Acute Major Depressive Disorder Research Articles

Vortioxetine in the treatment of major depression

Notwithstanding the high prevalence, functional burden, negative consequences and risk of chronicity of major depressive disorder, few innovative medications have been developed in recent years for the treatment of this heterogeneous disease. Vortioxetine is a multi-modal antidepressant that functions both as serotonin transporter (SERT) inhibitor and as 5-HT3, 5-HT7 and 5-HT1D receptors antagonist, 5-HT1A receptor agonist and 5-HT1B receptor partial agonist. A recent meta-analysis of 11 randomized, double-blind, placebo controlled, acute (6-8 weeks) treatment studies has demonstrated the efficacy of vortioxetine 5-20 mg/day in the treatment of depression, with an increasing effect associated with increasing dose. Additionally, vortioxetine 5-20 mg/day has shown efficacy on the whole range of depression symptoms (as demonstrated by the improvement of all single-item MADRS scores). Vortioxetine has also been shown effective in the treatment of severe depression and depression with inadequate response to a previous SSRI or SNRI treatment, as well as in the prevention of relapse. In studies designed to assess cognition in depression, vortioxetine showed evidence of improving cognitive performance in patients with acute major depressive disorder. Vortioxetine appears well-tolerated, with very limited effects on weight gain and sexual functioning. The most commonly occurring adverse event (nausea) was generally transitory.

Different patterns of 5-HT receptor and transporter dysfunction in neuropsychiatric disorders--a comparative analysis of in vivo imaging findings.

Impairment of serotonin receptor and transporter function is increasingly recognized to play a major role in the pathophysiology of neuropsychiatric diseases including anxiety disorder (AD), major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). We conducted a PubMed search, which provided a total of 136 in vivo studies with PET and SPECT, in which 5-HT synthesis, 5-HT transporter binding, 5-HT1 receptor binding or 5-HT2 receptor binding in patients with the primary diagnosis of acute AD, MDD, BD or SZ was compared to healthy individuals. A retrospective analysis revealed that AD, MDD, BD and SZ differed as to affected brain region(s), affected synaptic constituent(s) and extent as well as direction of dysfunction in terms of either sensitization or desensitization of transporter and receptor binding sites.

Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians.

Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear. To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD. English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research. Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms. Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings. 45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief. High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence. Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD. Agency for Healthcare Research and Quality.

Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

To describe the efficacy, tolerability and safety of brexpiprazole for the treatment of schizophrenia and as adjunct for major depressive disorder (MDD). The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'brexpiprazole' OR 'OPC-34712', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information. Brexpiprazole is a new dopamine D2 receptor partial agonist that received approval for the treatment of schizophrenia and for adjunctive use for the treatment of MDD based on a clinical trial development programme that included two pivotal Phase III trials of brexpiprazole monotherapy in acute schizophrenia, and two pivotal Phase III trials of adjunctive brexpiprazole in acute MDD in patients who demonstrated inadequate response to standard antidepressant therapy. In addition, results from a 52-week relapse prevention/maintenance randomised placebo-controlled withdrawal study in patients with schizophrenia are available. In these trials, brexpiprazole was administered once daily and titrated to target doses. The recommended dose for the treatment of schizophrenia is 2-4 mg/day and that for MDD, 2 mg/day. Pooling together all the available data for the recommended target dose of brexpiprazole for acute schizophrenia from the above studies, the percentage of responders is 45.5% vs. 31.0% for placebo, yielding a NNT of 7 (95% CI 5-12). In the relapse prevention/maintenance trial, significantly fewer patients relapsed in the brexpiprazole group compared with placebo (13.5% vs. 38.5%), resulting in a NNT of 4 (95% CI 3-8). When the results for brexpiprazole 1, 2 and 3 mg from the two Phase III MDD trials are pooled together, 23.2% of the patients receiving brexpiprazole were responders, vs. 14.5% for placebo, yielding a NNT of 12 (95% CI 8-26). Brexpiprazole was well tolerated - for schizophrenia, discontinuation rates because of an adverse event (AE) were overall lower for patients receiving brexpiprazole vs. placebo, and for MDD a total of 3% of brexpiprazole-treated patients and 1% of placebo-treated patients discontinued because of AEs, resulting in a NNH of 53 (95% CI 30-235). Although the most commonly encountered AE noted in product labelling was akathisia (5.5% in the acute schizophrenia trials and 8.6% in the MDD trials), differences from placebo were small, generating a non-significant NNH of 112 for patients with schizophrenia and a modest NNH of 15 (95% CI 11-23) for patients with MDD. Short-term weight gain appears modest; however, more outliers with an increase of ≥ 7% of body weight were evident in open-label 52-week safety studies. Effects on glucose and lipids were small. Minimal effects on prolactin were observed, and no clinically relevant effects on the ECG QT interval were evident. Clinical trials of brexpiprazole support its efficacy at the recommended target dose of 2-4 mg/day for the treatment of schizophrenia, and at the recommended target dose of 2 mg/day as adjunct to antidepressant medication for the treatment of MDD. Head-to-head comparisons with other available agents among patients with schizophrenia and MDD in the 'real world' are needed.

