Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis.

BACKGROUND: Improvement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.AimsWe aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission. METHOD: We obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants. Primary outcome was week 6 response; secondary outcomes were week 6 remission and week 12 response and remission. We compared models that only included improvement in total score by week 2 (total improvement model) with models that also included improvement in individual symptoms. RESULTS: For week 6 response, the area under the receiver operating characteristic curve and negative and positive predictive values of the total improvement model were 0.73, 0.67 and 0.74 compared with 0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased for week 12 outcomes. Of predicted non-responders, 29% actually did respond by week 6 and 43% by week 12, which was decreased from the baseline (overall) probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with continuous rather than dichotomous early improvement, including individual items did not enhance model performance. CONCLUSIONS: Examining individual symptoms adds little to the predictive ability of early improvement. Additionally, early non-improvement does not rule out response or remission, particularly after 12 rather than 6 weeks. Therefore, our findings suggest that routinely adapting pharmacological treatment because of limited early improvement would often be premature.Declaration of interestNone.

Improvement after two sessions of electroconvulsive therapy predicts final remission in in-patients with major depression.

OBJECTIVE: To investigate whether early improvement, measured after two electroconvulsive therapy (ECT) sessions, is a good predictor of eventual remission in severely depressed in-patients receiving ECT. METHOD: A prospective cohort study was performed that included 89 major depressive disorder in-patients treated with bilateral ECT. Sensitivity, specificity, and predictive values were computed for various definitions of early improvement (15%, 20%, 25%, and 30% reduction on the Montgomery Asberg depression rating scale (MADRS) score) after 1 week (i.e. two sessions) of ECT regarding prediction of remission (final MADRS score ≤ 9). RESULTS: A 15% reduction in MADRS score appeared to be the best definition of early improvement, with modest sensitivity (51%) and relatively good specificity (79%). Kaplan-Meier analysis showed a more than 2-week shorter time to remission in patients with early improvement compared with patients lacking early improvement. CONCLUSION: Early improvement during an ECT course may be assessed after two ECT sessions. Such improvement, defined as a 15% reduction in the MADRS score, is a moderately sensitive predictor for eventual remission in an in-patient population with severe major depression.

Predictors of the effectiveness of an early medication change strategy in patients with major depressive disorder.

BACKGROUND: Patients with Major Depressive Disorder (MDD) who are non-improvers after two weeks of antidepressant treatment have a high risk of treatment failure. Recently, we did not find differences in outcomes in non-improvers randomized to an early medication change (EMC) strategy compared to treatment as usual (TAU). This secondary analysis investigated possible predictors of higher remission rates in the EMC strategy. METHODS: Of 192 non-improvers (i.e. decrease of ≤20% on the HAMD-17 depression scale) after a two-week treatment with escitalopram, n = 97 were randomized to EMC (immediate switch to high doses of venlafaxine XR) and n = 95 to TAU (continued escitalopram until day 28 with non-responders switched to venlafaxine XR). We first analyzed patient characteristics, psychopathological features and subtypes of MDD by logistic regression analyses as possible predictors of remission rates. In a second investigation, we analyzed the predictors, which showed a significant association in the first analysis before Bonferroni-Holm correction by chi-squared tests separated for treatment groups. All analyses were corrected by Bonferroni-Holm method. RESULTS: The first analyses yielded no statistically significant results after correction for multiple testing. In the second analyses, however, patients with prior medication at study entry showed higher remission rates in EMC than in TAU (24.2% versus 8.6%, p = 0.017; Bonferroni-Holm corrected significance level: p = 0.025.). Furthermore, patients with a recurrent course of MDD benefited less from treatment as usual (p = 0.009; Bonferroni-Holm corrected significance level: p = 0.025). Age, sex, age of onset, psychiatric or somatic comorbidities, and other subtypes of MDD did not predict remission rates. CONCLUSIONS: Although in our first analysis we found statistically non-significant results, the second analysis showed significant differences in remission rates between patients with or without previous medication and in patients with recurrent MDD or the first depressive episode. It would therefore be valuable to examine in larger and prospective studies whether remission rates can be increased by quick escalation of treatment in certain subgroups of patients. Promising subgroups to be tested are patients who were previously medicated, and who show a recurrent course of MDD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00974155 . Registered at the 10th of September 2009. Retrospectively registered.

