Use Of Serotonin Reuptake Inhibitors Research Articles

The effects of perinatal fluoxetine exposure on emotionality behaviours and cortical and hippocampal glutamatergic receptors in female Sprague-Dawley and Wistar-Kyoto rats

RationaleThere is increasing concern regarding the use of selective serotonin reuptake inhibitors (SSRIs) in pregnancy. Animal studies repeatedly show increased anxiety- and depressive-like behaviours in offspring exposed perinatally to SSRIs, however much of this research is in male offspring. ObjectivesThe primary aim of this study was to investigate the effects of perinatal SSRI exposure on emotionality-related behaviours in female offspring and associated glutamatergic markers, in Sprague-Dawley (SD) rats and in the Wistar-Kyoto (WKY) rat model of depression. Secondly, we sought to investigate the glutamatergic profile of female WKY rats that may underlie their depressive- and anxiety-like phenotype. MethodsWKY and SD rat dams were treated with the SSRI, fluoxetine (FLX; 10 mg/kg/day), or vehicle, throughout gestation and lactation (5 weeks total). Female adolescent offspring underwent behaviour testing followed by quantitative immunoblot of glutamatergic markers in the prefrontal cortex and ventral hippocampus. ResultsNaïve female WKY offspring displayed an anxiety-like and depressive-like phenotype as well as reductions in NMDA and AMPA receptor subunits and PSD-95 in both ventral hippocampus and prefrontal cortex, compared to SD controls. Perinatal FLX treatment increased anxiety-like and forced swim immobility behaviours in SD offspring but did not influence behaviour in female WKY offspring using these tests. Perinatal FLX exposure did not influence NMDA or AMPA receptor subunit expression in female WKY or SD offspring; it did however have restricted effects on group I mGluR expression in SD and WKY offspring and reduce the glutamatergic synaptic scaffold, PSD-95. ConclusionThese findings suggest female offspring of the WKY strain display deficits in glutamatergic markers which may be related to their depressive- and anxiety-like phenotype. While FLX exposed SD offspring displayed increases in anxiety-like and depressive-like behaviours, further studies are needed to assess the potential impact of developmental FLX exposure on the behavioural phenotype of female WKY rats.

Selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitors and epidemiological characteristics associated with prenatal diagnosis of congenital heart disease.

Identify early pregnancy associations of congenital heart disease (CHD) in a multiethnic cohort. This retrospective observational cohort study compared the general obstetric population to women who gave birth at a referral centre in Australia between 2012 and 2017, after 20 weeks' of gestation, with a pregnancy affected by CHD. We defined mood disorder and anxiety as a history of self-reported or medically diagnosed anxiety, depression, postpartum depression or bipolar disorder. We compared epidemiological factors between 30 842 general obstetric patients and 470 obstetric patients with a foetus affected by CHD. Multivariate analysis showed independent associations between CHD and use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in the first trimester (relative risk [RR] 4.14, 95% CI 2.58-6.65), history of anxiety or mood disorder with no SSRI/SNRI first trimester (RR 2.20, 95% CI 1.77-2.74), folate and/or pregnancy multivitamin use in the first trimester (RR 0.69, 95% CI 0.55-0.87) and increased risk with maternal age >40 years (RR 2.30, 95% CI 1.57-3.38). Our data show maternal mood disorders with and without SSRI or SNRI use, maternal age >40 years and lack of multivitamin/folate use to be independently associated with CHD in pregnancy.

Study finds small risk of type 2 diabetes in young users of SSRIs

Children and adolescents initiating use of a selective serotonin reuptake inhibitor (SSRI) antidepressant are at a slightly increased risk of developing type 2 diabetes, a cohort study has concluded. The study examined outcomes for both publicly and privately insured individuals, with type 2 diabetes risk found to be higher in the publicly insured group.

Evaluation of Emotional Adverse Effects of Antidepressants: A Follow-up Study.

