Non-selective Serotonin Reuptake Inhibitor Research Articles

The Association Between Antidepressant Use and Drug-Induced Liver Injury: A Nationwide, Population-Based Case-Control Study in Taiwan.

The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury. The population-based case-control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury. The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12-1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01-1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16-1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13-1.24), and others (aOR 1.27; 95%CI 1.14-1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18-1.29). SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

Diagnosis and treatment of mental disorders – a review of the scientific literature

Introduction: Unambiguous definition of mental disorders is difficult, mainly because of the heterogeneity of this group of diseases and the clarity of the line between pathology and normal. The definition proposed by the World Health Organization (WHO) is widely accepted. In practice, definitions from the legislation of a country are also important. Aim of the work: The purpose of this study is to discuss the basic issues of diagnosis and treatment of mental disorders. Material and method: A method of non-systematic literature review from databases such as scientific Google Scholar, PubMed, CinalHl, Scopus, Arianta, Web of Science was used. Results and conclusions: In the treatment of mental disorders, I use pharmacological and non-pharmacological methods. Psychopharmaceuticals are divided into several groups depending on their mechanism of action. Their selection depends mainly on the diagnosed disease entity and tolerance to treatment. The most widely used group of drugs is the group of non-selective serotonin reuptake inhibitors (SSRIs). Non-pharmacological methods include psychotherapy, electroconvulsive therapy, deep brain stimulation, and psychosurgery.

Comparative short-term efficacy and acceptability of a combination of pharmacotherapy and psychotherapy for depressive disorder in children and adolescents: a systematic review and meta-analysis

BackgroundAlthough the clinical efficacy and safety of combination of pharmacotherapy and psychotherapy in the treatment of depressive disorders in children and adolescents have been studied, the results remain controversial. This meta-analysis aimed to study the short-term efficacy and acceptability of combined therapy for children and adolescents with depressive disorders.MethodsWe conducted a systematic search in multiple databases for randomised controlled trials (RCTs), up to 31 December 2020, that assessed the combination of pharmacotherapy and psychotherapy against other active treatment options (pharmacotherapy, psychotherapy and placebo combined psychotherapy) in children and adolescents ( ≤ 18 years old) with depressive disorder. This study was registered with PROSPERO (CRD42020196701).ResultsA total of 14 RCTs involving 1,325 patients were included. For the primary and secondary outcomes, there were no statistically significant differences between the compared interventions in terms of remission (odds ratios [OR] = 1.37; 95% confidence interval [CI]: 0.93 to 2.04), acceptability (OR = 0.99; 95% CI: 0.72 to 1.38), efficacy (standardised mean differences = -0.07; 95% CI: -0.32 to 0.19), and suicidality (OR = 1.17; 95% CI: 0.67 to 2.06). Limited evidence showed that the combination of fluoxetine (OR = 1.90, 95% CI: 1.10 to 3.29) or non-selective serotonin reuptake inhibitors (non-SSRI) (OR = 2.46, 95% CI: 1.06 to 5.72) with cognitive-behavioural therapy (CBT) was superior to other active treatment options. Most included trials were rated as ‘some concerns’ in terms of risk of bias assessment.ConclusionThere is no evidence from the limited available data that all combined therapies are superior to other active treatment options for the acute treatment of depressive disorder in children and adolescents. However, it showed that fluoxetine or non-SSRI pharmacotherapies combined with CBT might be superior to other therapies in short-term. Mixed characteristics (e.g. age) and small sample size of non-SSRI combined therapy may influence the generalisability of the results.

Obsessive-Compulsive Disorders.

