Specific Serotonergic Antidepressants Research Articles

Comparison of Protective Effects of Antidepressants Mediated by Serotonin Receptor in Aβ-Oligomer-Induced Neurotoxicity.

Amyloid β-peptide (Aβ) synthesis and deposition are the primary factors underlying the pathophysiology of Alzheimer's disease (AD). Aβ oligomer (Aβo) exerts its neurotoxic effects by inducing oxidative stress and lesions by adhering to cellular membranes. Though several antidepressants have been investigated as neuroprotective agents in AD, a detailed comparison of their neuroprotection against Aβo-induced neurotoxicity is lacking. Here, we aimed to elucidate the neuroprotective effects of clinically prescribed selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants at the cellular level and establish the underlying mechanisms for their potential clinical applications. Therefore, we compared the neuroprotective effects of three antidepressants, fluoxetine (Flx), duloxetine (Dlx), and mirtazapine (Mir), by their ability to prevent oxidative stress-induced cell damage, using SH-SY5Y cells, by evaluating cell viability, generation of reactive oxygen species (ROS) and mitochondrial ROS, and peroxidation of cell membrane phospholipids. These antidepressants exhibited potent antioxidant activity (Dlx > Mir > Flx) and improved cell viability. Furthermore, pretreatment with a 5-hydroxytryptamine 1A (5-HT1A) antagonist suppressed their effects, suggesting that the 5-HT1A receptor is involved in the antioxidant mechanism of the antidepressants' neuroprotection. These findings suggest the beneficial effects of antidepressant treatment in AD through the prevention of Aβ-induced oxidative stress.

Effects of medication on dopamine transporter imaging using [123I]I-FP-CIT SPECT in routine practice.

Dopamine transporter (DAT) imaging is used to support the diagnosis of neurodegenerative parkinsonian disorders. Specific medications have been reported to confound the interpretation of[123I]I-FP-CIT SPECT scans, but there is limited data. The aim of the current study is to identify potential medication effects on the interpretation of[123I]I-FP-CIT SPECT scans in routine practice. Consecutive patients undergoing a[123I]I-FP-CIT SPECT/CT scan on a 360° CZT camera between September 2019 and December 2022 were included. An exhaustive review of patient medications (antidepressants, antipsychotics, anti-epileptics, anti-parkinsonians, benzodiazepines, lithium, opioids, and stimulants) was performed. Two experienced nuclear physicians, blinded to the medication reports, interpreted the[123I]I-FP-CIT SPECT scans visually and a semi-quantitative analysis was performed using a local normal database. The study included 305 patients (71.0 ± 10.4, 135 women) and 145 (47.5%) visually interpreted normal scans. In normal scans, the striatum/occiput radioligand uptake ratio was decreased by noradrenergic and specific serotonergic antidepressants (NASSAs) (n = 15, z-score of - 0.93) and opioid medication (tramadol, n = 6, z-score of - 0.85) and was associated with a younger age in the multivariate analysis. In the overall population, the striatum/occiput ratio was influenced by NASSAs and associated with consensual visual analysis, age, sex, and anti-parkinsonian medications related to the status of the disease. Our study confirms the potential impact of antidepressant (NASSA) and opioid (tramadol) medications on the semi-quantitative analysis of[123I]I-FP-CIT SPECT scans. However, when performing a visual analysis, only NASSAs significantly impacted the interpretation of[123I]I-FP-CIT SPECT scans.

Trends, Patterns and Associated User Characteristics of Antidepressant Prescriptions in Older Adults: A Nationwide Descriptive Cohort Study in Denmark.

