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How impactful is the use of Sertraline, Fluoxetine, and Escitalopram monotherapy on psychological distress among adults with depression in the real world? Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. Medical Expenditure Panel Survey (MEPS) longitudinal data files from 1 January 2012 to 31 December 2019 (panel 17–23) were used to assess the effects of Sertraline, Fluoxetine and Escitalopram on psychological distress among adult outpatients diagnosed with a major depressive disorder. Participants aged 20–80 years without comorbidities, who initiated antidepressants only at rounds 2 and 3 of each panel, were included. The impact of the medicines on psychological distress was assessed using changes in Kessler Index (K6) scores, which were measured only in rounds 2 and 4 of each panel. Multinomial logistic regression was conducted using the changes in the K6 scores as a dependent variable. A total of 589 participants were included in the study. Overall, 90.79% of the study participants on monotherapy antidepressants reported improved levels of psychological distress. Fluoxetine had the highest improvement rate of 91.87%, followed by Escitalopram (90.38%) and Sertraline (90.27%). The findings on the comparative effectiveness of the three medications were statistically insignificant. Sertraline, Fluoxetine, and Escitalopram were shown to be effective among adult patients suffering from major depressive disorders without comorbid conditions. [ABSTRACT FROM AUTHOR]

The article focuses on the safety assessment of 14 antidepressants prescribed in the U.S. Cited are antidepressants that were deemed the safest classes in the event of excess dosing, the methods used in addition to a fatal toxicity index (FTI) to compare agents on nonlethal but significant adverse effects resulting from toxic exposure, and rates of mortality and morbidity associated with bupropion.

Objective: To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss.Design: Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive.Setting: Four clinical sites.Patient(s): A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin.Interventions(s): Not applicable.Main Outcome Measure(s): Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated.Result(s): A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug.Conclusion(s): Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study.Clinical Trial Registration Number: NCT00467363. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Antidepressants increase the risk of falls and fracture in older adults. However, risk estimates vary considerably even in comparable populations, limiting the usefulness of current evidence for clinical decision making. Our aim was to apply a common protocol to cohorts of older antidepressant users in multiple jurisdictions to estimate fracture risk associated with different antidepressant classes, drugs, doses, and potential treatment indications. DESIGN: Retrospective (2009–2014) cohort study. SETTING: Five jurisdictions in the United States, Canada, United Kingdom, and Taiwan. PARTICIPANTS: Older antidepressant users—subjects were followed from first antidepressant prescription or dispensation to first fracture or until the end of follow‐up. MEASUREMENTS: The risk of fractures with antidepressants was estimated by multivariable Cox proportional hazards models using time‐varying measures of antidepressant dose and use vs nonuse, adjusting for patient characteristics. RESULTS: Between 42.9% and 55.6% of study cohorts were 75 years and older, and 29.3% to 45.4% were men. Selective serotonin reuptake inhibitors (SSRIs) (48.4%‐60.0%) were the predominant class used in North America compared with tricyclic antidepressants (TCAs) in the United Kingdom and Taiwan (49.6%‐53.6%). Fracture rates varied from 37.67 to 107.18 per 1,000. The SSRIs citalopram (hazard ratio [HR] = 1.23; 95% confidence interval [CI] = 1.11‐1.36 to HR = 1.43; 95% CI = 1.11‐1.84) and sertraline (HR = 1.36; 95% CI = 1.10‐1.68), the SNRI duloxetine (HR = 1.41; 95% CI = 1.06‐1.88), TCAs doxepin (HR = 1.36; 95% CI = 1.00‐1.86) and imipramine (HR = 1.16; 95% CI = 1.05‐1.28), and atypicals (HR = 1.34; 95% CI = 1.14‐1.58) increased fracture risk in some but not all jurisdictions. In the United States and the United Kingdom, fracture risk with all classes was higher when prescribed for depression than chronic pain, a trend that is likely explained by drug choice. CONCLUSION: The fracture risk for patients may be reduced by selecting paroxetine, an SSRI with lower risk than citalopram, the SNRI venlafaxine over duloxetine, and the TCA amitriptyline over imipramine or doxepin. There is uncertainty about the risk associated with the atypical antidepressants. J Am Geriatr Soc 68:1494‐1503, 2020. [ABSTRACT FROM AUTHOR]