This article describes the phenomenology and clinical presentation of obsessive-compulsive disorder (OCD), a common but underdiagnosed psychiatric disorder. Guidance for effectively identifying obsessive-compulsive symptoms is provided, and treatment options, including psychotherapy, pharmacologic management, and neuromodulation approaches for treatment-resistant OCD, are discussed. OCD affects 2% to 3% of adults worldwide and is associated with substantial individual disability and societal costs. Lack of recognition of common OCD symptom types, in addition to shame and fear of stigma on the part of patients, has created an average delay in diagnosis by almost 10 years and a delay in effective treatment (ie, a treatment gap) of nearly 2 years. Cognitive-behavioral therapy (CBT), specifically a form of CBT that includes a type of behavioral intervention called exposure and response prevention, remains the most effective form of treatment for OCD. If CBT is not effective or not available, pharmacologic treatment with selective serotonin reuptake inhibitors (SSRIs) or clomipramine, a nonselective serotonin reuptake inhibitor, can also be of benefit. Neuromodulation approaches such as deep brain stimulation and transcranial magnetic stimulation are rapidly emerging as effective treatments for OCD, particularly for patients who have not experienced an adequate response to psychotherapy or pharmacologic management. OCD affects more than one in every 50 adults in the United States but is recognized and adequately treated in fewer than half of those affected. Early intervention and appropriate treatment can substantially reduce OCD symptom severity, improve quality of life, and minimize the functional disability associated with this chronic and often debilitating illness.

Clinical phenotypes of depressed patients with evidence of inflammation and somatic symptoms

Whether depressed patients with evidence of inflammation are more appropriate candidates for immunotherapies is being tested in several clinical trials, which are selecting patients based on elevated C-reactive protein (CRP) and inflammation-related symptoms. However, studies of the clinical and phenotypic profile of depressed patients with elevated CRP are relatively scarce. We have investigated detailed clinical characteristics of 84 depressed patients, grouped as those with (CRP≥3 mg/L) and without (CRP<3 mg/L) inflammation. All patients met the International Classification of Diseases 10th Revision criteria for current depressive episode and had somatic symptoms of depression. We report that depressed patients with inflammation are more likely to be older (P=0.04), have higher body mass index (P<0.01), and be on non-selective serotonin reuptake inhibitor antidepressants (P=0.04). After adjusting for potential confounders, the inflammation group had higher depression severity (adjusted mean difference, 8.82; 95% CI, 3.91–13.72), somatic symptoms (adjusted mean difference, 3.25; 95% CI, 1.58–4.92), state anxiety (adjusted mean difference, 9.25; 95% CI, 3.82–14.67), perceived stress (adjusted mean difference, 4.58; 95% CI, 1.98–7.18), and fatigue (adjusted mean difference, 9.71; 95% CI, 3.09–6.33), but not anhedonia. The inflamed group also had poorer quality of life (adjusted mean difference, −0.18; 95% CI, −0.32–0.05). At individual depressive symptom level, the inflammation group had increased guilty feelings (adjusted odds ratio [OR], 7.28; 95% CI, 2.09–31.17), pessimism (adjusted OR, 5.38; 95% CI, 1.53–22.73), concentration difficulties (adjusted OR, 4.56; 95% CI, 1.32–19.02), and indecisiveness (adjusted OR, 4.21; 95% CI, 1.15–18.54). Our findings highlight the clinical features associated with inflammation in depressed patients with somatic symptoms, including poor quality of life, supporting the need for intervention targeting this group. These results could also aid patient and outcome selection in future clinical trials testing immunotherapies in depression. Replication of these findings in larger samples is required.

A Systematic Review and Meta-Analysis Considering the Risk for Congenital Heart Defects of Antidepressant Classes and Individual Antidepressants.