Antidepressant use in older adults (≥65 years) is understudied in large population-based samples, particularly in recent years and regarding user characteristics. We aimed to describe the trends, patterns, and associated user characteristics of all antidepressant prescriptions redeemed by older adults at community pharmacies in Denmark during 2015-2019. This register-based study used a cross-sectional design to characterize antidepressant prescription trends and patterns, and a cohort design to describe user characteristics associated with antidepressant prescription initiation. We used descriptive statistics to characterize trends and patterns, and Poisson regression for analyzing user characteristics. During the years 2015-2019, 17.9% of 1.2 million older adults redeemed 4.84 million antidepressant prescriptions, where 48.5% were selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (26.2%), serotonin-norepinephrine reuptake inhibitors (12.7%), tricyclic antidepressants (11.2%), and others (1.4%). Amitriptyline and nortriptyline, considered potentially inappropriate medications, were among the 10 most frequently redeemed antidepressants. Only 60.5% of prescriptions had a treatment indication of depression. Prescription-proportion trends by drug classes and individual antidepressants remained consistent. A higher incidence rate ratio (IRR) and 95% confidence interval (CI) of initiating antidepressants was associated with female sex (IRR 1.20, 95% CI 1.07-1.34), older age (e.g., 81-85years vs. 65-70years: IRR 1.74, 95% CI 1.44-2.11), living in rural areas (North Denmark vs. Capital Region: IRR 1.31, 95% CI 1.09-1.58), and having somatic and psychiatric diagnoses (e.g., per one psychiatric diagnosis: IRR 1.10, 95% CI 1.05-1.15), while a lower ratio was associated with being non-Western (vs. Danish: IRR 0.50, 95% CI 0.28-0.89) and having hospital contacts for psychiatric treatment (per each contact: IRR 0.96, 95% CI 0.93-1.00). SSRIs were the most commonly redeemed antidepressants, with consistent trends in Danish older adults. Besides clinical conditions, sociodemographics, e.g., sex, age, ethnicity, and place of residence, may influence antidepressant use.

Antidepressant use and risk of self-harm among people aged 40 years or older: A population-based cohort and self-controlled case series study

SummaryBackgroundStudies on the association between antidepressants and self-harm in adults were mostly conducted over a decade ago and have inconsistent findings. We aimed to compare self-harm risks by antidepressant classes among people aged 40 years or older with depression.MethodsIndividuals aged ≥40 years with depression who initiated antidepressant treatment between 2001 and 2015 were retrieved from the Hong Kong Clinical Data Analysis & Reporting system, and were followed up until December 31, 2016. We conducted self-controlled case series (SCCS) analyses to estimate the incidence rate ratio (IRR) of self-harm comparing the pre-exposure (90 days before the first antidepressant use), index exposure (the first antidepressant use), and subsequent exposure (subsequent antidepressant use) periods to nonexposed periods. We applied Cox proportional hazard regressions to estimate the hazard ratio (HR) of self-harm comparing five antidepressant classes (tricyclic and related antidepressant drugs [TCAs], selective serotonin reuptake inhibitors [SSRIs], noradrenergic and specific serotonergic antidepressants [NaSSAs], serotonin–norepinephrine reuptake inhibitors [SNRIs], and others).FindingsA total of 48,724 individuals were identified. SCCS analyses (N = 3,846) found that the increased self-harm risk occurred during the pre-exposure (IRR: 22.24; 95% CI, 20.25-24.42), index exposure (7.03; 6.34-7.80), and subsequent exposure periods (2.47; 2.18-2.79) compared to the unexposed period. Cohort analyses (N = 48,724) found an association of higher self-harm risks in short-term (one year) for NaSSAs vs. TCAs (HR, 2.13; 95% CI, 1.53-2.96), SNRIs vs. TCAs (1.64; 1.01-2.68), and NaSSAs vs. SSRIs (1.75; 1.29-2.36) in the 40-64 years group. The higher risk remained significant in long-term (> one year) for NaSSAs vs. TCAs (1.55; 1.26-1.91) and NaSSAs vs. SSRIs (1.53; 1.26-1.87). In the 65+ group, only short-term differences were observed (SSRIs vs. TCAs [1.31; 1.03-1.66], SNRIs vs. SSRIs [0.44; 0.22-0.87], and SNRIs vs. NaSSAs [0.43; 0.21-0.87]).InterpretationWithin-person comparisons did not suggest that antidepressant exposure is causally associated with an increased risk of self-harm in people with depression. Between-person comparisons revealed differences in self-harm risks between certain pairs of antidepressant classes. These findings may inform clinicians’ benefit-risk assessments when prescribing antidepressants.FundingNil.

