Rostral anterior cingulate cortex activity in the theta band predicts response to antidepressive medication.

During the last 10 years the knowledge about rostral anterior cingulate cortex (ACC) activity in major depression has substantially increased. Several groups have independently described a relationship between resting activity in this area and response to antidepressant treatment. We have recently confirmed a relationship between resting activity of rostral ACC activity and response in a group of 20 patients with major depression using resting theta activity. In this earlier study regions of interest (ROI) were defined in order to establish regional specificity. Differences between responders and nonresponders were only found in the ACC-ROI, but not in the posterior cingulate region. We have now reanalyzed our data using a whole brain voxelwise approach, in order not to miss any other relevant functional differences. In addition to major differences between responders and nonresponders in the rostral ACC, we have identified a nearby region in the midline orbito-frontal region.     

Functional impairment‐based segmentation of anterior cingulate cortex in depression and its relationship with treatment effects

In major depressive disorder (MDD), the anterior cingulate cortex (ACC) is widely related to depression impairment and antidepressant treatment response. The multiplicity of ACC subdivisions calls for a fine‐grained investigation of their functional impairment and recovery profiles. We recorded resting state fMRI signals from 59 MDD patients twice before and after 12‐week antidepressant treatment, as well as 59 healthy controls (HCs). With functional connectivity (FC) between each ACC voxel and four regions of interests (bilateral dorsolateral prefrontal cortex [DLPFC] and amygdalae), subdivisions with variable impairment were identified based on groups'' dissimilarity values between MDD patients before treatment and HC. The ACC was subdivided into three impairment subdivisions named as MedialACC, DistalACC, and LateralACC according to their dominant locations. Furthermore, the impairment pattern and the recovery pattern were measured based on group statistical analyses. DistalACC impaired more on its FC with left DLPFC, whereas LateralACC showed more serious impairment on its FC with bilateral amygdalae. After treatment, FCs between DistalACC and left DLPFC, and between LateralACC and right amygdala were normalized while impaired FC between LateralACC and left amygdala kept dysfunctional. Subsequently, FC between DistalACC and left DLPFC might contribute to clinical outcome prediction. Our approach could provide an insight into how the ACC was impaired in depression and partly restored after antidepressant treatment, from the perspective of the interaction between ACC subregions and critical frontal and subcortical regions.     

Plasma fibrinogen: now also an antidepressant response marker?

Major depressive disorder (MDD) is one of the leading causes of global disability. It is a risk factor for noncompliance with medical treatment, with about 40% of patients not responding to currently used antidepressant drugs. The identification and clinical implementation of biomarkers that can indicate the likelihood of treatment response are needed in order to predict which patients will benefit from an antidepressant drug. While analyzing the blood plasma proteome collected from MDD patients before the initiation of antidepressant medication, we observed different fibrinogen alpha (FGA) levels between drug responders and nonresponders. These results were replicated in a second set of patients. Our findings lend further support to a recently identified association between MDD and fibrinogen levels from a large-scale study.     

A review of fMRI studies during visual emotive processing in major depressive disorder

Objectives. This review synthesized literature on brain activity, indexed by functional magnetic resonance imaging (fMRI), during visual affective information processing in major depressive disorder (MDD). Activation was examined in regions consistently implicated in emotive processing, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), amygdala, thalamus/basal ganglia and hippocampus. We also reviewed the effects of antidepressant interventions on brain activity during emotive processing. Methods. Sixty-four fMRI studies investigating neural activity during visual emotive information processing in MDD were included. Results. Evidence indicates increased ventro-rostral ACC activity to emotive stimuli and perhaps decreased dorsal ACC activity in MDD. Findings are inconsistent for the PFC, though medial PFC hyperactivity tends to emerge to emotive information processing in the disorder. Depressed patients display increased amygdala activation to negative and arousing stimuli. MDD may also be associated with increased activity to negative, and decreased activity to positive, stimuli in basal ganglia/thalamic structures. Finally, there may be increased hippocampus activation during negative information processing. Typically, antidepressant interventions normalize these activation patterns. Conclusion. In general, depressed patients have increased activation to emotive, especially negative, visual stimuli in regions involved in affective processing, with the exception of certain PFC regions; this pattern tends to normalize with treatment.     