Antidepressant use during the first trimester is reported in 4-8% of pregnancies. The use of some selective serotonin reuptake inhibitors during the first trimester has been identified as increasing the odds for congenital heart defects; however, little is known about the safety of non-selective serotonin reuptake inhibitor antidepressants. The objective of this study was to assess the odds of congenital heart defects associated with the use of antidepressants during the first trimester of pregnancy, and to update the literature as newer studies have been published since the latest systematic literature review and meta-analysis. PubMed and Embase were searched till 3 June, 2020. Study quality was assessed, and study details were extracted. Meta-analyses were performed using RevMan 5.4, which assessed: (1) any antidepressant usage; (2) classes of antidepressants; and (3) individual antidepressants. Twenty studies were identified, encompassing 5,337,223 pregnancies. The odds ratio for maternal use of any antidepressant during the first trimester of pregnancy and the presence of congenital heart defects from the random effects meta-analysis was 1.28 (95% confidence interval [CI] 1.17-1.41). Significant odds ratios of 1.69 (95% CI 1.37-2.10) and 1.25 (95% CI 1.15-1.37) were reported for serotonin norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors, respectively. A non-statistically significant odds ratio of 1.02 (95% CI 0.82-1.25) was reported for the tricyclic antidepressants. Analyses of individual SSRIs produced significant odds ratios of 1.57 (95% CI 1.25-1.97), 1.36 (95% CI 1.08-1.72), and 1.29 (95% CI 1.14-1.45) for paroxetine, fluoxetine, and sertraline, respectively. The norepinephrine-dopamine-reuptake inhibitor bupropion also produced a significant odds ratio of 1.23 (95% CI 1.01-1.49). The selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor classes of antidepressants pose a greater risk for causing congenital heart defects than the tricyclic antidepressants. However, this risk for individual antidepressants within each class varies, and information regarding some antidepressants is still lacking.

The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases.

Depression is common in older adults and those with cardiovascular disease. Although selective serotonin reuptake inhibitors generally have been shown to be safe to treat depression in these patients, it is important to identify additional antidepressants when selective serotonin reuptake inhibitors are not effective. This qualitative narrative review summarizes what is known about the cardiovascular side effects of some of the newer antidepressants. Twelve novel non-selective serotonin reuptake inhibitor antidepressants were identified from the literature: venlafaxine, desvenlafaxine, duloxetine, milnacipran, levomilnacipran, mirtazapine, bupropion, vilazodone, vortioxetine, agomelatine, moclobemide, and ketamine-esketamine. A search restricted to publications written in English was conducted in PubMed and Google Scholar with the following search criteria: the specific antidepressant AND (QT OR QTc OR "heart rate" OR "heart rate variability" OR "hypertension" OR "orthostatic hypotension" OR "cardiovascular outcomes" OR "arrhythmia" OR "myocardial infarction" OR "cardiovascular mortality") AND (geriatric OR "older adults" OR "late life depression" OR "cardiovascular disease" OR "hospitalized" OR "hospitalized"). The recommended use, dosing ranges, cardiovascular effects, and general advantages and disadvantages of each of the drugs are discussed. Levomilnacipran and vilazodone have not received enough study to judge their safety in older patients or in those with, or at high risk for, cardiovascular disease. There is at least some evidence for possible adverse events with each of the other newer antidepressants that could be of concern in these patients. Nevertheless, with careful administration and attention to the potential adverse reactions for each drug, these may provide safe effective alternatives for older adults and patients with cardiovascular disease who do not respond to selective serotonin reuptake inhibitor antidepressants. However, more research on the safety and efficacy of these drugs in these specific patient populations is urgently needed.

Comparative effects of antidepressants of various pharmacological groups on the behavior of adult Danio rerio

The depressive disorders remain one of the global problems of modern society. Many issues related to this topic remain open for discussion. It is reliably known that tropical fish Danio rerio (zebrafish) are the most studied and practical model methods of preclinical studies. They have several advantages over other laboratory animals. Danio Rerio is great for modeling stress and depression in order to identify the manifestations of medication to identify the manifestations of this condition.&#x0D; Methods. Danio Rerio when exposed to non-selective antidepressants and related serotonin reuptake inhibitors. Danio Rerio is under stress and depression due to acute exposure to caffeine and the subsequent use of antidepressants with timely recording and processing of the results.&#x0D; Results. The effect of sertraline on the Danio rerio group in order to identify the state of stress and depression was more effective in comparison with the results obtained using amitriptyline as an antidepressant.&#x0D; Conclusions. Sertraline in therapeutic concentration has a greater rate of elimination from anxiety and depression, which in turn allows us to argue about its greater effectiveness. In medical practice, it is better to prescribe drugs of the group of selective serotonin reuptake inhibitors in order to achieve a faster effect.

Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance.

Objective: To describe the clinical characteristics of adolescents with antidepressant treatment-resistant major depressive disorder (MDD) and to examine the utility of the Antidepressant Treatment Record (ATR) in categorizing treatment resistance in this population. Methods: Adolescents with treatment-resistant MDD enrolled in an interventional study underwent a baseline evaluation with the ATR, Children's Depression Rating Scale-Revised (CDRS-R), and Clinical Global Impressions-Severity (CGI-S) scales. Demographic and clinical characteristics were examined with regard to ATR-defined level of resistance (level 1 to ≥3) using analysis of variance and χ2 tests. Results: In adolescents with treatment-resistant MDD (N = 97), aged 12-21 years, most were female (65%), white (89%), and had recurrent illness (78%). Patients were severely ill (median CGI-S score of 5), had a mean CDRS-R score of 63 ± 10, and 17.5% had been hospitalized for depression-related symptoms. Fifty-two patients were classified as ATR 1, whereas 32 were classified as ATR level 2 and 13 patients as ≥3, respectively. For increasing ATR-defined levels, illness duration increased from 12.0 (range: 1.5-31.9) to 14.8 (range: 1.8-31.7) to 19.5 (range: 2.5-36.2) months and the likelihood of treatment with serotonin norepinephrine reuptake inhibitors (SNRIs) and dopamine norepinephrine reuptake inhibitors (DNRIs) similarly increased (p = 0.006 for both SNRIs and DNRIs) as did the likelihood of treatment with mixed dopamine serotonin receptor antagonists (χ2 = 17, p < 0.001). Conclusions: This study underscores the morbidity and chronicity of treatment-resistant MDD in adolescents. The present characterization of related clinical features describes the use of nonselective serotonin reuptake inhibitors in adolescents with treatment-resistant depression and raises the possibility that those with the greatest medication treatment resistance are less likely to have had recurrent episodes. The study also demonstrates the utility of the ATR in categorizing treatment resistance in adolescents with MDD.

Depressive Symptoms, Antidepressant Use, and Hypertension in Young Adulthood.

Among adults, depressive symptoms are associated with higher rates of cardiovascular disease; however, the evidence is mixed regarding the association between depressive symptoms and hypertension, especially among young adults. The deleterious effects of some antidepressant medications on blood pressure may contribute to mixed findings. Adolescents enrolled in Add Health (N = 11,183) (1994-2008) completed an abbreviated Center for Epidemiologic Studies Depression Scale at three waves (mean ages, 16, 22, and 29). Antidepressant use was measured at age 22 and at age 29. Hypertension at age 29 was defined as measured systolic blood pressure of 140 mm Hg or greater, diastolic blood pressure of 90 mm Hg or greater, or staff-inventoried anti-hypertensive medication use. The prevalence of hypertension at age 29 was 20%. High depressive symptoms in adolescence or young adulthood were not associated with hypertension in young adulthood. Antidepressant use at age 29 was associated with increased prevalence of hypertension (prevalence ratio [PR], 1.4; 95% CI, 1.2, 1.7) and an interaction with sex was observed (PRMen, 1.6; 95% CI, 1.2, 2.0; PRWomen, 1.2; 95% CI, 0.89, 1.6; pinteraction = 0.0227). Selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor antidepressant use were associated with hypertension (PRSSRI, 1.3; 95% CI, 1.0, 1.6; PRnon-SSRI, 1.6; 95% CI, 1.2, 2.1). In this sample, antidepressant use, but not depressive symptoms, was associated with hypertension in young adulthood. Further research is recommended to examine joint and independent relationships between depression and antidepressant use and hypertension among young adults. See video abstract at, http://links.lww.com/EDE/B355.