The sociodemographic and clinical phenotype of European patients with major depressive disorder undergoing first-line antidepressant treatment with NaSSAs

Since selective serotonin reuptake inhibitors, that are recommended as first-line antidepressant psychopharmacotherapy for major depressive disorder (MDD), may not be the optimal choice for every patient, antidepressants with different modes of action exerting a distinct set of expectant effects, represent a valuable alternative. Despite the previously observed increased prescription rates of noradrenergic and specific serotonergic antidepressants (NaSSAs) - particularly mirtazapine - in Europe, the individual profiles of patients primarily prescribed NaSSAs in real-world settings have not been systematically investigated yet. In this secondary analysis based on a European, cross-sectional, naturalistic, multicenter study involving 1410 adult males and females with primary MDD, sociodemographic and clinical variables were compared between patients dispensed NaSSAs and those with alternative first-line antidepressants. Hereby, NaSSAs were administered in 8.6 % of the sample (mirtazapine: n = 114, mianserin: n = 7). We detected associations with older mean age, male sex, unemployment, as well as additional melancholic and catatonic features, inpatient treatment, lower mean daily-dosages of the administered antidepressants but higher rates of augmentation with low-potency antipsychotics, and greater mean reductions of depressive symptoms during their current major depressive episodes. Although the study design is unsuitable to draw any causal conclusions, our findings provide a realistic picture of patients eligible for first-line antidepressant treatment with NaSSAs, especially mirtazapine, and underscore the role of this AD substance class in severe MDD. Further, they may represent a promising basis for future systematic research focusing on precision diagnostics and treatment in MDD, that would ideally result in faster responses and better outcomes, especially in the so-called difficult-to-treat conditions including treatment resistant depression.

Antidepressants induce toxicity in human placental BeWo cells

Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs) are broadly used for the treatment of depression. Depression is one of the most common psychiatric disorders in pregnant women and SSRIs are commonly prescribed for depression during pregnancy. The placenta regulates the transport of nutrients and oxygen between the maternal and fetal circulation, and is essential for the survival and growth of the fetus. The present study investigated the effects of antidepressants on human placental BeWo cells.BeWo cell viability was significantly decreased following exposure to sertraline (SSRI), paroxetine (SSRI), fluvoxamine (SSRI), and duloxetine (SNRI), whereas escitalopram (SSRI), venlafaxine (SNRI), and mirtazapine (NaSSA) showed little or no effects. Extracellular lactate dehydrogenase activity was increased by sertraline, paroxetine, fluvoxamine, and duloxetine, indicating toxicity to the cells. Sertraline increased the production of cellular reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Sertraline decreased the cellular ATP content in a time and concentration-dependent manner. Caspase-3/7 activity and apoptotic cells, detected using the phosphatidylserine-specific fluorescent probe Apotracker Green, were increased by sertraline.Our findings suggest that antidepressants, such as sertraline, paroxetine, fluvoxamine, and duloxetine, induce toxicity in human placental BeWo cells. Sertraline may induce ROS-dependent apoptosis in human placental cells. These results are useful for further studies to determine the optimal dosage of antidepressants for pregnant women.

Management of psychiatric disorders in patients with cancer.

Management of psychiatric disorders in patients with cancer.

Management of Psychiatric Disorders in Patients with Respiratory Diseases.

Management of Psychiatric Disorders in Patients with Respiratory Diseases.

Antidepressant Use and Risk of Suicidal Behavior in Older Persons With Depression: A Cohort Study in Hong Kong

Background: Depression is highly prevalent in older adults and requires treatment. However, debate persists on whether antidepressant use is associated with an elevated risk of suicidal behavior. This study aims to examine the short- and long-term risk of suicidal behavior by various classes of antidepressants in older persons with depression. Methods: Persons aged 40 years and above and received a clinical diagnosis of depression between January 1, 2001, and December 31, 2016 were identified from the Clinical Data Analysis and Reporting System in Hong Kong. The risk of suicidal behavior in persons who were prescribed antidepressants was compared with persons who were not prescribed any antidepressant drugs. Antidepressants were classified as tricyclic and related antidepressant drugs (TCAs), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSAs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and others. Incidence and adjusted hazard ratio (aHR) of subsequent self-harm and suicide within one-year and the whole study period were estimated by age groups. Results: A total of 34,927 persons aged 40-64 years, and 19,300 persons aged 65+ years were included. In the younger age group, the highest short-term and long-term risks were found in others (aHR, 2.33; 1.02-5.34) and NaSSAs (2.88; 2.15-3.86), respectively. In the older age group, no significant association was observed between antidepressant use and suicidal behavior across all antidepressant classes. Conclusion: The self-harm and suicide associated risks vary across antidepressant classes and age groups. Cautions are always needed for antidepressant prescriptions.

