Selective Serotonin-norepinephrine Reuptake Inhibitors Research Articles

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.

REM density is associated with treatment response in major depression: Antidepressant pharmacotherapy vs. psychotherapy

Major depression is one of the most common psychiatric illnesses. Interestingly, a few studies have indicated the existence of depression subgroups, which respond differently to the available treatment options. Previously, sleep abnormalities have been suggested to indicate amenability to different treatment regimens. Thereby, especially REM-sleep parameters seem to play a prominent role, and REM-sleep dysregulation has been repeatedly discussed as a potential endophenotype of depression. With that said, estimating therapy outcome in order to choose the best line of treatment is of utmost importance to patients suffering from depression.The present study looks deeper into these clues by investigating the capability of polysomnographic sleep parameters to predict treatment response in depressed patients to either pharmacotherapy or psychotherapy. Moderately to severely depressed patients (n = 38) were randomly assigned to either psychotherapy (i.e. interpersonal psychotherapy) or pharmacotherapy (i.e., monotherapy with selective serotonin reuptake inhibitors, SSRI, or selective serotonin noradrenalin reuptake inhibitors, SSNRI). Prior to treatment, all patients underwent polysomnography in the sleep laboratory. After treatment, responders and non-responders of both treatment groups were compared regarding their baseline sleep parameters.Higher baseline REM density, i.e. the amount of rapid eye movements during REM sleep, predicted better response to antidepressant pharmacotherapy. In the psychotherapy group, the effect seemed reversed but was not statistically significant. No other sleep parameter predicted treatment response.Our findings support the notion that REM-sleep dysregulation is indeed indicative of a distinct endophenotype of depression and that pharmacotherapy with SSRI/SSNRI might be superior to psychotherapy in these patients.

Tolerability of High-Dose Venlafaxine After Switch From Escitalopram in Nonresponding Patients With Major Depressive Disorder.

Within a single depressive episode, most patients receive different antidepressants because of an inadequate response to the first-line antidepressant. A commonly used strategy is to switch from a selective serotonin reuptake inhibitor to a selective serotonin-norepinephrine reuptake inhibitor. However, little is known about the tolerability of this switch with consideration of dose and drug concentration in blood. After 4 weeks of inadequate response to escitalopram (10-20 mg/d), medication was switched to another 4 weeks of venlafaxine (VF, 150-375 mg/d) in 234 depressed patients. Serum concentrations, depression severity, and adverse drug reactions (ADRs) were assessed weekly. The switch of medication led to an increase of ADRs such as reduced salivation (+11%), orthostatic dizziness (+11%), and sweating (+9.8%). The most frequent ADRs during treatment with VF were reduced salivation (28.6%), sweating (24.6%), and orthostatic dizziness (15.8%). In patients receiving high-dose VF, a significant improvement of depressive symptomatology was observed, and most ADRs decreased during the course of treatment, even in patients above the therapeutic reference range. Patients and physicians were aware of medication, and there was no direct comparison with the herein presented switch of medication. This study provides important information about the tolerability of a commonly used antidepressant treatment strategy. More detailed information about putative ADRs may help clinicians increase compliance through effective patient education. Because ADRs of VF were associated with the plasma concentration, therapeutic drug monitoring is recommended to guide the therapy and manage problems of tolerability.

Pulsed Radiofrequency Ablation: An Alternative Treatment Modality for Radiation-Induced Brachial Plexopathy.