Emotional adverse effects due to antidepressant use may cause difficulties for the clinician in the treatment of depression. In this prospective study, the emotional adverse effects of antidepressants were evaluated in various aspects. Ninety eight patients diagnosed with major depressive disorder were included in the study. At 2nd, 4th, 8th, 12th, and 16th weeks, patients were assessed with Montgomery-Asberg Depression Rating Scale (MADRS), and the antidepressant dose was increased in patients with less than a 50% reduction at each visit compared with the initial MADRS score. The Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQESA) was used at the 8th-week and 16th-week visits. A significant difference is found in the OQESA score at the 8th-week visit compared with the 16th-week assessment (P < 0.001, t = 5.73). There were significant correlations between MADRS scores and OQESA scores both at the 8th (r = 0.346, P = 0.05) and the 16th (r = 0.490, P < 0.001) weeks. In regression analyses, at eighth-week assessment, MADRS score (B = 1.487, P = 0.002) and selective serotonin reuptake inhibitor use (B = 14.014, P = 0.023) had a significantly predicted OQESA score. In this study, it is found that, as the rate of remitted patients is increased, OQESA scores get decreased, and furthermore, the OQESA score of the remitted group is statistically low when compared with that of the nonremitted group at the 8th- and 16th-week visits. Oxford Questionnaire on the Emotional Side-effects of Antidepressants and MADRS scores are significantly correlated in all assessments. These results suggest that the score obtained from OQESA may be related not only to the emotional adverse effects of antidepressants but also to the residual symptoms of depression.

Selective Serotonin Reuptake Inhibitor Use Among Army Aviators.

INTRODUCTION: Mental health is an important aspect of Army aviation medicine given that it significantly impacts career longevity, readiness, and healthcare usage. One of the most commonly used classes of medications to treat mental health disorders is the selective serotonin reuptake inhibitor (SSRI). Here we present a descriptive epidemiological review of SSRI use in Army aviators over a 10-yr period.METHODS: An archival dataset retrieved from the U.S. Army Aeromedical Electronic Resource Office covering the years 2005 to 2015 was queried for cases of SSRI use. Frequencies were generated by primary diagnoses and aeromedical disposition for the SSRI subset of data.RESULTS: A total of 114 unique cases of SSRI use were identified (122 total aeromedical outcomes). These cases included 41 waiver recommendations, 59 suspension recommendations, and 22 cases of waiver continuations. The top five most common primary diagnoses were depressive disorder (N 32), anxiety state (N 21), posttraumatic stress disorder (N 16), single major depressive episode (N 13), and adjustment disorder with depressed mood (N 12).DISCUSSION: Understanding of the etiology, pathophysiology, and treatment of mental health disorders particularly within the safety-focused and unforgiving aviation environment has continued to evolve. With the application of evidence-based policy, deliberate aeromedical decision-making, and methodical risk mitigation, SSRI use does have a place within aviation. Aviators suffering in silence with deleterious impact to performance and safety or aircrew seeking services on the outside without knowledge or oversight of certification authorities must remain in the past.Kelley AM, Bernhardt K, McPherson M, Persson JL, Gaydos SJ. Selective serotonin reuptake inhibitor use among Army aviators. Aerosp Med Hum Perform. 2020; 91(11):897900.

Selective serotonin reuptake inhibitor use is associated with worse sleep-related breathing disturbances in individuals with depressive disorders and sleep complaints: a retrospective study.

The effects of serotonergic agents on respiration neuromodulation may vary according to differences in the serotonin system, such as those linked to depression. This study investigated how sleep-related respiratory disturbances relate to depression and the use of medications commonly prescribed for depression. Retrospective polysomnography was collated for all 363 individuals who met selection criteria out of 2,528 consecutive individuals referred to a specialized sleep clinic (Ottawa, Canada) between 2006 and 2016. The apnea-hypopnea index (AHI), oxygen saturation nadir, and oxygen desaturation index during REM and NREM sleep were analyzed using mixed analyses of covariance comparing 3 main groups: (1) medicated individuals with depressive disorders (antidepressant group; subdivided into the selective serotonin reuptake inhibitor and norepinephrine-dopamine reuptake inhibitor subgroups), (2) non-medicated individuals with depressive disorders (non-medicated group), and (3) mentally healthy control patients (control group). Individuals with depressive disorders (on antidepressants or not) had significantly higher AHIs compared to control patients (both P ≤ .007). The antidepressant group had a lower NREM sleep oxygen saturation nadir and a higher NREM sleep oxygen desaturation index than the control and non-medicated groups (all P ≤ .009). Within individuals with depressive disorders, independent of depression severity, the selective serotonin reuptake inhibitor group had a lower oxygen saturation nadir and a higher oxygen desaturation index during NREM sleep than the norepinephrine-dopamine reuptake inhibitor (both P ≤ .045) and non-medicated groups (both P < .001) and a higher NREM sleep AHI than the non-medicated group (P = .014). These findings suggest that the use of selective serotonin reuptake inhibitors may be associated with impaired breathing and worse nocturnal oxygen saturation in individuals with depressive disorders and sleep complaints, but this needs to be confirmed by prospective studies.

