas por los expertos temáticos. Los tratamientos farmacológicos con las tecnologías que se encuentran dentro del escenario actual son: Tratamiento de primera línea: sertralina y fluoxetina. Tratamiento de segunda línea: no se identificó ninguna tecnología. INSUMOS Y MÉTODOS: Esta sección presenta los supuestos, parámetros y métodos utilizados para el modelo de estimación del impacto presupuestal. Cada una de las fuentes de información, estructuración de casos tipo y supuestos de modelación que fueron discutidos con el grupo de expertos temáticos en espacios de participación promovidos por el IETS. DISTRIBUCIÓN DE LA POBLACIÓN EN EL ESCENARIO ACTUAL: De acuerdo a la Base de Datos Única de Afiliados del Sistema General en Salud (BDUA) para el año 2017 se registran 32.768.685 personas mayores de 18 años en Colombia; al aplicar la prevalencia de TOC identificada previamente, se estimaron 1.540.128,195 casos. Considerando que entre estos pacientes el 33% presentan comorbilidades, el número de casos que tendrían únicamente diagnóstico de TOC correspondería a 508.242 casos. Para establecer la probabilidad de requerir tratamiento farmacológico en los pacientes con diagnóstico de TOC, el consenso de expertos y el estudio publicado por Martin P, en el año 2003 establecen que aproximadamente el 68% de los pacientes con TAG requieren tratamiento farmacológico de primera línea (22); tomando esta probabilidad se estiman para Colombia 345.605 casos de TOC como población objetivo para el presente AIP. Para establecer la probabilidad de requerir tratamiento farmacológico de segunda línea en los pacientes con diagnóstico de TOC, se extrajeron las probabilidades de respuesta a los tratamientos de primera línea reportadas en el análisis de costo-efectividad de escitalopram comparado con paroxetina, fluoxetina, sertralina, fluvoxamina y clomipramina como terapia de mantenimiento para pacientes con trastorno obsesivo compulsivo en Colombia (21). Considerando este estudio, se estableció que la probabilidad de respuesta a los tratamientos de primera línea es de 0,515, por lo tanto, por propiedades de probabilidades complementarias, se estimó que el 48% (1-p) de los pacientes requerirían tratamiento de segunda línea, dando como resultado una estimación de 165.890 casos. MÉTODOS DE COSTEO Y COSTOS: Se obtuvo como primera medida los registros sanitarios vigentes por parte del INVIMA para el primer semestre del 2017. Para la valoración de los medicamentos se utilizó SISMED para el año 2016 (enero-diciembre), tomando como base el canal institucional laboratorio. Para cada tratamiento se identificó la dosis promedio recomendada para cada tecnología sugerida en la fuente de información Micromedex ® 2017 (23), la periodicidad y la duración del tratamiento. El precio promedio, mínimo y máximo por tableta o unidad calculada corresponde al precio ponderado de las diferentes presentaciones del medicamento, el cual comprende tanto los genéricos como las moléculas originales. Con lo anterior se buscó determinar un precio ponderado del principio activo, y no de una molécula en particular. Adicionalmente se revisaron las circulares de regulación de precios del Ministerio de Salud, con el fin de identificar si a la fecha existe un precio máximo regulado de alguna de las alternativas de comparación. El procedimiento para calcular los precios de los medicamentos siguió las recomendaciones del manual metodológico para la elaboración de evaluaciones económicas del IETS. RESULTADOS: Los resultados que se presentan en el informe corresponde al impacto presupuestal total e incremental obtenidos en los escenarios 1 y 2 para los tratamientos de TOC de primera y segunda línea.

Prescription Pattern of Antidepressants for Children and Adolescents in Korea Based on Nationwide Data.

Antidepressant prescription for youths has recently been on the increase. There is a growing concern over the increasing off-label usage of antidepressants. Current data on off-label antidepressant usage vary across countries and healthcare systems. Therefore, we examined the extent and pattern of antidepressant prescription for Korean children and adolescents using population-based data. Our data was retrieved from the Korean National Health Insurance Service National Sample Cohort of the year 2013. Among 0.2 million children and adolescents aged 6-18 years from the cohort, subjects who had received any antidepressant medication in the year 2013 were investigated for the prescribed medication, concomitant psychotropic medication, and the associated diagnosis. A total of 2,190 children and adolescents (boys, 55.4%) received antidepressant medication. The most common diagnosis was depressive disorders (n = 469, 21.4%), followed by attention-deficit/hyperactivity disorder (n = 442, 20.2%). Among the prescriptions (n = 3,370), escitalopram (n = 650, 24.1%) and fluoxetine (n = 553, 20.5%) were the two most frequently prescribed drugs. A majority of prescriptions (n = 2,039, 60.5%) included concomitant psychotropic agents, consisting of antipsychotics (n = 901, 26.7%), sedatives (n = 263, 26.3%), medication for attention-deficit/hyperactivity disorder (n = 822, 24.4%), and some others. Our study shows the prescription pattern of antidepressants for children and adolescents in Korea, of which a large proportion is off-label. The results call for close monitoring by clinicians treating this population.

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study.

Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage -20 or 40 mg per day of citalopram. We found that sociodemographic characteristics affected treatment response in the same direction in the two dose groups, but these effects reached statistical significance only in the 40 mg per day dose group. In the latter, higher improvement rate was associated with having a working employment status (P=0.0219), longer education (P=0.0053), high income (P=0.01) or a private insurance (P=0.0031), and the higher remission rate was associated with having a working employment status (P=0.0326) or longer education (P=0.0484). Moreover, the magnitude of the effect of the sociodemographic characteristics on mood, measured as the percent of patients showing a positive outcome when exposed to favorable living conditions, was much greater-up to 37-fold-in the 40 compared to the 20 mg per day dose group. Overall, our results indicate that citalopram amplifies the influence of the living conditions on mood in a dose-dependent manner. These findings provide a potential explanation for the variable efficacy of SSRIs and might lead to the development of personalized strategies aimed at enhancing their efficacy.

