Treatment Of Major Depressive Episodes Research Articles

Editorial Foreword - Milnacipran: recent findings in depression

Editorial Foreword - Milnacipran: recent findings in depression Stuart Montgomery1, Mike Briley2 1Imperial College School of Medicine, London, England, UK; 2NeuroBiz Consulting and Communication, Castres, FranceMilnacipran: recent findings in depressionMilnacipran is a serotonin and norepinephrine reuptake inhibitor (SNRI) which was first approved for the treatment of major depressive episodes in France in December 1996. It is currently marketed for this indication (as Ixel®, Toledomin®, Tivanyl® or Dalcipran®) in over 45 countries worldwide including Japan. It was approved for the management of fibromyalgia in the US in 2009.This supplement, which is based on a symposium at the International Forum on Mood and Anxiety (IFMAD) held in Monaco in November 2009, highlights several recent clinical studies with milnacipran in depression.

Publication Bias and the Efficacy of Antidepressants

Publication Bias and the Efficacy of Antidepressants

The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression

Meta-analysis of all available trials of Venlafaxine in the treatment of major depressive disorders, including treatment resistant depression and long-term relapse prevention. We conducted a meta-analysis comparing venlafaxine and tricyclics, or selective serotonin reuptake inhibitors (SSRIs), in major depression. We also included trials comparing venlafaxine and alternative antidepressants in subjects with treatment resistant depression, or compared with placebo in long-term relapse prevention. Trials were identified through searches of Medline, Embase, Cochrane Library and through accessing unpublished trials held by the manufacturer. Results based on intention to treat analyses where available, were pooled using theoretically exact conditional maximum likelihood methods for fixed effects (primary analyses), and numerical simulation using a Gibbs sampler for full random effects. Compared to all SSRIs for the treatment of major depression (fluoxetine, paroxetine, sertraline, citalopram, escitalopram and fluvoxamine), venlafaxine was associated with a greater response [odds ratio 1.15 (95% CI 1.02-1.29)] and remission [odds ratio 1.19 (95% CI 1.06-1.34)]. Overall drop out rates appeared similar for SSRIs and venlafaxine. Compared to tricyclics, response to venlafaxine was estimated to be greater by exact method, odds ratio 1.21 (95% CI 1.03-1.43), but not statistically significantly different, using a full random effects method odds ratio 1.22 (95% CI 0.96-1.54). We observed no difference in remission rates (odds ratio 1.06 (95% CI 0.74-1.63)). Tricyclics were less well tolerated with higher overall drop out rates. Compared to alternative antidepressants in treatment resistant depression (trials included comparison with sertraline, bupropion, fluoxetine, citalopram, and one with a range of agents-mostly SSRIs), the odds ratio for response was 1.35 (95% CI 1.19-1.54). The odds ratio for remission was 1.35 (95% CI 1.20-1.52). Compared to placebo the odds ratio for relapse prevention with venlafaxine was 0.37 (95% CI 0.27-0.51). This meta analysis provides evidence of the clinical efficacy of venlafaxine in achieving therapeutic response and remission in patients with major depression. Venlafaxine appears more effective than SSRIs, and at least as effective as tricyclic antidepressants, in the treatment of major depressive episode. Venlafaxine appeared more effective than comparators in treatment resistant depression. In addition, venlafaxine effective in reducing relapse when given long term after major depressive episode.

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The Safety of the Electroconvulsive Therapy-Escitalopram Combination

It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the treatment of major depressive episodes may be enhanced by concurrent administration of antidepressant medication. Therefore, the issue of how safe the combination of these 2 treatment modalities is warrants investigation. Escitalopram (ESC) is a novel selective serotonin reuptake inhibitor that seems to have a favorable side effect profile. To the best of our knowledge, there is no report on the safety of the ECT-ESC combination. We report the cases of 3 female inpatients with major depressive episode--two in the context of major depressive disorder and one in the context of bipolar disorder I--who underwent ECT while concurrently receiving ESC (20 mg/d) as part of their regimen. In all cases, the combination was well tolerated, and only minimal side effects were reported.

Urinary Retention During Combined Treatment of Postpsychotic Depression With Duloxetine and Olanzapine

Duloxetine, a dual-reuptake inhibitor of serotonin and norepinephrine, has been approved for the treatment of major depressive episodes and for female stress urinary incontinence. At present, only sparse experiences are available regarding antidepressive treatment in patients with a psychotic lifetime diagnose, whereas this group of patients often suffer from major depressive episodes. Here, we describe the first case of a male patient with postpsychotic depression who developed the severe side effect of urinary retention during antidepressive treatment with duloxetine combined with olanzapine. After remission of his psychotic episode, the patient presented with depressed mood, psychomotor inhibition, sleep disturbance, and suicidal ideas. Without changing the antipsychotic therapy, we implemented duloxetine (60 mg/d) and the patient significantly improved. However, he increasingly suffered from obstructive voiding difficulties and complained about a weak urinary stream and incomplete voiding leading to unacceptable dribbling. The urinary retention disappeared completely within 1 week after discontinuation of duloxetine. We switched to venlafaxine (150 mg/d) and were able to keep the depression in remission. This case report demonstrates for the first time the onset of urinary retention in postpsychotic depression and during combined treatment with duloxetine and olanzapine. We therefore suggest increased attention on voiding function in particular if several pharmacological agents are combined.