A comparative study to assess the effect of escitalopram and amitriptyline on psychomotor functions in patients of depression

Background: Depression is a most common and widespread of all psychiatric disorders. Treatment of depression includes the use of antidepressants commonly used clinically such as tricyclic antidepressants, selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitor, and monoamine oxidase inhibitors. Certain antidepressants apart from improvement in the symptoms found to have detrimental effect on cognitive and psychomotor function. Objective of this study was to assess and to compare the effect of escitalopram and amitriptyline on cognitive and psychomotor functionsMethods: Effect of escitalopram and amitriptyline on psychomotor function was assessed by using Critical flicker fusion frequency (CFF) and Reaction time (RT) in patients of mild to moderate depression at the end of 2nd and 4th week of monotherapy.Results: Patients in both the group have their RT remained significantly higher (p&lt;0.001) in comparison with control and CFF remained significantly lower at the end of both the week. There was a significant rise in CFF in escitalopram group as compared to amitriptyline (p&lt;0.001). Escitalopram showed a significant improvement in Visual reaction time (VRT), Auditory reaction time (ART) and Choice reaction time (CRT) (p&lt;0.001) compared to amitriptyline at both the follow ups.Conclusions: Findings of this study support the use of Selective serotonin reuptake inhibitor (SSRI) i.e. escitalopram which had shown less impairment of psychomotor function in patients of Depression as compared to amitriptyline (Tricyclic antidepressant), in special subgroups of population who operate machinery, drive vehicle or require alertness for the work.

Can selective serotonin reuptake inhibitors have a neuroprotective effect during COVID-19?

The absence of a specific treatment for SARS-CoV-2 infection led to an intense global effort in order to find new therapeutic interventions and improve patient outcomes. One important feature of COVID-19 pathophysiology is the activation of immune cells, with consequent massive production and release of inflammatory mediators that may cause impairment of several organ functions, including the brain. In addition to its classical role as a neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) has immunomodulatory properties, downregulating the inflammatory response by central and peripheral mechanisms. In this review, we describe the roles of 5-HT in the regulation of systemic inflammation and the potential benefits of the use of specific serotonin reuptake inhibitors as a coadjutant therapy to attenuate neurological complications of COVID-19.

Role of functional pharmacological therapy in post-stroke depression: a narrative review.

ObjectiveWe conducted a narrative review to investigate whether antidepressant therapy, including the use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) or the use of supportive drugs (i.e., citicoline or choline alfoscerate) as a substitute for antidepressant therapy, reduces depression in patients with cerebrovascular diseases.MethodsA systematic search of the PubMed and Web of Science databases was performed, including review articles and other studies to identify additional citations. Only 4 of 1566 publications met the inclusion/exclusion criteria and were selected.ResultsStudies showed that post-stroke depression (PSD) could be treated with antidepressant therapy, as well as supportive drugs such as citicoline or choline alfoscerate, which may have antidepressant effects.ConclusionsThe findings support the efficacy of citicoline as a treatment for depression. Studies aimed to discover the characteristics of these psychostimulants in relation to PSD treatment should be performed.

Pharmacologic treatment and SUDEP risk: A nationwide, population-based, case-control study.