Relationship between anti-depressant use and lung cancer survival

ObjectivesIn recent years, the anti-cancer properties of several commonly used drugs have been explored, with drugs such as aspirin and beta-blockers associated with improved cancer outcomes. Previous preclinical work demonstrated that tricyclic anti-depressants have antitumor efficacy in lung cancer. Our goal was to examine the association between anti-depressant use and survival in lung cancer. Materials and methodsWe examined the association between use of common anti-depressants and survival in 1097 lung cancer patients from the NCI-Maryland lung cancer study. The types of anti-depressants included in the study were norepinephrine and dopamine reuptake inhibitors, serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, non-selective serotonin reuptake inhibitors, and tricyclic anti-depressants. Anti-depressant use was extracted from the medical history section of a detailed interviewer-administered questionnaire. Specific use in the three months before a lung cancer diagnosis was determined. Cox portioned hazards modeling was used to estimate the association between anti-depressant use with lung cancer-specific death with adjustment for potential confounding co-factors. ResultsAnti-depressant use was associated with extended lung cancer-specific survival. In an analysis of specific classes of anti-depressant use, NDRIs and TCAs were associated with improved survival. Importantly, the extended survival associated with anti-depressants was maintained after adjustment for the clinical indications for these drugs, suggestive of a direct effect on lung cancer biology. ConclusionsConsidering the manageable and largely tolerable side effects of anti-depressants, and the low cost of these drugs, these results indicate that evaluation of anti-depressants as adjunct therapeutics with chemotherapy may have a translational effect for lung cancer patients. Microabstract•Catecholamine signaling is increasingly recognized in connection with cancer.•The relationship between antidepressant use and survival was assessed in 1097 lung cancer patients.•Antidepressants, which modulate catecholamines, are associated with lung cancer survival.•Of the six drug classes tested, TCAs and NDRIs are the main forms associated with outcome.•Both TCAs and NDRIs are associated with prolonged patient survival.

Non-tricyclic and Non-selective Serotonin Reuptake Inhibitor Antidepressants and Recurrent Falls in Frail Older Women

To determine the risk of recurrent falls associated with antidepressants other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) among frail older women. This is a secondary analysis of the Zoledronic acid in frail Elders to STrengthen bone, or ZEST, trial data treated as a longitudinal cohort in 181 frail, osteoporotic women aged ≥65 years in long-term care. The primary exposure was individual non-TCA/non-SSRI antidepressants (i.e., serotonin norepinephrine reuptake inhibitors, mirtazapine, trazodone, and bupropion) at baseline and 6 months. The main outcome was recurrent (at least two) falls within 6 months after antidepressant exposure. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were derived using a generalized estimating equations model. At least 15% of women experienced recurrent falls between 0-6 and 6-12 months. At baseline and 6 months, 18.2% and 6.9% had a non-TCA/non-SSRI antidepressant, respectively. Adjusting for demographics, health status, and other drugs that increase risk of falls, non-TCA/non-SSRI antidepressant exposure significantly increased the risk of recurrent falls (AOR: 2.14; 95% CI: 1.01-4.54). Fall risk further increased after removing bupropion from the non-TCA/non-SSRI antidepressant group in sensitivity analyses (AOR: 2.73; 95% CI: 1.24-6.01). Other antidepressant classes may not be safer than TCAs/SSRIs with respect to recurrent falls in frail older women.

Antidepressant Use Is Associated With an Increased Risk of Developing Microbleeds.

