Serotonin-norepinephrine Reuptake Research Articles

Exploring vortioxetine combination with intranasal esketamine: A feasible alternative to SSRI/SNRI? - Insights from the REAL-ESK study

BackgroundTreatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with other oral antidepressants. AimTo assess the efficacy of Vortioxetine plus ESK-NS in mitigating depressive symptoms and emotional blunting, as well as its tolerability in TRD subjects, compared to the standard-of-care of SSRI/SNRI plus ESK-NS. MethodsWe conducted a post-hoc analysis of the REAL-ESK study. The study included twenty TRD patients, ten subjects taking Vortioxetine as the main oral antidepressant with ESK-NS, and ten subjects taking SSRI or SNRI with ESK-NS. Psychometric assessments (Montgomery-Åsberg Depression Rating Scale/MADRS, Brief Psychiatric Rating Scale/BPRS) were conducted at baseline(T0), one month(T1), and three months after the treatment initiation(T2). ResultsThe combination of Vortioxetine and ESK-NS was as effective as the standard-of-care in reducing depressive symptoms, with a higher effect size in reducing emotional blunting at T2. The safety and tolerability profile of the Vortioxetine+ESK-NS combination appeared to be better, with a lower rate of treatment-emergent adverse events. ConclusionThe combination of Vortioxetine and ESK-NS may be a valuable alternative to the standard-of-care SSRI/SNRI plus ESK-NS in TRD patients, particularly regarding the reduction of emotional blunting and potentially a better safety and tolerability profile. Further randomized controlled trials with larger sample sizes and prospective designs are needed to confirm these findings.

Venlafaxine antagonizes the noradrenaline-promoted colon cancer progression by inhibiting the norepinephrine transporter

Epidemiological studies have demonstrated that the use of antidepressants is associated with a decreased risk of colorectal cancer (CRC); however, the mechanisms behind this association are yet unknown. Adrenergic system contributes to the stress-related tumor progression, with norepinephrine (NE) mainly secreted from adrenergic nerve fibers. Norepinephrine serotonin reuptake inhibitors are successfully used antidepressants. This study demonstrates that a widely used antidepressant venlafaxine (VEN) antagonizes NE-promoted colon cancer in vivo and in vitro. Bioinformatic analysis suggested that NE transporter (NET, SLC6A2), a target of VEN, was closely associated with the prognosis of clinical patients with CRC. In addition, the knockdown of NET antagonized the effect of NE. The NET-protein phosphatase 2 scaffold subunit alpha/phosphorylated Akt/vascular endothelial growth factor pathway partially mediates the antagonizing effect of VEN on NE’s actions in colon cancer cells. These were also confirmed by in vivo experiments. Our findings revealed for the first time that, in addition to its primary function as a transporter, NET also promotes NE-enhanced colon cancer cell proliferation, tumor angiogenesis, and tumor growth. This provides direct experimental and mechanistic evidence for the use of antidepressant VEN in the treatment of CRC and a therapeutic potential for repurposing existing drugs as an anti-cancer approach to improve the prognosis of patients with CRC.

P130 An audit of urinary drug screening use in multiple sleep latency and maintenance of wakefulness testing in an Australian tertiary centre

Abstract Multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT) are objective measures of excessive daytime sleepiness, used in diagnosing and monitoring patients with sleep disorders. MSLT and MWT can be affected by substances such as psychotropics, stimulants, opioids and sedatives. Recent studies demonstrate high prevalence of positive urine drug screening (UDS) results in patients undergoing MSLT and MWT. We retrospectively audited patients who underwent UDS with MSLT/MWT at a tertiary centre from 1st January 2019 to 1st January 2020. The following data was collected: MSLT/MWT/UDS results, sleep disorder diagnosis/es, return to driving/work after testing and pre-existing and subsequent prescription of stimulants/wakefulness-promoting agents/psychotropics/sodium oxybate. Our cohort featured 32 patients (23 female). 29 MSLTs and 3 MWTs were performed. Median age was 31 years old. 13 patients were on wakefulness-promoting agents/psychotropics when tested, where 8 were on serotonin–norepinephrine reuptake inhibitors/selective serotonin reuptake inhibitors. 13 patients (~45%) had a reduced mean sleep latency (MSL), where 10 minutes was used as the cut-off. All 3 MWTs were within normal limits. 5 patients (~16%) had a positive UDS. 1 patient had a low MSL and tested positive for cannabinoids and opioids. The other 4 patients with normal MSL tested positive for benzodiazepines (2), cannabinoids (1) and opioids (1). All patients were cleared for work and 85% of patients who had a low MSL returned to work during follow-up. The rate of positive UDS in patients undergoing MSLT/MWT was comparable to existing publications and re-emphasizes the relevance of mandating UDS prior to MSLT/MWT.