ObjectiveWe conducted a nationwide case–control study in Sweden to test the hypothesis that antiepileptic drugs (AEDs) mono- or polytherapy, adherence, antidepressants, neuroleptics, β-blockers, and statins are associated with sudden unexpected death in epilepsy (SUDEP) risk.MethodsIncluded were 255 SUDEP cases and 1,148 matched controls. Information on clinical factors and medications came from medical records and the National Patient and Prescription Registers. The association between SUDEP and medications was assessed by odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for potential risk factors including type of epilepsy, living conditions, comorbidity, and frequency of generalized tonic-clonic seizures (GTCS).ResultsPolytherapy, especially taking 3 or more AEDs, was associated with a substantially reduced risk of SUDEP (OR 0.31, 95% CI 0.14–0.67). Combinations including lamotrigine (OR 0.55, 95% CI 0.31–0.97), valproic acid (OR 0.53, 95% CI 0.29–0.98), and levetiracetam (OR 0.49, 95% CI 0.27–0.90) were associated with reduced risk. No specific AED was associated with increased risk. Regarding monotherapy, although numbers were limited, the lowest SUDEP risk was seen in users of levetiracetam (0.10, 95% CI 0.02–0.61). Having nonadherence mentioned in the medical record was associated with an OR of 2.75 (95% CI 1.58–4.78). Statin use was associated with a reduced SUDEP risk (OR 0.34, 95% CI 0.11–0.99) but selective serotonin reuptake inhibitor use was not.ConclusionThese results provide support for the importance of medication adherence and intensified AED treatment for patients with poorly controlled GTCS in the effort to reduce SUDEP risk and suggest that comedication with statins may reduce risk.

Autoreceptor control of serotonin dynamics

BackgroundSerotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding involves genomics, neurochemistry, electrophysiology, and behavior. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders. This paper presents a new deterministic model of serotonin metabolism and a new systems population model that takes into account the large variation in enzyme and transporter expression levels, tryptophan input, and autoreceptor function.ResultsWe discuss the steady state of the model and the steady state distribution of extracellular serotonin under different hypotheses on the autoreceptors and we show the effect of tryptophan input on the steady state and the effect of meals. We use the deterministic model to interpret experimental data on the responses in the hippocampus of male and female mice, and to illustrate the short-time dynamics of the autoreceptors. We show there are likely two reuptake mechanisms for serotonin and that the autoreceptors have long-lasting influence and compare our results to measurements of serotonin dynamics in the substantia nigra pars reticulata. We also show how histamine affects serotonin dynamics. We examine experimental data that show very variable response curves in populations of mice and ask how much variation in parameters in the model is necessary to produce the observed variation in the data. Finally, we show how the systems population model can potentially be used to investigate specific biological and clinical questions.ConclusionsWe have shown that our new models can be used to investigate the effects of tryptophan input and meals and the behavior of experimental response curves in different brain nuclei. The systems population model incorporates individual variation and can be used to investigate clinical questions and the variation in drug efficacy. The codes for both the deterministic model and the systems population model are available from the authors and can be used by other researchers to investigate the serotonergic system.

Effects of Preexisting Psychotropic Medication Use on a Cohort of Patients with Ischemic Stroke Outcome.

Background Several studies investigated the use of selective serotonin reuptake inhibitors (SSRI) after ischemic stroke to improve motor recovery. However, little is known about the effects of preexisting psychotropic medication use (PPMU), such as antidepressants, on a long-term ischemic stroke functional disability. Objective We sought to determine the prevalence of PPMU and whether PPMU relates to the long-term clinical outcome in a cohort of patients presenting with acute ischemic strokes. Methods We retrospectively analyzed 323 consecutive patients who presented with an acute ischemic stroke in a single institution between January 2015 and December 2017. Baseline characteristics, functional disability as measured by the modified Rankin Scale (mRS), and major adverse cardiovascular complications (MACE) within 365 days were recorded. The comparison groups included a control group of ischemic stroke patients who were not on psychotropic medications before and after the index ischemic stroke and a second group of poststroke psychotropic medication use (PoMU), which consisted of patients started on psychotropic medication during the index admission. Results The prevalence of PPMU in the studied cohort was 21.4% (69/323). There was a greater proportion of females in the PPMU than in the comparison groups (P < 0.001), while vascular risk factors were similar in all groups, except for an increased presence of posterior circulation infarcts in the PPMU (37.4% vs. 18.8%, P < 0.001). Among the patients with available 1-year follow-up data (n = 246), we noted significantly greater improvement in stroke deficits, measured by National Institute of Health Stroke Scale (NIHSS) between PPMU and PoMU vs. control (3 (0-7) versus 1 (0-4), P = 0.041). The 1-year mRS was worse in PPMU and PoMU compared to the control group (2 (IQ 1-3) vs. 2 (IQ 0-3) vs. 1 (IQ 0-2), respectively, P = 0.013), but delta mRS reflecting the degree of mRS improvement showed no significant difference between any PMU and control patients (P = 0.76). There was no statistically significant difference in MACE. Conclusion PPMU in ischemic stroke is common; it can be beneficial in ischemic stroke in the long-term clinical outcome and is not associated with increased risks of MACE.

