Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study. Does prior antidepressant treatment of major depression impact brain function during current treatment? Early Changes in Prefrontal Activity Characterize Clinical Responders to Antidepressants Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design. Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program. Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized, double-blind clinical trial with nortriptyline and paroxetine. Improving patients' beliefs about antidepressants in primary care: a cluster-randomized controlled trial of the effect of a depression care program. Clinical predictors of response to antidepressants in elderly patients A randomized trial of psychiatric consultation with distressed high utilizers. Update to the study protocol for a randomized controlled trial comparing mindfulness-based cognitive therapy with maintenance anti-depressant treatment depressive relapse/recurrence: the PREVENT trial Prognostic subgroups for citalopram response in the STAR*D trial. fMRI response to negative words and SSRI treatment outcome in major depressive disorder: A preliminary study Neural correlates of emotional processing in depression: changes with cognitive behavioral therapy and predictors of treatment response. Concurrent Cognitive Control Training Augments the Antidepressant Efficacy of tDCS: A Pilot Study A Cognitive–Emotional Biomarker for Predicting Remission with Antidepressant Medications: A Report from the iSPOT-D Trial A Preliminary Study: Efficacy of Mindfulness-Based Cognitive Therapy versus Sertraline as First-line Treatments for Major Depressive Disorder Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study
BACKGROUND Antidepressant treatment failure is a common problem worldwide . In this study , we assess whether or not an important aspect of depression , cognitive impairment , is untreated by antidepressants by study ing the effect of acute antidepressant treatment on a range of cognitive domains . METHODS In this r and omised longitudinal study , which is part of the International Study to Predict Optimized Treatment in Depression ( iSPOT-D ) trial , we assessed the effects of acute antidepressant treatment in a large patient population , across clinical remission outcomes , on a range of cognitive domains : attention , response inhibition , executive function during visuospatial navigation , cognitive flexibility , verbal memory , working memory , decision speed , information processing speed , and psychomotor response speed . We enrolled patients from primary or specialty care clinics in a multicentre , international , open-label , r and omised , prospect i ve trial . Eligible patients ( aged 18 - 65 years ) were previously untreated or were willing to undergo a 1-week medication washout before the study start , and could not have had inadequate response to study medications in the past . We enrolled a large population of medication-free ( ie , untreated ) out patients in a depressive episode and assessed them for cognitive function at enrolment ( pre-treatment ) , and again after 8 weeks of treatment with one of three antidepressant drugs ( escitalopram , sertraline , or venlafaxine extended-release ) . Patients were r and omly assigned ( 1:1:1 ) to one of the three antidepressants using a blocked r and omisation procedure ( block size of 12 ) . As a comparison group , we also simultaneously enrolled matched healthy participants . Healthy participants received no medication or intervention , but were assessed for change in cognitive and clinical measures during the same interval and testing protocol . Therefore , this group acts as a test-retest control for the primary outcome measure examined in this study , change in cognitive measures over 8 weeks of treatment in depressed patients . This study is registered with Clinical Trials.gov , number NCT00693849 . FINDINGS Between Dec 8 , 2008 , and Sept 30 , 2011 , we enrolled 1008 eligible people into the study .  Impairment in five domains-attention , response inhibition , verbal memory , decision speed , and information processing-showed no relative improvement with acute treatment ( controlling for time or repeated testing ) , irrespective of antidepressant treatment group , even in patients whose depression remitted acutely according to clinical measures . Broader cognitive impairment was associated with greater illness chronicity ( earlier illness onset ) but not with symptom severity or previous antidepressant failures . INTERPRETATION Depression is associated with impairments in higher-order cognitive functions and information processing , which persist independently of clinical symptom change with treatment . We recorded no difference between the three antidepressants tested , with none showing efficacy for these impairments . Although the 8-week treatment period limits interpretation to acute treatment effects , it does highlight cognitive impairment as an untargeted contributor to incomplete treatment success . FUNDING Brain Re source Company Operations Pty Ltd and NIH The relationship between prior antidepressant treatment and prefrontal brain functional response to subsequent treatment with antidepressant medication or placebo is unknown . Eighty-nine adults with Major Depressive Disorder ( MDD ) , characterized as antidepressant-experienced or antidepressant-naive , received one week of single-blind placebo treatment prior to eight weeks of r and omized treatment with medication ( fluoxetine