Serum Ghrelin Levels and the Effects of Antidepressants in Major Depressive Disorder and Panic Disorder

Background: Two opposing models for the action of ghrelin in the behavioral responses to stress were recently proposed. Some studies suggest that an increase in ghrelin contributes to the mechanisms responsible for the development of stress-induced depression and anxiety, while others suggest that it helps minimize what otherwise would be more severe manifestations of depression and anxiety following stress. Methods: We measured serum ghrelin levels, Profile of Mood States (POMS) scores and State-Trait Anxiety Inventory scores in nonresponders (treatment-resistant patients; 30) and responders (38) with major depressive disorder (MDD), nonresponders (29) and responders (51) with panic disorder and 97 healthy controls. Results: The ghrelin concentration in nonresponders with MDD was higher than that of responders with MDD and normal controls. The ghrelin concentration in nonresponders with panic disorder was higher than that of normal controls. POMS vigor scores in patients with MDD and panic disorder were significantly decreased compared with those in healthy controls. Other POMS scores in patients with MDD and panic disorder were significantly increased compared with those of healthy controls. Trait and state anxiety of the State-Trait Anxiety Inventory in MDD and panic disorder patients were higher than those in healthy controls. Conclusions: These results indicate that decreased serum ghrelin levels might be associated with antidepressant treatment to confer the maximum therapeutic effect in patients with MDD and panic disorder.     

Vascular endothelial growth factor: Potential predictor of treatment response in major depression

Objectives: The aim of the study was to evaluate baseline plasma VEGF levels as a potential predictor of response to antidepressant pharmacotherapy. The study also sought to determine whether baseline plasma VEGF would be useful in predicting treatment outcome when two pharmacodynamically diverse agents with established antidepressant efficacy, escitalopram and quetiapine, were administered monotherapeutically to MDD patients. Methods: Two groups of qualifying MDD subjects were enrolled. One group was treated with escitalopram and the other with quetiapine. Plasma concentrations of VEGF were measured using Randox Technologies at baseline, and at weeks 8 and 12 of treatment. Results: We stratified the MDD patients into those who remitted and those who failed to respond. Mean baseline VEGF for the remitters and non-responders was 9.61 and 5.40?pg/ml, respectively (P?Conclusions: Our results suggest that VEGF may predict response to antidepressant treatment and may ultimately prove to be a potential biomarker that can be measured with a routine blood draw at the point of service.     

Resting state brain network function in major depression – Depression symptomatology,antidepressant treatment effects,future research

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker.     

Serotonin transporter residual availability during long-term antidepressant therapy does not differentiate responder and nonresponder unipolar patients.

BACKGROUND: Serotonin transporters (SERT) are a major target for antidepressant medication, although there have been limited in vivo studies of SERT availability in patients being treated with antidepressants. It is not known whether SERT availability differs in treatment-responsive and -nonresponsive patients receiving long-term treatment. In this study, we used single photon emission computed tomography (SPECT) to compare SERT residual availability in unipolar responders and nonresponders during long-term antidepressant treatment. Dopamine transporter (DAT) availability was also assessed in the same patients to examine the relationship between the two transporter systems. METHODS: Twenty-four medicated unipolar patients were recruited, of whom 11 were responders and 13 were nonresponders. All patients underwent SPECT with [123I] beta-carbomethoxy-3-beta-(4 iodophenyl)tropane. Brain SERT was measured in the brain stem and diencephalon, and DAT was measured in the striatum. Residual availability was calculated as a ratio of specific to nonspecific uptake, with the occipital region used as the nonspecific reference region. RESULTS: There was no difference between responders and nonresponders in SERT availability. Dopamine transporter availability was similar in responders and nonresponders, and there was no association between SERT and DAT availability. CONCLUSIONS: Serotonin transporter availability does not discriminate responders and nonresponders during long-term treatment with antidepressants.     