Outcomes and Laboratory and Clinical Findings of Asthma and Allergic Patients Admitted With Covid-19 in a Spanish University Hospital.

Individual susceptibility and clinical outcome of Covid-19 are variable and mortality is also very variable across countries, being particularly high in Spain. Comorbidities might increase the risk for less favourable outcomes, but it has been reported that patients with antecedents of asthma or allergic diseases were under-represented among hospitalized Covid-19 patients. Aiming to compare the clinical evolution of patients with antecedents of asthma or allergic diseases and patients without these antecedents, we analyzed a series of 113 consecutive patients with Covid-19 in a regional hospital in Spain. We collected and analyzed the putative effect of the 16 most common co-morbidities, previous treatment with 33 drug classes, symptoms, radiological, and laboratory findings at admission and drug therapy after admission. Predictors of long hospital stays were older age (P = 0.002), low oxygen saturation (P = 0.001) and bilateral radiological findings at admission (P = 0.023). Predictors of Intensive Care Unit (ICU) admission were the previous use of calcium-channel blockers (P = 0.005), proton pump inhibitors (P = 0.017), low oxygen saturation (P = 0.002), high leukocyte count (P = 0.011), and high D-dimer values (P = 0.005). Predictors of mortality were older age (P = 0.001), antecedents of cerebrovascular disorders (P = 0.034), previous use of oral anticoagulants (P = 0.009) or selective serotonin reuptake inhibitors (P = 0.003), and increased levels of interleukin-6 (P = 0.001). Patients with antecedents of allergic diseases were about ten years younger (P = 0.003) and had fewer comorbidities (P = 0.026) than the rest of the patients. In conclusion, antecedents of allergic diseases might influence hospitalization risk in relatively young patients.

Role of Depression and Anxiety Disorders in Takotsubo Syndrome: The Psychiatric Side of Broken Heart.

Takotsubo syndrome (TTS), also called broken heart syndrome, is an acute and transient cardiac wall motion abnormality of the left ventricle. The patient prototype is a post-menopausal woman with myocardial infarction-like symptoms (angina pectoris, breathlessness, palpitations, etc.) who has experienced sudden emotional or physical stress. Although prognosis is generally considered relatively benign, both complications and recurrence rates are not insignificant. Pathophysiological mechanisms underlying TTS are not entirely understood, but the sympathetic system over-activity has a leading role. Moreover, since emotional stress frequently triggers TTS and since precedent diagnosis of psychiatric disorders sometimes coexists, the psychological response to stress could be another potential therapeutic target. Indeed, this article aims to explore the association between underlying depression and anxiety disorders and TTS, as well as to find ideal therapeutic options useful to treat and prevent TTS. Thus in our review, we considered case reports, case-control studies, and review articles from PubMed. Papers dealing with Takotsubo syndrome and anxiety disorder or depression were selected. We included papers published since 2010 and whose abstract was in English. We concluded that anxiety disorders, but not depression, are associated with a higher occurrence of TTS. There is a link between anxiety, TTS, and inflammation leading to increased sympathetic activity. Nevertheless, patients with pre-admission psychiatric disorders have a higher risk of recurrent TTS. Importantly, the use of selective serotonin reuptake inhibitors (SSRIs) could be a potential therapeutic aid in preventing TTS's recurrence in selected patients.