Rapid attainment of target trough concentrations of tacrolimus for early improvement of clinical symptoms in patients with ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: The target trough concentration of tacrolimus for ulcerative colitis is recommended to be 10-15 ng/mL in the initial two weeks and 5-10 ng/mL in the later phase. However, the effectiveness of rapid attainment of these target trough concentrations of tacrolimus in patients with ulcerative colitis is still unclear. In the present study, we evaluated the clinical efficacy and safety of rapid attainment of target trough concentrations of tacrolimus in patients with ulcerative colitis. METHODS: A prospective cohort was conducted at Gifu University Hospital in Gifu, Japan. Hospitalized patients who received tacrolimus for the treatment of ulcerative colitis between April 2009 and March 2017 were enrolled. Since June 2011, the initial loading dose of tacrolimus increased from 0.05 to 0.1-0.2 mg/kg/d, and the maintenance dose to achieve the target trough concentration was determined to be 12.5 ng/mL by proportional calculation with measured blood concentration. The period required to attain target trough concentration and the clinical efficacy before and after dosage modification was compared. RESULTS: The initial dose after dosage modification was significantly increased compared to that before dosage modification (0.10 [0.04-0.22], median [range] mg/kg/d vs 0.05 [0.03-0.05] mg/kg/d, P < 0.001). The period required to attain a target trough concentration over 10 ng/mL was significantly shortened by dosage modification (6 [4-14] days before dosage modification vs 4.5 [2-8] days after modification, P = 0.048). Further, stool frequency score was significantly improved after dosage modification, without affecting the incidence of adverse events. WHAT IS NEW AND CONCLUSION: Our findings suggest that rapid attainment of the target trough concentration of tacrolimus improves clinical symptoms in patients with ulcerative colitis.

Early improvement in PANSS-30, PANSS-8, and PANSS-6 scores predicts ultimate response and remission during acute treatment of schizophrenia.

OBJECTIVE: PANSS-8 and PANSS-6 are derived from the 30-item Positive and Negative Syndrome Scale (PANSS-30). We investigate whether PANSS-8 or PANSS-6 is a reliable, valid, sensitive to change measure, and scalable, and whether early improvement using them can predict response/remission. METHOD: Data were from 3 trials for 270 schizophrenia inpatients receiving antipsychotics. Internal consistency, validity, sensitivity to change, and scalability using PANSS-30, PANSS-8, and PANSS-6 at each assessment were examined. Early improvement was defined as at least 20% reduction of PANSS-30, PANSS-8, or PANSS-6 scores at week 2. Response was defined as at least 40% reduction of PANSS-30 and remission as a score of PANSS-8 ≤ 3 on each item at endpoint. Receiver operating characteristic analysis was used to determine which rating scale had better discriminative capacity. RESULTS: PANSS-8 and PANSS-6 showed acceptable internal consistency, were highly correlated with PANSS-30, and had sensitivity to change. PANSS-8 and PANSS-6 were scalable at each assessment, except for PANSS-6 at baseline. Early improvement using PANSS-8 or PANSS-6 had comparable predictive values with that of PANSS-30 for response/remission. CONCLUSION: PANSS-8 and PANSS-6 are clinically useful measures. Early improvement, regardless of whether PANSS-30, PANSS-8, or PANSS-6 is used, is a statistically significant predictor of response/remission.

Sub-hubs of baseline functional brain networks are related to early improvement following two-week pharmacological therapy for major depressive disorder.