Depression is one of the most commonly diagnosed and debilitating illness in the United States (US) (AADD, 2018; NIH, 2018) and it afflicts over 300 million people around the world (WHO, 2018). Though genetics, biological make-up, environment, and psychological factors play a role in the predisposition of depression, it crosses all ages, racial/ethnic groups, and socioeconomical status (NIH, 2018). Depression incidence has cost the U.S over 67 billion in direct cost of Medicare resulting in occupational injury and morbidity (Asfaw & Souza, 2012). Although patients experience many recurrent episodes, Major Depressive Disorder (MDD) is the "most common mood disorder having at least one single major depressive episode" (Stahl, p. 239). the purpose of this paper is to discuss and review current drugs and treatment for MDD. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate national trends in electrocardiogram (EKG) monitoring in Veterans Affairs (VA) beneficiaries prescribed high‐dose citalopram before and after the 2011–12 Food and Drug Administration (FDA) safety warnings. Design: Interrupted time‐series analyses. Setting: National VA healthcare system data linked to Medicare data for veterans dually eligible for VA and Medicare services. Participants: Adult VA outpatients prescribed citalopram or sertraline from February 2010 to September 2013 (N=1,068,816). Measurements: EKG monitoring for VA outpatients prescribed high‐dose citalopram (>40 mg/d aged ≤60, >20 mg/d aged >60) or sertraline. Results: For individuals prescribed high‐dose citalopram, EKG monitoring increased from 9.0% before the start of the first FDA warning to a peak of 12.6% for individuals aged 18 to 60 and from 14.0% to 19.4% for individuals aged 61 to 100. However, following the second FDA warning in 2012, EKG monitoring declined, returning to prewarning levels in both age groups. EKG monitoring did not increase in individuals with a history of previous cardiac risk factors prescribed high‐dose citalopram in either age group. Conclusions: EKG frequency did not significantly change in individuals with cardiac risk factors at greatest potential risk for QT prolongation. Lack of responsiveness to the FDA warnings may be due to many factors, including lack of clarity about which individuals should undergo EKG monitoring, provider substitution of alternative antidepressants for citalopram, conflicting evidence regarding risk for adverse cardiac events with high‐dose citalopram use, and lack of provider knowledge regarding the warnings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Placebo-controlled clinical trials have led to concern over possible increased risk of suicide-related events in some populations exposed to antidepressants.Aims: To evaluate the risk of suicide attempts by antidepressant drug class and the presence or absence of depression.Method: A retrospective propensity-matched new-user cohort study was used to compare participants with incident depression classified by antidepressant treatment with each other and with the general population.Results: Among the treated group, the suicide attempt rate peaked in the month prior to diagnosis then decreased steadily over the next 6 months. Among the pharmacologically untreated group, the highest rate was seen in the second month after diagnosis. Cohorts with depression had significantly higher suicide attempt risk than the general population, but the treated group did not differ significantly from the untreated group.Conclusions: Patients on antidepressants did not have significantly higher risk compared with untreated patients. No significant differences were observed for patients treated with individual serotonin-noradrenaline reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) or by class (SSRI v. SNRI cohorts). [ABSTRACT FROM AUTHOR]

Objective: Prior research evaluated various effects of the 2004 black-box warning by the U.S. Food and Drug Administration (FDA) on the risk of suicidality among children associated with use of antidepressants, but the warning's effect on dosing of antidepressants has not been evaluated. This study estimated whether the initial antidepressant dose prescribed decreased and the proportion of patients who augmented the dose on the second fill increased following the 2004 warning and its 2007 expansion to young adults. Methods: The study utilized the LifeLink Health Plan Claims Database. The study cohort consisted of commercially insured children (ages 5-17), young adults (18-24), and adults (25-64) who initiated a selective serotonin reuptake inhibitor (SSRI) (citalopram, fluoxetine, paroxetine, or sertraline) from January 1, 2000, to December 31, 2009. Dose per day was determined by days' supply, strength, and quantity dispensed. Initiation with a low dose and augmentation of >1 mg/day on the second prescription before and after the 2004 warning were considered. Results: Of 51,948 children who initiated an SSRI, 15% initiated with a low dose before the 2004 warning compared with 31% after the warning; there was a smaller change among young adults (6 percentage points) and adults (3 percentage points). The overall increase in dose augmentations among children and young adults was driven by the increase in patients initiating with a low dose. Conclusions: The proportion of commercially insured children initiating an SSRI with a low dose was higher after the 2004 FDA warning on the risk of suicidality among children, suggesting improved prescribing practices surrounding SSRI dosing among children. [ABSTRACT FROM AUTHOR]