Venlafaxine-induced damage to seminiferous epithelium, spermiation, and sperm parameters in rats: A correlation with high estrogen levels.

Venlafaxine (selective serotonin and norepinephrine reuptake inhibitor) use has increased worldwide. However, the impact of venlafaxine on testes and sperm parameters has not been investigated. We evaluated venlafaxine impact on testicular and sperm parameters and verified whether the changes are reversible. Animals from venlafaxine-35days and venlafaxine-65days groups received 30mg/kg of venlafaxine for 35days. Control-35days and control-65days received distilled water. In control-65days and venlafaxine-65days, the treatment was interrupted for 30days. Sperm concentration, morphology, motility, and mitochondrial activity were analyzed. Number of step 19 spermatids (NLS), frequency of tubules with spermiation failure, Sertoli cells number, and TUNEL-positive germ cells were quantified. Testicular aromatase, connexin 43 (Cx43) immunoexpression, Cx43 protein levels, and Cx43 expression were evaluated. Either intratesticular testosterone or estrogen levels were measured. Venlafaxine impaired sperm morphology, reduced sperm concentration, mitochondrial activity, and sperm motility. The frequency of tubules with spermiation failure and NLS increased in parallel to increased Cx43 immunoexpression; mRNA and protein levels; and aromatase, testosterone, and estrogen levels. An increase in germ cell death and decreased Sertoli cells number were observed. In venlafaxine-65days, except for sperm motility, mitochondrial activity, Sertoli cells number, and germ cell death, all other parameters were partially or totally recovered. Venlafaxine increases testosterone aromatization and Cx43. This drug, via high estrogen levels, disturbs Sertoli cells, induces germ cell death, and impairs spermiation and sperm parameters. The restoration of spermiation associated with the decreased Cx43 and hormonal levels in venlafaxine-65days reinforces that high estrogen levels are related to venlafaxine-induced changes. The presence of damaged Sertoli cells, germ cell death, and low sperm motility in venlafaxine-65days indicates that interruption of treatment for 30days was insufficient for testicular recovery and points to a long-term estrogen impact on the seminiferous epithelium.

Evaluation of a Pharmacist Managed Telephone Pain Clinic for Neuropathy Treatment

Pain is prevalent in our society, affecting more than a quarter-million U.S. adults and leading to poor patient outcomes. At the Veteran’s Affairs San Diego Healthcare System (VASDHS), a Telephone Pain Clinic (TPC) was developed to improve these outcomes. The purpose of this study was to evaluate the effectiveness of TPC in improving neuropathic pain. A retrospective cohort study was conducted at the VASDHS comparing pre- and post- self-rated Numeric Rating Scale (NRS-11), an 11-point scale from 0 to 10 with 0 equaling no pain and 10 equaling most severe pain. Patients were included if they were referred and enrolled to the TPC for neuropathic pain. They were excluded if they were co-managed by another pain provider or were referred for any other pain conditions. A total of 830 TPC patients were screened between January 2008 to December 2009 and 52 patients met criteria. Patients who participated in the clinic were found to have a significant 0.83 (p = 0.014) reduction in mean pain score from baseline (6.62, SD 1.96) to discharge (5.79, SD 2.49). At discharge, pain medications that were increased were use of serotonin and norepinephrine reuptake inhibitors (SNRIs), pregabalin, and capsaicin. Management by the TPC showed promise and trends toward reducing pain experienced by patients with diabetic neuropathy, fibromyalgia, or postherpetic neuralgia. The TPC also may be more effective in maximizing evidenced-based pharmacotherapy for neuropathic pain, suggesting expertise by pharmacist clinical specialists.

