Weeks Of Antidepressant Treatment Research Articles

Not all types of depressed patients who persist with their antidepressant treatment improve in side effect complaints: A comparison of treatment completers and dropouts in the STAR*D trial.

There is a "traditional belief" that antidepressant side effect complaints improve with medication persistence; however, support for this theory has remained inconclusive. We aimed to examine if side effect complaints improved over time by modeling the relationship between side effect complaints and time at dropout for patients receiving citalopram during the first level of acute treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. We categorized the 2833 patients into five patterns by week of dropout. We used pattern-mixture modeling to model change in side effect complaints (frequency, intensity, and burden) over the 12-week course of treatment, while accounting for attrition and depressive severity. Using post-hoc linear contrasts, we compared the attrition patterns with the completers' pattern for severity of side effect complaints at each respective last visit prior to dropout as well as averaged side effect complaints across the duration of treatment. We also reported frequencies and tolerability of side effects for nine organ/function systems over the course of treatment. Patients who dropped out early exhibited worsening side effect burden and patients who dropped out later showed improvements in side effect frequency and intensity. Treatment completers improved in all side effect complaints over the course of treatment. Early attrition patterns had more severe side effect complaints for both tests of post-hoc linear contrasts than later attrition patterns and completers. Side effect complaints from antidepressant treatment improve over time, but only for some types of patients. As a precaution for early dropout, clinicians should monitor patients who exhibit worsening and more severe side effect complaints-especially in the first 6 weeks of antidepressant treatment. In addition, clinicians may want to consider changing the type of treatment early on for these patients, rather than encouraging them to persist with their current medication.

The Functioning Assessment Short Test (FAST): Clinically meaningful response threshold in patients with major depressive disorder receiving antidepressant treatment

BackgroundFunctional impairment is common in patients with major depressive disorder (MDD). The Functioning Assessment Short Test (FAST) provides a detailed clinician-rated assessment of functioning across multiple aspects of daily life. This study aimed to establish clinically relevant response thresholds for the FAST in patients with MDD receiving antidepressant treatment. MethodsData were derived from three 8-week clinical trials of antidepressant therapy in patients with MDD that included assessment of functioning using the FAST as a pre-specified endpoint. The minimal clinically important difference (MCID) and threshold for response in terms of change in FAST total score were determined using anchor-based methods. ResultsAfter 8 weeks of antidepressant treatment, the mean reduction in FAST total score in patients considered clinically minimally improved (Clinical Global Impression–Improvement [CGI-I] score of 3) was 7–9 points (~20 % reduction). The threshold for functional response (reduction in FAST total score from baseline in patients with a CGI-I score of ≤2 at week 8) was 16–19 points (~50 % reduction). The threshold for functional response was higher in patients with MDD and comorbid generalized anxiety disorder than in those with MDD alone (mean reduction in FAST total score at 8 weeks: 26 points [63 %]). LimitationsShort-term studies. ConclusionsThese results provide further validation of the FAST for assessing functioning in patients with MDD. In patients with MDD, the suggested MCID for FAST total score is 7–9 points and the proposed threshold for response is a reduction from baseline of approximately 50 %.

Integrated Single-Cell RNA-seq and ATAC-seq Reveals Heterogeneous Differentiation of CD4+ Naive T Cell Subsets is Associated with Response to Antidepressant Treatment in Major Depressive Disorder.

