Early Symptom Change Research Articles

Early Change as a Predictor of Treatment Outcome in Patients with a Personality Disorder

A significant proportion of patients with a personality disorder do not benefit from treatment. Monitoring treatment progress can help adjust ineffective treatments. This study examined whether early changes in symptoms and personality dysfunction during the first phase of therapy could predict treatment outcomes. Data from 841 patients who received specialized treatment for personality disorders were analyzed. The study focused on whether changes in the Outcome Questionnaire-45.2 (OQ-45.2) symptom distress scale (SD), the General Assessment of Personality Disorder (GAPD), and Severity Indices of Personality Problems (SIPP) in the early phase of therapy predicted post-treatment personality dysfunction, as measured by the SIPP and GAPD. Early changes within a specific SIPP domain were the strongest predictors of post-treatment outcomes in that same domain. Early changes in symptoms significantly predicted outcomes in Self-Control, Relational Functioning, and Identity Integration, while the GAPD predicted outcomes in Self-Control and Social Attunement on the SIPP. For the GAPD, early changes on the GAPD itself, followed by early changes on the OQ-45 SD and the SIPP domain Social Attunement, were significant predictors. Thus, when it comes to personality dysfunction, early changes in a specific domain or measure are the best predictors of outcomes in that same domain. While the OQ-45 predicted some aspects of personality dysfunction, it should not replace disorder-specific measures. Additionally, the SIPP domains and the GAPD should not be used interchangeably to predict each other. In sum, considering these factors, monitoring early change can be useful in assessing progress in the treatment of patients with personality disorders.

Location-scale modeling as an integrative approach to symptom dynamics during psychotherapy: An illustration with depressive symptoms.

Depressive symptom dynamics, including change trajectories and symptom variability, have been related to therapy outcomes. However, such dynamics have often been examined separately and related to outcomes of interest using two-step analyses, which are characterized by several limitations. Here, we show how to overcome these limitations using location-scale models in a dynamic structural equation modeling framework. We introduce location-scale modeling in an accessible manner to pave the way for its use in research integrating within-person dynamics and intervention-related change in psychopathology, and we illustrate this modeling approach in a large-scale internet-based intervention for depression (N = 1,656). Using eight data points sampled across about 8 weeks, we predicted improvement across the intervention (50% symptom reduction) as a function of early change and symptom variability. Early symptom change was associated with a more likely improvement across therapy. Variability of symptoms beyond change trajectories during the intervention was associated with less likely improvement. Location-scale models, and dynamic structural equation modeling more generally, are well suited to modeling how patterns of symptom change during psychotherapy are related to important (e.g., therapy) outcomes. Our illustrative application of location-scale modeling showed that symptom variability was associated with less overall improvement in depressive symptoms. However, this finding requires replication with more intensive sampling of symptoms before final conclusions can be drawn on when and how to distinguish maladaptive from adaptive variability during psychotherapy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Select or adjust? How information from early treatment stages boosts the prediction of non-response in internet-based depression treatment.

Internet-based interventions produce comparable effectiveness rates as face-to-face therapy in treating depression. Still, more than half of patients do not respond to treatment. Machine learning (ML) methods could help to overcome these low response rates by predicting therapy outcomes on an individual level and tailoring treatment accordingly. Few studies implemented ML algorithms in internet-based depression treatment using baseline self-report data, but differing results hinder inferences on clinical practicability. This work compares algorithms using features gathered at baseline or early in treatment in their capability to predict non-response to a 6-week online program targeting depression. Our training and test sample encompassed 1270 and 318 individuals, respectively. We trained random forest algorithms on self-report and process features gathered at baseline and after 2 weeks of treatment. Non-responders were defined as participants not fulfilling the criteria for reliable and clinically significant change on PHQ-9 post-treatment. Our benchmark models were logistic regressions trained on baseline PHQ-9 sum or PHQ-9 early change, using 100 iterations of randomly sampled 80/20 train-test-splits. Best performances were reached by our models involving early treatment characteristics (recall: 0.75-0.76; AUC: 0.71-0.77). Therapeutic alliance and early symptom change constituted the most important predictors. Models trained on baseline data were not significantly better than our benchmark. Fair accuracies were only attainable by involving information from early treatment stages. In-treatment adaptation, instead of a priori selection, might constitute a more feasible approach for improving response when relying on easily accessible self-report features. Implementation trials are needed to determine clinical usefulness.