Association of Selective Serotonin Reuptake Inhibitors With the Risk of Type 2 Diabetes in Children and Adolescents

Concerns exist that use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of developing type 2 diabetes (T2D) in adults, but evidence in children and adolescents is limited. In the absence of a randomized clinical trial, evidence must be generated using real-world data. To evaluate the safety of SSRI use in children and adolescents with respect to the associated risk of T2D. This cohort study of patients aged 10 to 19 years with a diagnosis for an SSRI treatment indication was conducted within the nationwide Medicaid Analytic eXtract (MAX; January 1, 2000, to December 31, 2014) and the IBM MarketScan (January 1, 2003, to September 30, 2015) databases. Data were analyzed from November 1, 2018, to December 6, 2019. New users of an SSRI medication and comparator groups with no known metabolic adverse effects (no antidepressant exposure, bupropion hydrochloride exposure, or psychotherapy exposure). Within-class individual SSRI medications were compared with fluoxetine hydrochloride. Incident T2D during follow-up. Intention-to-treat effects were estimated using Cox proportional hazards regression models, adjusting for confounding through propensity score stratification. As-treated effects to account for continuous treatment were estimated using inverse probability weighting and marginal structural models. A total of 1 582 914 patients were included in the analysis (58.3% female; mean [SD] age, 15.1 [2.3] years). The SSRI-treated group included 316 178 patients in the MAX database (publicly insured; mean [SD] age, 14.7 [2.1] years; 62.2% female) and 211 460 in the MarketScan database (privately insured; mean [SD] age, 15.8 [2.3] years; 63.9% female) with at least 2 SSRI prescriptions filled, followed up for a mean (SD) of 2.3 (2.0) and 2.2 (1.9) years, respectively. In publicly insured patients, initiation of SSRI treatment was associated with a 13% increased hazard of T2DM (intention-to-treat adjusted hazard ratio [aHR], 1.13; 95% CI, 1.04-1.22) compared with untreated patients. The association strengthened for continuous SSRI treatment (as-treated aHR, 1.33; 95% CI, 1.21-1.47), corresponding to 6.6 (95% CI, 4.2-10.4) additional cases of T2D per 10 000 patients treated for at least 2 years. Adjusted HRs were lower in privately insured patients (intention-to-treat aHR, 1.01 [95% CI, 0.84-1.23]; as-treated aHR, 1.10 [95% CI, 0.88-1.36]). Findings were similar when comparing SSRI treatment with psychotherapy (publicly insured as-treated aHR, 1.44 [95% CI, 1.25-1.65]; privately insured as-treated aHR, 1.21 [95% CI, 0.93-1.57]), whereas no increased risk was observed compared with bupropion treatment publicly insured as-treated aHR, 1.01 [95% CI, 0.79-1.29]; privately insured as-treated aHR, 0.87 [95% CI, 0.44-1.70]). For the within-class analysis, no medication had an increased hazard of T2D compared with fluoxetine. These findings suggest that children and adolescents initiating SSRI treatment may be at a small increased risk of developing T2D, particularly publicly insured patients. The magnitude of association was more modest than previously reported, and the absolute risk was small. The potential small risk should be viewed in relation to the efficacy of SSRIs for its major indications in young patients.

Association of Selective Serotonin Reuptake Inhibitor Use After Intracerebral Hemorrhage With Hemorrhage Recurrence and Depression Severity

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat poststroke depression but are associated with increased incidence of first-ever intracerebral hemorrhage (ICH) in the general population. The decision to treat ICH survivors with SSRIs must therefore balance potential risks of ICH recurrence with presumed benefits on depressive symptoms. To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms. Longitudinal ICH cohort study at a tertiary care center enrolling from January 2006 to December 2017, with follow-up for a median of 53.2 months (interquartile range, 42.3-61.2 months). The study included 1279 consenting individuals (1049 White, 89 Black, 77 Hispanic, and 64 other race/ethnicity) of 1335 eligible patients presenting with primary ICH and who were discharged alive from initial hospitalization for stroke. We conducted univariable and multivariable analyses for ICH recurrence risk and depression severity, including subset analyses for patients with 1 or more of the following characteristics associated with high ICH recurrence risk: (1) lobar ICH; (2) presence of the apolipoprotein ε2/ε4 gene variants; (3) prior history of ICH/TIA/ischemic stroke; and (4) Black or Hispanic race/ethnicity. Mean age of study participants was 71.3 years, with 602 women (47%); of the 1279 participants, 1049 were White, 89 were Black, 77 were Hispanic, and 64 were other race/ethnicity. SSRI exposure was associated with both ICH recurrence (subhazard ratio [SHR], 1.31; 95% CI, 1.08-1.59) and resolution of post-ICH depression (SHR, 1.53; 95% CI, 1.12 2.09). Among those individuals at high risk for recurrent ICH, SSRIs were associated with further elevation in risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22-2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes). The association of SSRI with reduced depressive symptoms did not differ between high those at high risk for recurrent ICH and all other ICH survivors. Selective serotonin reuptake inhibitor exposure after ICH is associated with both improvement in depressive symptoms and increased risk of recurrent hemorrhagic stroke. Clinical history, neuroimaging data, and genetic biomarkers may help to identify survivors of ICH more likely to safely tolerate SSRI use.