or venlafaxine ; n = 47 ) or placebo ( n = 42 ) in one of three similar placebo-controlled trials . Brain function was assessed at baseline , end of placebo lead-in , and during r and omized treatment using quantitative electroencephalography ( qEEG ) . The authors assessed change in prefrontal theta-b and cordance ( PFC ) in antidepressant-experienced vs. antidepressant-naive subjects . Treatment history groups differed significantly on PFC change during the placebo lead-in even when controlling for clinical and demographic variables ( F(1,62 ) = 4.27 , p = .04 ) . As assessed in linear mixed models that examined treatment history ( antidepressant-experienced or antidepressant-naive ) , treatment assignment ( medication or placebo ) , and their interaction as predictors , treatment history also predicted PFC change during the r and omized phase of treatment even when controlling for pretreatment clinical and demographic and symptom improvement during treatment ( F(1,5o ) = 5.20 , p = .03 ) . The interaction was not significant . Post hoc analyses showed that antidepressant-experienced subjects treated with placebo showed PFC changes that did not differ from PFC changes seen in the medication group . Results suggest that prefrontal brain functional changes during treatment for MDD may differ depending upon prior treatment with antidepressant medication Previous studies have shown that changes in brain function precede clinical response to antidepressant medications . Here we examined quantitative EEG ( QEEG ) absolute and relative power and a new measure , cordance , for detecting regional changes associated with treatment response . Fifty-one adults with unipolar depression completed treatment trials using either fluoxetine or venlafaxine vs. placebo . Data were recorded at baseline and after 48 h and 1 week on drug or placebo . Baseline and change from baseline values were examined for specific brain regions in four subject groups ( medication and placebo responders and nonresponders ) . No regional baseline QEEG differences were found among the groups ; there also were no significant changes in theta power over time . In contrast , medication responders uniquely showed significant decreases in prefrontal cordance at 48 h and 1 week . Clinical differences did not emerge until after four weeks . Subjects with greater changes in cordance had the most complete 8-week responses . These findings implicate the prefrontal region in mediating response to antidepressant medications . Cordance may have clinical applicability as a leading indicator of individual response UNLABELLED Remission rates for Major Depressive Disorder ( MDD ) are low and unpredictable for any given antidepressant . No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment . Biosignatures developed from the systematic exploration of multiple biological markers , which optimize treatment selection for individuals ( moderators ) and provide early indication of ultimate treatment response ( mediators ) are needed . The rationale and design of a multi-site , placebo-controlled r and omized clinical trial of sertraline examining moderators and mediators of treatment response is described . The target sample is 300 participants with early onset ( ≤30 years ) recurrent MDD . Non-responders to an 8-week trial are switched double blind to either bupropion ( for sertraline non-responders ) or sertraline ( for placebo non-responders ) for an additional 8 weeks . Clinical moderators include anxious depression , early trauma , gender , melancholic and atypical depression , anger attacks , Axis II disorder , hypersomnia/fatigue , and chronicity of depression . Biological moderator and mediators include cerebral cortical thickness , task-based fMRI ( reward and emotion conflict ) , resting connectivity , diffusion tensor imaging ( DTI ) , arterial spin labeling ( ASL ) , electroencephalograpy ( EEG ) , cortical evoked potentials , and behavioral/cognitive tasks evaluated at baseline and week 1 , except DTI , assessed only at baseline . The study is design ed to st and ardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods , and to use advanced data analytic methods to integrate these markers . A Differential Depression Treatment Response Index ( DTRI ) will be developed . The data , including biological sample s ( DNA , RNA , and plasma collected before and during treatment ) , will become available in a public scientific repository . CLINICAL TRIAL REGISTRATION Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression ( EMBARC ) . Identifier : NCT01407094 . URL : http:// clinical trials.gov/show/NCT01407094 OBJECTIVE The authors investigated patient characteristics predictive of treatment response in the National Institute of Mental Health ( NIMH ) Treatment of Depression Collaborative Research Program . METHOD Two hundred thirty-nine out patients with major depressive disorder according to the Research Diagnostic Criteria entered a 16-week multicenter clinical trial and were r and omly assigned to interpersonal psychotherapy , cognitive-behavior therapy , imipramine with clinical management , or placebo with clinical management . Pretreatment sociodemographic features , diagnosis , course of illness , function , personality , and symptoms were studied to identify patient predictors of depression severity ( measured with the Hamilton Rating Scale for Depression ) and complete response ( measured with the Hamilton scale and the Beck Depression Inventory ) . RESULTS One hundred sixty-two patients completed the entire 16-week trial . Six patient characteristics , in addition to depression severity previously reported , predicted outcome across all treatments : social dysfunction , cognitive dysfunction , expectation of improvement , endogenous depression , double depression , and duration of current episode . Significant patient predictors of differential treatment outcome were identified . 