Radiation therapy is used as a form of treatment for various neoplastic diseases. There are many potential adverse effects of this therapy, including radiation-induced neurotoxicity. Radiation-induced brachial plexopathy (RIBP) may occur due to the fibrosis of neural and perineural soft tissues, leading to ischemic damage of the axons and Schwann cells. The dose of radiation exceeds 55Gy in many patients who develop symptoms [1]. Current incidence in the United States is 1-2%, and RIBP is most commonly seen in patients who have undergone treatment for breast cancer, lung cancer, or lymphoma [1-3]. Common symptoms include numbness, paresthesia, dysesthesia, and occasional numbness of the arm. Pain is present in the shoulder and proximal arm and is typically mild to moderate in severity. Diagnosis is often made based on clinical presentation and evaluation of imaging to rule out concurrent malignant etiologies of the brachial plexus. Current recommended treatment includes physical therapy and medical management with anticonvulsants, tricyclic antidepressants, and selective serotonin-norepinephrine reuptake inhibitors.

Aspectos clínicos e principais formas de tratamento para Fibromialgia - Revisão de Literatura

A fibromialgia é considerada uma patologia incurável e uma síndrome idiopática por não ter sua fisiopatologia definida. O portador apresenta sintomas como dor crônica e generalizada, cansaço e dificuldade no sono. É considerada frequente e seu diagnóstico é realizado através da exclusão de outras patologias. Embora ainda não existe um tratamento efetivo, a terapia farmacológica auxilia os portadores a diminuírem os sintomas. O objetivo dessa revisão foi analisar a fisiopatologia envolvida no desenvolvimento da fibromialgia, bem como as terapias farmacológicas, plantas e compostos medicinais atualmente existentes e estudados para o tratamento desta patologia, considerando um período entre 2009 e 2020. Para tanto, os bancos de dados Scielo, Pubmed e Google Acadêmico foram consultados. Desse modo, pode-se constatar que as terapias farmacológicas existentes abrangem principalmente quatro classes de medicamentos que são as drogas antiepiléticas, antidepressivos tricíclicos, inibidores seletivos da recaptação de serotonina (ISRS) e inibidores da recaptação de serotonina noradrenalina, além de relaxantes musculares, benzodiazepínicos, antiinflamatórios analgésicos e fármacos fitoterápicos. Apesar das diversas diretrizes publicadas a respeito do tratamento da fibromialgia, até o momento inexiste terapia plenamente efetiva e diante disso evidencia-se a necessidade de novos fármacos específicos para essa patologia.

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

BACKGROUND AND OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta-Analyses.

This article reviewed the results of 21 recent meta-analyses examining the relationship between maternal use of antidepressants during pregnancy and negative outcomes in newborns and children. PubMed was searched for meta-analyses published in English between January 1, 2011, and November 30, 2019, by using combinations of the keywords pregnancy, antidepressants, review, meta-analysis, selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, neonatal outcomes, autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, infant, newborn, children, and offspring. The present review included a total of 21 relevant meta-analyses that met the inclusion criteria. Most of the meta-analyses reported that compared to non-users, the risks of preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, autism spectrum disorders, and ADHD in offspring of antidepressant users were significantly higher. Some meta-analyses also noted that the elevated risks were no longer statistically significant when pregnant women with psychiatric diagnoses treated with an antidepressant were compared with control patients who remained untreated. Although this review of current meta-analyses suggests a moderately increased risk of neonatal and childhood outcomes assessed with maternal use of antidepressants, it is difficult to ascertain whether these outcomes are independent of underlying maternal psychiatric disorders.

Predictors of quetiapine extended-release formulation add-on in older patients exposed to antidepressant drugs: A Danish register-based cohort study.