Obesity and major depression: Body-mass index (BMI) is associated with a severe course of disease and specific neurostructural alterations

Obesity is one of the most prevalent somatic comorbidities of major depressive disorder (MDD). Both disorders rank among the leading challenges in public health and have been independently characterized by gray matter alterations in partly overlapping brain structures. Hence, it appears crucial to investigate the possibility of a shared neurostructural correlate of this frequent comorbidity as well as its clinical implications.One hundred and fourty-four patients suffering from acute MDD and 141 healthy control subjects underwent structural MRI. Imaging data were analyzed using voxel-based morphometry (VBM). Body-mass-index (BMI) as well as state and course of disease were assessed.Higher BMI was associated with a highly comparable pattern of gray matter reductions in the medial prefrontal cortex, the orbitofrontal cortex, the caudate nucleus and the thalamus in MDD patients and healthy controls alike. In MDD-patients, BMI was associated with a more chronic course of disease and both BMI and chronicity of disorder were related to similar morphometric anomalies in medial prefrontal areas.In MDD, obese subjects might be characterized by a more chronic course of disease. Moreover, obesity and chronicity of disorder seem to share overlapping neurostructural anomalies in prefrontal areas involved in emotion regulation and impulse control. Hence, our data provide evidence for specific morphological alterations underlying this prevalent comorbidity. It further underlines the clinical importance of preventive measures against obesity accompanying MDD treatment.

Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis

Background:New generation antidepressant therapies, including serotonin–norepinephrine reuptake inhibitor (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few comprehensive studies compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in pediatric patients.Objective:Multiple-treatments meta-analysis (MTM) was conducted to assess efficacy, acceptability, and safety of contemporary interventions in children and adolescents with MDD.Methods:Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for randomized controlled trials (RCTs) comparing medicinal interventions (citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT, and placebo treatment for acute MDD from January 1988 to March 2013. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Bayesian methods were used to conduct a MTM including age and funding subgroups.Results:A total of 21 RCTs (4969 participants) were identified. Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest.Conclusions:Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD.

A Preliminary Study: Efficacy of Mindfulness-Based Cognitive Therapy versus Sertraline as First-line Treatments for Major Depressive Disorder.

Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. The primary aim of this pilot study was to investigate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) monotherapy, compared to sertraline monotherapy, for patients with acute MDD. This open-label, nonrandomized controlled trial examined a MBCT cohort (N=23) recruited to match the gender, age, and depression severity of a depressed control group (N=20) that completed 8 weeks of monotherapy with the antidepressant sertraline. The 17-item clinician-rated Hamilton Depression Severity Rating Scale (HAMD-17) was the primary outcome measure of depression to assess overall change after 8 weeks and rates of response and remission. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) was the secondary outcome measure to further assess depression severity. Both cohorts were demographically similar and showed significant improvement in depression ratings. No difference was found in the degree of change in HAMD-17 scores (t(34) = 1.42, p = .165) between groups. Secondary analysis showed statistically significant differences in mean scores of the QIDS-SR16 (t (32) = 4.39, p < 0.0001), with the MCBT group showing greater mean improvement. This study was limited by the small sample size and non-randomized, non-blinded design. Preliminary findings suggest that an 8-week course of MBCT monotherapy may be effective in treating MDD and a viable alternative to antidepressant medication. Greater changes in the self-rated QIDS-SR16 for the MBCT cohort raise the possibility that patients derive additional subjective benefit from enhanced self-efficacy skills.