Current Clinical Psychopharmacology in Borderline Personality Disorder.

Background Patients with Borderline Personality Disorder (BPD) manifest affective and behavioral symptoms causing personal distress, relationship difficulties, and reduced quality of life with global functioning impairment, mainly when the disease takes an unfavorable course. A substantial amount of healthcare costs is dedicated to addressing these issues. Many BPD patients receive medications, mostly those who do not respond to psychological interventions.Objective Our aim was to assess the efficacy of the most used strategies of pharmacological interventions in BPD with a comprehensive overview of the field.Methods We searched the PubMed database for papers focused on the most used psychotropic drugs for BPD. We included randomized controlled trials and open studies in adult patients with BPD, focusing on the efficacy and tolerability of single classes of drugs with respect to specific clinical presentations that may occur during the course of BPD.Results Specific second-generation antipsychotics (SGAs) or serotonergic antidepressants can be effective for different core symptoms of BPD, mainly including mood symptoms, anxiety, and impulse dyscontrol. Some atypical antipsychotics can also be effective for psychotic and dissociative symptoms. Specific antiepileptics can be useful in some cases in treating different BPD symptoms, mainly including mood instability, impulsiveness, and anger.Conclusion No medication is currently approved for BPD, and clinicians should carefully assess the benefits and risks of drug treatment. Further studies are needed to identify specific personalized treatment strategies, also considering the clinical heterogeneity and possible comorbidities of BPD.

Sex-related effects in major depressive disorder: Results of the European Group for the Study of Resistant Depression.

BackgroundSex‐related effects on the evolution and phenotype of major depressive disorder (MDD) were reported previously.MethodsThis European multicenter cross‐sectional study compared sociodemographic, clinical, and treatment patterns between males and females in a real‐world sample of 1410 in‐ and outpatients with current MDD.ResultsMale MDD patients (33.1%) were rather inpatients, suffered from moderate to high suicidality levels, received noradrenergic and specific serotonergic antidepressants (ADs) as first‐line AD treatment, generally higher mean AD daily doses, and showed a trend towards a more frequent administration of add‐on treatments. Female MDD patients (66.9%) were rather outpatients, experienced lower suicidality levels, comorbid thyroid dysfunction, migraine, asthma, and a trend towards earlier disease onset.ConclusionsThe identified divergencies may contribute to the concept of male and female depressive syndromes and serve as predictors of disease severity and course, as they reflect phenomena that were repeatedly related to treatment‐resistant depression (TRD). Especially the greater necessity of inpatient treatment and more complex psychopharmacotherapy in men may reflect increased therapeutic efforts undertaken to treat suicidality and to avoid TRD. Hence, considering sex may guide the diagnostic and treatment processes towards targeting challenging clinical manifestations including comorbidities and suicidality, and prevention of TRD and chronicity.

Sex differences in pharmacological treatment of major depressive disorder: results from the AMSP pharmacovigilance program from 2001 to 2017