Switching to Bupropion in Fluoxetine-Resistant Major Depressive Disorder

Up to 50% of patients with major depressive disorder (MDD) fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as an initial treatment. Switching to bupropion, for depressed patients not responding to SSRIs, is a popular strategy among clinicians. This study assesses the efficacy of bupropion SR in the management of MDD resistant to a prospective trial of fluoxetine. Twenty-nine patients with MDD refractory to an 8- to 12-week open-trial of fluoxetine were enrolled in an 8-week open-trial of bupropion SR. Both a completer analysis (n = 20) and a modified intent-to-treat analysis (n = 26) were performed to evaluate bupropion SR response rates. Using a completer analysis, seven patients (35.0%) were classified as responders, five (25.0%) partial responders, and eight (40.0%) nonresponders. A modified intent to treat analysis resulted in nine (34.6%) patients classified as responders, eight (30.8%) partial responders, and nine (34.6%) nonresponders. The overall proportion of remitters was 6/20 (30.0%) using a completer analysis and 6/26 (23.1%) using an MITT analysis. Approximately 60% of patients with MDD resistant to a prospective trial of fluoxetine experienced a full or partial response to bupropion SR. Bupropion SR should be considered as a potential treatment for patients who remain depressed despite treatment with SSRIs.     

The effects of antidepressant treatment on resting‐state functional brain networks in patients with major depressive disorder

Although most knowledge regarding antidepressant effects is at the receptor level, the neurophysiological correlates of these neurochemical changes remain poorly understood. Such an understanding could benefit from elucidation of antidepressant effects at the level of neural circuits, which would be crucial in identifying biomarkers for monitoring treatment efficacy of antidepressants. In this study, we recruited 20 first‐episode drug‐naive major depressive disorder (MDD) patients and performed resting‐state functional magnetic resonance imaging (MRI) scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor—escitalopram. Twenty healthy controls (HCs) were also scanned twice with an 8‐week interval. Whole‐brain connectivity was analyzed using a graph‐theory approach—functional connectivity strength (FCS). The analysis of covariance of FCS was used to determine treatment‐related changes. We observed significant group‐by‐time interaction on FCS in the bilateral dorsomedial prefrontal cortex and bilateral hippocampi. Post hoc analyses revealed that the FCS values in the bilateral dorsomedial prefrontal cortex were significantly higher in the MDD patients compared to HCs at baseline and were significantly reduced after treatment; conversely, the FCS values in the bilateral hippocampi were significantly lower in the patients at baseline and were significantly increased after treatment. Importantly, FCS reduction in the dorsomedial prefrontal cortex was significantly correlated with symptomatic improvement. Together, these findings provided evidence that this commonly used antidepressant can selectively modulate the intrinsic network connectivity associated with the medial prefrontal‐limbic system, thus significantly adding to our understanding of antidepressant effects at a circuit level and suggesting potential imaging‐based biomarkers for treatment evaluation in MDD. Hum Brain Mapp 36:768–778, 2015. © 2014 Wiley Periodicals, Inc.     

Changes in brain function of depressed subjects during treatment with placebo.

OBJECTIVE: It has been proposed that 50%-75% of the efficacy of antidepressant medication represents the placebo effect, since many depressed patients improve when treated with either medication or placebo. This study examined brain function in depressed subjects receiving either active medication or placebo and sought to determine whether quantitative electroencephalography (QEEG) could detect differences in brain function between medication and placebo responders. Both QEEG power and cordance, a new measure that reflects cerebral perfusion and is sensitive to the effect of antidepressant medication, were examined. METHOD: Fifty-one subjects with major depression were enrolled in one of two independent, 9-week double-blind, placebo-controlled studies in which either fluoxetine (N=24) or venlafaxine (N=27) was the active medication. Serial QEEG recordings were performed during the course of treatment. After 9 weeks, the blind was broken and subjects were classified as medication responders, placebo responders, medication nonresponders, or placebo nonresponders. RESULTS: No significant pretreatment differences in clinical or QEEG measures were found among the four outcome groups. Placebo responders, however, showed a significant increase in prefrontal cordance starting early in treatment that was not seen in medication responders (who showed decreased cordance) or in medication nonresponders or placebo nonresponders (who showed no significant change). There was no significant change in QEEG power during treatment. CONCLUSIONS: These findings suggest that "effective" placebo treatment induces changes in brain function that are distinct from those associated with antidepressant medication. If these results are confirmed, cordance may be useful for differentiating between medication and placebo responders.     