1 ) Low social dysfunction predicted superior response to interpersonal psychotherapy . 2 ) Low cognitive dysfunction predicted superior response to cognitive-behavior therapy and to imipramine . 3 ) High work dysfunction predicted superior response to imipramine . 4 ) High depression severity and impairment of function predicted superior response to imipramine and to interpersonal psychotherapy . CONCLUSIONS The results demonstrate the relevance of patient characteristics , including social , cognitive , and work function , for prediction of the outcome of major depressive disorder . They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities , which may be of value in the selection of patients for alternative treatments Cognitive dysfunction is common in older persons suffering from a major depression . However , the degree to which this dysfunction is reversible with successful treatment of the depression remains uncertain . The present study examined the effects that treatment ( r and omized double-blind design ) with either an SSRI ( paroxetine ) or a tricyclic antidepressant ( nortriptyline ) had on cognition in older depressed patients . The patients ' performance was compared to that of a group of normal controls of similar age and education . Patients and controls were administered measures of working memory , information-processing speed , episodic memory and attention five times over the course of a 12 week trial . At baseline , the patients performed more poorly than the elderly controls on all cognitive measures . While the patients ' performance did improve over the course of their treatment , the magnitude of this improvement did not exceed that produced in the elderly controls by practice alone . The same pattern of results was evident in both intent-to-treat and responder analyses . Thus , there was no evidence that the depressed patients ' cognitive performance normalized after response to antidepressant therapy . Neither the patients ' age at onset nor their baseline level of cognitive functioning influenced the amount by which their performance improved over the 12 week trial . There was no difference between paroxetine and nortriptyline in the amount of cognitive change associated with treatment . The present results suggest that cognitive dysfunction persists in older depressed patients even after their mood disorder has responded to antidepressant medications OBJECTIVE Many depressed patients have negative beliefs about antidepressants , leading to poor adherence , unfavorable depression outcome , and low perceived well-being , role functioning , and quality of life . Interventions to ameliorate beliefs are therefore needed . METHOD In a cluster-r and omized controlled trial conducted from September 1999 to January 2001 , 2 interventions to improve management of major depressive disorder  in primary care were compared : ( 1 ) a depression care program ( DCP ) , providing enhanced patient education , stimulation of active participation of general practitioners and patients in the treatment process , discussion of benefits and costs of taking antidepressant medication , and systematic follow-up and ( 2 ) a systematic follow-up program ( SFP ) .  Thirty general practitioners were r and omly assigned , and 211 patients with current major depressive disorder ( diagnosed according to DSM-IV ) were included . All patients were prescribed a selective serotonin reuptake inhibitor .  Beliefs were assessed at baseline , at week 10 , and at week 26 . Differences in change of beliefs between DCP and SFP groups were analyzed . RESULTS Changes in patients ' beliefs were more favorable in the DCP condition at week 10 and week 26 , compared with SFP only ( beliefs concerning appropriate medication-taking , week 10 : effect size = 0.39 , p = .012 ; week 26 : effect size = 0.55 , p = .001 ; beliefs concerning harmfulness , week 10 : effect size = 0.45 , p = .011 ; week 26 : effect size = 0.62 , p = .002 ) . CONCLUSION The depression care program ameliorates beliefs about antidepressants in primary care patients with major depressive disorder . The study results encourage the implementation of a depression care program in order to improve beliefs about antidepressant medication in primary care patients diagnosed with major depressive disorder A group of 42 patients , ages 55 and above , suffering from major depression were examined in an attempt to isolate clinical variables that would predict response to antidepressants . These patients were part of a placebo-controlled , double-blind study and were given either nortriptyline or phenelzine for 5 - 7 weeks . There was no significant difference in response rates between patients subclassified as endogenous or nonendogenous by either RDC or Newcastle criteria . No difference in response rates was found between the DSM-III melancholic and nonmelancholic subtypes . Neither drug preferentially treated a subtype . None of the 21 variables representing symptoms , demographic traits , or characteristics of the depressive illness were found to be significant predictors of antidepressant response This study reports the results of a r and omized trial of a psychiatric consultation intervention with distressed , high utilizing patients of 18 physicians in two primary care clinics .  