Data on drug prescription for outpatients with major depressive disorder (MDD) suggest women are more likely to be treated with psychotropic drugs, while data on sex differences regarding pharmacological treatment of psychiatric inpatients are currently not available. Drug utilization data from the program “Drug Safety in Psychiatry” (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) of 44,418 psychiatric inpatients with MDD were analyzed for sex differences between 2001 and 2017. Sex differences were analyzed using relative risks (RR) and 95% confidence intervals (95% CI). Time trends were analyzed by comparing the first (2001–2003) with the last time period (2015–2017). In general, men and women were equally likely to use psychotropic drugs. Monotherapy was more common in men. Women were more likely to utilize ≥ 4 psychotropic drugs. Antidepressant drugs (ADDs) were the most prescribed drug class. Men had a higher utilization of noradrenergic and specific serotonergic antidepressants (RR 1.15; 95% CI 1.12–1.19), especially mirtazapine (RR 1.16; 95% CI 1.12–1.19), but also of other ADDs such as bupropion (RR 1.50; 95% CI 1.35–1.68). Males had a slightly higher utilization of second-generation antipsychotic drugs (RR 1.06; 95% CI 1.03–1.09) and were less often treated with low-potency first-generation antipsychotic drugs (RR 0.86; 95% CI 0.83–0.90). Tranquilizing (e.g., benzodiazepines; RR 0.89; 95% CI 0.86–0.92) and hypnotic drugs (e.g., Z-drugs; RR 0.85; 95% CI 0.81–0.89) were less utilized in the treatment of male patients. Not all sex differences were stable over time. More sex differences were detectable in 2015–2017 than in 2001–2003. Findings suggest that certain psychotropic drugs are preferred in the treatment of men vs. women, however, sex differences found in this study are not as large as in ambulatory settings. To make evidence-based sex-specific recommendations in the treatment of MDD, differences in drug response and tolerability need to be further researched.

The impact of β-cyclodextrin on biological and chemical properties of mianserin hydrochloride in aqueous solution

Mianserin hydrochloride (MIA), a drug, which belongs to a group of tetracyclic, noradrenergic and specific serotonergic antidepressants, is one of the commonly used psychotropic drugs. Despite its important uses and having a number of other potential utilizations, MIA has quite significant side effects on a patient health, including some cytotoxicity. The MIA toxicity could be reduced by drug encapsulation inside a non-toxic carrier, like β-cyclodextrin molecules (β-CD). Cyclodextrins are cone shaped supramolecules with hydrophobic interior, where hydrophobic parts of molecule can be included, and with hydrophilic rims consisting of primary and secondary hydroxyl groups, which can interact with water molecules. This study investigated the characteristic and mechanism for interaction of MIA with β-CD, and evaluated the effects of complexation on MIA cytotoxicity. Chemical shift differences for protons in mianserin hydrochloride and β-cyclodextrin molecules, induced by the formation of the inclusion complexes, have been determined by proton nuclear magnetic resonance spectroscopy. The other chemical properties of mianserin hydrochloride in aqueous solution in the presence of β-cyclodextrin has been examined at 298.15 K with the use of mass spectrometry and circular dichroism. The results showed that interaction of MIA with β-CD occurred through incorporation of MIA aromatic rings inside probably more than one β-CD molecules. The effects of β-cyclodextrin, mianserin hydrochloride and complexes thereof on the viability of Chinese hamster cells were investigated in order to estimate the cytotoxicity of the drug. The viability of B14 cells treated with MIA + β-CD is higher than with MIA and the protective effect is the highest for complexes of MIA:β-CD in a 1:4 ratio.

Selective serotonin reuptake inhibitors and Alzheimer's disease.

Given the failure to develop disease-modifying therapies for Alzheimer’s disease (AD), strategies aiming at preventing or delaying the onset of the disease are being prioritized. While the debate regarding whether depression is an etiological risk factor or a prodrome of AD rages on, a key determining factor may be the timing of depression onset in older adults. There is increasing evidence that untreated early-onset depression is a risk factor and that late-onset depression may be a catalyst of cognitive decline. Data from animal studies have shown a beneficial impact of selective serotonin reuptake inhibitors on pathophysiological biomarkers of AD including amyloid burden, tau deposits and neurogenesis. In humans, studies focusing on subjects with a prior history of depression also showed a delay in the onset of AD in those treated with most selective serotonin reuptake inhibitors. Paroxetine, which has strong anticholinergic properties, was associated with increased mortality and mixed effects on amyloid and tau deposits in mice, as well as increased odds of developing AD in humans. Although most of the data regarding selective serotonin reuptake inhibitors is promising, findings should be interpreted cautiously because of notable methodological heterogeneity between studies. There is thus a need to conduct large scale randomized controlled trials with long follow up periods to clarify the dose-effect relationship of specific serotonergic antidepressants on AD prevention.

Relationship between Recurrent Falls and Medication Use during Acute-Care Hospitalization: A Retrospective Descriptive Study.