Serotonin-specific antidepressants may increase the risk of adverse bleeding events. In a previous cross-sectional study, we did not observe an association between antidepressant use and presence of subclinical cerebral bleedings. In this study, we investigated longitudinally whether antidepressant use is associated with an increased risk of new subclinical cerebral microbleeds. In total, 2559 participants aged ≥45 years of the population-based Rotterdam Study, all without microbleeds at baseline, underwent baseline and repeat brain magnetic resonance imaging between 2005 and 2013 (mean time interval, 3.9 years; SD, 0.5) to determine the incidence of microbleeds. Antidepressant use (yes versus no) was assessed between baseline and follow-up scan. In additional analyses, antidepressants were classified as low, intermediate, or high affinity for the serotonin transporter, and alternatively as selective serotonin reuptake inhibitors or non-selective serotonin reuptake inhibitors. We used multivariable logistic regression models to investigate the association of antidepressants with incident microbleeds. Antidepressant use was associated with a higher cerebral microbleed incidence (odds ratio, 2.22; 95% confidence interval, 1.31-3.76) than nonuse. When stratified by affinity for the serotonin transporter, intermediate serotonin affinity antidepressant use was associated with an increased risk of developing microbleeds (odds ratio, 3.07; 95% confidence interval, 1.53-6.17). Finally, selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor use were both associated with increased microbleed incidence. Antidepressant use was associated with an increased risk of developing microbleeds. Our results may support findings from previous clinical studies about increased intracranial and extracranial bleeding risk in antidepressant users.

Prognostic Value of Heart Rate Variability in Patients With Cancer.

Previous studies have shown that autonomic dysfunction is associated with shorter survival in patients with advanced cancer. We examined the association between heart rate variability, a measure of autonomic function, and survival in a large cohort of patients with cancer. We retrospectively examined the records of 651 patients with cancer who had undergone ambulatory electrocardiogram monitoring for 20 to 24 hours. Time domain heart rate variability (SD of normal-to-normal beat interval [SDNN]) was calculated using power spectral analysis. Survival data were compared between patients with SDNN ≥ 70 milliseconds (Group 1, n = 520) and SDNN < 70 milliseconds (Group 2, n = 131). Two groups were similar in most variables, except that patients in group 2 had a significantly higher percentage of male patients (P = 0.03), hematological malignancies (P = 0.04), and use of non-selective serotonin reuptake inhibitor antidepressants (P = 0.04). Patients in group 2 had a significantly shorter survival rate (25% of patients in group 2 died by 18.7 weeks vs. 78.9 weeks in group 1 patients; P < 0.0001). Multivariate analysis showed that SDNN < 70 milliseconds remained significant for survival (hazard ratio 1.9 [95% confidence interval: 1.4-2.5]) independent of age, cancer stage, and performance status. The presence of cancer in combination with decreased heart rate variability (SDNN < 70 milliseconds) is associated with shorter survival time.

Risk of QT/QTc prolongation among newer non-SSRI antidepressants.

To review QT prolongation potential with newer nonselective serotonin reuptake inhibitor (non-SSRI) antidepressants. A PubMed literature search was performed from 1982 through June 16, 2014. Search terms included bupropion, desvenlafaxine, duloxetine, levomilnacipran, mirtazapine, venlafaxine, and vilazodone in combination with each of the following terms: cardiac toxicity, QTc prolongation, QT prolongation, torsades de pointes, and TdP. English-language human studies, case reports, package inserts, manufacturer electronic communications, and ArizonaCert database were utilized. Rare QT prolongation has been reported with venlafaxine at therapeutic doses and in overdose. Bupropion has also been linked to QT prolongation in overdose situations. In elderly patients with a variety of high-risk comorbidities, mirtazapine did demonstrate higher odds of sudden cardiac death and ventricular arrhythmias when compared with paroxetine. Largely because of a lack of available data, existing studies fail to demonstrate QT prolongation with desvenlafaxine, duloxetine, levomilnacipran, and vilazodone. Based on the current literature, risk of QT/QTc prolongation with the majority of newer non-SSRI antidepressants at therapeutic doses is low. The highest risk for QT prolongation appears to exist in overdose situations with venlafaxine and bupropion. Given the few to nonexistent controlled studies and confounding variables present in case reports, it is difficult to draw conclusions on QT prolongation risk with many of the newer non-SSRI antidepressants.