Transcranial direct current stimulation for the treatment of drug-resistant depression

transcranial direct current stimulation (tDCS) is recently receiving a renewed interest as a tool for the treatment of major depressive episodes. The aim of this study is to test the potential of tDCS as add-on therapy in drug-resistant depressed patients.

Escitalopram versus IRSNa

Escitalopram has shown some different pharmacologic properties compared to its racemic molecule, citalopram. When comparing with venlafaxine, similar efficacy of this drug was observed, notably when considering the frequency of responders [50% of decrease on the Montgomery and Asberg Depression rating Scale (MADRS)] and the frequency of remitters (MADRS<12), even when the doses of both drugs were increased up to 20 mg per day for escitalopram and 225 mg per day for venlafaxine. In addition, a recent study conducted by Jonas et al. (2006) [Jonas J, Bose A, Alexopoulos G, et al. Double blind comparison of escitalopram and duloxetine in the acute treatment of Major Depressive Disorder 45th Annual Meeting of the American College of Neuropsychopharmacology December 2006] suggested a better efficacy of escitalopram in comparison to duloxetine. When considering severe major depressive episodes, the efficacy of escitalopram compared to noradrenalin and serotonin reuptake inhibitors (NaSRI) could be superior, with a more important rate of remitters in the escitalopram group. Regarding the tolerance of both types of drugs, the percentage of patients who withdrew the drug for side-effects would be higher in patients on venlafaxine. This increase in frequency of side-effects has been observed in different studies conducted with venlafaxine and duloxetine. All these data highlight the advantages of escitalopram in the treatment of major depressive episodes and escitalopram has, therefore, obtained marketing approval in France with some specific mentions in favour of this drug.

Efficacy of Quetiapine Monotherapy for the Treatment of Depressive Episodes in Bipolar I Disorder

To investigate the efficacy and tolerability of quetiapine monotherapy for the treatment of major depressive episodes in patients with bipolar I disorder, as a post hoc analysis of data from 2 large studies, the BipOLar DEpRession (BOLDER) I and II studies, which investigated the overall efficacy of quetiapine in both bipolar I and II disorder. A combined cohort of patients with depressive episodes in bipolar I disorder (DSM-IV criteria) (N = 694) from 2 nearly identical double-blind, randomized, placebo-controlled studies that each randomly assigned patients with bipolar I and II disorder to 8 weeks of treatment with quetiapine 300 or 600 mg/day or placebo was analyzed. The primary efficacy measure was change from baseline to end of treatment (week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores. In the combined cohort of patients with depressive episodes in bipolar I disorder from 2 studies, there were significantly greater clinical improvements in mean MADRS total scores among patients who received quetiapine compared with placebo from baseline to week 1 and through week 8 (at week 8: quetiapine 300 mg/day = -19.4; 600 mg/day = -19.6; placebo = -12.6; p < .001 for each dose), providing effect sizes of 0.78 and 0.80, respectively. Changes in MADRS were unrelated to reports of sedation and somnolence. The most common adverse events (AEs) with quetiapine were dry mouth, somnolence, sedation, dizziness, and constipation. Rates of withdrawal because of these AEs were relatively low. Quetiapine monotherapy (300 and 600 mg/day) is more effective than placebo and generally well tolerated for the treatment of depressive episodes in patients with bipolar I disorder.

A Case-Control Study of Antidepressants and Attempted Suicide During Early Phase Treatment of Major Depressive Episodes