Abstract: Recently, both the manufacturer of citalopram and the US Food and Drug Administration have warned health care providers and patients about new information implicating drug-induced QTc interval prolongation and torsade de pointes when using citalopram in doses >40 mg/day. This warning is not placed in the context of either benefits or risks in real-world clinical practice, leaving clinicians with an untenable choice between depriving patients of high-dose citalopram or malpractice litigation. We reviewed the literature and found no cases of citalopram-induced sudden cardiac death among patients taking up to 60 mg/day of citalopram and free of risk factors for QTc interval prolongation and torsade de pointes. Because psychotropic drug-induced sudden cardiac death is an outlier in the absence of identified risk factors for QTc interval prolongation and torsade de pointes, we do not believe current Phase 3 and Phase 4 studies provide sufficient information to limit current prescribing practices for citalopram (20 mg to 60 mg/day). We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, torsade de pointes, and sudden cardiac death so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as citalopram. [Copyright &y& Elsevier]

The article presents several case studies involving adverse drug reactions. The first case involves a 25-year-old male who had interstitial nephritis due to mesalazine therapy. The second case was a 68-year-old woman who had experienced vaginal-vault eversion following a high-dose glucocorticoid therapy. Also discussed is the severe complications experienced by eight patients at a medical center in Israel due to use of phosphate-containing Fleet enemas.

In courts case histories play a central part when a crime may have resulted from an effect of a prescribed drug; in civil cases where a person may have suffered damage from a drug; and in coroners' enquiries into the cause of unexplained deaths. The court must decide two important questions: 1. Can the suspected medication(s) cause this kind of effect? 2. Did it (or they) do so in this particular case? Many judges and coroners have not addressed these questions clearly and have not used expert witnesses consistently, on occasion disregarding scientific evidence. Courts need to appoint experts to explain and interpret the scientific evidence. Few judges are equipped to resolve contradictions between different experts. Brief accounts of five cases from four countries illustrate these points. The reluctance of legal processes to implicate drugs as a possible cause of violent behaviour leads to injustice. Courts must be required to obtain appropriate expert evidence, and be given independent data on which drugs can cause such behaviour. [ABSTRACT FROM AUTHOR]

Several factors have amplified concern about the possibility that antidepressant medication may contribute to induction of pediatric mania. These include the high rate of antidepressant medication prescription, the recent surge in the rate of diagnosis of pediatric bipolar disorder in the USA, and a growing number of case reports and clinical studies showing coincidence of manic symptoms with antidepressant pharmacotherapy in both youths and adults. However, the question of how medications and manic symptoms might be related is complicated, and decisive research studies with rigorous designs for evaluating the issues have not been published. The situation makes it difficult for practitioners to make good, evidence-based decisions. The scientific literature is ambiguous, and the stakes are high. We review the extant literature, offer seven different conceptual models of how medication and mania might be related, and comment on the evidence and clinical implications of each. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the bioavailability of two citalopram formulations (citalopram from Eurofarma LaboratÓrios Ltda., as the test formulation, and cipramil from Schering-Plough, Brazil, as the reference formulation) in healthy volunteers. Methods: The study had an open, randomized, two-period crossover design with a two-week washout interval between doses. The samples were obtained over a 168-hour interval after each oral administration of citalopram (one 20 mg tablet of each formulation). The analyte and the internal standard were extracted from plasma using diethylether: dichloromethane (70: 30, v/v) and the extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Chromatography was done isocratically using a Genesis C8 analytical column (4 μm, 2.1 mm i.d. × 100 mm). The method had a chromatographic run time of three minutes and a linear calibration curve over the range of 0.5 - 200 ng × ml-1 (r2 > 0.999887). The limit of quantification was 0.5 ng × ml-1. Results: The geometric mean and 90% confidence intervals (CI) for the citalopram/cipramil ratio were 98.28% (94.24 - 102.49%) for AUClast, 96.44% (90.20 - 103.11%) for AUCinf, and 98.54% (94.70 - 102.54%) for Cmax. Conclusion: Since the 90% CI for Cmax, AUClast and AUC(0-∞) ratios were all within the 80 - 125% interval proposed by the US Food and Drug Administration, we concluded that the citalopram formulation elaborated by Eurofarma LaboratÓrios Ltda. was bioequivalent to the cipramil formulation in its rate and extent of absorption. [ABSTRACT FROM AUTHOR]