Anomalous single‐subject based morphological cortical networks in drug‐naive,first‐episode major depressive disorder

Major depressive disorder (MDD) has been associated with disruptions in the topological organization of brain morphological networks in group‐level data. Such disruptions have not yet been identified in single‐patients, which is needed to show relations with symptom severity and to evaluate their potential as biomarkers for illness. To address this issue, we conducted a cross‐sectional structural brain network study of 33 treatment‐naive, first‐episode MDD patients and 33 age‐, gender‐, and education‐matched healthy controls (HCs). Weighted graph‐theory based network models were used to characterize the topological organization of brain networks between the two groups. Compared with HCs, MDD patients exhibited lower normalized global efficiency and higher modularity in their whole‐brain morphological networks, suggesting impaired integration and increased segregation of morphological brain networks in the patients. Locally, MDD patients exhibited lower efficiency in anatomic organization for transferring information predominantly in default‐mode regions including the hippocampus, parahippocampal gyrus, precuneus and superior parietal lobule, and higher efficiency in the insula, calcarine and posterior cingulate cortex, and in the cerebellum. Morphological connectivity comparisons revealed two subnetworks that exhibited higher connectivity strength in MDD mainly involving neocortex‐striatum‐thalamus‐cerebellum and thalamo‐hippocampal circuitry. MDD‐related alterations correlated with symptom severity and differentiated individuals with MDD from HCs with a sensitivity of 87.9% and specificity of 81.8%. Our findings indicate that single subject grey matter morphological networks are often disrupted in clinically relevant ways in treatment‐naive, first episode MDD patients. Circuit‐specific changes in brain anatomic network organization suggest alterations in the efficiency of information transfer within particular brain networks in MDD. Hum Brain Mapp 38:2482–2494, 2017. © 2017 Wiley Periodicals, Inc.     

Neural and behavioral correlates of negative self‐focused thought associated with depression

A central feature of major depression (MDD) is heightened negative self‐focused thought (negative‐SFT). Neuroscientific research has identified abnormalities in a network of brain regions in MDD, including brain areas associated with SFT such as medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). To our knowledge no studies have investigated the behavioral and neural correlates of negative‐SFT using a sentence completion task in a sample of individuals with varying depression histories and severities. We test the following hypotheses: (1) negative‐SFT will be associated with depression; and (2) depression and negative‐SFT will be related to resting‐state functional connectivity (rsFC) for brain regions implicated in SFT. Seventy‐nine women with varying depression histories and severities completed a sentence completion task and underwent resting‐state functional magnetic resonance imaging (rs‐fMRI). Standard seed‐based voxelwise rsFC was conducted for self‐network regions of interest: dorsomedial PFC (dmPFC) and pregenual ACC (pgACC). We performed linear regression analyses to examine the relationships among depression, negative‐SFT, and rsFC for the dmPFC and pgACC. Greater negative‐SFT was associated with depression history and severity. Greater negative‐SFT predicted increased rsFC between dmPFC and pgACC seeds and dorsolateral prefrontal (dlPFC) and parietal regions; depression group was also associated with increased pgACC‐dlPFC connectivity. These findings are consistent with previous literature reporting elevated negative‐SFT thought in MDD. Our rs‐fMRI results provide novel support linking negative‐SFT with increased rsFC between self‐network and frontoparietal network regions across different levels of depression. Broadly, these findings highlight a dimension of social‐affective functioning that may underlie MDD and other psychiatric conditions.     

Large‐scale dynamic causal modeling of major depressive disorder based on resting‐state functional magnetic resonance imaging

Major depressive disorder (MDD) is a serious mental illness characterized by dysfunctional connectivity among distributed brain regions. Previous connectome studies based on functional magnetic resonance imaging (fMRI) have focused primarily on undirected functional connectivity and existing directed effective connectivity (EC) studies concerned mostly task‐based fMRI and incorporated only a few brain regions. To overcome these limitations and understand whether MDD is mediated by within‐network or between‐network connectivities, we applied spectral dynamic causal modeling to estimate EC of a large‐scale network with 27 regions of interests from four distributed functional brain networks (default mode, executive control, salience, and limbic networks), based on large sample‐size resting‐state fMRI consisting of 100 healthy subjects and 100 individuals with first‐episode drug‐naive MDD. We applied a newly developed parametric empirical Bayes (PEB) framework to test specific hypotheses. We showed that MDD altered EC both within and between high‐order functional networks. Specifically, MDD is associated with reduced excitatory connectivity mainly within the default mode network (DMN), and between the default mode and salience networks. In addition, the network‐averaged inhibitory EC within the DMN was found to be significantly elevated in the MDD. The coexistence of the reduced excitatory but increased inhibitory causal connections within the DMNs may underlie disrupted self‐recognition and emotional control in MDD. Overall, this study emphasizes that MDD could be associated with altered causal interactions among high‐order brain functional networks.     