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.

A cross sectional study of psychotropic medicine use in Australia in 2018: A focus on polypharmacy.

To examine prescribed psychotropic medicine use on a given day in Australia (25 September 2018; World Pharmacists Day), with a focus on psychotropic polypharmacy. We used a 10% sample of individual-level nationwide dispensing claims to examine psychotropic medicine use on a given day. We estimated the prevalence of psychotropic medicine use in all ages stratified by age and sex. We also calculated the observed vs expected (had medicines been randomly combined) prevalence of psychotropic combinations used. We focused on combinations of clinical significance as well combinations of psychotropics with medicines prescribed to manage cardiovascular risk and disease. Serotonin reuptake inhibitors, serotonin-noradrenalin reuptake inhibitors/noradrenaline reuptake inhibitors, tricyclic antidepressants and gabapentinoids dominated psychotropic use. The use of any psychotropic as a proportion of people in the Australian population increased with age, peaking at the 85-89 year age group and declining thereafter. Combinations of medicines from the same subclass generally occurred at lower than expected frequencies. However, combinations including atypical antipsychotics occurred more frequently than expected; e.g. 7.4× with anticonvulsants and 2.2× with other atypical antipsychotics. This was also the case for combinations of sedatives, e.g. anxiolytic with hypnotic benzodiazepines (3.8×). Lipid-lowering drugs and antidiabetic medicines were combined with psychotropics at frequencies close to those expected had they been randomly combined. Psychotropic use in older adults and certain psychotropic combinations that are not well supported with evidence remain prevalent and greater consideration of the drivers of this potentially inappropriate prescribing is required.

Annals for Educators - 16 June 2020.

Annals for Educators - 16 June 2020.

Prevalence and risk factors of excessive daytime sleepiness in major depression: A study with 703 individuals referred for polysomnography

Background: To date, few studies have investigated the prevalence and risk factors of excessive daytime sleepiness (EDS) in major depression. Thus, the aim of the present study was to examine the prevalence and risk factors of EDS in a large sample of individuals with major depression.Methods: Data from 703 individuals with major depression were retrospectively collected from the sleep laboratory research database of Erasme Hospital for analysis. A score of > 10 on the Epworth Sleepiness Scale was used as the cut-off for EDS. Logistic regression analyses were conducted to examine the clinical and demographic risk factors of EDS in major depression.Results: The prevalence of EDS in our sample was 50.8%. Multivariate logistic regression analysis revealed that the following were significant risk factors of EDS in major depression: non-use of short to intermediate half-life benzodiazepine receptor agonists, BMI ≥ 25 kg/m², age < 60 years, C-reactive protein > 7 mg/L, Beck Depression Inventory score ≥ 16, atypical depression, apnea-hypopnea index ≥ 15/h, and use of selective serotonin reuptake inhibitors or serotonin–norepinephrine reuptake inhibitors.Limitations: To evaluate EDS, we used the Epworth Sleepiness Scale, which only allows for a subjective measure of daytime sleepiness.Conclusion: EDS is a common symptom in individuals with major depression. In this subpopulation, interventions are possible for most risk factors of EDS, which justifies improved management of this symptom to avoid its negative consequences.

Duloxetine-induced rapid eye movement sleep behavior disorder: a case report

BackgroundTricyclic antidepressants and selective serotonin reuptake inhibitors have been reported to induce the symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) or to exacerbate REM sleep without atonia. With this case report, we found an association between typical RBD and duloxetine, a serotonin-noradrenaline reuptake inhibitor.Case presentationWe present a case of a 62-year-old woman who experienced enactment behaviors with violent dreams that were associated with increased tonic or phasic chin electromyography activity during REM sleep after treated with duloxetine. RBD symptoms were gradually reduced and completely ceased after discontinuation of duloxetine for 37 days.ConclusionThe current case appears to be the first observation of duloxetine-induced RBD. We describe features of RBD induced by duloxetine that are similar and different from that induced by tricyclic antidepressants and selective serotonin reuptake inhibitors.

New developments in the management of narcolepsy.

Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%–0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy’s strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABAA receptor agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs investigated include GABAB agonists (baclofen), melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretin peptide replacement administered either through an intracerebroventricular route or intranasal route. Hypocretin neuronal transplant and transforming stem cells into hypothalamic neurons are also discussed in this article. Immunotherapy to prevent hypocretin neuronal death is reviewed.