Accumulating evidence suggests that early improvement after two-week antidepressant treatment is predictive of later outcomes of patients with major depressive disorder (MDD); however, whether this early improvement is associated with baseline neural architecture remains largely unknown. Utilizing resting-state functional MRI data and graph-based network approaches, this study calculated voxel-wise degree centrality maps for 24 MDD patients at baseline and linked them with changes in the Hamilton Rating Scale for Depression (HAMD) scores after two weeks of medication. Six clusters exhibited significant correlations of their baseline degree centrality with treatment-induced HAMD changes for the patients, which were mainly categorized into the posterior default-mode network (i.e., the left precuneus, supramarginal gyrus, middle temporal gyrus, and right angular gyrus) and frontal regions. Receiver operating characteristic curve and logistic regression analyses convergently revealed excellent performance of these regions in discriminating the early improvement status for the patients, especially the angular gyrus (sensitivity and specificity of 100%). Moreover, the angular gyrus was identified as the optimal regressor as determined by stepwise regression. Interestingly, these regions possessed higher centrality than others in the brain (P < 10(-3)) although they were not the most highly connected hubs. Finally, we demonstrate a high reproducibility of our findings across several factors (e.g., threshold choice, anatomical distance, and temporal cutting) in our analyses. Together, these preliminary exploratory analyses demonstrate the potential of neuroimaging-based network analysis in predicting the early therapeutic improvement of MDD patients and have important implications in guiding earlier personalized therapeutic regimens for possible treatment-refractory depression.

Predictive factors for early clinical improvement after intra-arterial thrombolytic therapy in acute ischemic stroke.

BACKGROUND: In acute ischemic stroke, the speed of improvement after intra-arterial thrombolytic therapy (IAT)-mediated recanalization varies. This study aimed to identify clinical and radiological variables that are predictive of early improvement (EI) after IAT in acute ischemic stroke. METHODS: This single-center retrospective cohort study included 141 consecutive patients who underwent IAT for terminal internal carotid and/or middle cerebral artery (MCA) occlusions. EI was defined as a National Institutes of Health Stroke Scale (NIHSS) score less than 3 or NIHSS score improvement of 8 points or more within 72 hours of IAT. The EI and non-EI groups were compared in terms of clinical and radiological findings before and after IAT. RESULTS: Forty-nine patients showed EI (34.8%). Multivariate analysis revealed that atrial fibrillation (odds ratio [OR] .35, 95% confidence interval [CI] .14-.89, P = .028) and hyperdense MCA sign (OR .39, CI .15-.97, P = .042) were related with lack of EI. The independent EI predictors were less extensive parenchymal lesion on baseline computed tomography (OR 4.92, CI 1.74-13.9, P = .003), intermediate to good collaterals (OR 3.28, CI 1.16-9.31, P = .026), and recanalization within 6 hours of symptom onset (OR 5.2, CI 1.81-14.94, P = .002). EI associated with favorable outcomes (modified Rankin scale score 0-2) at discharge (88% versus 7%; P < .001) and 3 months after discharge (92% versus 18%; P < .001). CONCLUSIONS: The clinical and radiological variables maybe useful for predicting EI and favorable long-term outcomes after IAT.

Real-world data of tenecteplase vs. alteplase in the treatment of acute ischemic stroke: a single-center analysis.

Background: This retrospective observational cohort study aimed to evaluate whether tenecteplase's use for acute ischemic stroke (AIS) has time management advantages and clinical benefits. Methods: 144 AIS patients treated with alteplase and 120 with tenecteplase were included. We compared baseline clinical characteristics, key reperfusion therapy time indices [onset-to-treatment time (OTT), door-to-needle time (DNT), and door-to-puncture time (DPT)] and clinical outcomes (24-h post-thrombolysis NIHSS improvement, and intracranial hemorrhage incidence) between the groups using univariate analysis. We assessed hospital stay durations and used binary logistic regression to examine tenecteplase's association with DNT and DPT target times, NIHSS improvement, and intracranial hemorrhage. Results: Baseline characteristics showed no significant differences except hyperlipidemia and atrial fibrillation. OTT (133 vs. 163.72, p = 0.001), DNT (36.5 vs. 50, p < 0.001) and DPT (117 vs. 193, p = 0.002) were significantly faster in the tenecteplase group. The rates of DNT ≤ 45 min (65.83% vs. 40.44%, p < 0.001) and DPT ≤ 120 min (59.09% vs. 13.79%, p = 0.001) were significantly higher in the tenecteplase group. Tenecteplase was an independent predictor of achieving target DNT (OR 2.951, 95% CI 1.732-5.030; p < 0.001) and DPT (OR 7.867, 95% CI 1.290-47.991; p = 0.025). Clinically, the proportion NIHSS improvement 24 h post-thrombolysis was higher in the tenecteplase group (64.17% vs. 50%, p = 0.024). No significant differences were observed in symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (ICH). Patients receiving tenecteplase had shorter hospital stays (6 vs. 8 days, p < 0.001). Tenecteplase was an independent predictor of NIHSS improvement at 24 h (OR 1.715, 95% CI 1.011-2.908; p = 0.045). There was no significant association between thrombolytic choice and sICH or any ICH. Conclusion: Tenecteplase significantly reduced DNT and DPT. It was associated with early neurological function improvement (at 24 h), without compromising safety compared to alteplase. The findings support tenecteplase's application in AIS.