Aims: Drug regulators issue safety advisories to warn clinicians and the public about new evidence of harmful effects of medicines. It is unclear how often these messages are covered by the media. Our aim was to analyse the extent of media coverage of two medicines that were subject to safety advisories from 2007 to 2016 in Australia, Canada, the United Kingdom and the United States., Methods: Two medicines widely used to treat mental health or physical conditions were selected: citalopram and denosumab. Media reports were identified by searching LexisNexis and Factiva. Reports were included if they stated at least one health benefit or harm. A content analysis of the reports was conducted., Results: In total, 195 media reports on citalopram and 239 on denosumab were included. For citalopram, 43.1% (84/195) of the reports mentioned benefits, 85.6% (167/195) mentioned harms and 9.7% (19/195) mentioned the harm described in the advisories (cardiac arrhythmia). For denosumab, 94.1% (225/239) of the reports mentioned benefits and 39.7% (95/239) mentioned harms. The harms described in the advisories were rarely mentioned: 10.9% (26/239) of the reports mentioned osteonecrosis and ≤5% mentioned any of the other harms (atypical fractures, hypocalcaemia, serious infections and dermatologic reactions)., Conclusions: We found limited media coverage of the harms highlighted in safety advisories. Almost two-thirds of the media stories on denosumab did not include any information about harms, despite the many advisories during this time frame. Citalopram coverage covered harms more often but rarely mentioned cardiac arrhythmias. These findings raise questions about how to better ensure that regulatory risk communications reach the general public., (© 2020 The British Pharmacological Society.)

Aim: To evaluate the comparative risk of hip fracture or osteoporosis among US Veterans based on selective serotonin reuptake inhibitor (SSRI) exposure., Patients & Methods: A retrospective cohort study of eligible US Veterans Health Administration patients enrolled in 2003-2004 was performed to examine SSRIs' 2-, 5- and 10-year impact on bone health using multiple logistic regression., Results: Veterans on SSRIs were found to be 56.7% more likely over a 10-year period to suffer a hip fracture (risk ratio: 1.567; 95% CI: 1.464-1.676) and 34.6% more likely to develop osteoporosis (risk ratio: 1.346; 95% CI: 1.319-1.374) when compared with those who were SSRI naive., Conclusion: SSRI usage was associated with greater risk of hip fracture and osteoporosis over a 10-year period in the veteran population, with similar effect sizes to smaller studies.