Cost-utility analysis of vortioxetine versus agomelatine, bupropion SR, sertraline and venlafaxine XR after treatment switch in major depressive disorder in Finland

ABSTRACTBackground: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin–norepinephrine reuptake inhibitors.Methods: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted.Results: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks.Conclusion: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland.

Quetiapine Monotherapy for Chronic Military PTSD

Evidence is limited on efficacy of atypical antipsychotics in post-traumatic stress disorder (PTSD). The 2010 practice guideline from the Department of Veterans Affairs (VA) and Department of Defense did not recommend monotherapy (http://www.healthquality.va.gov/guidelines/MH/ptsd/), although it allowed consideration of low-dose risperidone and quetiapine. The quetiapine recommendation was based on a single open-label trial for patients not responding to selective serotonin or norepinephrine–serotonin reuptake …

A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder.

To review the antidepressant efficacy of S-Adenosyl-L-Methionine (SAMe) both in monotherapy and/or in augmentation with antidepressants to better understand its potential role in the treatment of patients with Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). A MEDLINE/PubMed search was carried out by using the following set of keywords: ((SAMe OR SAdenosyl- L-Methionine) AND (major depressive disorder OR depression)). Data Selection and Data Extraction: No language or time restrictions were placed on the electronic searches. Randomized controlled trials and open trials involving humans were here included and analyzed. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. SAMe is an important physiologic compound, playing a central role as precursor molecule in several biochemical reactions. Numerous studies have shown that SAMe may affect the regulation of various critical components of monoaminergic neurotransmission involved in the pathophysiology of MDD. Some findings have suggested its antidepressant efficacy in treating MDD. Several randomized controlled trials have supported that the antidepressant efficacy of SAMe in monotherapy is superior to placebo and tricyclic antidepressants. Recent findings have also demonstrated its efficacy in patients nonresponsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Overall, SAMe is a well-tolerated medication, which may offer considerable advantages as an alternative to antidepressant drugs or as an add-on therapy in the treatment of MDD and TRD. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy of this drug.

Review of antidepressants in the treatment of neuropathic pain

Abstract Introduction Neuropathy is a pathological pain disorder characterized by burning, stabbing, and cramping sensations. There are multiple etiologies for this pain such as diabetes, vascular disorders, and chemotherapy treatment. Neurotransmitters, such as norepinephrine and serotonin, are thought to play a part in the modulation of this pain. The objective of this review is to summarize the current literature to support the efficacy and impact of adverse events of the various classes of antidepressants utilized in the treatment of neuropathic pain. Methods A Medline/Pubmed search was conducted to identify randomized clinical trials within the last 12 years examining the efficacy and safety of antidepressants for the treatment of neuropathy. Systematic reviews and meta-analyses were also included. Results Antidepressants are commonly used in the treatment of neuropathy, with meta-analyses supporting the use of tricyclic antidepressants and selective norepinephrine serotonin reuptake inhibitors. Trials indicate that venlafaxine, duloxetine, and tricyclic antidepressants (TCAs) have comparable efficacy, but TCAs have a higher incidence of adverse effects. Other antidepressants, such as citalopram, paroxetine, and bupropion have limited evidence supporting their use in neuropathy. Discussion Based on the evidence reviewed, venlafaxine and duloxetine should be used as first-line agents. TCAs should be used as second-line agents, due to higher incidence of adverse effects. Other treatment options include citalopram, paroxetine, and bupropion, but data supporting their efficacy is limited.

Chronic Pain Pharmacological Treatment in Patients with Depressive Disorders

Background and Objective: Frequently patients with chronic pain show depressive disorders. The co-morbidity of pain and depressive disorders has a negative impact on the patient’s outcome, with an increase of the costs relating to health expenses, a reduction of productivity and a reduction of a probable remission of depressive symptoms. Following the evidences till now examined and reported, the study group elaborated recommendations for the pain and depressive disorder treatment. Databases and Data Treatment: We searched all potentially relevant publications in Medline database from 1990 to 2014. A quality assessment was conducted categorizing following a power of evidence criteria. Results: Forty-six relevant publications were identified: 34 randomized and controlled studies (RCT), 11 metaanalyses or reviews of literature and 1 observational open-label. Conclusions: In a condition of co-morbidity of chronic pain and depressive disorder there is poor evidence for the tricyclic antidepressant efficacy. Among the inhibitors of the serotonin-noradrenalin reuptake, duloxetine proved to be efficient in the short-long term treatment of the pain and depressive disorder states. There is poor evidence for the inhibitor use of serotonin re-uptake in the co-morbidity states of arthritis pain and depressive disorder, against their higher efficacy in the irritable bowel syndrome