Early improvement with cariprazine as a predictor of antidepressant, anxiolytic, and antimanic response in bipolar I mania and depression: A pooled post hoc analysis of randomized cariprazine trials.

BACKGROUND: Early symptomatic improvement may predict treatment response in bipolar I disorder. Cariprazine has demonstrated early treatment effects in bipolar I depression and mania studies; therefore, we assessed whether early improvement with cariprazine predicts eventual treatment response. METHODS: Post hoc analyses used pooled data from randomized, double-blind, placebo-controlled bipolar I depression (NCT02670538, NCT02670551) and mania (NCT00488618, NCT01058096, NCT01058668) trials. In depression studies (cariprazine 1.5 mg/d, 3 mg/d, or placebo), early improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) total scores (≥25 % improvement at day 15) and subsequent depressive/anxiety symptom response status (≥50 % improvement at week 6) were assessed. In mania studies (cariprazine 3-12 mg/d or placebo), early improvement in Young Mania Rating Scale (YMRS) total scores (≥25 % improvement at day 7) and manic symptom response status (≥50 % improvement at week 3) were assessed. RESULTS: Patients with bipolar I depression and early MADRS improvement were approximately 4- to 6-times as likely to achieve MADRS or HAM-A response than those without early improvement; patients with early HAM-A improvement were approximately 3- to 4-times as likely to achieve MADRS or HAM-A response. A subset of patients without early improvement with cariprazine 1.5 mg/d (20 %-31 %) subsequently responded following up-titration. Patients with mania and early YMRS improvement were approximately 5 times more likely to have manic symptom response than those without early improvement. LIMITATIONS: Post hoc analysis; relatively short study durations; flexible-dosing (mania studies). CONCLUSIONS: Early symptom improvement with cariprazine may inform therapeutic decisions for patients with bipolar I disorder.

Early and continuous neurologic improvements after intravenous thrombolysis are strong predictors of favorable long-term outcomes in acute ischemic stroke.