Aromatase inhibitor use, side effects and discontinuation rates in gynecologic oncology patients

ObjectiveAromatase inhibitors (AI) are frequently prescribed in gynecologic oncology. We sought to define the frequency and duration of AI use, characterize AI side effects and determine the reasons for discontinuation in these patients. MethodsUterine and ovarian cancer patients with AI use for gynecologic cancer therapy were identified retrospectively. Data were abstracted from the electronic medical record, including cancer type, stage, prior cancer treatments, body mass index, concurrent medications, prevalence of AI side effects before and during AI therapy, length of AI treatment and reason for AI discontinuation. Results146 women received AI therapy, with 68 for ovarian cancer (46.6%) and 78 for uterine cancer (53.4%). The majority (71.9%) had advanced stage disease at diagnosis. 54.1% noted AI-associated side effects within the first three visits after starting AI therapy. The most common side effects were arthralgias (29.5%), hot flashes (25.3%), new/worsening fatigue (16.4%), muscle or joint stiffness (8.2%) and myalgias (6.8%). The mean duration of therapy was 14.7 months. Gabapentin or selective serotonin reuptake inhibitor (SSRI) use was associated with decreased musculoskeletal side effects (gabapentin: p < .001, OR 0.88, 95% CI 0.83–0.94; SSRI: p < .001, OR 0.82, 95% CI 0.77–0.89). The most common reason for AI discontinuation was disease progression (87.9%), with 5.0% discontinuing due to side effects and 7.1% for other reasons. ConclusionAI therapy for gynecologic cancers is frequently associated with musculoskeletal side effects, but rarely leads to treatment discontinuation. Thus, AI side effects should be assessed in gynecologic cancer patients to allow potential mitigation of symptoms through adjunct therapies.

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Induced by Long-Term Use of Citalopram and Short-Term Use of Naproxen

Patient: Female, 88-year-oldFinal Diagnosis: Syndrome of inappropriate antidiuretic hormone secretionSymptoms: Decreased appetite • malaise • nauseaMedication:—Clinical Procedure: LaboratorySpecialty: Endocrinology and Metabolic • Geriatrics • NephrologyObjective:Rare co-existance of disease or pathologyBackground:Use of selective serotonin reuptake inhibitors (SSRIs) has been reported to be associated with the syndrome of inappropriate antidiuretic hormone (SIADH), although it is uncommon. Nonsteroidal anti-inflammatory drugs (NSAIDs), as a sole agent, are an even rarer cause of SIADH. Despite being documented in the literature, the understanding of the mechanism of both agents is limited. Here, we report a case of a patient taking both of these medications, a dangerous combination that led to the development of SIADH.Case Report:An 88-year-old woman with a history of asymptomatic chronic hyponatremia presented to our facility with symptomatic acute-on-chronic hyponatremia after she started using naproxen in addition to her daily citalopram. Her hyponatremia symptoms resolved after discontinuing these 2 offending agents, along with administration of fluid restriction and oral sodium supplements.Conclusions:Naproxen is commonly prescribed and is often taken by elderly patients to control long-term or short-term pain. SSRIs, on the other hand, are a first-line treatment for depression and are usually prescribe by a psychiatrist. Hyponatremia is a rare medication adverse effect that should be kept in mind when treating these patients with either of these medications, and should especially be considered when combining them. Medication reconciliation should be done carefully by the provider to avoid adverse effects and drug interactions. When hyponatremia is encountered, options for future medication prescriptions include rechallenging with the same medication, switching to a different medication with the same mechanism of action, or using a medication from another class altogether. Monitoring of serum sodium level is warranted when titrating the offending agent.