No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight

ObjectiveThe health and longevity effects of body weight reduction resulting from exercise and caloric restriction in rodents are well known, but less is known about whether similar effects occur with weight reduction from the use of a pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake inhibitor.Results & ConclusionUsing data from a two-year toxicology study of sibutramine in CD rats and CD-1 mice, despite a dose-dependent reduction in food intake and body weight in rats compared to controls, and a body weight reduction in mice at the highest dose, there was no compelling evidence for reductions in mortality rate.

Fibromyalgia and bipolar disorder: a potential problem?

To screen patients with fibromyalgia for bipolar disorder and to determine if there were any clinical clues, other than the Mood Disorders Questionnaire (MDQ), which might suggest a diagnosis of comorbid bipolar disorder. A total of 128 consecutive new fibromyalgia patients referred to a tertiary care center rheumatology practice were enrolled and assessed using a standard clinical protocol that included the completion of four screening questionnaires: (i) MDQ for bipolar disorder, (ii) Beck Depression Inventory (BDI) for depression, (iii) Epworth Sleepiness Scale (ESS) for daytime sleepiness, and (iv) Fibromyalgia Impact Questionnaire Disability Index (FIQ-DI) to assess for functional capacity. A quarter of the fibromyalgia subjects, 25.19%, had a positive screen for bipolar disorder (MDQ >or= 7); 78.12% were clinically depressed (BDI >or= 10); and 52.13% reported daytime sleepiness (ESS >or= 10). Fibromyalgia subjects who screened positive for bipolar disorder had more severe depression than those with a negative screen [median BDI: 26.0 (19.0, 32.0) versus 15.0 (9.0, 24.0), p < 0.001]. We report a high prevalence of positive testing for bipolar disorder in this fibromyalgia cohort. Clinical data and questionnaire instruments other than nonspecific high depression severity failed to identify these patients. Since the norepinephrine serotonin reuptake inhibitors duloxetine and milnacipran have been recently approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia, and because patients with bipolar disorder may experience destabilization of mood when treated with such agents, patients with fibromyalgia should be systematically screened for bipolar disorder prior to treatment.

Metabolic, Digestive, and Reproductive Adverse Events Associated With Antimanic Treatment in Children and Adolescents

To identify factors associated with incident metabolic and reproductive adverse events in children and adolescents. A retrospective cohort design evaluating Medicaid medical and pharmacy claims made in South Carolina between January 1996 and December 2005 was employed for 3,657 children and adolescents (aged 17 years old and younger) prescribed 1 of 3 antimanic medications (ie, lithium, carbamazepine, or valproic acid derivatives) and a random sample of 4,500 children and adolescents not treated with psychotropic medications. Compared to the control sample, the treated cohort was more likely to be diagnosed with obesity/weight gain (odds ratio [OR] = 1.89), type 2 diabetes mellitus (OR = 2.50), dyslipidemia (OR = 1.89), nausea (OR = 1.61), anorexia (OR = 3.85), and sexual/reproductive adverse events (OR = 2.04). Within the treated cohort, incident dyslipidemia was more likely for those prescribed carbamazepine (OR = 1.52) compared to valproate and coprescribed antipsychotics (OR = 1.47) or selective serotonin reuptake inhibitors (SSRIs) (OR = 1.49) compared to those not taking antipsychotics or taking serotonin-norepinephrine reuptake inhibitor/heterocyclic (SNRI/other) antidepressants. The odds of developing nausea/vomiting were higher for those prescribed carbamazepine (OR = 1.70) or lithium (OR = 1.49) compared to valproate, and those coprescribed psychostimulants (OR = 1.25) compared to those not taking psychostimulants. The odds of developing obesity/weight gain and type 2 diabetes mellitus were higher for those coprescribed SSRIs (ORs = 1.72, 2.58) or antipsychotics (ORs = 1.69, 1.77) compared to those taking SNRI/other antidepressants or not taking antipsychotics. Incident sexual/reproductive adverse events were more likely for those coprescribed SSRIs (OR = 2.02) compared to those taking SNRI/other antidepressants. Commonly employed psychotropic agents are associated with clinically significant metabolic, digestive, and reproductive-related adverse events. Treatment decisions in young populations are usefully informed by the somatic consequences of the medication options.