This study investigated which comorbidities or comedications increased the probability of receiving quetiapine extended-release formulation (quetiapine XR) as an add-on treatment. Danish administrative registers were used as data sources. The study period was from 01 January 2011 to 01 July 2017. New users of selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), atypical antidepressants (AAD), and tricyclic antidepressants (TCA) aged ≥65 years were included in the study population. A multivariable Cox regression model was used to find predictors for receiving quetiapine XR add-on within the first year of antidepressant therapy. A total of 123 655 new users of SSRI, SNRI, TCA, and AAD were eligible. The study population was composed of 57.7% females and the mean age was 77.2 years (SD 7.9 years). SSRI users comprised 49.6% of the study population. Among users of antidepressants, 171 (0.14%) patients received quetiapine XR as add-on treatment. In the adjusted analyses, female patients (HR 0.70; 95%CI 0.52-0.95) and glucocorticoid users (HR 0.41; 95%CI 0.21-0.80) had a significantly lower hazard of receiving quetiapine XR. Patients with dementia (HR 2.43; 95%CI 1.52-3.87) had a significantly higher hazard of receiving quetiapine XR than patients without this condition. When compared with SSRI users, AAD (HR 1.80; 95%CI 1.31-2.46) and TCA users (HR 0.18; 95%CI 0.06-0.49) had an increased/reduced hazard of receiving quetiapine XR, respectively. This study suggests that the choice of prescribing quetiapine add-on is driven by patient's differences in comorbidities, comedications and the type of antidepressant drug.

Antidepressant use and colorectal cancer morbidity and mortality: A dose-response meta analysis.

The risk of colorectal cancer associated to antidepressant use remains unclear. The purpose of this meta-analysis was to investigate the risk of colorectal cancer associated to antidepressant use.Medline, Embase, Web of Science, and Cochrane Database were accessed from the dates of their establishment to October 2018, to collect study of antidepressant use and colorectal cancer morbidity and mortality. Then a meta-analysis was conducted using Stata 12.0 software.A total of 11 publications involving 109,506 participants were included. The meta-analysis showed that antidepressant use was not associated with colorectal cancer morbidity (relevant risk (RR): 0.97; 95% confidence interval (CI): 0.94-1.01) and mortality (RR: 1.08; 95% CI: 0.99-1.17). Subgroup analysis showed selective serotonin reuptake inhibitor (RR: 0.99; 95% CI: 0.96-1.03) or serotonin norepinephrine reuptake inhibitor (RR: 1.04; 95% CI: 0.86-1.26) were not associated with colorectal cancer risk; however, TCA was associated with colorectal cancer risk decrement (RR: 0.92; 95% CI: 0.87-0.98). Furthermore, the results also showed that antidepressant use was not associated with colorectal cancer risk in Europe and North America (RR: 0.97; 95% CI: 0.92-1.02) and Asia (RR: 1.00; 95% CI: 0.95-1.26). Additionally, a dose-response showed per 1 year of duration of antidepressant use incremental increase was not associated with colorectal cancer risk (RR: 0.96; 95% CI: 0.87-1.09).Evidence suggests that antidepressant use was not associated with colorectal cancer morbidity and mortality. The cumulative duration of antidepressant use did not utilized played critical roles.

SUN-303 Effects of Open-Label, Adjunctive Ganaxalone Treatment on Resistant Depression in Postmenopausal Women: A Pilot Study