EPA-1376 – Interpersonal psychotherapy in the treatment of mental illness in the vulnerable economic scenario nowadays: an exploratory study with depressed outpatients

Introduction Portugal is a country with severe economic difficulties for the last 2 years. Considering the volatile and vulnerable economic social system today, in Portugal, the number of jobs decreased, unemployment increased and, as a consequence, mental illnesses as well. Because of it, and, the request for quicker treatments of mental health by the population are increasing significantly. Objective Our objective is to evidence in Portugal one of the very first IPT researches as an advisable treatment of acute major depressive disorder, mainly in the current economic scenario, contributing to evidence an effective way to combat mental illness in Portugal. Methods The ongoing longitudinal study consist of adult outpatients (n=50), diagnosed with acute major depressive episode. The intensity of depression was measured is sessions 1, 6 and 10, with the Center for Epidemiological Studies Depression Rating Scale (CES-D). The procedure is focused in one of four IPT problem areas (role transitions, disputes, grief and loss, and difficulties initiating or sustaining relationships). Results The first results show significant trend to identify the Disputes as the main problem-area. The intensity of the depression is significant lower along sessions with same patients. In 8th session, there is a significant decrease of the depressive symptomatology and the patient is more functional and adapted. Conclusions Our research evidences the vulnerability to social context amidst the Portuguese economic crisis to depression, as well it evidences the effectiveness of IPT as a brief psychotherapy that responds to the current needs of a population with growing economic difficulties.

Acute Antidepressive Efficacy of Lithium Monotherapy, Not Citalopram, Depends on Recurrent Course of Depression

Studies of the 1970s and 1980s showed lithium monotherapy to be an effective treatment of acute unipolar major depressive disorder (MDD) and hence as a potential alternative to monoaminergic antidepressants.The objective was to conduct the first comparison of a lithium monotherapy with a modern antidepressant in the acute treatment of MDD. Results were compared with citalopram's efficacy as shown in a different but methodologically identical study (including same researchers, same time, and same place).Thirty patients with an acute MDD (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] I) were treated with lithium monotherapy (study 1) or with citalopram monotherapy (study 2, N = 32) for 4 weeks.Response rates (decrease in Hamilton Depression Rating Scale score >50%) were 50% for lithium and 72% for citalopram (P = 0.12). Citalopram-treated subjects showed a greater decrease in Hamilton Depression Rating Scale scores (significant at 2 weeks). In the lithium study, only patients with a recurrent episode (DSM-IV: 296.3) responded (15/22), as opposed to none of 8 patients with a first/single episode (DSM-IV: 296.2) (P = 0.002). Patients with a single episode responded significantly more often to citalopram than to lithium (P = 0.007). Both drugs were well tolerated. Only one patient (citalopram) terminated the study prematurely owing to adverse effects.Our results do not support the use of lithium as an alternative to SSRI in the treatment of acute MDD. The finding of a better response to lithium in patients with a recurrent depression has not been reported before and warrants replication. The comparison is limited by the lack of a randomized double-blind design.

Lamotrigine (Lamictal IR) for the treatment of bipolar disorder

Introduction: Over the past decade the use of lamotrigine in bipolar disorder has increased. However, the evidence base suggests a more limited role for lamotrigine as part of an overall treatment regimen in bipolar disorder.Areas covered: We reviewed publications of randomized clinical trials of lamotrigine, emphasizing studies in bipolar disorder. The low burden of adverse effects with lamotrigine has been confirmed in these studies. Its lack of benefit in acute mania is established. Despite modest benefits for a subset of depressive episodes in bipolar disorder, it was not superior to placebo in well-designed studies. As monotherapy, in randomized, blinded trials in rapid cycling bipolar disorder it was not superior to placebo. Its role in maintenance treatment is relatively well established as one component of combination therapy, with evidence for benefits when combined with lithium or valproate. Combination regimens including lamotrigine appear to be superior to monotherapy. Monotherapy utilization of lamotrigine for maintenance treatment is not supported by these studies.Expert opinion: Lamotrigine has benefits in bipolar disorder management principally as a component of combination treatment which includes a mood stabilizer. The utility of lamotrigine in acute bipolar depression and major depressive disorder is modest.