Antidepressant Medication Prescribing Practices for Treatment of Major Depressive Disorder.

OBJECTIVE: The purpose of this study was to describe the prescribing practices of clinicians for patients with major depressive disorder (MDD). METHODS: This population-based, descriptive study of insured patients (N=54,107) identified people who were 18 years or older, had a claim for MDD, had at least one prescription for an antidepressant medication in 2013, and had continuous insurance coverage during the study period. Prescription claims were evaluated to determine the most commonly prescribed antidepressant medication and most common dose. RESULTS: The three most commonly prescribed antidepressant medications were citalopram (N=11,995, 22.2%), sertraline (N=10,791, 19.9%), and trazodone (N=9,501, 17.6%). The most common daily doses were 20 mg citalopram (N=6,304, 52.6%), 50 mg sertraline (N=4,173, 38.7%), and 100 mg trazodone (N=3,220, 33.9%). CONCLUSIONS: This is the first report of its kind that provides drug- and dosage-level details to demonstrate that antidepressant prescribing in clinical practice is largely within recommended guidelines.

Análisis de costo-efectividad del escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento para pacientes con trastorno de pánico en Colombia / Cost-effectiveness analysis of escitalopram compared to paroxetine, sertraline, fluoxetine, imipramine and fluvoxamine as maintenance therapy for patients with panic disorder in Colombia

Problema de investigación: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento en adultos con diagnóstico de trastorno de pánico en Colombia. Tipo de evaluación económica: Análisis de costo-efectividad. Población objetivo: Adultos colombianos con diagnóstico de trastorno de pánico. Intervención y comparadores: Intervención: escitalopram, Comparadores: paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina. Horizonte temporal: 32 semanas. Perspectiva: SGSSS de Colombia. Tasa de descuento: No aplica. Estructura del modelo: Se estructuró un árbol de decisión, teniendo en cuenta modelos publicados en la literatura. Fuentes de datos de efectividad y seguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayo s clínicos a leatorizados. Desenlaces y valoración: Ausencia de crisis de pánico, Semanas libres de crisis de pánico. Costos incluidos: Costo de los medicamentos, Costo de procedimientos, Costo de los eventos adversos. Fuentes de datos de costos: SISMED, Manual tarifario ISS 2001. Resultados del caso base: Para el caso base, escitalopram, fluvoxamina y fluoxetina e imipramina fueron tecnologías dominadas por sertralina y paroxetina. El costo adicional por crisis de pánico evitada en tratamiento con paroxetina comparado con trasertralina se estimó en $4.814.953. Análisis de sensibilidad: Los análisis de sensibilidad y el diagrama de tornado muestran a la probabilidad de lograr ausencia de crisis de pánico y la probabilidad de recaída, como a las variables con mayor impacto sobre las estimaciones de la razón de costo-efectividad. Conclusiones y discusión: De acuerdo con los hallazgos aquí presentados, paroxetina, ofrece mayor razón de costo-efectividad, respecto a sus comparadores. No obstante, es \r\nnecesario tener en cuenta que cualquiera de las alternativas aquí estudiadas, puede ser costo-efectiva, debido a que las pequeñas variaciones en la probabilidad de ausencia de crisis de pánico pueden cambiar el resultado. La principal limitación de este estudio es la ausencia de información roveniente de estudios de investigación clínica, que muestre el desempeño comparativo entre las tecnologías, así como el seguimiento de los participantes en los estudios, en escenarios de más largo plazo que los existentes al momento de elaborar este documento.(AU)

Análisis de impacto presupuestal de escitalopram, paroxetina y fluvoxamina como terapia de mantenimiento para pacientes adultos con trastorno de pánico en Colombia / Budget impact analysis of escitalopram, paroxetine and fluvoxamine as maintenance therapy for adult patients with panic disorder in Colombia

Tecnologías evaluadas: Nuevas: escitalopram, paroxetina y fluvoxamina. Actuales: sertralina, fluoxetina e imipramina. Población: Pacientes mayores de 18 años con trastorno de pánico en Colombia. Perspectiva\tLa perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el SGSSS en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1.Costos incluidos: Precios por mg de los medicamentos analizados. Fuente de costos: Los precios de cada tecnología fueron calculados con la base de datos SISMED. Escenarios: En el escenario 1 se considera una igualación progresiva de las participaciones de mercado de todos los medicamentos analizados, igualándose en el año 3. En el escenario 2, además de dicha igualación de participaciones de mercado, se asume un precio común para las nuevas alternativas, siguiendo las metodologías de inclusión de grupos terapéuticos definidas por el Ministerio de Salud y Protección Social. Resultados: Para la inclusión en el POS de escitalopram, paroxetina y fluvoxamina como terapia de mantenimiento para pacientes con trastorno de pánico en Colombia, se requeriría una inversión estimada de $12.563.676.367 en el año 1 y de $22.925.604.761 en el año 3. En el caso en el que los medicamentos del escenario nuevo sean incluidos con un precio común basado en las metodologías de grupos terapéuticos del Ministerio de Salud y Protección Social, el impacto presupuestal se reduciría a $1.318.634.602 en el año 1 y $2.861.023.939, en el año 3.(AU)