Although recurrent falls during hospitalization lead to discharge to nursing homes, their association with medications has not been comprehensively assessed. We aimed to assess risk factors for recurrent falls focusing on medications during hospitalization in an acute-care setting. This retrospective descriptive study was conducted in Tokyo Women's Medical University, Medical Center East. Patients who experienced a fall during hospitalization were included and the incidence of recurrent falls was assessed during hospitalization. Multivariate logistic regression analysis was performed to assess the relationship between recurrent falls and medications and to calculate odds ratio and 95% confidence interval. Sensitivity analysis was performed on data stratified by sex or age. This study included 124 patients with an incidence of 20 (16%) recurrent falls. Multivariate logistic regression analysis revealed that selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were associated with recurrent falls (odds ratio = 5.98, 95% confidence interval: 1.38-25.9, p = 0.02). Additionally, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were significant risk factors for recurrent falls in women and those aged > 80 years. Selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were associated with an increased risk of recurrent falls during hospitalization in an acute-care setting. Clinicians should pay attention to patients receiving selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants, especially women and aged > 80 years old.

Antidepressants and the Risk of Hemorrhagic Stroke in the Elderly: a Nested Case–Control Study

Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed in the elderly due to a more favorable risk profile than other antidepressants (ADs). However, SSRIs are associated with an increased risk of gastrointestinal bleeding, while evidence on the risk of hemorrhagic stroke (HS) is limited. Therefore, we compared the risk of HS associated with the use of ADs in the elderly. Based on data from the German Pharmacoepidemiological Research Database (GePaRD), a case-control study matched on age, sex, and health insurance provider, nested in a cohort of incident users of ADs ≥ 65years of age was performed. Cases were identified from hospital discharge diagnoses, and exposure was identified from outpatient prescriptions. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Based on 4059 cases and 40,590 controls, an increased risk of HS was found in current use of SSRIs (OR 1.39, 95% CI 1.22-1.58), selective serotonin and noradrenaline reuptake inhibitors (1.69, 1.35-2.11), noradrenergic and specific serotonergic ADs (1.44, 1.22-1.69), and noradrenaline reuptake inhibitors (3.81, 1.54-9.43) compared with tri- and tetracyclic antidepressants. An increased risk of HS was seen in patients with a high baseline risk of bleeding and in patients with depression. The risk of HS varied between individual ADs. Our study shows that the use of medications inhibiting serotonin and/or noradrenaline reuptake increases the risk of HS in patients aged 65years and older and that the risk varies across individual ADs.

Suicidal Ideation and Suicidal Behavior as Rare Adverse Events of Antidepressant Medication: Current Report from the AMSP Multicenter Drug Safety Surveillance Project.

BackgroundSuicidal ideations, suicide attempts, and fatal suicides are rare adverse drug reactions to antidepressant drugs, but they essentially are clinically relevant. Drawing on a larger dataset of the European drug surveillance program, the present naturalistic study updates a previous contribution (Stübner et al., 2010).MethodsFirst an analysis of the comprehensive data collected in 81 psychiatric hospitals from 1993 to 2014 by the European drug surveillance program Arzneimittelsicherheit in der Psychiatrie was made. All documented single cases of suicidal ideations or behavior judged as adverse drug reactions to antidepressant drugs were carefully assessed as to their clinical features and drug prescriptions.ResultsAmong 219,635 adult hospitalized patients taking antidepressant drugs under surveillance, 83 cases of suicidal adverse drug reactions occurred (0.04%): 44 cases of suicidal ideation, 34 attempted suicides, and 5 committed suicides were documented. Restlessness was present in 42 patients, ego-dystonic intrusive suicidal thoughts or urges in 39 patients, impulsiveness in 22 patients, and psychosis in 7 patients. Almost all adverse drug reactions occurred shortly after beginning antidepressant drug medication or increasing the dosage. Selective serotonin reuptake inhibitors caused a higher incidence of suicidal ideation and suicidal behavior as adverse drug reactions than noradrenergic and specific serotonergic antidepressants or tricyclic antidepressants, as did monotherapy consisting of one antidepressant drug, compared to combination treatments.ConclusionsThe study supports the view that antidepressant drug-triggered suicidal ideation and suicidal behavior (primarily with selective serotonin reuptake inhibitors) are rare. Special clinical features (restlessness, ego-dystonic thoughts or urges, impulsiveness) may be considered as possible warning signs. A combination therapy might be preferable to antidepressant drug monotherapy when beginning treatment.