BACKGROUND: Intravenously administered tissue plasminogen activator (IV tPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Considerable proportion of AIS patients demonstrate changes in their neurologic status within the first 24 hours of intravenous thrombolysis with IV tPA. However, there are little available data on the course of clinical recovery in subacute 2- to 24-hour window and its impact. We evaluated whether neurologic improvement at 2 and 24 hours after IV tPA bolus can predict functional outcomes in AIS patients at 3 months. METHODS: Data for consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset during 2007-2011 were prospectively entered in our thrombolyzed registry. National Institutes of Health Stroke Scale (NIHSS) scores were recorded before IV tPA bolus, at 2 and 24 hours. Early neurologic improvement (ENI) at 2 hours was defined as a reduction in NIHSS score by 10 or more points from baseline or an absolute score of 4 or less points at 2 hours. Continuous neurologic improvement (CNI) was defined as a reduction of NIHSS score by 8 or more points between 2 and 24 hours or an absolute score of 4 or less points at 24 hours. Favorable functional outcomes at 3 months were determined by modified Rankin Scale (mRS) score of 0-1. RESULTS: Of 2460 AIS patients admitted during the study period, 263 (10.7%) received IV tPA within the time window; median age was 64 years (range 19-92), with 63.9% being men, a median NIHSS score of 17 points (range 5-35), and a median onset-to-treatment time of 145 minutes (range 57-270). Overall, 130 (49.4%) thrombolyzed patients achieved an mRS score of 0-1 at 3 months. The female gender, age, and baseline NIHSS score were found to be significantly associated with CNI on univariate analysis. On multivariate analysis, NIHSS score at onset and female gender (odds ratio [OR]: 2.218, 95% confidence interval [CI]: 1.140-4.285; P=.024) were found to be independent predictors of CNI. Factors associated with favorable outcomes at 3 months on univariate analysis were younger age, female gender, hypertension, NIHSS score at onset, recanalization on transcranial Doppler (TCD) monitoring or repeat computed tomography (CT) angiography, ENI at 2 hours, and CNI. On multivariate analysis, NIHSS score at onset (OR per 1-point increase: .835, 95% CI: .751-.929, P<.001), 2-hour TCD recanalization (OR: 3.048, 95% CI: 1.537-6.046; P=.001), 24-hour CT angiographic recanalization (OR: 4.329, 95% CI: 2.382-9.974; P=.001), ENI at 2 hours (OR: 2.536, 95% CI: 1.321-5.102; P=.004), and CNI (OR: 7.253, 95% CI: 3.682-15.115; P<.001) were independent predictors of favorable outcomes at 3 months. CONCLUSIONS: Women are twice as likely to have CNI from the 2- to 24-hour period after IV tPA. ENI and CNI within the first 24 hours are strong predictors of favorable functional outcomes in thrombolyzed AIS patients.

A diagnostic test to examine early improvement as a predictor of later response to lurasidone in bipolar depression.

INTRODUCTION: Kato et al. reported results of a 6-week, double-blind, randomized, placebo-controlled trial of lurasidone in adults with bipolar depression (BDep). AIM: We performed a post hoc analysis using data from the lurasidone trial to predict later responses from early improvements. METHODS: An early improvement was defined as a ≥20% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 2; response was defined as a ≥50% reduction in MADRS total score at Week 6; symptomatic remission were defined as a score of ≤8 on MADRS total score at Week 6. RESULTS: Both sensitivity and negative predictive value (NPV) were higher for the remission outcome than for the response outcome. The interpretation of sensitivity and NPV in the lurasidone group when remission is an outcome is as follows. It means (1) that, from all remitters at Week 6, 80.6% was identified as such at Week 2 on the basis of their early improvement and (2) that a patient showing non-improvement at 2 weeks had 93.5% probability of being a non-remitters at Week 6. However, the values of specificity for both response and remission in the lurasidone group were not high. CONCLUSION: Patients who did not show an early response at Week 2 cannot be predicted with a high probability to also show poor improvement at Week 6. In fact, some patients who did not show early response at 2 weeks might have marked improvement at 6 weeks.

A comparison of self- and observer-rated scales for detecting clinical improvement during repetitive transcranial stimulation (rTMS) treatment of depression.

Clinical outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) for treatment of Major Depressive Disorder (MDD) vary widely, and no single mood rating scale is standard for assessing rTMS outcomes. This study of 708 subjects undergoing clinical rTMS compared the performance of four scales in measuring symptom change during rTMS treatment. Self-report and observer ratings were examined weekly with the Inventory of Depressive Symptomatology 30-item (IDS), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item (POMS), and Hamilton Depression Rating Scale 17-item (HDRS). While all scales were correlated and detected significant improvement, the degree of improvement over time as well as response (33-50%) and remission (20-24%) rates varied significantly. Higher baseline severity was associated with lower likelihood of remission, and greater improvement by sessions 5 and 10 predicted response across all scales. Use of only a single scale to assess outcome conferred 14-36% risk of failing to detect response/remission indicated by another scale. The PHQ was most likely to indicate improvement and least likely to miss response or remission. These findings indicate that assessment of symptom burden during rTMS treatment may be most accurately assessed through use of multiple instruments.