Early symptom change contributes to the outcome prediction of cognitive behavioral therapy for depression patients: A machine learning approach

BackgroundLimited evidence exists regarding the association between early symptom change and later outcomes of cognitive behavioral therapy (CBT). This study aimed to apply machine learning algorithms to predict continuous treatment outcomes based on pre-treatment predictors and early symptom changes and to uncover whether additional variance could be explained compared to regression methods. Additionally, the study examined early subscale symptom changes to determine the most significant predictors of treatment outcome. MethodsWe investigated CBT outcomes in a large naturalistic dataset (N = 1975 depression patients). The sociodemographic profile, pre-treatment predictors, and early symptom change, including total and subscale scores were used to predict the Symptom Questionnaire (SQ)48 score at the 10th session as a continuous outcome. Different machine learners were compared to linear regression. ResultsEarly symptom change and baseline symptom score were the only significant predictors. Models with early symptom change explained 22.0 % to 23.3 % more variance than those without early symptom change. Specifically, the baseline total symptom score, and the early symptom score changes of the subscales pertaining to depression and anxiety were the top three predictors of treatment outcome. LimitationExcluded patients with missing treatment outcomes had slightly higher symptom scores at baseline, indicating possible selection bias. ConclusionEarly symptom change improved the prediction of treatment outcomes. The prediction performance achieved is far from clinical relevance: the best learner could only explain 51.2 % of the variance in outcomes. Compared to linear regression, more sophisticated preprocessing and learning methods did not substantially improve performance.

P348 Disease trajectories in ulcerative colitis: Early identification of patients with endoscopic remission at Week 52

Abstract Background Clinical understanding of different disease courses in response to targeted therapies in ulcerative colitis (UC) is lacking. Symptom load over time can help to define different trajectories leading to outcome measures at week 52. This post hoc analysis from the GEMINI 1 study of vedolizumab (VDZ) vs placebo for the treatment of moderately to severely active UC1 aimed to define different clinical patterns of response that led to Week 52 endoscopic remission based on daily collection of symptom data: rectal bleeding (RB) and stool frequency (SF). Methods RB and SF data, each scored 0 to 3, were extracted from the diary cards of patients who were treated with VDZ up to Week 50, had clinical outcome assessed at Week 52 and had sufficient diary data. From the daily scores, six different daily symptom score rules comprising RB alone or various combinations of RB and SF (Table 1) were derived. Each of the six symptom score rules was then accrued over the time to derive cumulative symptom scores (area under the curve [AUC]). The AUCs at Weeks 6, 10, 14 and 22 for each rule were evaluated for sensitivity and specificity to predict endoscopic remission at Week 52, which was defined as Mayo endoscopic subscore of ≤1 point. Results Of the 895 pts included in the GEMINI 1 study, 217 pts were treated with VDZ, had sufficient RB and SF data and Week 52 outcome data. Of these, 157 (72.4%) achieved endoscopic remission at Week 52. Rule 4, with a score of 0 if both RB=0 and SF≤1 or 1 if not, was consistently better at predicting response at Week 52, i.e., had largest area under the receiver-operator characteristic (ROC) curve (Week 10 and Week 14 shown in Table 2). Area under ROC curve for Rule 4 was 0.7317 (0.6578, 0.8057) and 0.7534 (0.6810, 0.8258) at Week 10 and Week 14, respectively (Fig 1). Rule 4 had better predictive performance than the use of RB Mayo score (RB1) alone or the simple dichotomization (RB2, 0 if RB≤1, 1 if RB >1) [Table 2]. AUCs for Rule 4 differed between pts with vs without endoscopic remission at Week 52, with differences evident as early as Week 10: median AUC=41 for pts with endoscopic remission vs 70 for pts without (Fig 2). Conclusion The daily collection of RB and SF symptoms during the first weeks of therapy with VDZ identifies patients with a high likelihood for endoscopic emission at Week 52. Early clinical symptom change is a simple method for tight monitoring of patients with UC. The identification of preferential responder populations in which marked reduction of suffering are combined with hard endpoints could help in establishing treatment optimization algorithms for targeted therapies.