Resistance to selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor treatment occurs in about 50% to 70% of patients with major depressive disorder (MDD), a condition associated with significant morbidity that affects women at higher rates than men. Few well-tolerated, effective augmentation therapies are available for such patients, and new therapeutic strategies for resistant depression are needed. The neuroactive steroid metabolite of progesterone, allopregnanolone, is a positive allosteric modulator of GABAA receptors and a putative treatment for mood disorders. We performed a pilot study to determine whether an oral allopregnanolone analog (ganaxolone) may be effective adjunctive therapy for resistant depression in postmenopausal women. Ten postmenopausal women (age 62.8±6.3 years, range 53–69) with resistant depression [current DSM-IV major depressive episode per the Structured Clinical Interview for DSM-IV, Montgomery-Asberg Depression Rating Scale (MADRS) ≥16 despite treatment with an adequately dosed antidepressant for ≥6 weeks] were studied. Open-label ganaxolone (225 mg BID, increased to 450 mg BID if tolerated) was administered for 8 weeks, followed by a 2-week taper. Mean total MADRS depression score (primary endpoint) decreased by 8 weeks [24.4±1.6 (SEM) to 12.8±2.9, p=0.015] and persisted over the two-week taper (p=0.019); 44% of subjects experienced response (score decrease ≥50%) and remission (final score <10), which persisted in 100% and 50% of subjects at 10 weeks, respectively. Secondary endpoints showed significant improvement, including the Inventory of Depressive Symptomatology-Self-Report (IDS-SR; p=0.003), MADRS Reduced Sleep subscale (p<0.001), Symptoms of Depression Questionnaire (SDQ) total score (p=0.012), and SDQ subscales for disruptions in sleep quality (p=0.003) and changes in appetite and weight (p=0.009) over 8 weeks. No significant effects were observed on quality of life or sexual function. All subjects experienced sleepiness and fatigue; 60% experienced dizziness. In conclusion, adjunctive ganaxolone in this open label pilot study appeared to exert antidepressant effects in postmenopausal women with resistant depression but produces sedation with twice-daily dosing. The observed positive effects on sleep and the potential for sustained treatment effects merit further study, as ganaxolone may be particularly beneficial to patients with depression and insomnia. Randomized, placebo-controlled studies are necessary to rule out placebo effects. Given the sedation experienced by most participants, nighttime dosing only should be considered for future studies. Finally, should rigorous studies confirm an antidepressant effect, it will be important to identify subsets of women who respond (e.g. women with neuroactive steroid dysregulation) and mechanisms of action.

SAT-737 Low-Dose Testosterone Augmentation for Treatment-Resistant Depression in Women: An 8-Week, Two-Site, Randomized, Placebo-Controlled Study

Objective: Nonresponse to selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor treatment is common in patients with major depressive disorder (MDD), particularly in women, occurring in about 70% of patients despite adequate dosing. Well-tolerated augmentation strategies are needed, particularly ones that do not cause or exacerbate symptoms such as fatigue and sexual dysfunction. Low-dose testosterone has been shown to improve depression symptom severity, fatigue and sexual function in small studies of women not formally diagnosed with MDD. We sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with treatment-resistant MDD. A functional MRI (fMRI) substudy examined effects of testosterone on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. Methods: Randomized, double-blind, placebo-controlled, 8-week trial of adjunctive testosterone cream (AndroFeme® 1, Lawley Pharmaceuticals, Australia) in 101 women, ages 21–70, with treatment-resistant MDD. Testosterone was titrated to achieve blood levels near the upper normal reference limit. Primary outcome measure was depression severity by Montgomery-Asberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. fMRI substudy (n=20) primary outcome was change in ACC activity. Results: Mean age was 47±14 (SD) years and mean baseline MADRS score was 26.6±5.9. Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS depression scores decreased in both arms [testosterone: 26.8±6.3 to 15.3±9.6; placebo: 26.3±5.4 to 14.4±9.3 (baseline to 8 weeks, respectively)], with no difference between groups (p=0.91). Fatigue and sexual function improved without differences between groups. There were no group differences in side effects. fMRI results demonstrated a relationship between ACC activation and androgen levels pretreatment but no difference in ACC activation with treatment. Conclusions: This rigorously designed, double-blinded clinical trial did not find significant group differences between adjunctive low dose transdermal testosterone and placebo for antidepressant augmentation in women with treatment-resistant MDD and had a high placebo response rate. Low-dose testosterone was well tolerated but failed to differentially impact overall depressive symptom severity, fatigue, or sexual dysfunction. Testosterone did not result in greater activity in a brain region (ACC) implicated in MDD etiopathology compared to placebo. Thus, the addition of low-dose testosterone to ineffective antidepressant treatment should not be recommended for women with MDD. Further studies using strategies designed to reduce placebo effects may be warranted.