Baseline anxiety, and early anxiety/depression improvement in anxious depression predicts treatment outcomes with escitalopram: A CAN-BIND-1 study report.

INTRODUCTION: Although anxiety symptoms frequently co-occur with major depressive disorder, few studies examined the prediction of treatment outcomes among participants with anxious depression receiving antidepressants. We investigated whether baseline anxiety, and early improvements in anxiety and depression symptoms predict eventual treatment outcomes. METHODS: 111 participants with anxious depression, defined using ≥ 10 on GAD-7, received escitalopram (10-20 mg) for 8 weeks. Covariate-adjusted logistic regression was conducted to examine the impact of baseline anxiety, and to assess the extent week 2 anxiety (GAD-7) and depression (QIDS-SR) percentage improvement associates with week 8 anxiety (GAD-7) and depression (MADRS) response/remission. Optimum improvement thresholds were identified using receiving-operating-curve analysis and their predictive values assessed. RESULTS: Greater percentage improvement in anxiety and depression after the first 2 weeks of treatment significantly increased odds of achieving week 8 anxiety and depression response/remission (OR:1.01-1.04, p<0.05). Early anxiety (68.4%/87.2%) and depression (52.2%/83.0%) improvement thresholds around 30 and 40% provided moderate to high positive predictive value (PPV) for predicting week 8 anxiety response/remission, as well as moderate to high negative predictive value (NPV) for predicting week 8 depression response/remission (anxiety:70.8%/91.7%; depression:72.2%/90.1%). Baseline anxiety severity predicted anxiety outcomes at weeks 2 and 8. LIMITATIONS: Trial lacked placebo group. CONCLUSION: In anxious depression, early improvement in anxiety may be better than depression in predicting anxiety outcomes, with similar or higher PPVs. Both improvement types perform similarly in predicting depression outcomes, with the lack of improvement predictive of non-response and non-remission. Finally, baseline anxiety predicts eventual anxiety but not depression outcomes.

The network analysis of depressive symptoms before and after two weeks of antidepressant treatment.

BACKGROUND: A substantial proportion of patients do not benefit from selective serotonin reuptake inhibitors (SSRIs). We used network analysis to examine changes in symptom associations over time to identify SSRIs treatment targets for patients with major depressive disorder (MDD). METHODS: This study was a post-hoc analysis of data originated from the 2-week open-label phase of a multicenter clinical trial. A total of 474 participants who completed 2-week paroxetine treatment and subsequent evaluation were included in this analysis. The sample was divided into early improvement (a reduction of the HAMD-17 total score ⩾20% at week 2) and not early improvement. The network analysis was performed to compare the pattern of relationships among depressive symptoms at baseline and endpoint. In addition, we compared the network structure of the participants who achieved early improvement with those without early improvement. RESULTS: We found that the network structure and global strength increased significantly from baseline to endpoint (P<0.05). The baseline network of early improvers was more strongly connected than that of the participants who did not reach early improvement, and the global strength was significantly different (P = 0.049). Psychological anxiety and depressed mood were central symptoms of the early improvers, while somatic anxiety, insomnia, gastrointestinal symptoms and feelings of guilt were central in the network among the participants who did not show early improvement. CONCLUSIONS: The connectivity of symptom network significantly increased with treatment. The baseline network connectivity of symptoms is tighter in early improvers than those without early improvement, and their central symptoms are different.

Early improvement as a predictor of final remission in patients with treatment-resistant depression receiving electroconvulsive therapy with ketofol anesthesia.

OBJECTIVE: To examine whether early symptom improvement can predict eventual remission following electroconvulsive therapy (ECT) with ketamine plus propofol (ketofol) anesthesia in patients with treatment-resistant depression (TRD). METHODS: Thirty Han Chinese subjects suffering from TRD were administered ketofol anesthesia during ECT. Remission was defined as a score of ≤7 on the 17-item Hamilton Depression Rating Scale (HAMD-17). Receiver operating characteristic (ROC) curves were applied to identify the number of ECT sessions (i.e., 1, 2, 3, or 4 ECT sessions) that had the best discriminative capacity for eventual remission. The best definition of early improvement to predict final remission was determined by using the Youden index. RESULTS: Of the 30 patients with TRD, 16 (53.3%) and 30 (100%) were classified as remitters and responders, respectively. A 45% reduction in the HAMD-17 score after 3 ECT sessions was the optimum definition of early improvement in the prediction of eventual remission, with relatively good sensitivity (88%) and specificity (93%). Patients with than without early improvement had a greater possibility of achieving favorable ECT outcomes. CONCLUSION: Final remission of TRD following ECT with ketofol anesthesia appeared to be predicted by early improvement, as indicated by a 45% reduction in HAMD-17 score after 3 ECT sessions.