RWD43 Early Symptom-Change Contributes to the Outcome Prediction of Cognitive Behavioral Therapy for Depression Patients: A Machine Learning Approach

This study aimed to apply machine learning algorithms to predict treatment outcomes in depression based on pre-treatment predictors and early symptom changes to uncover whether additional variance could be explained.

Abstract 10852: Stable versus Dynamic Cardiac Symptom Characteristics Are Associated With Adverse Outcomes Among Individuals Transported by Ambulance for Suspected Acute Coronary Syndrome

Introduction: Acute coronary syndrome (ACS) is a potential life-threatening emergency; therefore, rapid diagnosis and life-saving reperfusion therapies are essential to prevent adverse outcomes. Patients with suspected ACS experience an array of symptoms, which cause patients to seek care (9-1-1 or self-transport) to the emergency department [ED]). Little is known, however, about the prognostic value of symptom characteristics experienced in the very early period of evolving ACS and its impact on adverse patient outcomes. The purpose of this study was to determine if early symptom changes reported in the prehospital period are associated with adverse outcomes. Methods Adults > 21 years of age with non-traumatic chest pain and/or anginal equivalent symptoms transported by ambulance were included. Cardiac symptoms were measured prospectively with the ACS Symptom Checklist, a validated 13-item tool that takes approximately one-minute to complete. Trained EMS personnel administered the ACS Symptom Checklist during ambulance transport (T1) and research specialists measured symptoms again in the ED (T2), after acute triage care was completed. Symptom changes were categorized as an increase, decrease, or both from T1 to T2. Changes in symptoms between T1 and T2 were defined as stable (0-3 symptoms) or dynamic ( > 4 symptoms). Adverse hospital outcomes included death, reinfarction, and/or new onset heart failure. Results To date, a total of 280 patients presenting to the ED by ambulance with suspected ACS have been enrolled (mean age 60.1 + 15.5 years; 51.2% female; 14.3% final diagnosis of ACS). Of 255(91.1%) patients with complete data, 143(51.1%) experienced stable symptoms and 112(40%) experienced dynamic symptoms. Patients with stable changes had significantly higher rates of adverse outcomes compared to patients with dynamic changes (11.9 versus 2.9%, p=0.007). Patients reporting shortness of breath at T1 or T2 were over 4 times likely to experience an adverse event (p=0.003, p=0007). Conclusions Patients with suspected ACS who have stable symptom changes were more likely to have an adverse hospital outcome. The underlying mechanism of plaque rupture in ACS may account for these differences in symptom characteristics but needs further study.

Modelling trajectories of change in psychopathology and well-being during eating disorder outpatient treatment

Objective: There are considerable differences in how eating disorder (ED) patients respond to treatment. This study aimed to identify change trajectories of mental health during treatment. Method: Longitudinal data of 442 patients was used with five time points during a year of outpatient treatment. ED psychopathology and well-being were used as primary measures. A series of latent growth mixture models were applied to model trajectories of change. Results: Three latent classes were found for ED psychopathology and well-being. For ED psychopathology, a high baseline severity and slow recovery class (55.9% of the patients), a high baseline severity followed by a substantial recovery class (19.9%) and a moderate baseline severity and no significant recovery class (24.2%) were found. For well-being, a low baseline followed by a slow growth class (44.6%), a low baseline and substantial growth class (9.5%) and a moderate and stable well-being class (45.9%) was found. General psychopathology, early symptom change, hope for recovery, intrinsic motivation and the ED type were predictive of class membership in either ED psychopathology or well-being. Conclusions: This study shows variability in ED psychopathology and well-being change trajectories, modelled in meaningful latent recovery classes. These results may have clinical implications, such as adjusting patients’ treatment based on change trajectories.