An exploratory study of combination buspirone and melatonin SR in Major Depressive Disorder (MDD): A possible role for neurogenesis in drug discovery

We used in vitro neurogenesis-based human neural stem cell (hNSCs) assays and rodent in vivo behavioral assays to identify potential novel antidepressants. A combination of buspirone and melatonin displayed antidepressant activity in these assays whereas neither buspirone nor melatonin alone showed any antidepressant-like profile. After evaluating numerous combination ratios, we determined that low dose buspirone 15 mg combined with melatonin-SR 3 mg yielded optimal antidepressant efficacy in our pre-clinical platform. The low dose of buspirone suggested that antidepressant efficacy might be achieved with only minimal adverse event liability. Based on these data, we conducted an exploratory 6-week, multi-center, double-blind, randomized, placebo- and comparator-controlled study of the combination of buspirone and melatonin in subjects with acute Major Depressive Disorder (MDD). The combination treatment revealed a significant antidepressant response in subjects with MDD on several measures (Clinical Global Impression of Severity and Improvement, Inventory of Depressive Symptomatology) compared to either placebo or buspirone 15 mg monotherapy. These preliminary findings have clinical implications and suggest that a platform of pre-clinical neurogenesis matched with confirmatory behavioral assays may be useful as a drug discovery strategy.

Interpersonal psychotherapy (IPT) in major depressive disorder

In this article, we will introduce interpersonal psychotherapy as an effective short-term treatment strategy in major depression. In IPT, a reciprocal relationship between interpersonal problems and depressive symptoms is regarded as important in the onset and as a maintaining factor of depressive disorders. Therefore, interpersonal problems are the main therapeutic targets of this approach. Four interpersonal problem areas are defined, which include interpersonal role disputes, role transitions, complicated bereavement, and interpersonal deficits. Patients are helped to break the interactions between depressive symptoms and their individual interpersonal difficulties. The goals are to achieve a reduction in depressive symptoms and an improvement in interpersonal functioning through improved communication, expression of affect, and proactive engagement with the current interpersonal network. The efficacy of this focused and structured psychotherapy in the treatment of acute unipolar major depressive disorder is summarized. This article outlines the background of interpersonal psychotherapy, the process of therapy, efficacy, and the expansion of the evidence base to different subgroups of depressed patients.

Contribution of spontaneous improvement to placebo response in depression: A meta-analytic review

ObjectivesIt is unknown to what degree spontaneous improvement accounts for the large placebo response observed in antidepressant trials for Major Depressive Disorder (MDD). The purpose of this study was to estimate the spontaneous improvement observed in treatment-seeking individuals with acute MDD by determining the symptom change in depressed patients assigned to wait-list controls in psychotherapy studies. MethodThe databases PubMed and PsycINFO were searched to identify randomized, prospective studies randomizing outpatients to psychotherapy or a wait-list control condition for the treatment of acute MDD. Standardized effect sizes calculated from each identified study were aggregated in a meta-analysis to obtain a summary statistic for the change in depression scores during participation in a wait-list control. ResultsTen trials enrolling 340 participants in wait-list control conditions were identified. The estimated effect size for the change in depression scores during wait-list control was 0.505 (95% CI 0.271–0.739, p < 0.001), representing an average improvement of 4 points on the Hamilton Rating Scale for Depression. DiscussionDepressed patients acutely experience improvement even without treatment, but spontaneous improvement is unlikely to account for the magnitude of placebo response typically observed in antidepressant trials. These findings must be interpreted in light of the small number wait-list control participants available for analysis as well as certain methodological heterogeneity in the psychotherapy studies analyzed.