Eight‐week antidepressant treatment reduces functional connectivity in first‐episode drug‐naïve patients with major depressive disorder

Previous neuroimaging studies have revealed abnormal functional connectivity of brain networks in patients with major depressive disorder (MDD), but findings have been inconsistent. A recent big‐data study found abnormal intrinsic functional connectivity within the default mode network in patients with recurrent MDD but not in first‐episode drug‐naïve patients with MDD. This study also provided evidence for reduced default mode network functional connectivity in medicated MDD patients, raising the question of whether previously observed abnormalities may be attributable to antidepressant effects. The present study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03294525","term_id":"NCT03294525"}}NCT03294525) aimed to disentangle the effects of antidepressant treatment from the pathophysiology of MDD and test the medication normalization hypothesis. Forty‐one first‐episode drug‐naïve MDD patients were administrated antidepressant medication (escitalopram or duloxetine) for 8 weeks, with resting‐state functional connectivity compared between posttreatment and baseline. To assess the replicability of the big‐data finding, we also conducted a cross‐sectional comparison of resting‐state functional connectivity between the MDD patients and 92 matched healthy controls. Both Network‐Based Statistic analyses and large‐scale network analyses revealed intrinsic functional connectivity decreases in extensive brain networks after treatment, indicating considerable antidepressant effects. Neither Network‐Based Statistic analyses nor large‐scale network analyses detected significant functional connectivity differences between treatment‐naïve patients and healthy controls. In short, antidepressant effects are widespread across most brain networks and need to be accounted for when considering functional connectivity abnormalities in MDD.     

Electroconvulsive therapy treatment responsive multimodal brain networks

Electroconvulsive therapy is regarded as the most effective antidepressant treatment for severe and treatment‐resistant depressive episodes. Despite the efficacy of electroconvulsive therapy, the neurobiological underpinnings and mechanisms underlying electroconvulsive therapy induced antidepressant effects remain unclear. The objective of this investigation was to identify electroconvulsive therapy treatment responsive multimodal biomarkers with the 17‐item Hamilton Depression Rating Scale guided brain structure–function fusion in 118 patients with depressive episodes and 60 healthy controls. Results show that reduced fractional amplitude of low frequency fluctuations in the prefrontal cortex, insula and hippocampus, linked with increased gray matter volume in anterior cingulate, medial temporal cortex, insula, thalamus, caudate and hippocampus represent electroconvulsive therapy responsive covarying functional and structural brain networks. In addition, relative to nonresponders, responder‐specific electroconvulsive therapy related brain networks occur in frontal‐limbic network and are associated with successful therapeutic outcomes. Finally, electroconvulsive therapy responsive brain networks were unrelated to verbal declarative memory. Using a data‐driven, supervised‐learning method, we demonstrated that electroconvulsive therapy produces a remodeling of brain functional and structural covariance that was unique to antidepressant symptom response, but not linked to memory impairment.     

Rapid‐acting antidepressant ketamine,its metabolites and other candidates: A historical overview and future perspective

Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one‐third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists an unmet medical need for rapidly acting antidepressants with beneficial effects in treatment‐resistant patients with MDD or BD. Accumulating evidence suggests that the N‐methyl‐D‐aspartate receptor (NMDAR) antagonist ketamine produces rapid and sustained antidepressant effects in treatment‐resistant patients with MDD or BD. Ketamine is a racemic mixture comprising equal parts of (R)‐ketamine (or arketamine) and (S)‐ketamine (or esketamine). Because (S)‐ketamine has higher affinity for NMDAR than (R)‐ketamine, esketamine was developed as an antidepressant. On 5 March 2019, esketamine nasal spray was approved by the US Food and Drug Administration. However, preclinical data suggest that (R)‐ketamine exerts greater potency and longer‐lasting antidepressant effects than (S)‐ketamine in animal models of depression and that (R)‐ketamine has less detrimental side‐effects than (R,S)‐ketamine or (S)‐ketamine. In this article, the author reviews the historical overview of the antidepressant actions of enantiomers of ketamine and its major metabolites norketamine and hydroxynorketamine. Furthermore, the author discusses the other potential rapid‐acting antidepressant candidates (i.e., NMDAR antagonists and modulators, low‐voltage‐sensitive T‐type calcium channel inhibitor, potassium channel Kir4.1 inhibitor, negative modulators of γ‐aminobutyric acid, and type A [GABA_A] receptors) to compare them with ketamine. Moreover, the molecular and cellular mechanisms of ketamine’s antidepressant effects are discussed.     