The mechanism involved in major depressive disorder (MDD) is well-studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single-cell RNA-sequencing (scRNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA-seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen-activated protein kinases (MAPK)pathway is identified. E-twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

The impact of antidepressant treatment on the network structure of neurocognition and core emotional depressive symptoms among depressed individuals with a history of suicide attempt: An 8-week clinical study

BackgroundA more in-depth understanding of the relationship between depressive symptoms, neurocognition and suicidal behavior could provide insights into the prognosis and treatment of major depressive disorder (MDD) and suicide. We conducted a network analysis among depressed patients examining associations between history of suicide attempt (HSA), core emotional major depression disorder, and key neurocognitive domains. MethodDepressed patients (n = 120) aged 18–65 years were recruited from a larger randomized clinical trial conducted at the Douglas Institute in Montreal, Canada. They were randomly assigned to receive one of two antidepressant treatments (i.e., escitalopram or desvenlafaxine) for 8 weeks. Core emotional MDD and key neurocognitive domains were assessed pre-post treatment. ResultsAt baseline, an association between history of suicide attempt (HSA) and phonemic verbal fluency (PVF) suggested that HSA patients reported lower levels of the latter. After 8 weeks of antidepressant treatment, HSA became conditionally independent from PVF. Similar results were found for both the HAM-D and the QIDS-SR core emotional MDD/neurocognitive networks. ConclusionNetwork analysis revealed a pre-treatment relationship between a HSA and decreased phonemic VF among depressed patients, which was no longer present after 8 weeks of antidepressant treatment.

Rumination in patients with major depressive disorder before and after antidepressant treatment

BackgroundRumination is a maladaptive response to distress characteristic of Major Depressive Disorder (MDD). It is unclear to what degree rumination is associated with depression severity prior to treatment and how it responds to antidepressant treatment. Therefore, we evaluated the association between rumination and depression severity in 92 untreated patients with MDD and explored the changes in rumination after initiation of antidepressant medication. MethodWe measured rumination using the Rumination Response Scale (RRS) and depression severity with the Hamilton Depression Rating Scale (HDRS17 or HDRS6) before and after initiation of 12 weeks of antidepressant treatment. The association between RRS and pre-treatment HDRS17 was evaluated using a linear regression model. RRS at week 4, 8, and 12 across treatment response categories (remission vs. non-response) were evaluated using a mixed effect model. ResultsRRS was positively associated with depression severity prior to treatment at a trend level (p = 0.06). After initiation of treatment RRS decreased significantly (p < 0.0001) and remitters exhibited lower rumination compared to non-responders at week 4 (p = 0.03), 8 (p = 0.01), and 12 (p = 0.007). LimitationsThe study had no placebo group. ConclusionsAlthough pre-treatment rumination did not significantly associate with depressive symptoms, rumination was closely connected to change in depressive symptoms. Tormented patients could be reassured that rumination symptoms may be alleviated over the course of antidepressant treatment.

A genome-wide association study of escitalopram treatment outcomes in patients with major depressive disorder

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e − 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e − 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression.

Prediction of Early Antidepressant Efficacy in Patients with Major Depressive Disorder Based on Multidimensional Features of rs-fMRI and P11 Gene DNA Methylation: Prédiction de l'efficacité précoce d'un antidépresseur chez des patients souffrant du trouble dépressif majeur d'après les caractéristiques multidimensionnelles de la méthylation de l'ADN du gène P11 et de la IRMf-rs.

This study established a machine learning model based on the multidimensional data of resting-state functional activity of the brain and P11 gene DNA methylation to predict the early efficacy of antidepressant treatment in patients with major depressive disorder (MDD). A total of 98 Han Chinese MDD were analysed in this study. Patients were divided into 51 responders and 47 nonresponders according to whether the Hamilton Depression Rating Scale-17 items (HAMD-17) reduction rate was ≥50% after 2 weeks of antidepressant treatment. At baseline, the Illumina HiSeq Platform was used to detect the methylation of 74 CpG sites of the P11 gene in peripheral blood samples. Resting-state functional magnetic resonance imaging (rs-fMRI) scan detected the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in 116 brain regions. The least absolute shrinkage and selection operator analysis method was used to perform feature reduction and feature selection. Four typical machine learning methods were used to establish support vector machine (SVM), random forest (RF), Naïve Bayes (NB), and logistic regression (LR) prediction models based on different combinations of functional activity of the brain, P11 gene DNA methylation and clinical/demographic features after screening. The SVM model based on ALFF, ReHo, FC, P11 methylation, and clinical/demographic features showed the best performance, with 95.92% predictive accuracy and 0.9967 area under the receiver operating characteristic curve, which was better than RF, NB, and LR models. The multidimensional data features combining rs-fMRI, DNA methylation, and clinical/demographic features can predict the early antidepressant efficacy in MDD.

