Selective Serotonin-norepinephrine Reuptake Inhibitors Research Articles

Posttraumatic Stress Disorder and Anxiety-Related Conditions.

This article provides a synopsis of current assessment and treatment considerations for posttraumatic stress disorder (PTSD) and related anxiety disorder characteristics. Epidemiologic and neurobiological data are reviewed as well as common associated symptoms, including sleep disruption, and treatment approaches to these conditions. PTSD is no longer considered an anxiety-related disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition classification and instead is associated with trauma/stressor-related disorders. PTSD symptoms are clustered into four domains including intrusive experiences, avoidance, mood, and arousal symptoms. Despite this reclassification, similarities exist in consideration of diagnosis, treatment, and comorbidities with anxiety disorders. PTSD and anxiety-related disorders are heterogeneous, which is reflected by the neural circuits involved in the genesis of symptoms that may vary across symptom domains. Treatment is likely to benefit from consideration of this heterogeneity.Research in animal models of fear and anxiety, as well as in humans, suggests that patients with PTSD and generalized anxiety disorder have difficulty accurately determining safety from danger and struggle to suppress fear in the presence of safety cues.Empirically supported psychotherapies commonly involved exposure (fear extinction learning) and are recommended for PTSD. Cognitive-behavioral therapy has been shown to be effective in other anxiety-related disorders. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used in the treatment of PTSD and anxiety disorders in which pharmacologic intervention is supported. Treating sleep disruption including sleep apnea (continuous positive airway pressure [CPAP]), nightmares, and insomnia (preferably via psychotherapy) may improve symptoms of PTSD, as well as improve mood in anxiety disorders. PTSD has a lifetime prevalence that is close to 10% and shares neurobiological features with anxiety disorders. Anxiety disorders are the most common class of mental conditions and are highly comorbid with other disorders; treatment considerations typically include cognitive-behavioral therapy and pharmacologic intervention. Developing technologies show some promise as treatment alternatives in the future.

Exposure to duloxetine during pregnancy and risk of congenital malformations and stillbirth: A nationwide cohort study in Denmark and Sweden

The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths. A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates. Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.

Clinical effects of two different doses of duloxetine compared to conventional analgesic therapy in patients with osteoarthritis knee

Background: Pain is the leading symptom of knee osteoarthritis (OA) leading to significant morbidity and decreased quality of life. Duloxetine, a selective serotonin norepinephrine reuptake inhibitor, has been demonstrated to have a centrally acting analgesic effect. Aims and Objectives: To evaluate the efficacy and safety of two different doses of duloxetine and compare with conventional pharmacotherapy in treatment of chronic pain due to osteoarthritis of knee. Materials and Methods: 90 patients with symptomatic knee OA were randomly divided into 3 groups to receive duloxetine 40 mg & 3g paracetamol/day (Group A), duloxetine 20 mg & 3g paracetamol/day (Group B) and paracetamol 3gm/day (Group C). Patients were followed up for 6 months to assess pain relief and functional improvement. Visual Analogue Scale (VAS) for assessing pain intensity and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire physical function subscale for assessing physical function were used. Results: Reduction in VAS score from baseline was significantly high in groups A and B as compared to C at 1 month, 3 months and 6 months. Reduction in WOMAC score from baseline were also significantly high in groups A and B as compared to C at 1 month, 3 month and 6 months. Adverse effects in Group A were significantly high as compared to group B and C. Patients discontinuing due to adverse effects were significantly high in group A. Conclusion: Lower dose of duloxetine is associated with significant pain reduction and improved function with lesser adverse effects in patients with pain due to knee OA.