To estimate the relative risk of suicide attempts in child and adult outpatients initiating antidepressants for major depressive episodes compared to those not treated with antidepressants. A nested matched case-control study was performed with Medicaid administrative data (January 1, 1999-December 31, 2000) of out-patients treated for a major depressive episode. Beneficiaries initiating treatment for a major depressive episode were selected, excluding those who had recently received inpatient psychiatric treatment or outpatient treatment of pregnancy, major depressive episodes, bipolar disorder, schizophrenia or other psychoses, mental retardation, dementia, or delirium or recent treatment with a mood stabilizer, antidepressant, or antipsychotic. The outcome was treatment for a suicide attempt during the first 120 days after starting treatment for a major depressive episode. Controls were matched to cases on age, sex, race/ethnicity, recent treatment of substance use disorder, severity and type of major depressive episode, and other factors. Separate analyses were performed for adults (aged 19 to 64 years) and children (aged 6 to 18 years). Among children, antidepressant treatment was associated with a significant increase in suicide attempts (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.06 to 4.10; cases, N = 51; controls, N = 239; p = .03). Among adults, antidepressant treatment was not significantly related to risk of suicide attempts (OR = 0.85, 95% CI = 0.57 to 1.28; cases, N = 185; controls, N = 893; p = .44), although among adult males, antidepressants were associated with a significant protective effect (OR = 0.32, 95% CI = 0.12 to 0.83; cases, N = 57; controls, N = 268; p = .01). In these outpatients initiating treatment for a major depressive episode, antide-pressant treatment appears to be associated with an increased risk of treated suicide attempts in children and a decreased risk in adult males.

Comparison of Users and Non-Users of Mental Health Services Among Depressed Women: A National Study

ABSTRACT Risk factors for major depressive episodes (MDE), determinants of not seeking treatment for it and types of health care service accessed by women who received treatment for MDE were examined using data collected in the Health and Mental Health cycle of the Canadian Community Health Survey, 2002. Of the 1,186 women with MDE, 45% did not receive treatment for it. The highest rates of MDE were found among women under 30 years of age, single mothers with young children, low income women, those with chronic health conditions, high levels of daily stress and low levels of social support. The odds of not seeking treatment for MDE were highest for single mothers with adult children, women with low social support and those with little formal education. The type of mental health services accessed by women with MDE was strongly associated with their age, education, length of time in Canada, language skills, income adequacy, physical health, stress level and chronic health conditions. Our findings signify a need for screening women at high risk of depression, especially those identified as more likely not to seek treatment.

Moderne antidepressive Therapie

A systematic review on empirical results of current guidelines and recommendations with focus on efficacy and tolerability of antidepressant pharmacological treatment options. A critical, systematic evaluation of peer reviewed surveys, meta-analyses and guidelines is provided with the focus on evidence based consequences for the psychiatric clinical practice in the treatment of major depressive episodes. Most of modern and classic antidepressants have not proved differences in studies regarding comparative effectiveness. In contrast clinical decisions are increasingly guided by differences of tolerability, which are clearly documented in the current literature. Many algorithm based treatment options exist to face the common problem of treatment resistance. The multitude of effective antidepressant options provides an individual and patient orientated treatment. To achieve an optimal utilization of these options, an orientation on multi-step treatment plans is useful.

A prospective study of escitalopram in the treatment of major depressive episodes in the presence or absence of anxiety

This open, multicenter, prospective study in France assessed the efficacy and tolerability of escitalopram in patients with depression, with or without comorbid anxiety. Escitalopram was administered over a 12-week treatment period to 790 depressed patients, including 482 patients with at least one concomitant anxiety disorder. The study was completed by 649 patients. At baseline, the mean Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and decreased to 12.4 at end point (last observation carried forward [LOCF]). The MADRS score decreased by 20.5 points in patients with no anxiety disorder and by 18.3 points in patients with at least one concomitant anxiety disorder. The mean Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points in patients with no anxiety disorder and by 15.5 points in patients with at least one anxiety disorder. Adverse events were reported by 246 patients (31%). The most frequent adverse events were nausea in 65 patients (8%) and headache in 38 patients (5%); 61 patients (8%) discontinued treatment due to adverse events. Escitalopram was well tolerated and efficacious in reducing symptoms of depression in patients with or without comorbid anxiety over a 12-week treatment period.

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A Clinical Approach to Mild Cognitive Impairment

A Clinical Approach to Mild Cognitive Impairment

Depression and epilepsy: a new perspective on two closely related disorders.

Depression is the most frequent psychiatric comorbidity in epilepsy. Yet, it remains under-recognized and untreated in a significant number of patients. It may mimic primary depressive disorders, but in a significant percentage of patients, depression presents with atypical pleomorphic characteristics. The use of screening self-rating scales may help to identify depressive episodes in patients with epilepsy, but a diagnosis cannot be established by the sole use of these instruments without an additional, in-depth evaluation. Timely recognition and treatment of depression is of the essence in epilepsy patients, as its persistence is an independent predictor of poor quality of life, increased suicidal risk, greater use of health services, and higher medical costs not related to the psychiatric treatment. Neurologists will often find themselves in the position of being the only health care provider available to initiate treatment. Accordingly, they should be well trained to provide psychopharmacologic treatment for major depressive episodes, dysthymic disorders, and minor depression. However, patients with suicidal ideation, psychotic symptoms, or bipolar disorders should be referred immediately to the care of a psychiatrist.