Stress Hormone Dynamics Are Coupled to Brain Serotonin 4 Receptor Availability in Unmedicated Patients With Major Depressive Disorder: A NeuroPharm Study.

A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR). Further, we evaluate if CAR changes with antidepressant treatment, including a selective serotonin reuptake inhibitor, and if pretreatment CAR can predict treatment outcome. Sixty-six patients (76% women) with a moderate to severe depressive episode underwent positron emission tomography imaging with [11C]SB207145 for quantification of brain 5-HT4R binding using BPND as outcome. Serial home sampling of saliva in the first hour from awakening was performed to assess CAR before and after 8 weeks of antidepressant treatment. Treatment outcome was measured by change in Hamilton Depression Rating Scale 6 items. In the unmedicated depressed state, prefrontal and anterior cingulate cortices 5-HT4R binding was positively associated with CAR. CAR remained unaltered after 8 weeks of antidepressant treatment, and pretreatment CAR did not significantly predict treatment outcome. Our findings highlight a link between serotonergic disturbances in MDD and cortisol dynamics, which likely is involved in disease and treatment mechanisms. Further, our data support 5-HT4R agonism as a promising precision target in patients with MDD and disturbed stress hormone dynamics.

Psilocybin therapy: A novel approach to treating depression

Psilocybin therapy: A novel approach to treating depression

Tissue-Specific Oxysterols as Predictors of Antidepressant (Escitalopram) Treatment Response in Patients With Major Depressive Disorder

BackgroundThere is growing evidence that disturbances in cholesterol metabolism may be involved in major depressive disorder (MDD). However, it is not known if cholesterol metabolites present in the brain and periphery can be used to diagnose and predict an MDD patient’s response to antidepressant treatment. MethodsA total of 176 subjects (85 patients with MDD and 91 healthy control subjects) were included in this study. The expression of peripheral and brain-specific oxysterols and related gene polymorphisms were investigated in all subjects. The severity of depression was measured using the 17-item Hamilton Depression Rating Scale, 16-item Quick Inventory of Depressive Symptoms–Self-Report, and Patient Health Questionnaire-9 for all patients with MDD before and after 12 weeks of antidepressant treatment. ResultsPatients with MDD expressed higher plasma levels of 24(S)-hydroxycholesterol (24OHC) (mainly secreted from the brain) compared with healthy control subjects, and the higher levels of 24OHC were associated with 24OHC synthetase (CYP46A1) gene polymorphisms. In patients with MDD, an improved response to the 12-week antidepressant treatment was associated with a reduction of both 24OHC and 27OHC (mainly secreted from the peripheral system) levels relative to baseline levels. Nonresponders exhibited increased levels of oxysterols at the end of treatment compared with baseline. The superior reduction in oxysterol levels correlated with better outcomes from the antidepressant treatment. ConclusionsThese data suggest a potential role for oxysterols as diagnostic and treatment response–related indicators for MDD.

Impact of Undertreatment of Depression on Suicide Risk Among Children and Adolescents With Major Depressive Disorder: A Microsimulation Study.