A comparison of clinical characteristics of older adults treated with antidepressants in general and psychiatric hospitals in Asia.

This study compared the demographics, clinical characteristics, and antidepressant prescription patterns between Asian patients aged 50 years and older attending psychiatric hospitals and those attending general hospitals. In total, 955 patients (604 in general hospitals, 351 in psychiatric hospitals) aged 50 years or older treated with antidepressants in 10 Asian countries and territories were examined. Patients' demographics, clinical features, and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. Binary logistic regression revealed that high income and diagnosis of schizophrenia were independently associated with psychiatric hospital treatment, whereas outpatient care, diagnosis of anxiety disorders, and multiple major medical conditions were independently associated with general hospital treatment. In addition, tetracyclic and noradrenergic and specific serotonergic antidepressants were more likely to be prescribed in general hospitals. Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia.

Prescribing patterns of psychiatric drugs in major depressive disorder – Findings from a large European multicenter, cross-sectional study

IntroductionThe multicenter, cross-sectional survey summarizes the current prescription patterns of psychopharmacological medications in patients with major depressive disorder (MDD) treated in European university psychiatric centers.MethodsThe study included a total of 1181 MDD patients who were recruited in 9 academic sites across 8 European countries. Socio-demographic, clinical, and psychopharmacological characteristics were collected within a detailed clinical interview and the current depressive symptom severity was measured by the Montgomery and Åsberg Depression Rating Scale (MADRS). Symptom reduction during the present MDD episode was analyzed by calculating retrospective MADRS scores. Descriptive statistics, analyses of variance (ANOVAs), and Spearman correlation analyses were performed to examine the impact of various features on the applied pharmacological strategies.ResultsRegarding first-line antidepressant medication, the most frequently prescribed drug classes were selective serotonin reuptake inhibitors (SSRIs) (53.4%), serotonin-norepinephrine reuptake inhibitors (SNRIs) (23.6%), noradrenergic and specific serotonergic antidepressants (NaSSAs) (8.2%), tricyclic antidepressants (TCA) (5.1%), and the melatonergic antidepressant agomelatine (5.0%). The most commonly used individual antidepressants were escitalopram (18.4%), venlafaxine (15.2%), sertraline (12.9%), paroxetine (9.1%), mirtazapine (8.2%), duloxetine (7.0%), and fluoxetine (6.5%). Among the patients, 59.4% were treated with polypsychopharmaceutical medications (mean: 2 drugs) and for the number of individual drugs, we found a significant correlation with the present MADRS total score and the MADRS total score change during the current depressive episode.ConclusionConsistent with surveys investigating primarily municipal psychiatric treatment centers, we could replicate the observation that SSRIs are the most commonly used antidepressants in MDD for the first time for European university centers.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The Relationship between Psychotropic Drug Use and Suicidal Behavior in Japan: Japanese Adverse Drug Event Report.

Introduction: Very few studies have explored the adverse effect of psychotropic drugs worldwide. Methods: This study analyzed 1 813 suicide-related drug reports involving 553 patients collected from the Japanese National Adverse Drug Report Database between October 2001 and January 2012 to investigate psychotropic drugs associated with completed suicide vs. other suicide-related behaviors, including ideation and self-injury. The drugs investigated included antidepressants, antipsychotics, benzodiazepines, non-benzodiazepine hypnotic agents, noradrenergic and specific serotonergic antidepressants, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and other drugs. Results: These reports referenced 300 (54.2%) individuals who completed suicide. Adjusting for age, sex, and drugs used, the multivariate model revealed that participants who took antipsychotics were 1.70 times (95% CI, 1.11-2.61) more likely to complete suicide compared with those who did not. All other drugs became non-significant. Compared with those who took only one medication, those prescribed more than 4 drugs were more likely to complete suicide (OR 4.44, 95% CI, 2.40-8.20). Discussion: Antipsychotic drugs and polypharmacy may be regarded as predictors of completed suicide.