Desvenlafaxine Extended Release

▴ Desvenlafaxine extended release (ER) is a once-daily selective serotonin-noradrenaline (norepinephrine) reuptake inhibitor approved in the US for the treatment of major depressive disorder in adult patients. ▴ In two of three well designed, 8-week clinical trials, desvenlafaxine ER 50 mg/day (the recommended dosage) significantly improved depression at study end, as assessed by the 17-item Hamilton Rating Scale for Depression (primary endpoint), compared with placebo. ▴ A significant difference between desvenlafaxine ER 50 mg/day and placebo treatment groups was achieved in some, but not all, secondary measures of depression or anxiety in two of three trials, including the Clinical Global Impression-Improvement and -Severity scales, the Montgomery-Asberg Depression Rating Scale and the Covi Anxiety Scale. ▴ In two of three trials, patients receiving desvenlafaxine ER 50 mg/day for 8 weeks experienced greater improvements in health-related quality of life (as assessed by the Sheehan Disability Scale and the WHO 5-item Well-Being Index) than those receiving placebo. ▴ Desvenlafaxine ER 50 mg/day was generally well tolerated by patients in 8-week trials. Most cases of nausea, the most common adverse event, were of mild to moderate severity.

Improvement in Subjective Sleep in Major Depressive Disorder With a Novel Antidepressant, Agomelatine

Patients with major depressive disorder (MDD) experience sleep disturbances that may be worsened by some antidepressant drugs early in treatment. The aim of this study was to assess the subjective quality of sleep of patients receiving agomelatine, a new antidepressant with melatonergic MT(1) and MT(2) receptor agonist and 5-HT(2C) antagonist properties, compared with that of patients receiving venlafaxine, a serotonin-norepinephrine reuptake inhibitor. This double-blind, randomized study involved 332 patients with MDD (DSM-IV criteria), lasted 6 weeks, and compared the effects of agomelatine 25-50 mg/day and venlafaxine 75-150 mg/day, with a possible dose adjustment at 2 weeks. Subjective sleep was assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ), and the main efficacy criterion was the "getting to sleep" score. Antidepressant efficacy was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) global improvement scale. The study was performed between November 2002 and June 2004. After 6 weeks, the antidepressant efficacy of agomelatine was similar to that of venlafaxine. The LSEQ "getting to sleep" score was significantly better with agomelatine (70.5 +/- 16.8 mm) than with venlafaxine (64.1 +/- 18.2 mm); the between-treatment difference at the last visit was 6.36 mm (p = .001), and the difference was already significant at week 1. Secondary sleep items, including LSEQ quality of sleep (p = .021), sleep awakenings (p = .040), integrity of behavior (p = .024), and sum of HAM-D items 4, 5, and 6 (insomnia score) (p = .044), were also significantly improved compared to venlafaxine, as was the CGI global improvement score (p = .016). Incidence of adverse events was 52.1% with agomelatine and 57.1% with venlafaxine, and withdrawals due to adverse events were more common with venlafaxine than with agomelatine (13.2% vs. 4.2%). Agomelatine showed similar antidepressant efficacy with earlier and greater efficacy in improving subjective sleep than venlafaxine in MDD patients.

Texas Children's Medication Algorithm Project: Update From Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder

To revise and update consensus guidelines for medication treatment algorithms for childhood major depressive disorder based on new scientific evidence and expert clinical consensus when evidence is lacking. A consensus conference was held January 13-14, 2005, that included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review, update, and incorporate the most current data to inform and recommend specific pharmacological approaches and clinical guidance for treatment of major depressive disorder in children and adolescents. Consensually agreed on medication algorithms for major depression (with and without psychosis) and comorbid attention-deficit disorders were updated. These revised algorithms also incorporated approaches to address issues of suicidality, aggression, and irritability. Stages 1, 2, and 3 of the algorithm consist of selective serotonin reuptake inhibitor and norepinephrine serotonin reuptake inhibitor medications whose use is supported by controlled, acute clinical trials and clinical experience. Recent studies provide support that selective serotonin reuptake inhibitors in addition to fluoxetine are still encouraged as first-line interventions. The need for additional assessments, precautions, and monitoring is emphasized, as well as continuation and maintenance treatment. Evidence and expert clinical consensus support the use of selected antidepressants in the treatment of depression in youths. The use of the recommended antidepressant medications requires appropriate monitoring of suicidality and potential adverse effects and consideration of other evidence-based treatment alternatives such as cognitive behavioral therapies.