Undertreatment of depression is common among children and adolescents, but evidence of the impact of undertreatment of depression on risk of suicide is limited due to the low base rate of suicide in the population and lack of sufficient data sources. We developed a microsimulation model that uses evidence from multiple sources to study the impact of different durations of antidepressant treatment on suicide risk in a synthesized sample that is nationally representative of children and adolescents with major depressive disorder. Compared with receiving no treatment, suicide rate and risk of suicide attempt both decreased with increasing duration of antidepressant treatment (for 12 weeks, suicide rate ratios = 0.78 (95% credible interval (CrI): 0.58, 1.15), 36 weeks, 0.65 (95% CrI: 0.44, 0.90), and 52 weeks, 0.63 (95% CrI: 0.45, 0.72); for suicide attempt: 12 weeks, suicide risk ratios = 0.68 (95% CrI: 0.62, 0.69), 36 weeks, 0.56 (95% CrI: 0.52, 0.57), and 52 weeks, 0.55 (95% CrI: 0.51, 0.56). The suicide rate and risk of suicide attempt were lower in children than in adolescents. Males had a lower risk of suicide attempt but higher suicide rate than females. The findings from the microsimulation model show that completion of 12-36 weeks of antidepressant treatment may reduce suicide attempt and suicide among children and adolescents with major depressive disorder.

Association between cholesterol and response to escitalopram and nortriptyline in patients with major depression: Study combining clinical and register-based information

Little is known whether cholesterol levels affect depression treatment outcomes. We aimed to study the association between baseline and changes in blood cholesterol levels with drug-specific antidepressant response and long-term prognosis in patients with major depressive disorder (MDD). From the Danish site of the GENDEP trial, we included patients with MDD randomized to escitalopram or nortriptyline treatment. Total and free cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and depression severity using the Montgomery-Åsberg Depression rating scale (MADRS) were measured at baseline and after 26 weeks of treatment initiation. By linkage with nationwide registers, we analyzed psychiatric and cardiometabolic hospital contacts during the five years after the trial. We assessed the association of cholesterol levels with a) depression severity using linear and mixed effects regression analyses; and b) the register-based outcomes using Cox regression analyses. Among 78 patients (mean age 38 years, 74% women, mean MADRS score 28 [SD=4.5]), baseline cholesterol levels were not correlated with antidepressant response. Among 58 patients with measurements at week 0 and 26, cholesterol levels significantly increased in both treatment groups. Only in patients using escitalopram did the increase in total and free cholesterol and LDL correlate with improved antidepressant response. Baseline or changes in cholesterol were not associated with 5-year outcomes. Secondary analyses on a rather small sample. This study provides clinical insight into potential drug-specific associations between increases in cholesterol levels and antidepressant response to escitalopram but not nortriptyline. • Cholesterol levels increased during 26 weeks of antidepressant treatment • Among those treated with escitalopram, the increase correlated with improved response • We found no correlation between change in cholesterol and response in the nortriptyline group • Baseline or change in cholesterol levels were not associated with differential 5-year prognosis

Quantitative magnetic resonance spectroscopy of depression: The value of short-term metabolite changes in predicting treatment response.

Although various prediction models of the antidepressant response have been established, the results have not been effectively applied to heterogeneous depression populations, which has seriously limited their clinical value. This study tried to build a more specific and stable model to predict treatment response in depression based on short-term changes in hippocampal metabolites. Seventy-four major depressive disorder (MDD) patients and 20 healthy controls in the test set were prospectively collected and retrospectively analyzed. Subjects underwent magnetic resonance spectroscopy (MRS) once a week during 6 weeks of treatment. Hippocampal regions of interest (ROIs) were extracted by using a voxel iteration scheme combined with standard brain templates. The short-term differences in hippocampal metabolites between and within groups were screened. Then, the association between hippocampal metabolite changes and clinical response was analyzed, and a prediction model based on logistic regression was constructed. In addition, a validation set (n = 60) was collected from another medical center to validate the predictive abilities. After 2-3 weeks of antidepressant treatment, the differences in indicators (tCho wee0-2, tCho wee0-3 and NAA week0-3) were successfully screened. Then, the predictive abilities of these three indicators were revealed in the logistic regression model, and the optimal prediction effect was found in d(tCho) week0-3-d(NAA) week0-3 (AUC = 0.841, 95%CI = 0.736-0.946). In addition, their predictive abilities were further confirmed with the validation set. The small sample size and the need for multiple follow-ups limited the statistical ability to detect other findings. The predictive model in this study presented accurate prediction and strong verification effects, which may provide early guidance for adjusting the treatment regimens of depression and serve as a checkpoint at which the eventual treatment outcome can be predicted.