Bipolar women's antepartum psychotropic exposure and offspring risk of attention-deficit/hyperactivity disorder and autism spectrum disorder

BackgroundWomen with bipolar disorder (BD) may continue psychotropics during pregnancy. The association of exposure to antidepressant, antipsychotics, and mood stabilizers with offspring risks of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) remains unexplored in mothers with BD. MethodsA total of 5669 pregnant women with BD and 5669 psychiatrically healthy controls were identified between 2002 and 2011 from the Taiwan Longitudinal Health Insurance Database. We analyzed the odds ratios (ORs) of psychotropic types and exposure periods (3 months before pregnancy [3MbPreg] and first, second, and third trimesters [T1, T2, T3, respectively]) on the risk of ADHD and ASD by using adjusted logistic regression analyses. ResultsAntidepressant exposure during 3MbPreg (OR=2.15, 95% CI=1.45–3.20), T1 (OR=2.62, 95% CI=1.68–4.09), T2 (OR=2.33, 95% CI=1.18–4.63), and T3 (OR=2.33, 95% CI=1.67–6.61) was associated with increased offspring risk of ADHD, particularly for selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor. Mood stabilizer exposure during 3MbPreg increased the risks of ADHD (OR=2.39, 95% CI=1.45–3.95) and ASD (OR=3.89, 95% CI=1.30–11.65); a higher ADHD risk was associated with valproic acid (OR=2.43, 95% CI=1.32–4.47) and lamotrigine exposure (OR=8.24, 95% CI = 1.49–45.67); ASD risk was higher for lithium exposure (OR=6.75, 95% CI=1.41–32.28). LimitationIn claims-data analyses, several clinical parameters or potential confounders may be incompletely captured. ConclusionsAntidepressants were associated with higher offspring risk of ADHD over all gestation periods among mothers with BD than psychiatrically healthy controls, while mood stabilizers were associated with higher risk of ADHD and ASD during 3MbPreg.

Failure of Losartan in a Clinical Trial for Posttraumatic Stress Disorder: Lack of Efficacy or Spotlight on the Power of Placebo?

Posttraumatic stress disorder (PTSD) is a debilitating disorder that affects around 8% of the U.S. population (1). PTSD is characterized by a variety of symptoms, including hyperarousal/vigilance, difficulty sleeping, and intrusive thoughts related to the traumatic event that can be extremely debilitating to the individual. The current medications for PTSD that are approved by the U.S. Food and Drug Administration are limited to selective serotonin reuptake inhibitors or norepinephrine reuptake inhibitors, which are only moderately effective and do not help the majority of patients.

The Relationship Between Maternal Antidepressants and Neonatal Hypoglycemia: A Systematic Review.

The aim of the article is to review systematically current researches investigating the relationship between intrauterine exposure to antidepressants and neonatal hypoglycemia. This paper included studies published in electronic databases from January 2005 to July 2020. The searched keywords were as follows: antidepressants, pregnancy, selective serotonin reuptake inhibitors (SSRIs), citalopram, fluoxetine, paroxetine, escitalopram, sertraline, fluvoxamine, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), venlafaxine, tricyclic antidepressants (TCAs), neonatal outcomes, neonatal hypoglycemia, imipramine, clomipramine, amitriptyline, bupropion, trazodone, and mirtazapine. This review examined 10 relevant studies. The odds ratio/risk ratio reported in the studies were 1.33-1.73 for any antidepressant, 1.30-1.35 for SSRI, 1.42-2.11 for SNRI, and 2.07 for TCAs. The risk of neonatal hypoglycemia in infants exposed to maternal TCAs appears to be slightly higher compared to infants exposed to maternal SSRIs. Data from current studies consistently show that exposure to maternal antidepressants during pregnancy may be related to increased risk of neonatal hypoglycemia in infants.

Review Highlights Gaps in Knowledge of Perinatal Mental Health

Review Highlights Gaps in Knowledge of Perinatal Mental Health

Transcriptional analyses reveal different mechanism of toxicity for a chronic exposure to fluoxetine and venlafaxine on the brain of the marine fish Dicentrarchrus labrax

Selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitor (SNRI) are prescribed for clinical depression and detected in aquatic ecosystems. The main aim of this study was to explore and evaluate transcriptional responses of neurotransmitter genes in the brain of a marine fish species, European seabass, and to analyze global brain transcriptomic changes by a RNA-seq technology (MACE, massive analysis of cDNA ends). The juveniles were exposed to two psychopharmaceuticals: (i) fluoxetine (FLX) at the concentration of 0.5 μg/L and 50 μg/L; (ii) venlafaxine (VENX) at the concentration of 0.01 μg/L and 1 μg/L. The exposures were performed for 21 days, followed by a 7-day recovery period to assess the reversibility of effects. Both psychopharmaceuticals affected differentially the neurotransmitter mRNA expression analyzed by RT-qPCR (serotonin receptors: 5-ht3a, 5-ht3b; dopamine receptors: d2, d3; neurotransmitter transporter: sert, vmat; degrading enzyme: mao). Transcriptomic analyses after 21 days of exposure revealed 689 and 632 significant different transcripts by FLX at 0.5 and 50 μg/L, respectively, and 432 and 1250 by VENX at 0.01 and 1 μg/L, respectively, and confirmed different mechanism of toxicity between both compounds. At environmental concentrations, more general pathways including energy metabolism were affected, while at the higher concentration effects on neurotransmitter pathways were observed (FLX: exocytosis and vesicle formation; VENX: small molecule catabolism regulating dopamine and tyrosine level). These results provided new insights into the chronic effects of psychopharmaceutical compounds on marine fish and suggest the need of a separate ecotoxicological risk analysis.

Efficacy and adverse events of selective serotonin noradrenaline reuptake inhibitors in the management of postoperative pain: A systematic review and meta-analysis

Study objectiveSelective-serotonin-noradrenaline-reuptake inhibitors (SSNRI) might be an interesting option for postoperative pain treatment. Objective was to investigate postoperative pain outcomes of perioperative SSNRI compared to placebo or other additives in adults undergoing surgery. DesignSystematic review of randomised controlled trials (RCT) with meta-analysis and GRADE assessment. SettingAcute and chronic postoperative pain treatment. PatientsAdult patients undergoing surgery. InterventionsPerioperative administration of SSNRI. MeasurementsPrimary outcomes were postoperative acute pain at rest/during movement (measured on a scale from 0 to 10), number of patients with chronic postsurgical pain (CPSP) and with SSNRI-related adverse events. Main resultsFourteen RCTs (908 patients) were included. We have high-quality evidence that duloxetine has no effect on pain at rest at 2 h (MD: −0.02; 95% confidence interval (CI) −0.51 to 0.47), but probably reduces it at 48 h (MD: −1.16; 95%CI −1.78 to −0.54). There is low- and moderate-quality evidence that duloxetine has no effects on pain during movement at 2 h (MD: −0.42; 95%CI −1.53 to 0.69) and 48 h (MD: −0.91; 95% CI −2.08 to 0.26), respectively. We have very low-quality evidence that duloxetine might reduce pain at rest (MD: −0.45; 95%CI −0.74 to −0.15) and movement (MD: −1.19; 95%CI −2.32 to −0.06) after 24 h. We have low-quality evidence that duloxetine may reduce the risk of CPSP at 6 months (RR:0.35; 95%CI 0.14 to 0.90). There is moderate-quality evidence that duloxetine increases the risk of dizziness (RR:1.72; 95%CI 1.26 to 2.34). ConclusionAt the expense of a higher risk for dizziness, SSNRI may be effective in reducing postoperative pain between 24 and 48 h after surgery. However, the results of the meta-analyses are mostly imprecise and duloxetine might only be used in individual cases.Protocol registration: CRD42018094699

Psychotropic drug-induced hyponatremia: results from a drug surveillance program\u2013an update

Hyponatremia (HN) is the most common electrolyte imbalance (defined as a serum sodium concentration Na(S) of < 130 mmol/l) and often induced by drugs including psychotropic drugs. AMSP (Arzneimittelsicherheit in der Psychiatrie) is a multicenter drug surveillance program that assesses severe or unusual adverse drug reactions (ADRs) occurring during treatment with psychotropic drugs. This study presents data from 462,661 psychiatric inpatients treated in participating hospitals between 1993 and 2016 and serves as an update of a previous contribution by Letmaier et al. (JAMA 15(6):739–748, 2012). A total of 210 cases of HN were observed affecting 0.05% of patients. 57.1% of cases presented symptomatically; 19.0% presented with severe symptoms (e.g., seizures, vomiting). HN occurred after a median of 7 days following the first dose or dose increase. Incidence of HN was highest among the two antiepileptic drugs oxcarbazepine (1.661% of patients treated) and carbamazepine (0.169%), followed by selective serotonin-norepinephrine reuptake inhibitors (SSNRIs, 0.088%) and selective serotonin reuptake inhibitors (0.071%). Antipsychotic drugs, tricyclic antidepressants, and mirtazapine exhibited a significantly lower incidence of HN. The risk of HN was 16–42 times higher among patients concomitantly treated with other potentially HN-inducing drugs such as diuretic drugs, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and proton pump inhibitors. Female SSNRI-users aged ≥ 65 years concomitantly using other HN-inducing drugs were the population subgroup with the highest risk of developing HN. The identification of high-risk drug combinations and vulnerable patient subgroups represents a significant step in the improvement of drug safety and facilitates the implementation of precautionary measures.

Selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for anxiety, obsessive-compulsive, and stress disorders: A 3-level network meta-analysis.

BackgroundAnxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis.Methods and findingsWe searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies’ databases. No restriction was made regarding comorbidities with any other mental disorder, participants’ age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration’s risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD −0.56, 95% CI −0.62 to −0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials.ConclusionsIn this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy.

Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery.

Background and AimsPlatelet‐stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin’s impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection.Approach and ResultsConsecutive patients undergoing hepatic resection (n = 754) were retrospectively included from prospectively maintained databases from two European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRIs/SNRIs was recorded, and patients were followed up for postoperative liver dysfunction (LD), morbidity, and mortality. Perioperative intraplatelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRIs/SNRIs showed a higher incidence of morbidity, severe morbidity, LD, and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio [OR], 1.56; 95% confidence interval [CI], 1.07‐2.31; severe morbidity OR, 1.86; 95% CI, 1.22‐2.79; LD OR, 1.96; 95% CI, 1.23‐3.06; LD requiring intervention OR, 2.22; 95% CI, 1.03‐4.36). Further, multivariable analysis confirmed the independent association of SSRIs/SNRIs with postoperative LD, which was closely associated with postoperative 90‐day mortality and 1‐year overall survival.ConclusionsWe observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRIs/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) During Pregnancy and the Risk for Autism spectrum disorder (ASD) and Attention deficit hyperactivity disorder (ADHD) in the Offspring: A True Effect or a Bias? A Systematic Review & Meta-Analysis.

An inconsistent association between exposure to SSRIs and SNRIs and the risk for ASD and ADHD in the Offspring was observed in observational studies. Some suggest that the reported association might be due to unmeasured confounding. We aimed to study this association and to look for sources of bias by performing a systematic review and meta-analysis. Medline, Embase, and the Cochrane Library were searched up to June 2019 for studies reporting on ASD and ADHD in the Offspring following exposure during pregnancy. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random- effects models and odds ratios (OR), and 95% confidence intervals (CI) were calculated for each outcome using the adjusted point estimate of each study. Eighteen studies were included in the meta-analysis. We found an association between SSRIs/ SNRIs prenatal use and the risk for ASD and ADHD (OR=1.42, 95% CI: 1.23-1.65, I2=58%; OR=1.26, 95% CI: 1.07-1.49, I2=48%, respectively). Similar findings were obtained in women who were exposed to SSRIs/SNRIs before pregnancy, representing statistically significant association with ASD (OR=1.39, 95% CI: 1.24-1.56, I2=33%) and ADHD (OR=1.63, 95% CI: 1.50-1.78, I2=0%) in the Offspring, although they were not exposed to those medications in utero. Although we found an association between exposure to SSRIs/SNRIs during pregnancy and the risk for ASD and ADHD, an association with those disorders was also present for exposure pre-pregnancy, suggesting that the association might be due to unmeasured confounding. We are aiming to further assess the role of potential unmeasured confounding in the estimation of the association and perform a network meta-analysis.

Duloxetine suppresses BMP-4-induced release of osteoprotegerin via inhibition of the SMAD signaling pathway in osteoblasts.