Use of serotonin reuptake inhibitors is not associated with increased bleeding after CABG.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) are the most commonly prescribed antidepressants worldwide. Studies suggest that SSRI/SNRIs can increase bleeding following different surgical procedures, including open heart surgery, but results are conflicting. The objective of this study was to analyse their effects on bleeding after coronary artery bypass grafting (CABG). Of 1237 patients that underwent CABG in Iceland in 2007-2016, 97 (7.8%) used SSRIs/SNRIs preoperatively and were compared to a reference group (n = 1140). Bleeding was assessed using 24-h chest-tube output, number of RBC units transfused and reoperation for bleeding. Thirty-day mortality rates and incidence of complications were also compared. The two groups were comparable with respect to preoperative and operative variables, with the exception of BMI being significantly higher in the SSRI/SNRI group (30.2 vs. 28.3kg/m2, p < 0.001). No significant differences were observed between groups in 24-h chest-tube output [815 (SSRI/SNRI) vs. 877ml (reference), p = 0.26], number of RBC units transfused (2.2 vs. 2.2, p = 0.99) or the rate of reoperation for bleeding (4.1% vs. 6.0%, p = 0.61). The incidences of complications and 30-day mortality rate were also similar. Using three different criteria, preoperative use of SSRIs/SNRIs was not shown to increase bleeding after CABG. Furthermore, short-term complications as well as 30-day mortality rates did not differ from those of controls. Thus, temporary cessation of SSRI/SNRI treatment prior to CABG to decrease the risk of bleeding is unwarranted.

DUOX2, a common modulator in preventive effects of monoamine-based antidepressants on water immersion restraint stress- and indomethacin- induced gastric mucosal damage

Multiple kinds of monoamine-based antidepressants have been shown prophylactic effects in experimentally induced gastric ulcer. The loss of redox homeostasis plays a principle role in the development of peptic mucosal damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are one of the most important sources of reactive oxygen species within the gastrointestinal tract. It is unclear whether there are some common NADPH oxidases modulated by monoamine-based antidepressants in different gastric mucosal damage models. We explored the effects of selective serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine on the reactive oxygen species production and antioxidant capacity in the gastric mucosa of water immersion restraint (WIRS) or indomethacin treated rats, and examined the role of NADPH oxidases in the protective effects. Pretreated duloxetine prevented the increase of gastric mucosal NADPH oxidase activity and NADPH oxidase inhibitor apocynin dose-dependently protected gastric mucosa from damage by the two factors. Furthermore, dual oxidase 2 (DUOX2) and NADPH oxidase4 (NOX4) are involved in the protective effects of duloxetine in both models. We then examined NADPH oxidases expression modulated by the other monoamine-based antidepressants including selective serotonin reuptake inhibitor (SSRIs) fluoxetine, tricyclic agent (TCAs) amitriptyline and monoamine oxidase inhibitor (MAOs) moclobemide in the two models, and all the three antidepressants reduced the DUOX2 expression in the gastric mucosa. So DUOX2 was a common modulator in the preventive effects of all the monoamine-based antidepressants on WIRS- and indomethacin-induced gastric lesion. Our work provided a peripheral joint molecular target for monoamine modulatory antidepressants, which may be helpful to reveal the mechanisms of this kind of drugs more than monoamine regulation.

Antidepressant Withdrawal: A Guide for Primary Care Clinicians

Thirty million office visits annually are the result of a mental health disorder, and 33% occur in an outpatient clinic. Depression, a common diagnosis in the primary care setting, is often treated with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic and atypical antidepressants. However, withdrawal symptoms can occur with the abrupt cessation of the medication. This article discusses the clinical features associated with withdrawal syndrome and how to prevent them with an adequate taper of antidepressants.

Recent advances in liquid chromatographic methods for the determination of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors

Depression is now the second largest public health burden throughout the world. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have replaced older antidepressants to become first-line medications to treat this disease with increased remission rates and markedly decreased incidence of severe adverse events. Traditional and modern bioanalytical strategies for SSRI and SNRI determination are being continuously improved. There has also been a recent increase in the use of unconventional sample preparation methods. This review critically evaluates the development of SSRI and SNRI liquid chromatographic analytical methods published between 2014 and mid-2019, with special attention to novel sample preparation methods.