Reduced cerebral cortex thickness is related to overexpression of exosomal miR-146a-5p in medication-free patients with major depressive disorder.

Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD). In this case-control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities. In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC. The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD.

Evaluating cognitive disturbances as treatment target and predictor of antidepressant action in major depressive disorder: A NeuroPharm study

Cognitive disturbances in major depressive disorder (MDD) constitute a critical treatment target and hold promise as an early predictor of antidepressant treatment response; yet their clinical relevance is not fully established. Therefore, we here investigate if (1) cognitive performance improves over the course of antidepressant treatment and (2) cognitive performance at baseline is predictive of antidepressant treatment response. In the NeuroPharm study (clinical trial id: NCT02869035), 92 antidepressant-free patients with a moderate to severe depressive episode were assessed with a comprehensive cognitive test battery including both cold (emotion-independent) and hot (emotion-dependent) tasks. Patients were tested before and after 12 weeks of standard antidepressant treatment with escitalopram in flexible doses of 10–20 mg. Performance improved across most cognitive domains over the course of antidepressant treatment. Notably, these improvements were independent of improvement in mood symptoms, emphasizing that cognitive disturbances are a distinct symptom and therefore treatment target in MDD. Results did not suggest that performance on any single cognitive measure at baseline was associated with later clinical response to antidepressant treatment. However, a small cluster of patients (N = 28) with globally disturbed cognition at baseline exhibited poorer clinical response after 8 but not 12 weeks of antidepressant treatment, suggesting that severe cognitive disturbances may delay treatment response. Thus, while pretreatment cognitive performance on individual tests may not be useful as clinical markers of treatment response, profiles capturing performance across different cognitive domains may be useful for stratification of patients with MDD and could be helpful in future intervention trials.

Prefrontal cortex neural activity predicts reduction of non-suicidal self-injury in adolescents with major depressive disorder: An event related potential study.

Non-suicidal self-injury (NSSI) is common in adolescent MDD, which is also a risk factor for suicide. However, there is few research on biomarkers and predictors about treatment response of NSSI. The purpose of this study was to find the difference of P300 between adolescent MDD with NSSI and healthy controls, and to explore whether the baseline electrophysiological level can predict the change of NSSI after treatment. We collected 62 first-episode drug-naïve MDD adolescents with NSSI (MDD with NSSI group) and 44 healthy controls (HC group). The demographic data, HAMD score, self-injury frequency and electrophysiological level of NSSI group and HC group were collected. The HAMD score, frequency of NSSI in was also collected after 8 weeks of antidepressant treatment. Compared to HC, the latency of the N2, P3a, and P3b components were significantly prolonged, whereas the amplitude of P3a and P3b were decreased in the MDD with NSSI group (P < 0.001). The frequency of self-injury decreased significantly after treatment (P < 0.001). Regression analysis showed that the amplitudes of P3b had a significant positive predictive effect on the rate of change of NSSI frequency after 8 weeks. P3b at baseline can be used as potential predictor for the reduction of NSSI in adolescent MDD.

Venlafaxine XR treatment for older patients with major depressive disorder: decision trees for when to change treatment

BackgroundPredictors of antidepressant response in older patients with major depressive disorder (MDD) need to be confirmed before they can guide treatment.ObjectiveTo create decision trees for early identification of older patients...