Psychiatric consultation was associated with a significant increase in the use of antidepressants in intervention patients compared with controls in the first 6 months after intervention . Intervention patients were also significantly more likely to continue  antidepressant treatment  than control patients . The primary care physicians receiving psychiatric consultations increased the rate of prescribing antidepressant medications  in their practice from 32 prescriptions filled per 1,000 visits before their participation in four consultations to 44 new prescriptions per 1,000 visits in the 12-month period after . There were no significant differences between intervention patients and controls at 6 and 12 months after r and omization in psychiatric distress , functional disability , or utilization of health care ( ambulatory visits , radiographic and laboratory testing services , admissions to inpatient medical care ) Background Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society . Medication and psychological therapies are effective for treating depression and maintenance anti-depressants ( m-ADM ) can prevent relapse . However , individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term . A recently developed treatment , mindfulness-based cognitive therapy ( MBCT ) , shows potential as a brief group program for people with recurring depression . This trial asks the policy research question ; is MBCT with support to taper/discontinue antidepressant medication ( MBCT-TS ) superior to m-ADM in terms of : a primary outcome of preventing depressive relapse/recurrence over 24 months ; and secondary outcomes of ( a ) depression free days , ( b ) residual depressive symptoms , ( c ) antidepressant medication ( ADM ) usage , ( d ) psychiatric and medical co-morbidity , ( e ) quality of life , and ( f ) cost effectiveness ? An explanatory research question also asks whether an increase in mindfulness skills is the key mechanism of change . The design is a single-blind , parallel r and omized controlled trial examining MBCT-TS versus m-ADM with an embedded process study . To answer the main policy research question the proposed trial compares MBCT-TS with m-ADM for patients with recurrent depression . Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care . Results Depressive relapse/recurrence over two years is the primary outcome variable . Analyses will be conducted following CONSORT st and ards and overseen by the trial ’s Data Monitoring and Safety Committee . Initial analyses will be conducted on an intention-to-treat basis , with subsequent analyses being per protocol . The explanatory question will be addressed in two mutually informative ways : quantitative measurement of potential mediating variables pre- and post-treatment and a qualitative study of service users ’ views and experiences . Conclusions If the results of our exploratory trial are extended to this definitive trial , MBCT-TS will be established as an alternative approach to maintenance antidepressants for people with a history of recurrent depression . The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches . Trial registration Trial registered 7 May 2009 ; IS RCT N26666654 OBJECTIVE Few data exist to help clinicians predict likelihood of treatment response in individual patients with major depressive disorder ( MDD ) . Our aim was to identify subgroups of MDD patients with differential treatment outcomes based on presenting clinical characteristics . We also sought to quantify the likelihood of treatment success based on the degree of improvement and side effects after 2 and 4 weeks of selective serotonin reuptake inhibitor ( SSRI ) pharmacotherapy . METHOD We analyzed data from the first treatment phase of the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) trial , in which subjects with a DSM-IV diagnosis of MDD were treated for 8 - 14 weeks with open-label citalopram . A receiver operating characteristic ( ROC ) analysis was conducted to determine homogenous subgroups with different rates of response and remission in depressive symptoms . Included predictor variables were initial clinical characteristics , initial improvement , and side effects after 2 and 4 weeks of SSRI treatment . The primary outcome measures were treatment response ( defined as a greater than 50 % reduction in 17-item Hamilton Depression Rating Scale [ HDRS-17 ] score from baseline ) and remission ( defined as an HDRS-17 score ≤ 17 ) . RESULTS Baseline clinical characteristics were able to identify subgroups from a low likelihood of response of 18 % ( income < $ 10,000 , comorbid generalized anxiety disorder , < 16 years of education ; P < .01 ) to a high likelihood of response of 68 % ( income ≥ $ 40,000 , no comorbid posttraumatic stress disorder ; P < .01 ) . Among baseline clinical characteristics , employment status ( N = 2,477 ; χ²₁ = 78.1 ; P < .001 ) and income level ( N = 2,512 ; χ²₁ = 77.7 ; P < .001 ) were the most informative in predicting treatment outcome . For the models at weeks 2 and 4 , treatment success was best predicted by early symptom improvement . CONCLUSIONS Socioeconomic data such as low income , education , and unemployment were most discriminative in predicting a poor response  to citalopram , even with disparities in access to care accounted for . This finding implies that socioeconomic factors may be more useful predictors of medication response than traditional psychiatric diagnoses or past treatment history . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00021528 Clinical ly useful predictors of treatment outcome in major depressive disorder ( MDD ) remain elusive . We examined associations between functional magnetic resonance imaging ( fMRI ) blood oxygen level dependent ( BOLD ) signal during active negative word processing and subsequent  selective serotonin reuptake inhibitor ( SSRI ) treatment outcome in MDD . Unmedicated MDD subjects ( n=17 ) performed an emotional word processing fMRI task , and then received eight weeks of st and ardized antidepressant treatment with escitalopram . Lower pre-treatment BOLD responses to negative words in midbrain , dorsolateral prefrontal cortex , paracingulate , anterior cingulate , thalamus and cau date nuclei correlated significantly with greater improvement following escitalopram treatment . Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance . Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48 % of the variance in response to treatment . This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli . Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design . Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy ( CBT ) in previous studies using the same task . Future studies may examine prediction of differential outcome across treatments in the context of a r and omized controlled trial Major depressive disorder ( MDD ) is characterized by the presence of disturbances in emotional processing . However , the neural correlates of these alterations , and how they may be affected by therapeutic interventions , remain unclear . The present study addressed these issues in a preliminary investigation using functional magnetic resonance imaging ( fMRI ) to examine neural responses to positive , negative , and neutral pictures in unmedicated MDD patients ( N = 22 ) versus controls ( N = 14 ) . After this initial scan , MDD patients were treated with cognitive behavioral therapy ( CBT ) and scanned again after treatment . Within regions that showed pre-treatment differences between patients and controls , we tested the association between pre-treatment activity and subsequent treatment response as well as activity changes from pre- to post-treatment . This study yielded three main findings . First , prior to treatment and relative to controls , patients exhibited overall reduced activity in the ventromedial prefrontal cortex ( PFC ) , diminished discrimination between emotional and neutral items in the amygdala , cau date , and hippocampus , and enhanced responses to negative versus positive stimuli in the left anterior temporal lobe ( ATL ) and right dorsolateral PFC . Second , CBT-related symptom improvement in MDD patients was predicted by increased activity at baseline in ventromedial PFC as well as the valence effects in the ATL and dorsolateral PFC . Third , from pre- to post-treatment , MDD patients exhibited overall increases in ventromedial PFC activation , enhanced arousal responses in the amygdala , cau date , and hippocampus , and a reversal of valence effects in the ATL . The study was limited by the relatively small sample that was able to complete both scan sessions , as well as an inability to determine the influence of comorbid disorders within the current sample . Nevertheless , components of the neural networks corresponding to emotion processing disturbances in MDD appear to resolve following treatment and are predictive of treatment response , possibly reflecting improvements in emotion regulation processes in response to CBT BACKGROUND Major depressive disorder ( MDD ) is frequently associated with underactivity of the dorsolateral prefrontal cortex ( DLPFC ) which has led to this brain region being identified as an important target for the development of neurobiological treatments . Transcranial direct current stimulation ( tDCS ) administered to the DLPFC has antidepressant efficacy , however the magnitude of antidepressant outcomes are limited . Concurrent cognitive activity has been shown to enhance tDCS induced stimulation effects . Cognitive control training ( CCT ) is a new cognitive therapy for MDD that aims to enhance DLPFC activity via behavioral methods . HYPOTHESIS We tested the hypothesis that co-administration of DLPFC tDCS and CCT would result in a greater reduction in depressive symptomology than administration of tDCS or CCT alone . METHODS 27 adult participants with MDD were r and omized into a three-arm sham-controlled between-groups pilot study comparing the efficacy of 2 mA tDCS + CCT , sham tDCS + CCT and sham CCT + 2 mA tDCS ( 5 sessions administered on consecutive working days ) . Blinded assessment s of depression severity and cognitive control were conducted at baseline , end of treatment and a three week follow up review . RESULTS All three treatment conditions were associated with a reduction in depression severity at the end of five treatment sessions . However , only administration of tDCS + CCT result ed in sustained antidepressant response at follow up , the magnitude of which was greater than that observed immediately following conclusion of the treatment course . CONCLUSIONS The results provide preliminary evidence that concurrent CCT enhances antidepressant outcomes from tDCS . In the current sample , participants receiving concurrent tDCS and CCT continued to improve following cessation of treatment . The clinical superiority of a combined therapeutic approach was apparent even in a small sample and following a relatively short treatment course Depression involves impairments in a range of cognitive and emotional capacities . It is unknown whether these functions can inform medication choice when considered as a composite predictive biomarker . We tested whether behavioral tests , grounded in the neurobiology of cognitive and emotional functions , predict outcome with common antidepressants .  