Striatal Activity to Reward Anticipation as a Moderator of the Association Between Early Behavioral Inhibition and Changes in Anxiety and Depressive Symptoms From Adolescence to Adulthood

The early childhood temperament of behavioral inhibition (BI), characterized by inhibited and fearful behaviors, has been associated with heightened risk for anxiety and depression across the lifespan. Although several neurocognitive correlates underlying vulnerability to the development of anxiety among inhibited children have been identified, little is known about the neurocognitive correlates underlying vulnerability to the development of depression. To examine whether blunted striatal activation to reward anticipation, a well-documented neurocognitive vulnerability marker of depression, moderates the association between early BI and the developmental changes in depression and anxiety from adolescence to adulthood. Participants in this prospective longitudinal study were recruited at age 4 months between 1989 and 1993 in the US. Follow-up assessments extended into 2018 (age 26 years). Data were analyzed between September 2021 to March 2022. BI was measured through an observation paradigm in infancy (ages 14 and 24 months). Neural activity to anticipated rewards during a monetary incentive delay task was measured using functional magnetic resonance imaging in adolescence (between ages 15-18 years; 83 individuals had usable data). Anxiety and depressive symptoms were self-reported across adolescence to young adulthood (ages 15 and 26 years; n = 108). A latent change score model, accounting for the interdependence between anxiety and depression, tested the moderating role of striatal activity to reward anticipation in the association between early BI and changes in anxiety and depressive symptoms. A region of interest approach limited statistical tests to regions within the striatum (ie, nucleus accumbens, caudate head, caudate body, putamen). Of 165 participants, 84 (50.1%) were female and 162 (98%) were White. Preliminary analyses revealed significant increases in anxiety and depressive symptoms across ages 15 to 26 years, as well as individual variation in the magnitude of changes. Main analyses showed that reduced activity in the nucleus accumbens to reward anticipation moderated the association between early BI and increases in depressive (β = -0.32; b = -4.23; 95% CI, -7.70 to -0.76; P = .02), and more depressive symptoms at age 26 years (β = -0.47; b = -5.09; 95% CI, -7.74 to -2.43; P < .001). However, there were no significant interactions associated with latent changes in anxiety across age nor anxiety at age 26 years. Activity in the caudate and putamen did not moderate these associations. Blunted reward sensitivity in the ventral striatum may be a developmental risk factor connecting an inhibited childhood temperament and depression over the transition to adulthood. Future studies should examine the efficacy of prevention programs, which target maladaptive reward processing and motivational deficits among anxious youths, in reducing risks for later depression.

Patient-oriented measures for phase 3 studies of tralokinumab for the treatment of atopic dermatitis (ECZTRA 1, 2, and 3)

BackgroundTralokinumab, as monotherapy or in combination with topical corticosteroids (TCS), has exhibited marked efficacy through 52 weeks in phase 3 trials of adults with moderate-to-severe atopic dermatitis and additional efficacy in a long-term extension trial. Early changes in patient-reported symptoms have not been communicated. ObjectiveTo evaluate early changes in patient-reported outcomes (PROs) across the ECZTRA 1, 2, and 3 tralokinumab trials. MethodsMonotherapy data (ECZTRA 1 + 2) was pooled; ECZTRA 3 evaluated tralokinumab plus optional TCS. The PROs were assessed through the trials. ResultsA total of 1596 and 380 patients were randomized in ECZTRA 1 and 2 and ECZTRA 3, respectively. Baseline demographics and clinical characteristics were similar between groups. Early separation from placebo was observed in percentage improvement in worst average daily pruritus numerical rating score (NRS) (week 1, ECZTRA 1 + 2; week 2, ECZTRA 3) and from day 2 in ECZTRA 1 and 2 daily data. More tralokinumab-treated patients achieved clinically meaningful improvements (≥ 4 points) in NRS by week 2 (ECZTRA 1 + 2) or week 3 (ECZTRA 3) vs placebo. Improvements in eczema-related sleep NRS were seen within 2 weeks (week 1, ECZTRA 1 + 2; week 2, ECZTRA 3), supported by similar improvements in other sleep measures. Meaningful changes in Dermatology Life Quality Index were observed from week 2 (ECZTRA 1 + 2). Results were supported by numerical differences from placebo in Patient-Oriented Eczema Measure total score (week 2, both data sets). ConclusionTralokinumab with or without TCS exhibited early and clinically meaningful improvements vs placebo in several PROs, which may be beneficial to patients because atopic dermatitis symptom relief is a key treatment concern for patients.