The metabolic syndrome and related characteristics in major depression: inpatients and outpatients compared: Metabolic differences across treatment settings

ObjectiveWe aimed to systematically compare patients with major depressive disorder from three different treatment settings (a primary care outpatient, a secondary care outpatient and one inpatient sample), with regard to metabolic syndrome (MetSyn) prevalences, individual MetSyn components and related metabolic variables. MethodThe outpatient samples were drawn from the ongoing Netherlands Study of Depression and Anxiety (302 primary care and 445 secondary care outpatients). The inpatient sample (n=80) was recruited from five Dutch mental health hospitals. The assessments of MetSyn and related variables [waist circumference (WC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, systolic and diastolic blood pressure (SBP, DBP), body mass index (BMI), waist–hip ratio (WHR), LDL and total cholesterol (TC)] were compared using analysis of (co)variance and regression analysis, whereas medication analyses examined the extent to which clinical differences (e.g., depression severity or medication use) mediated the observed metabolic differences across setting. ResultsMetSyn prevalences (26% primary, 24% secondary care and 28% inpatients) did not significantly differ (P=.71). WC, BMI, LDL cholesterol, glucose and DBP were not significantly different across settings. However, WHR, TC and triglyceride levels were higher in inpatients than in both outpatients groups, while HDL cholesterol levels and SBP were lower. There was some mediating role for tricyclic and non-selective serotonin-reuptake inhibitor antidepressant use, but overall, the mediating role of clinical differences was limited. ConclusionsAlthough overall MetSyn prevalences did not differ, patterns of individual MetSyn-related variables differed more markedly across depressed inpatients and outpatients. Inpatients showed more adverse WHR and serum lipid profiles, while SBP levels were lower.

Region-specific regulation of 5-HT1B receptors in the rat brain by chronic venlafaxine treatment

Venlafaxine is a non-selective serotonin and noradrenaline reuptake inhibitor antidepressant drug for which clinical studies have suggested a high level efficacy and a possible early action onset compared to the classical antidepressants. Its therapeutic effects might be due, at least in part, to adaptive changes in serotonergic neurotransmission, through the activation of the different 5-HT receptor subtypes. 5-HT(1B) receptors are located in the axon terminals of both serotonergic and non-serotonergic neurons, where they act as inhibitory autoreceptors or heteroreceptors, respectively. However, the information about the involvement of this subtype in the mechanism of action of antidepressants is limited and quite controversial. The aim of this study was to evaluate the effect of venlafaxine (10 mg kg⁻¹ day⁻¹, p.o.) after 21 days of treatment on the density of 5-HT(1B) receptors and their functionality in rat brain. Effects of chronic venlafaxine were evaluated at different levels of 5-HT(1B) receptor by using receptor autoradiography, [³⁵S]GTPγS binding, and the regulation of body temperature induced by selective 5-HT(1B) agonist. Our results show that venlafaxine induced an increase in sensitivity of 5-HT(1B) receptors in hypothalamus both at G-protein level and the control of core temperature without affecting the receptor density. These results demonstrate that adaptive changes on 5-HT(1B) receptors induced by chronic administration of venlafaxine exhibit regional differences suggesting that the hypothalamus might be an important site of drug action.

Do continued antidepressants protect against dementia in patients with severe depressive disorder?

Studies on humans show that depressive disorder is associated with an increased risk of developing cognitive dysfunction, and animal studies suggest that antidepressants may have neuroprotective abilities. On the basis of these observations, it was hypothesized that treatment with antidepressants may decrease the risk of developing dementia in patients with depression. We investigated whether continued treatment with antidepressants is associated with a decreased rate of dementia in a population of patients discharged from psychiatric healthcare service with a diagnosis of depression. We used register data on all prescribed antidepressants in all patients discharged from psychiatric healthcare service with a diagnosis of depression and with subsequent diagnoses of dementia in Denmark from 1995 to 2005. A total of 37 658 patients with a diagnosis of depression at their first psychiatric contact and who were exposed to antidepressants after discharge were included in the study. A total of 2007 patients (5.3%) were subsequently diagnosed with dementia of any kind. The rate of dementia decreased during periods of two or more prescriptions of older antidepressants compared with the period of only one prescription of older antidepressants [relative risk (RR)=0.83 (95% confidence interval (CI)=0.70-0.98)]. This finding was replicated with Alzheimer's disease as the outcome [RR=0.66 (95% CI=0.47-0.94)] but not with dementia of other kinds as the outcome [RR=0.88 (95% CI=0.73-1.06)]. In contrast, during periods of continued use of selective serotonin reuptake inhibitors or newer nonselective serotonin reuptake inhibitors, the rate of dementia was not decreased, regardless of the subtype of dementia. It was concluded that continued long-term treatment with older antidepressants is associated with a reduced rate of dementia in patients treated in psychiatric healthcare settings, whereas continued treatment with other kinds of antidepressants is not. Methodological reasons for these findings cannot be excluded because of the nonrandomized nature of data.