A description of next-step switching versus augmentation practices for outpatients with treatment-resistant major depressive disorder enrolled in an academic specialty clinic.

BACKGROUND: There is a paucity of naturalistic studies from depression specialty clinics describing the next-step (augmentation versus switching) practices of clinicians for outpatients with major depressive disorder (MDD) resistant to an antidepressant trial of adequate dose and duration. METHODS: Eighty-five MDD outpatients enrolled in one of two specialty clinics, who had not achieved remission after a first adequate prospective antidepressant trial conducted at the clinic underwent either augmentation (n = 36) or switching (n=49) of their antidepressant regimen. Outcome was defined with the use of the Clinical Global Impressions (CGI) Scale. RESULTS: Nonresponders (CGI-I>3) following the first antidepressant trial were more likely to have their treatment switched than patients who experienced incomplete response (CGI-I<4, CGI-S>1) (67.2% versus 28.5%, p = 0.001). Incomplete responders during the first trial who went on to receive augmentation had higher remission rates (60.0% versus 0%, p=0.01), lower endpoint depression severity scores (1.8 +/- 1.1 versus 3.3 +/- 0.8, p = 0.01) and greater clinical improvement scores (1.6 +/- 1.1 versus 3.0 +/- 0.0, p=0.03) than incomplete responders who had their antidepressant regimen switched. Although nonresponders to the first treatment who were switched experienced greater symptom improvement than nonresponders who were augmented (2.7 +/- 1.1 versus 3.4 +/- 1.2, p=0.03), there was no significant difference (p>0.05) between these two groups with respect to remission rates (18.6% versus 14.2%, respectively) and endpoint depressive severity (3.0 +/- 1.4 versus 3.4 +/- 1.4, respectively). CONCLUSIONS: In this nonrandomized, naturalistic treatment setting, nonresponders to an adequate, prospective antidepressant trial were more likely to have their antidepressant regimen switched, while patients with incomplete response during the first trial were more likely to have their regimen augmented. In addition, patients with incomplete response who had their treatment augmented had better outcome than patients with incomplete response who had their treatment switched.     

Testing anxious depression as a predictor and moderator of symptom improvement in major depressive disorder during treatment with escitalopram

The purpose of this analysis was to explore the potential role of anxious MDD as a treatment predictor and moderator in major depressive disorder (MDD) using a large escitalopram clinical trial dataset. Individual patient-level data from 13 double-blinded, randomized, controlled trials in patients with MDD were pooled. Both univariate, last observation carried forward (LOCF) analyses and repeated measurements analyses without imputation (MMRM) were carried out for change in symptom scores, response and remission rates. Of 3,919 patients, 48.0% were classified as having anxious MDD depression (HAMD) somatization/anxiety subscale score ≥7 at baseline. Patients with anxious MDD were less likely to report symptom improvement on some outcome measures than patients without anxious MDD (predictor analysis). Specifically, the difference in response rates for patients with vs. patients without anxious MDD according to the MADRS (55.6% vs. 57.7%, respectively) was not statistically different. However, the difference in remission rates for patients with versus without anxious MDD according to the MADRS (37.6% vs. 44.1%, respectively) was statistically significant. Escitalopram was more effective than placebo, and as effective as the SSRIs and SNRIs, in the treatment of anxious MDD. The present analysis provides some evidence that the presence of an anxious MDD subtype is a predictor of poor response. There was no difference in the response to treatment of patients with or without anxious MDD to escitalopram, SSRIs, or SNRIs. The present analysis did not support the notion that SNRIs are more effective than escitalopram in the treatment of anxious MDD, nor was there evidence to support treatment moderating effects for anxious MDD.