Functional connectivity of the hippocampus in predicting early antidepressant efficacy in patients with major depressive disorder.

BAKGROUD: The hippocampus is involved in the pathophysiology of major depressive disorder (MDD), and its structure and function have been reported to be related to the antidepressant response. This study aimed to identify relationships between hippocampal functional connectivity (FC) and early improvement in patients with MDD and to further explore the ability of hippocampal FC to predict early efficacy. METHODS: Thirty-six patients with nonpsychotic MDD were recruited and underwent resting-state functional magnetic resonance imaging scans at baseline. After two weeks of treatment with escitalopram, patients were divided into subgroups with early improved depression (EID, n= 19) and nonimproved depression (NID, n=17) . A voxelwise FC analysis was performed with the bilateral hippocampus as seeds, two-sample t-tests were used to compare hippocampal FC between groups. Receiver operating characteristic (ROC) curves were constructed to determine the best FC measures and optimal threshold for differentiating EID from END. RESULTS: The EID group showed significantly higher FC between the left hippocampus and left inferior frontal gyrus and precuneus than the END group. And the left hippocampal FC of these two regions were positively correlated with the reduction ratio of the depressive symptom scores. The ROC curve analysis revealed that summed FC scores for these two regions exhibited the highest area under the curve, with a sensitivity of 0.947 and specificity of 0.882 at a summed score of 0.14. LIMITATIONS: The sample used in this study was relatively small. CONCLUSIONS: These findings demonstrated that FC of the left hippocampus can predict early efficacy of antidepressant.

Treatment of COPD with Long-Acting Bronchodilators: Association Between Early and Longer-Term Clinically Important Improvement.

INTRODUCTION: This post hoc analysis of the "Early MAXimization of bronchodilation for improving COPD stability" (EMAX) trial investigated whether patients achieving early clinically important improvement (CII) sustained longer-term improvements and lower risk of clinically important deterioration (CID). METHODS: Patients were randomized to umeclidinium/vilanterol, umeclidinium, or salmeterol for 24 weeks. The patient-reported outcomes (PROs) Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms, St George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) were assessed. CII, defined as attaining minimum clinically important differences (MCID) in ≥2 PROs, was assessed at Weeks 4, 12 and 24. CID was defined as a deterioration in CAT, SGRQ, TDI by the MCID and/or a moderate/severe exacerbation from Day 30. RESULTS: Of 2425 patients, 50%, 53% and 51% achieved a CII at Weeks 4, 12 and 24, respectively. Patients with a CII at Week 4 versus those without had significantly greater odds of achieving a CII at Weeks 12 and 24 (odds ratio: 5.57 [95% CI: 4.66, 6.66]; 4.09 [95% CI: 3.44, 4.86]). The risk of a CID was higher in patients who did not achieve a CII at Week 4 compared with patients who did (hazard ratio [95% CI]: 2.09 [1.86, 2.34]). Patients treated with umeclidinium/vilanterol versus either monotherapy had significantly greater odds of achieving CII at Weeks 4, 12 and 24. CONCLUSION: Achieving a CII at Week 4 was associated with longer-term improvement in PROs and a reduced risk of deterioration. Further research is required to investigate the importance of an early response to treatment on the long-term disease course.

Early improvements of individual symptoms as a predictor of treatment response to asenapine in patients with schizophrenia.