Antidepressant Prescriptions: An Acute Window for Falls in the Nursing Home

Although many studies have implicated antidepressants as a risk factor for falls, it is not clear if risk accrues with duration of use or if there are acute risks associated with initiation of the prescription. We conducted a case-crossover study of nursing home residents with a fall to determine the effect of an antidepressant change (defined as the new prescription of an antidepressant or increasing the dose of a previously used antidepressant) on fall risk. Among 1,181 nursing home fallers, we compared the frequency of antidepressant changes during the hazard period (1-7 days before the fall) with the frequency of antidepressant changes during the control period (8-14 days before the fall). Odds ratios were estimated using conditional logistic regression models. Results were estimated for non-selective serotonin reuptake inhibitors (SSRI) and SSRI prescriptions, separately. Mean age was 88 years, and 71% were females. Seventy participants experienced an antidepressant change during the hazard and/or control periods. The maximum effect of falling occurred within 2 days of a non-SSRI change (odds ratio: 4.7, 95% confidence interval, 1.3-16.2). The effect on falling was no longer significant at 5 days (odds ratio: 1.9, 95% confidence interval, 0.9-4.0). No association was found between SSRI changes and falls. Nursing home residents are at high risk of falls during the days following a new prescription or increased dose of a non-SSRI antidepressant. Increased surveillance should occur, particularly during the first 48 hours, in an effort to decrease falls.

Persisting Decline in Depression Treatment After FDA Warnings

In October 2003 the Food and Drug Administration (FDA) issued a Public Health Advisory about the risk of suicidality for pediatric patients taking antidepressants; a boxed warning, package insert, and medication guide were implemented in February 2005. The warning was extended to young adults aged 18 to 24 years in May 2007. Immediately following the 2003 advisory, unintended declines in case finding and non-selective serotonin reuptake inhibitor substitute treatment were shown for pediatric patients, and spillover effects were seen in adult patients, who were not targeted by the warnings. To determine whether the unintended declines in depression care persisted for pediatric, young adult, and adult patients. Time series analyses. Ambulatory care settings nationally. Patients Pediatric, young adult, and adult cohorts of patients with new episodes of depression (n = 91 748, 70 311, and 630 748 episodes, respectively). Post-FDA advisory trends were compared with expected trends based on preadvisory patterns using a national integrated managed care claims database from July 1999 through June 2007. Depression diagnosis; antidepressant, antipsychotic, and anxiolytic prescriptions; and psychotherapy visits. Changes in pediatric depression care were similar to changes for adults. National diagnosis rates of depression returned to 1999 levels for pediatric patients and below 2004 levels for adults. Primary care providers continued significant reductions in new diagnoses of depression (44% lower for pediatric, 37% lower for young adults, 29% for adults); diagnoses by mental health providers who were not psychiatrists increased. Numbers of prescriptions of anxiolytic and atypical antipsychotic medications did not significantly change from preadvisory trends. Psychotherapy increased significantly for adult, though not pediatric, cases. Selective serotonin reuptake inhibitor use decreased in all cohorts; serotonin-norepinephrine reuptake inhibitor increased for adults. Diagnosing decreases persist. Substitute care did not compensate in pediatric and young adult groups, and spillover to adults continued, suggesting that unintended effects are nontransitory, substantial, and diffuse in a large national population. Policy actions are required to counter the unintended consequences of reduced depression treatment.