Objective: In 2011-2012 the U.S. Food and Drug Administration (FDA) issued safety announcements cautioning providers against prescribing high doses of citalopram given concerns for QT prolongation. The authors evaluated Veterans Affairs (VA) national trends in citalopram use and dose compared with alternative antidepressants after the FDA warnings., Methods: Time series analyses estimated the effect of the FDA warnings on citalopram and other antidepressant across three periods: before the first FDA warning in August 2011, after the 2011 FDA warning until the second warning in March 2012, and after the 2012 FDA warning. In a National VA health system, adult VA outpatients prescribed citalopram or alternative antidepressants from February 2010 to September 2013 were studied. Outpatient use of high-dose citalopram (>40 or >20 mg daily in adults aged > 60 years) including the proportion of patients prescribed citalopram and difference between study periods., Results: Between the first and second FDA warnings, among patients aged 18-60, high-dose citalopram use decreased by 2.0% per month (p < 0.001) and by 1.9% per month (p < 0.001) for older adults. After the second FDA warning in 2012, 30.7% of older patients remained on doses higher than the newly recommended dose of 20 mg. Reductions in overall use of citalopram were accompanied by significant increases in prescriptions of alternative antidepressants, with sertraline most widely prescribed., Conclusion: Although trends in high-dose citalopram use declined after the 2011-2012 FDA warnings, roughly one-third of older adults still remained on higher than recommended doses. Concomitant increases in sertraline and other antidepressant prescriptions suggest potential substitution of these medications for citalopram., (Copyright © 2017 American Association for Geriatric Psychiatry. All rights reserved.)

Cocaine dependence continues to be a highly prevalent disorder, which is associated with significant morbidity and mortality. Numerous medications have been investigated as potential adjunctive therapeutic measures, but with minimal success. None have been given Food and Drug Administration approval for treatment of cocaine dependence. (Am J Addict 2011;00:1-2) [ABSTRACT FROM AUTHOR]

Reports that the Food and Drug Administration is now asking pharmaceutical manufacturers to add label warnings that some antidepressants may pose a risk for suicidal behavior, the most serious potential symptom of the condition the drugs are meant to treat. List of the drugs involved; Some side effects associated with antidepressants; Evaluation of the safety and efficacy of some antidepressants in depressed youth; Highlights of some clinical trials; Need for further research.

The article reports on a 2012 decision which the U.S. Food and Drug Administration made to approve the solid and liquid form of the generic version of the drug Lexapro, which is used to treat depression and generalized anxiety disorder and is manufactured by Teva/IVAX Pharmaceuticals. Research which investigated the drug's side effects is discussed.

Abstract: Acquired Long QT syndrome is a disorder caused by medications, electrolyte imbalances, and drug interactions. This syndrome is associated with an increased risk of a characteristic life-threatening cardiac arrhythmia, known as torsade de pointes (TdP). In the setting of Long QT syndrome (LQTS), selective serotonin reuptake inhibitors (SSRIs) can precipitate TdP. We report the first case of LQTS and TdP induced by citalopram in the United States. After discontinuation of citalopram, the QT/QTc interval normalized after 3 days and resolved further episodes of TdP. Patients on citalopram should be monitored closely for QT/QTc interval to prevent torsade de pointes. [Copyright &y& Elsevier]

The article reports that two genetic markers are linked with suicidal thoughts in patients taking the antidepressant citalopram or Celexa, according to research from the National Institute of Mental Health. Forest Labs, which manufactures Celexa, reports that 8 million people in the U.S. and 30 million worldwide, have been prescribed the drug. Scientists screened genetic material from adults with major depression who were taking Celexa. The author reveals that variants of the genes GRIK2 and GRIA3, which regulate how the brain processes glutamate, an amino acid that helps mediate communication between brain neurons, increased the chances that those adults would contemplate suicide.

Introduction: Evidence increasingly points to the potential development of harmful cardiac side effects concomitant with the use of a number of psychotropic drugs, primarily traditional antipsychotics and tricyclic antidepressants., Areas Covered: The US Food and Drug Administration announced safety warnings associated with the use of citalopram with QT interval prolongation in 2011 and 2012. This paper explores the clinical background of QT interval prolongation, clinical data related to antidepressants and QT interval prolongation, the clinical implications of safety issues associated with the use of antidepressants and future research directions., Expert Opinion: Currently available evidence proposes that citalopram may not be definitely associated with the increase of cardiac mortality, although it should be related with increase of QT prolongation. A firm consensus regarding the cardiac safety issues associated with antidepressants has to be established in near future. Hence, the choice of an individual antidepressant regarding cardiac safety issues should be based on multiple factors; clinicians may need to select the best available antidepressant for each individual based on that patient's vulnerability, the proven efficacy and safety of each agent and a reasonable benefit:risk ratio, based on currently available findings.