Early response to cognitive behavioral therapy for body dysmorphic disorder as a predictor of outcomes

Individuals with body dysmorphic disorder (BDD) suffer from distressing or impairing preoccupations with perceived imperfections in their appearance. This often-chronic condition is associated with significant functional impairment and elevated rates of psychiatric comorbidity and morbidity, including depression, substance use disorders, and suicidality. Cognitive behavioral therapy (CBT) for BDD has been shown to be efficacious. However, this intervention is long (up to 24 weeks) relative to many manualized approaches for other related conditions, there is a significant shortage of clinicians trained in CBT for BDD, and some patients drop out of treatment and/or do not respond. Thus, there is great interest in understanding and predicting who is most likely to respond, to better allocate clinical resources. This secondary data analysis of participants enrolled in prior uncontrolled and controlled studies of CBT for BDD explored whether early response to CBT, operationalized as percentage change in symptom severity within the first four weeks and the first 12 weeks of this 24-week treatment, predicts clinical outcomes for patients with BDD (n = 90). The findings indicated that minimal early symptom change was not indicative of eventual non-response. This suggests that patients and clinicians should not be discouraged by limited early improvement but should instead continue with a full course of treatment before reevaluating progress and alternative interventions. Overall, the results support the view that treatment success is more likely if a longer CBT protocol is followed. More work is needed to understand mechanisms of change and thus match optimal interventions to patient characteristics.

DOP38 Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1

Abstract Background Upadacitinib (UPA), an oral, reversible JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, or tyrosine kinase 2 (TYK2), demonstrated significantly greater efficacy compared with placebo (PBO) for induction of remission in patients with moderately to severely active ulcerative colitis (UC) in two phase 3 trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026). This analysis evaluated the efficacy of UPA on early symptomatic improvement for the first 14 days, using pooled data from U-ACHIEVE Induction and U-ACCOMPLISH. Methods U-ACHIEVE and U-ACCOMPLISH were multicentre, double-blind, PBO-controlled trials that enrolled patients who have had moderately to severely UC with an Adapted Mayo Score of 5 to 9 points and centrally reviewed endoscopy subscore of 2 to 3. A total of 998 patients were randomized to receive UPA 45mg once daily (QD) (n=658) or PBO (n=328) for 8 weeks (wks) in a 2:1 ratio. First dose of study drug was administered on Day 0. Improvement in symptoms including stool frequency subscore (SFS), rectal bleeding subscore (RBS), abdominal pain, and bowel urgency were analysed from daily symptom diary data. Multivariate regression analysis was used to determine if early changes in UC symptoms could be used to evaluate a potential correlation with patients’ likelihood of achieving clinical response or clinical remission per Adapted Mayo score at the end of induction. Results Baseline characteristics were similar between both treatment groups. Patients treated with UPA 45 mg QD experienced significant improvement in daily symptoms, with significantly more subjects achieving SFS≤1 (p&amp;lt;0.001), RBS of 0 (p&amp;lt;0.05), and SFS of 0 (p&amp;lt;0.05) as early as day 1 and maintained through day 14 (Figure 1). A significantly higher percentage of patients who received UPA 45 mg QD compared to PBO, achieved abdominal pain=0 and the absence of bowel urgency within 3 days of beginning treatment through day 14 (p&amp;lt;0.05). Multivariate analysis revealed that patients who achieved day 7 SFS≤1 (OR 2.42, 95% CI, 1.53–3.82) were more likely to attain clinical response (Table). Patients who attained day 7 SFS≤1 (OR 2.53, 95% CI 1.59–4.00) or day 7 bowel urgency absent (OR 2.40, 95% CI 1.52–3.79) were more likely to achieve clinical remission at week 8. Conclusion UPA 45 mg QD significantly improved UC symptoms as early as day 1, providing patients with rapid symptom relief. Patients who achieved early symptom improvement were more likely to attain clinical remission or clinical response at week 8. [Clinicaltrials.gov, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026)]