AIM: It is well accepted that early improvement with antipsychotics predicts subsequent response in patients with schizophrenia. However, no study has examined the contribution of individual symptoms rather than overall symptom severity as the predictors. Thus, we aimed to detect individual symptoms whose improvements could predict subsequent response in patients with schizophrenia during treatment with asenapine and examine whether a prediction model with individual symptoms would be superior to a model using overall symptom severity. METHODS: This study analyzed a dataset including 532 patients with schizophrenia enrolled in a 6-week double-blind, placebo-controlled, randomized trial of asenapine. Response to asenapine was defined as a ≥30% decrease in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 6. Stepwise logistic regression analyses were performed to investigate the associations among response and PANSS total/individual item score improvements at week 1 or week 2. RESULTS: Response was associated with early improvement in the following PANSS items: disturbance of volition, active social avoidance, poor impulse control at week 1; and active social avoidance, poor attention, lack of judgment and insight at week 2. Prediction accuracy was almost compatible between the model with individual symptoms and the model with PANSS total score both at weeks 1 and 2 (Nagelkerke R2 : .51, .42 and .55, .54, respectively). CONCLUSION: Early improvement in negative symptoms, poor attention and impulse control, and lack of insight, in particular predicted subsequent treatment response in patients with schizophrenia during treatment with asenapine as accurately as prediction based on overall symptom severity.

Connectivity between the anterior insula and dorsolateral prefrontal cortex links early symptom improvement to treatment response.

BACKGROUND: Early improvement (EI) following treatment with antidepressants is a widely reported predictor to the treatment response. This study aimed to identify the resting-state functional connectivity (rs-FC) and its related clinical features that link the treatment response at the time of EI. METHODS: This study included 23 first-episode treatment-naive patients with MDD. After 2 weeks of antidepressant treatment, these patients received 3.0 Tesla resting-state functional magnetic resonance imaging scanning and were subgrouped into an EI group (N = 13) and a non-EI group (N = 10). Using the anterior insula (rAI) as a seed region, this study identified the rs-FC that were associated with both EI and the treatment response at week 12, and further tested the associations of the identified rs-FC with either the clinical features or the early symptom improvement. RESULTS: Rs-FC between rAI and the left dorsolateral prefrontal cortex (dlPFC) was associated with EI (t21 = -6.091, p = 0.022 after FDR correction for multiple comparisons). This rs-FC was also associated with an interaction between EI and the treatment response at the week 12 (t21 = -5.361, p = 6.37e-5). Moreover, among the clinical features, this rs-FC was associated with the early symptom improvement in the insomnia, somatic symptoms, and anxiety symptoms, and these early symptom improvements were associated with the treatment response. CONCLUSION: Rs-FC between the rAI and the left dlPFC played a crucial role in the early antidepressant effect, which linked the treatment response. The early treatment effect relating to rAI may represent an early symptom improvement in self-perceptual anxiety, somatic symptoms and insomnia.

Predictability of Nonremitting Depression After First 2 Weeks of Antidepressant Treatment: A VAST-D Trial Report.

Objective: In this secondary analysis of data from the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, the authors sought to determine the effectiveness of early improvement (or lack thereof) for predicting remission from depression with antidepressant therapy. Methods: This study used data from the VAST-D study, a multisite, randomized, single-blind trial with parallel assignment to one of three medication interventions for 1,522 veterans whose major depressive disorder was unresponsive to at least one course of antidepressant treatment meeting minimal standards for dosage and duration. The authors calculated the positive predictive value (PPV) and negative predictive value (NPV) of early improvement on remission, response, or greater than minimal improvement from depression for various degrees of improvement (10%-50%) on the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C) at 1, 2, 4, and 6 weeks. Results: The end of week 2 of treatment was identified as the best time to evaluate early improvement. The presence of a ≥20% drop from the baseline QIDS-C score by the end of week 2 resulted in a PPV for remission of 38% and an NPV of 93% by week 12. Extending the observational window to week 6 minimally improved NPV (97%). This association did not differ across treatment groups. Conclusions: A lack of early improvement at the end of week 2 of antidepressant therapy can be used to inform clinical decisions on the likelihood of nonremission of depression during the subsequent 10 weeks, even when dosage optimization is incomplete.