Antidepressant-like activity of selective serotonin reuptake inhibitors combined with a NK1 receptor antagonist in the mouse forced swimming test

Substance P antagonists of the neurokinin-1 receptor type (NK1) have growing interest as new antidepressant therapies. It has been postulated that these drugs exert this putative therapeutic effect without direct interactions with serotonin (5-HT) neurons. In line with this assumption, previous intracerebral in vivo microdialysis experiments provided evidence that the NK1 receptor antagonists did not change basal cortical 5-HT levels. However, we found that increases in cortical 5-HT overflow caused by systemic injection of the selective serotonin reuptake inhibitor (SSRI), paroxetine was higher in freely moving (C57BL/6x129sv) NK1−/− mutants than in wild-type NK1+/+ mice [17]. More recently, a pharmacological study has led to a similar conclusion since GR205171, a NK1 receptor antagonist, potentiated paroxetine-induced increases in cortical 5-HT dialysate following its acute systemic or intra-raphe administration to wild-type mice [25]. In the present study, we tested whether an acute combination of SSRI and NK1 receptor antagonist could display antidepressant-like activity using the forced swimming test in Swiss mice. We found that a single systemic dose of GR205171 (10 and 30 mg/kg, i.p.) had no effect by itself. However, it selectively potentiated the antidepressant-like activity of subactive doses of two serotonergic antidepressant drugs, citalopram and paroxetine (without psychomotor stimulant activity), but not that of noradrenaline reuptake inhibitor, desipramine. In agreement with neurochemical data, the present study confirms that co-administration of a NK1 receptor antagonist with an antidepressant drug such as a SSRI may have a therapeutic potential to improve the treatment of major depressive episodes in human compared to SSRI alone.

Duloxetine Treatment of Major Depressive Episodes in the Course of Psychotic Disorders

During the course of psychotic disorders, patients often suffer from intercurrent major depressive episodes (MDEs), and suicides frequently occur. This constellation challenges further improvements in psychopharmacological therapy. The antidepressant duloxetine was recently introduced as a novel reuptake inhibitor of serotonin and noradrenaline. We provide the first reports on duloxetine treatment of MDEs in the course of psychotic disorders. In two cases this substance was successfully involved as an add-on to antipsychotic treatment consisting of clozapine or amisulpride. We achieved a response of the MDEs, as reflected by psychopathological rating scales. A significant rise in the clozapine serum level was detected, most likely because of pharmacokinetic interactions. Overall, the application of duloxetine was well tolerated; therefore, further investigations in prospective studies seem to be recommendable.

Clinical Features of Bipolar Depression Versus Major Depressive Disorder in Large Multicenter Trials

Failure to recognize bipolar disorder in patients who experience a major depressive episode may lead to inappropriate treatment and poorer outcomes. Clinical features that could distinguish bipolar from unipolar depression would facilitate more appropriate treatment selection. The authors used data from nonpsychotic outpatients participating in three large multicenter clinical trials conducted in the United States for the treatment of major depressive episodes to compare 477 subjects with a diagnosis of bipolar disorder and 1,074 with major depressive disorder. Bipolar depression was associated with family history of bipolar disorder, an earlier age at onset, a greater previous number of depressive episodes, and eight individual symptom items on the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale. Fears were more common in patients with bipolar disorder, whereas sadness; insomnia; intellectual (cognitive), somatic (muscular), respiratory, genitourinary complaints; and depressed behavior were more common in patients with unipolar depression. A logistic regression model correctly classified 86.9% of the subjects. Bipolar depression and major depressive disorder exhibit subtle differences in presentation, which may help guide the initial diagnosis.

Response to 4-month treatment with reboxetine in Parkinson's disease patients with a major depressive episode

Objective The aim of this study is to evaluate response to reboxetine in a 4-month follow-up study on depression in Parkinson's disease (PD), and to assess its tolerability profile. Methods A prospective 4-month follow-up study was performed in 17 PD patients with a major depressive episode. The intensity of depressive symptoms was evaluated mainly with the Hamilton Rating Scale for Depression (HAM-D), and PD was assessed with the Unified Parkinson Disease Rating Scale (UPDRS). Results Reboxetine causes a progressive decrease in depressive symptoms in PD patients; the initial score of 16.76 (2.68) on HAM-D decreased to 5.85 (2.42) at 4 months ( P<.002). Mean UPDRS scores did not show a statistically significant increase: 18.18 (2.6) at the beginning and 18.25 (2.4) at the end of the follow-up period ( P=.8). Conclusions Reboxetine, as first choice treatment for major depressive episodes in PD patients, seems to be effective in progressively improving depressive symptoms over the first 4 months of treatment until complete remission. Reboxetine does not seem to increase PD symptoms, whereas patients' quality of life improves.