Duloxetine, a selective serotonin-norepinephrine reuptake inhibitor, is currently recommended for the treatment of chronic painful disorders such as fibromyalgia, chronic musculoskeletal pain, and diabetic peripheral neuropathy. We previously demonstrated that bone morphogenetic protein-4 (BMP-4) stimulates osteoprotegerin (OPG) production in osteoblast-like MC3T3-E1 cells, and that p70 S6 kinase positively regulates OPG synthesis. The present study aimed to investigate the effect of duloxetine on BMP-4-stimulated OPG synthesis in these cells. Duloxetine dose-dependently suppressed OPG release stimulated by BMP-4. Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), reduced BMP-4-stimulated OPG release, whereas a selective and specific norepinephrine reuptake inhibitor, reboxetine, failed to affect OPG release. In addition, another SSRI sertraline also inhibited BMP-4-stimulated OPG release. On the other hand, siRNA of SMAD1 reduced the OPG release stimulated by BMP-4, indicating the involvement of the SMAD1/5/8 pathway in OPG release. Rapamycin inhibited BMP-4-stimulated p70 S6 kinase phosphorylation, and compound C suppressed the SMAD1/5/8 phosphorylation stimulated by BMP-4. Duloxetine did not affect BMP-4-induced phosphorylation of p70 S6 kinase but suppressed SMAD1/5/8 phosphorylation. Both fluvoxamine and sertraline also inhibited BMP-4-elicited phosphorylation of SMAD1/5/8. These results strongly suggest that duloxetine suppresses BMP-4-stimulated OPG release via inhibition of the Smad1/5/8 signaling pathway in osteoblasts.

Anxiety Disorders - Assessment and Management in General Practice

Anxiety is a normal physiological response to a threat. Anxiety disorders occur when this normal physiological response is associated with high levels of autonomic arousal, erroneous cognitions and dysfunctional coping strategies. Anxiety disorders are highly prevalent and present commonly to general practice. Anxiety disorders are often comorbid with other psychiatric and medical disorders and may be associated with significant morbidity.This article describes the diagnosis, assessment and management of anxiety disorders in the general practice setting.Assessment in patients presenting with anxiety symptoms involves excluding a medical cause, identifying features of specific anxiety disorders as well as other coexisting psychiatric disorders, and assessing the degree of distress. Management options include psychoeducation, psychological treatments (particularly cognitive behaviour therapy) and pharmacological treatments. Patients with a diagnosis of an anxiety disorder can access Medicare funded psychological care under a number of Australian government initiatives. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors are the first line pharmacological agents used to treat anxiety disorders. Regular review is vital to monitor for clinical improvement and more complex presentations may require specialist psychological or psychiatric referral.

Focus on Depression in Parkinson's Disease: A Delphi Consensus of Experts in Psychiatry, Neurology, and Geriatrics.

Major and minor forms of depression are significant contributors to Parkinson's disease morbidity and caregiver burden, affecting up to 50% of these patients. Nonetheless, symptoms of depression are still underrecognized and undertreated in this context due to scarcity of evidence and, consequently, consistent clinical guideline recommendations. Here, we carried out a prospective, multicentre, 2-round modified Delphi survey with 49 questions about the aetiopathological mechanisms of depression in Parkinson's disease (10), clinical features and connections with motor and nonmotor symptoms (10), diagnostic criteria (5), and therapeutic options (24). Items were assessed by a panel of 37 experts (neurologists, psychiatrists, and a geriatrist), and consensus was achieved in 81.6% of them. Depressive symptoms, enhanced by multiple patient circumstances, were considered Parkinson's disease risk factors but not clinical indicators of motor symptom and disease progression. These patients should be systematically screened for depression while ruling out both anhedonia and apathy symptoms as they are not necessarily linked to it. Clinical scales (mainly the Geriatric Depression Scale GDS-15) can help establishing the diagnosis of depression, the symptoms of which will require treatment regardless of severity. Efficacious and well-tolerated pharmacological options for Parkinson's comorbid depression were selective serotonin reuptake inhibitors (especially sertraline), dual-action serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine, and duloxetine), multimodal (vortioxetine, bupropion, mirtazapine, and tianeptine), and anti-Parkinsonian dopamine agonists (pramipexole, ropinirole, and rotigotine). Tricyclic antidepressants and combining type B monoamine oxidase inhibitors with serotonergic drugs have serious side effects in these patients and therefore should not be prescribed. Electroconvulsive therapy was indicated for severe and drug-refractory cases. Cognitive behavioural therapy was recommended in cases of mild depression. Results presented here are useful diagnostic and patient management guidance for other physicians and important considerations to improve future drug trial design.

Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors: Impact on trabecular bone score and bone mineral density in primary fibromyalgia

Background: Fibromyalgia is a chronic musculoskeletal pain disorder characterized by widespread pain at multiple tender points, sleep disturbance and fatigue, which subsequently affect quality of life.The aim of our study is to determine the correlation between consumption of SSRIs and SNRIs in patients with primary fibromyalgia, and BMD and TBS. Methods and Findings: A cross-sectional study carried out on 150 Egyptian participants. Patients were divided into 2 main groups: treatment group including 100 patients (50 on SSRI, and 50 on SNRI) diagnosed with primary myelofibrosis, and control group including 50 age-matched subjects (25 healthy individual, and 25 with primary myelofibrosis but receiving medications other than SSRI and SNRI).BMD and TBS were significantly low in SSRI and SNRI treatment groups compared to healthy control. In older population, lumbar spine (L1-L4) BMD and TBS decreased significantly in SSRI group. Also, control patients with primary fibromyalgia showed low BMD. Conclusion: Our study showed that patients with primary myelofibrosis, especially old population, whose treatment involved SSRIs or SNRIs had low BMD and low TBS. Additionally, patients with primary fibromyalgia who neither received SSRI nor SNRI also experienced low BMD. Thus, primary myelofibrosis could be considered as a contributing factor for low BMD.

Comparison of risk of cardiovascular disease related adverse events between selective serotonin reuptake inhibitor users and serotonin norepinephrine reuptake inhibitor users in Korean adult patients with depression: retrospective cohort study.

Serotonin norepinephrine reuptake inhibitor (SNRI) has been increasingly administered, but the associated cardiovascular disease (CVD) related adverse events risk is not clearly understood. So, we conducted a cohort study to identified CVD-related adverse events risk of SNRI comparing to selective serotonin reuptake inhibitor (SSRI). We used Korea Health Insurance Review and Assessment data. During the period from April 2009 to March 2011, patients who were prescribed SSRI or SNRI for depression, who were followed up till March 2018, were the subjects. Hemorrhagic stroke, ischemic stroke, and myocardial infarction were selected as the outcomes. High-dimensional propensity scores were used to adjust the unmeasured confounders. the cox proportional hazard model was used for the statistical analysis. A total of 1,016,136 patients diagnosed with depression over the age of 20 were screened and there were 64,739 SSRI users and 3,711 SNRI users in the group of patients. The adjusted hazard ratio did not differ between the two groups, but the subgroup analysis according to comorbidities showed a high risk of hemorrhagic stroke in SNRI users with hypertension or diabetes mellitus.

Exposure to tricyclic antidepressant nortriptyline affects early-life stages of zebrafish (Danio rerio)

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006–500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.

Exposure to serotonin selective reuptake inhibitors or serotonin noradrenaline reuptake inhibitors and sexual dysfunction: Results from an online survey.

Post-SSRI Sexual Dysfunction (PSSD) is characterized by sexual and emotional symptoms associated to the exposure to Selective Serotonin Reuptake Inhibitors (SSRI) or Serotonin Noradrenaline Reuptake Inhibitors (SNRI). The present study provides a comprehensive picture on demographic and clinical characteristics associated to PSSD. An online survey was run on subjects self-declaring as affected by PSSD. The survey collected socio-demographic and clinical data via questions created adhoc and three standardized scales (Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale, World Health Organization Wellbeing Index). A total of 135 subjects (115 males; mean age 31.9 ± 8.9 years) was analysed. The syndrome was more represented among young, heterosexual males after the exposure to SSRI/SNRI at relatively high doses. The major findings involved the temporal sequence of symptoms: 118 subjects had symptoms both during and after SSRI/SNRI administration, and 17 only after, thus deposing for a iatrogenic action of SSRI/SNRI. Different variables, represented by both emotional and sexual symptoms, accounted for the variability of the severity of the sexual dysfunction as well as of wellbeing. Based on the present results, PSSD is a complex iatrogenic syndrome in need of being further studied and understood.