Persistent Ventral Anterior Cingulate Cortex and Resolved Amygdala Hyper-responses to Negative Outcomes After Depression Remission: A Combined Cross-sectional and Longitudinal Study

BackgroundMajor depressive disorder (MDD) is a highly prevalent mood disorder affecting more than 300 million people worldwide. Biased processing of negative information and neural hyper-responses to negative events are hallmarks of depression. This study combined cross-sectional and longitudinal experiments to explore both persistent and resolved neural hyper-responses to negative outcomes from risky decision making in patients with current MDD (cMDD) and remitted MDD (rMDD). MethodsA total of 264 subjects participated in the cross-sectional study, including 117 patients with medication-naïve, first-episode current depression; 45 patients with rMDD with only 1 episode of depression; and 102 healthy control subjects. Participants completed a modified balloon analog risk task during functional magnetic resonance imaging. In the longitudinal arm of the study, 42 patients with cMDD were followed and 26 patients with rMDD were studied again after 8 weeks of antidepressant treatment. ResultsPatients with cMDD showed hyper-responses to loss outcomes in multiple limbic regions including the amygdala and ventral anterior cingulate cortex (vACC). Amygdala but not vACC hyperactivity correlated with depression scores in patients with cMDD. Furthermore, amygdala hyperactivity resolved while vACC hyperactivity persisted in patients with rMDD in both cross-sectional and longitudinal studies. ConclusionsThese findings provide consistent evidence supporting differential patterns of amygdala and vACC hyper-responses to negative outcomes during depression remission. Amygdala hyperactivity may be a symptomatic and state-dependent marker of depressive neural responses, while vACC hyperactivity may reflect a persistent and state-independent effect of depression on brain function. These findings offer new insights into the neural underpinnings of depression remission and prevention of depression recurrence.

Relationship between change in social evaluation learning and mood in early antidepressant treatment: A prospective cohort study in primary care.

Antidepressants are proposed to work by increasing sensitivity to positive versus negative information. Increasing positive affective learning within social contexts may help remediate negative self-schema. We investigated the association between change in biased learning of social evaluations about the self and others, and mood during early antidepressant treatment. Prospective cohort assessing patients recruited from primary care in South West England at four timepoints over the first 8 weeks of antidepressant treatment (n = 29). At each timepoint, participants completed self-report measures of depression (Beck Depression Inventory II (BDI-II) and Patient Health Questionnaire 9 (PHQ-9)), anxiety (Generalised Anxiety Disorder Questionnaire 7 (GAD-7)), and a computerised task measuring learning of social evaluations about the self, a friend and a stranger. We did not find evidence that learning about the self was associated with a reduction in PHQ-9 (b = 0.08, 95% CI: -0.05, 0.20, p = 0.239) or BDI-II scores (b = 0.10, 95% CI: -0.18, 0.38, p = 0.469). We found some weak evidence that increased positive learning about the friend was associated with a reduction in BDI-II scores (b = 0.30, 95% CI: -0.02, 0.62, p = 0.069). However, exploratory analyses indicated stronger evidence that increased positive learning about the self (b = 0.18, 95% CI: 0.07, 0.28, p = 0.002) and a friend (b = 0.22, 95% CI: 0.10, 0.35, p = 0.001) was associated with reductions in anxiety. Change in social evaluation learning was associated with a reduction in anxiety but not depression. Antidepressants may treat anxiety symptoms by remediating negative affective biases towards socially threatening information directed towards the self and close others. However, our findings are based on exploratory analyses within a small sample without a control group and are therefore at risk of type 1 errors and order effects. Further research with larger samples is required.

Treatment-resistant depression: therapeutic options when first-line treatments fail

SUMMARYThe Cochrane review by Davies et al aimed to address the lack of clarity on the risks and benefits of switching and augmentation strategies in the pharmacological treatment of treatment-resistant depression in adults who did not respond (or partially responded) to at least 4 weeks of antidepressant treatment at a recommended dose. This commentary assesses their review and their conclusion that augmenting the current antidepressant with mianserin or with an antipsychotic improves depressive symptoms over the short-term (8 to 12 weeks). Their results need to be treated with caution owing to the small body of evidence and individual comparisons supported by one, two or three studies, the limited evidence on long-term effects and the significant gaps in the literature (e.g. a lack of studies assessing dose increases).