Treatment patterns and sequences of pharmacotherapy for patients diagnosed with depression in the United States: 2014 through 2019

BackgroundUnderstanding how patients are treated in the real-world is vital to identifying potential gaps in care. We describe the current pharmacologic treatment patterns for the treatment of depression.MethodsPatients with depression were identified from four large national claims databases during 1/1/2014–1/31/2019. Patients had ≥2 diagnoses for depression or an inpatient hospitalization with a diagnosis of depression. Patients were required to have enrollment in the database ≥1 year prior to and 3 years following their first depression diagnosis. Treatment patterns were captured at the class level and included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, and antipsychotics. Treatment patterns were captured during all available follow-up.ResultsWe identified 269,668 patients diagnosed with depression. The proportion not receiving any pharmacological treatment during follow-up ranged from 29 to 52%. Of the treated, approximately half received ≥2 different classes of therapy, a quarter received ≥3 classes and more than 10% received 4 or more. SSRIs were the most common first-line treatment; however, many patients received an anxiolytic, hypnotic/sedative, or antipsychotic prior to any antidepressive treatment. Treatment with a combination of classes ranged from approximately 20% of first-line therapies to 40% of fourth-line.ConclusionsMany patients diagnosed with depression go untreated and many others receive a non-antidepressant medication class as their first treatment. More than half of patients received more than one type of treatment class during the study follow up, suggesting that the first treatment received may not be optimal for most patients.

Update on pharmacotherapy in psychodermatological disorders

Psychodermatological (PD) conditions encountered in dermatologic practice include primary psychiatric conditions such as delusions of parasitosis or secondary psychiatric conditions such as anxiety and depression due to dermatologic disease. The psychotropics include antipsychotic agents, anti-anxiety agents, antidepressants, and miscellaneous drugs such as anti convulsants. Anti psychotics are further divided into first-generation and second-generation drugs. Currently, second-generation drugs e.g., risperidone are preferred over first-generation drugs e.g., pimozide in delusional infestation owing to the side effect profile of the latter. Anti-anxiety agents include benzodiazepines used in acute anxiety and buspirone in chronic anxiety disorders. They are frequently prescribed along with antidepressants. Although dependence and necessity of tapering is a problem with benzodiazepines, delayed onset of action is a feature of buspirone. The commonly used antidepressants in dermatology include selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), selective serotonin norepinephrine reuptake inhibitors (venlafaxine, desvenlefaxine, and duloxetine), norepinephrine dopamine reuptake inhibitors (bupropion), tricyclic antidepressants (doxepin, amitriptyline, imipramine, and clomipramine), and tetracyclic antidepressants (mirtazapine). Miscellaneous drugs include anticonvulsants such as gabapentin and pregabalin, naltrexone, and N-acetyl cysteine. The principles of PD treatment are first establish the psychiatric diagnosis, followed by initiating drug treatment. The choice of drugs is dependent on multiple factors such as side-effect profile, drug interactions, and co-morbid conditions. Usually, drugs are started at a low dose and gradually increased. A literature search was done in Pubmed, Google Scholar, and Medline databases, and articles on treatment were analyzed.

Clinical Correlates of Rapid Eyeball Movement Sleep Behaviour Disorder with Clomipramine: A Case Control Study