Serotonin Transporter Polymorphism Modulates N-Back Task Performance and fMRI BOLD Signal Intensity in Healthy Women

ContextExploring intermediate phenotypes within the human brain's functional and structural circuitry is a promising approach to explain the relative contributions of genetics, complex behaviors and neural mechanisms in the development of major depressive disorder (MDD). The polymorphic region 5-HTTLPR in the serotonin transporter gene (SLC6A4) has been shown to modulate MDD risk, but the neural underpinnings are incompletely understood.Objective37 right handed healthy women between 21 and 61 years of age were invited to participate in an fMRI modified n-back study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR).ResultsShort 5-HTTLPR allele carriers showed more blood-oxygen-level-dependent (BOLD) bilateral prefrontal cortex activation in the right [F(2, 30) = 4.8, η2 = .25, p = .026] and left [F(2, 30) = 4.1, η2 = .22, p = .015] inferior frontal gyrus pars triangularis with increasing n-back task difficulty relative to long 5-HTTLPR allele carriers. Short 5-HTTLPR allele carriers had inferior task performance on the most difficult n-back condition [F(2, 30) = 4.9, η2 = .26, p = .014].ConclusionsThis activation pattern found in healthy at risk individuals resembles an activation pattern that is typically found in patients suffering from acute MDD. Altered function in these areas may reflect intermediate phenotypes and may help explain the increased risk of depression in short 5-HTTLPR allele carriers.

Functional anomalies in healthy individuals with a first degree family history of major depressive disorder

BackgroundIndividuals with major depressive disorder (MDD) process information with a bias towards negative stimuli. However, little is known on the link between vulnerability to MDD and brain functional anomalies associated with stimulus bias.MethodsA cohort of 38 subjects, of which 14 were patients with acute MDD and 24 were healthy controls (HC), were recruited and compared. The HC group included 10 healthy participants with a first degree family history of depression (FHP) and 14 volunteers with no family history of any psychiatric disease (FHN). Blood oxygen level dependence signals were acquired from functional magnetic resonance imaging (fMRI) during performance in a dot-probe task using fearful and neutral stimuli. Reaction times and the number of errors were also obtained.ResultsAlthough MDD patients and HC showed no behavioral difference, the MDD group exhibited smaller activation in the left middle cingulum. The MDD group also showed smaller activation in the left insula when compared to the HC group or the FHN group. Finally, FHP participants exhibited higher activation in the right Heschl's gyrus compared to FHN participants.ConclusionsThe present study shows that family risk for MDD is associated with increased activation in the Heschl's gyrus. Our results also suggest that acute MDD is linked to reduced activation in the insula and anterior cingulate cortex during processing of subliminal, not recognizable, masked fearful stimuli. Further research should confirm these results in a larger cohort of participants.

Resting state network alterations in major Depression

Major depressive disorder (MDD) is increasingly being conceptualized as a systems disorder mediated by a disturbance of multiple brain networks. The analysis of functional connectivity (fc) in the resting state has emerged as a powerful tool when applied to neuropsychiatric disorders. We employed resting state functional magnetic resonance imaging to examine fc in multiple resting state networks gained by means of probabilistic group Independent Component Analysis in 43 patients with acute MDD compared to 43 matched controls from a data-driven perspective. Individual network representations were estimated with the dual regression approach. Patients exhibited reduced fc in several networks. Contrary to our expectation that fc alterations would primarily be detected in affective and cognitive networks, effects were strongest in networks implicated in sensory processing, especially visual networks. Reduced fc was also detected in a basal ganglia network, consistent with a role of the basal ganglia in reward-related and affective processing. While imaging research in MDD has focused on networks directly implicated in mood regulation and cognition, these data suggest that network pathology in MDD is not confined to the primary mood-regulating circuit. Considering the heterogeneity of MDD, a systemic approach taking into account alterations in multiple networks may represent the most promising step for the definition of biologically relevant subgroups and potential biomarkers.

Association Between Citalopram Serum Levels and Clinical Improvement of Patients With Major Depression