Medication-free out patients with nonpsychotic major depressive disorder ( N=1008 ; 665 completers ) were assessed before treatment using 13 computerized tests of psychomotor , executive , memory – attention , processing speed , inhibitory , and emotional functions .  Matched healthy controls ( N=336 ) provided a normative reference sample for test performance . Depressed participants were then r and omized to escitalopram , sertraline , or venlafaxine – extended release , and were assessed using the  16-item Quick Inventory of Depressive Symptomatology ( QIDS-SR16 )  and the  17-item Hamilton Rating Scale for Depression . Given the heterogeneity of depression , analyses were furthermore stratified by pretreatment performance . We then used pattern classification with cross-validation to determine individual patient-level composite predictive biomarkers of antidepressant outcome based on test performance . A subgroup of depressed participants ( approximately one-quarter of patients ) were found to be impaired across most cognitive tests relative to the healthy norm , from which they could be discriminated with 91 % accuracy . These patients with generally impaired cognitive task performance had poorer treatment outcomes . For this impaired subgroup , task performance furthermore predicted remission on the QIDS-SR16 at 72 % accuracy specifically following treatment with escitalopram but not the other medications . Therefore , tests of cognitive and emotional functions can form a clinical ly meaningful composite biomarker that may help drive general treatment outcome prediction for optimal treatment selection in depression , particularly for escitalopram 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 , nonr and omized 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 = 0.165 ) between groups . Secondary analysis showed statistically significant differences in mean scores of the QIDS-SR16 ( t(32 ) = 4.39 , p < 0.0001 ) , with the MBCT group showing greater mean improvement . This study was limited by the small sample size and non-r and omized , non-blinded design . Preliminary findings suggest that an 8-week course of MBCT monotherapy may be effective in treating MDD and is 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 Patients with Major Depressive Disorder ( MDD ) may not respond to antidepressants for 8 weeks or longer . A biomarker that predicted treatment effectiveness after only 1 week could be clinical ly useful . We examined a frontal quantitative electroencephalographic ( QEEG ) biomarker , the Antidepressant Treatment Response ( ATR ) index , as a predictor of response to escitalopram , and compared ATR with other putative predictors . Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study . After 1 week of treatment with escitalopram , 10 mg , a second QEEG was performed , and the ATR was calculated . Subjects then were r and omly assigned to continue with escitalopram , 10 mg , or change to alternative treatments . Seventy-three evaluable subjects received escitalopram for a total of 49days . Response and remission rates were 52.1 % and 38.4 % , respectively . The ATR predicted both response and remission with 74 % accuracy . Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors . Responders had larger decreases in Hamilton Depression Rating Scale ( Ham-D(17 ) ) scores at day 7 ( P=0.005 ) , but remitters did not . Clinician prediction based upon global impression of improvement at day 7 did not predict outcome . Logistic regression showed that the ATR and early Ham-D(17 ) changes were additive predictors of response , but the ATR was the only significant predictor of remission . Future studies should replicate these results prior to clinical use
The available evidence suggests the early changes in cognition may predict treatment response in individuals with MDD .
The results depict an emerging trend towards early changes in facial emotion recognition ( i.e. , a hot cognitive process ) as a predictor of treatment outcome .
Conclusion : The identification of reliable early treatment predictors of antidepressant response would be clinical ly significant , enabling clinicians to more accurately evaluate the efficacy of selected treatment avenues .
HIGHLIGHTSCognitive dysfunction is a principal feature and determinant of health outcome in MDD.Cognitive changes have shown to occur prior to improvements in mood symptoms .
Early changes in emotional processing may predict treatment response in MDD
Background : Despite the widespread use of antidepressants in clinical practice , the current trial‐ and ‐error approach to medication selection contributes to treatment failure and underscores the need to identify reliable predictors of antidepressant response .
Since changes in measures of cognition have been reported to occur early in treatment and prior to improvements in overall mood symptoms , the present review aims to determine whether early changes in measures of cognition can predict response in individuals with MDD .