Introduction: Antidepressants have been implicated in causing Rapid eyeball movement sleep Behaviour Disorder (RBD). While Selective Serotonin Reuptake Inhibitor (SSRI) and Serotonin Norepinephrine Reuptake Inhibitors (SNRI) are more frequently implicated, Tricyclic Antidepressants (TCA) have been less studied. Aim: To characterise the clinical correlates of RBD on Clomipramine and to compare these parameters with those who didn’t develop RBD on treatment with clomipramine. Materials and Methods: It was a case control study in which participants who were on clomipramine and had developed RBD were studied, and a comparison was made with those participants who were on clomipramine but didn’t develop RBD. All the assessments were done in a single sitting. Patients who were on clomipramine, for any reason, were screened for presence of sleep disorder. Detailed interview was done for diagnosis and Statistical Manual of Mental Disorders (DSM-5) diagnosis of RBD to form the case group. From the group of participants, who didn’t meet the criteria for RBD, every 7th case was included to form the control group (NRBD group). Both the groups were interviewed for socio-demographic and clinical profile and Mini International Neuropsychiatric Interview (MINI Version 5) was applied for International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) of diagnosis of psychiatric disorders. Chi-square and Independent t-test were used to make the group comparisons. Pearson’s coefficient was used for correlation analysis. Results: A total of 164 participants, on clomipramine, were evaluated for presence of RBD, which was found in 20 and were included in the RBD group and 20 participants, were included in the NRBD group. Mean age of the participants in RBD group was 36.650±7.882 years. Mean duration of RBD development was 16.4 days (Range: 3-40 days). In comparison to the NRBD group, in the RBD group mean dosages (p=0.016), and mean duration of treatment (p=0.026) with clomipramine was significantly higher. Correlational analysis showed that duration of development of RBD correlated negatively with age (r=-0.479, p=0.034) and dosage of clomipramine (r=-0.095, p=0.690). Conclusion: RBD has higher prevalence and younger age of onset with clomipramine usage than earlier reported. Higher dosage increases the chance of developing RBD. Clinicians should be alert for identifying and managing RBD in all patients on antidepressants.

Treatment of posttraumatic stress disorder: Focus on pharmacotherapy.

Current clinical practice guidelines for the treatment of posttraumatic stress disorder offer varying recommendations regarding the use of pharmacotherapy. Many direct head-to-head comparisons of pharmacotherapy are lacking, and recommendations are based on meta-analyses and small trials. While selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors are considered first-line pharmacotherapy, clear distinctions do not exist when considering other classes of psychotropic medications. Ultimately, when selecting an appropriate medication for a patient diagnosed with posttraumatic stress disorder, the clinician needs to consider the current symptomatology being experienced, comorbid conditions, and evidence for efficacy of specific treatments prior to initiating medications.

DESIGN, SYNTHESIS AND STRUCTURAL ELUCIDATION OF ARYLOXYAMINOACETYLENIC DERIVATIVES AS ANTIDEPRESSANT ACTIVITY

Depression is the most common illness that affects a large number of individuals in all countries. It is believed that decreased levels of neurotransmitters such as serotonin, norepinephrine and dopamine are the main cause of depression. Selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (SNRIs), their mechanism is to increase the amount of neurotransmitters in the CNS. Design, synthesis and molecular docking of novel compounds namely amino acetylenic derivatives of aryloxy as isostere for aryloxypropylamine. The reaction of 7-methoxy-2-naphthol with propargylbromide generated 7-methoxy-2-(prop-2-yn-1-yloxy) naphthalene (ZR-1). ZR-1 was subjected to Mannich reaction yielded the derivatives of aryloxybutynylamines (ZR-2 to ZR-7). The Mp, FTIR, 1H-NMR, C13-NMR, DSC, elemental analysis and HPLC were consistent with the assigned structures. The molecular docking results obtained for aminoacetylenic compounds showed that the new novel 7-methoxy-2- {[4- (piperidine) but-2-yn-1-yl]oxy}-naphthalene (ZR-4) provide effective π overlap with binding sites of SERT protein by ionic, hydrogen bonding and overlap of aryl and cyclic amine moieties with the amino acids of transporter protein, which produce the binding energy (-109,69 kcal/mol) for ZR-4 relative to paroxetine (-114.18 kcal/mol), that may lead to promising drug in the treatment of depression.