Imaging studies have shown that serum concentrations of the selective serotonin reuptake inhibitor citalopram correlate with serotonin transporter (5-HTT) occupancy in vivo. In patients with major depressive disorders treated with citalopram, 80% 5-HTT occupancy was considered to be necessary for maximal therapeutic effects, which requires citalopram serum concentrations of at least 50 ng/mL. The aim of this study was to compare treatment outcome in patients with citalopram serum concentrations greater than and less than 50 ng/mL after 7 days of treatment. This study included inpatients with acute major depressive disorder according to International Classification of Disease, 10th Revision who were treated with citalopram. In weekly intervals, the severity of depression was assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17), and serum concentrations of citalopram were measured from baseline until week 5. Fifty-five patients were eligible for this analysis. After 7 days of treatment, 19 patients showed citalopram serum concentrations of 50 ng/mL or greater; 36 patients had lower concentrations. Patients at greater than the 50-ng/mL threshold had (i) lower mean HAMD-17 sum scores from day 7 to end point (P ≤ 0.018 for each analysis); (ii) a more pronounced HAMD-17 decrease (P ≤ 0.019 for each analysis), and (iii) 23 days' shorter duration of hospitalization (P = 0.033) than patients with levels of citalopram less than 50 ng/mL. As regards adverse effects, both patient groups were not significantly different. Despite therapeutic doses, a significant number of patients had serum concentrations less than 50 ng/mL, and these were associated with an unfavorable treatment outcome; therapeutic drug monitoring is recommended to optimize dosing citalopram in the early phase of treatment.

P02-38 - Biological alterations during remission of major depressive disorder

IntroductionThe natural course of Major Depressive Disorder (MDD) encompasses the occurrence of alternating intervals of major depressive episodes and remission. While several abnormalities in neural circuits related to acute MDD have been identified, the neural mechanisms underlying stable remission remain obscure.ObjectivesAcute MDD is characterized by increased amygdala and subgenual anterior cingulate cortex (sACC) activation and decreased connectivity between the amygdala and the sACC. Consequently, we expect those regions to be affected during remission.AimsTo determine whether active counter-regulatory mechanisms are implicated in the maintenance of full remission once antidepressant treatment has been discontinued.MethodsFunctional and structural magnetic resonance imaging was used to measure brain activation and volume of the amygdala and the sACC. Images were obtained from 38 healthy subjects without any psychiatric life-time diagnosis and 38 gender-matched drug-free remitted MDD patients. Furthermore, correlation analyses were performed with clinical variables.ResultsPatients with rMDD exhibited lower activation in the amygdala and the sACC and increased functional coupling between the amygdala and sACC compared to controls. This connectivity was particularly pronounced in patients characterized by a long cumulated time of depressive episodes. Similarly, structural connectivity results showed increased association between the amygdala and sACC volume in rMDD patients compared to controls.ConclusionsRemitted MDD is related to neural alterations within a neural circuit encompassing the amygdala and the sACC compared to controls. These findings suggest active counter-regulatory mechanisms likely contributing to the maintenance of remission once treatment has been discontinued.

Reduced olfactory bulb volume and olfactory sensitivity in patients with acute major depression

The purpose of this study was to assess olfactory function and olfactory bulb volume in patients with acute major depression in comparison to a normal population. Twenty-one patients diagnosed with acute major depressive disorder and 21 healthy controls matched by age, sex and smoking behavior participated in this study. Olfactory function was assessed in a lateralized fashion using measures of odor threshold, discrimination and identification. Olfactory bulb volumes were calculated by manual segmentation of acquired T2-weighted coronal slices according to a standardized protocol. Patients with acute major depressive disorder showed significantly lower olfactory sensitivity and smaller olfactory bulb volumes. Additionally, a significant negative correlation between olfactory bulb volume and depression scores was detected. Their results provide the first evidence, to our knowledge, of decreased olfactory bulb volume in patients with acute major depression. These results might be related to reduced neurogenesis in major depression that could be reflected also at the level of the olfactory bulb.

Dépressions sévères : particularités du trouble bipolaire

Bipolar depressions can present all the clinical aspects from a major depressive episode with a mild intensity to severe one. However, part of this severity comes from the bipolarity by itself. Bipolar disorders belong to the 10 most disabling conditions in the world. Moreover, the complexity of bipolar depressions comes also from the complexity to treat them. Antidepressants are difficult to use in bipolar subjects because the risk of switch, the possible induction of rapid cycles or of a chronic dysphoric state. Currently, guidelines are not very helpful for the choice of the treatment in case of an acute major depressive disorder. Indeed, the current guidelines give the choice between a mood stabilizer alone or associated with an antidepressant, either between an antipsychotic more or less associated with an antidepressant. A better understanding of the clinical heterogeneity of bipolar depression could help to solve a part of this complexity.