How does early symptom change predict subsequent course of depressive symptoms during psychotherapy?

Previous studies reported about the influence of early changes on treatment response. However, the question of whether early changes can predict the subsequent course of depressive symptoms during treatment with psychotherapy has not yet been clearly answered. We aimed to investigate whether symptom course in the first weeks at the level of individual session can predict the further symptom progression on a session to session level during psychotherapy treatment in patients with Major Depression (MD). Monocentric randomized controlled trial with psychotherapeutic treatment either with cognitive-behavioural therapy (CBT) or hypnotherapy (HT). The longitudinal course of weekly depressive symptoms during the six months treatment period was examined. In this RCT with 152 randomized patients suffering from current mild-to-moderate MD, depressive symptoms were assessed on a weekly basis during the 20 sessions' treatment with individual psychotherapy. We only included patients for which sufficient data for our analysis were available. Three different linear and quadratic mixed model analyses with random effects for each patient were tested: Early change was defined as the individual percentage symptom change during the first two, three, four and five weeks. Symptoms from session four, five, six and seven onward were predicted using different models, with early change added to the model in a final step. Calculating all models separately for CBT and HT lead to comparable results. A slow symptom decrease after session four, five, six, seven onward to the end of the treatment was found. However, adding early change to the model, had no effect on the further symptom course in all models. Symptom changes at early stages of psychotherapy should not be considered as being predictive for further symptom course. The individual early symptom change in a treatment with psychotherapy in the first two, three, four, or five weeks of treatment does not predict the subsequent symptom course from session four, five, six, or seven onward at a session to session level. Symptom changes at early stages of psychotherapy should not be considered as being predictive for further symptom course. We found a symptom reduction ranging from 3% to 16% in the first two, three, four, or five weeks. Treatment response between the first and last therapy session was found in 54.5%, the number of remitted patients (with PHQ-9 scores < 5) was 44.7%. A small symptom improvement of between 0.21 and 0.42 points in the PHQ-9 scores per week in later stages of psychotherapy is likely in all patients (with and without early symptom improvement).

Early changes in brain structure, functional connectivity and neuropsychiatric symptoms after HCV infection cure with direct-acting antivirals

IntroductionHepatitis C virus (HCV) infection is known to be associated with neuropsychiatric manifestations as part of the disease. Previous neuroimaging studies showed brain connectivity dysfunction among HCV-infected patientsObjectivesTo assess, by MR in resting state, the potential structural and connectivity changes before (BL) and after HCV eradication (FU12) with direct-acting antivirals (DAA), along with clinical parameters.Methods Twenty-one HCV-patients, aged≤55 years, without psychiatric history, nor advanced liver disease, and eligible for DAA, and 25 healthy controls were included. Evaluations were performed at BL and FU12. Brain volume and local gyrification index (LGI) were assessed in MR-T1, and functional connectivity by seed-based analysis (left insula). Depression (MADRS/PHQ9) and neurotoxicity symptomatology (NRS) were assessed. We compared patients between BL/FU12, and controls by means of paired/independent T-test analysis.ResultsSubstained virologycal response was obtained in all patients (100%). Depressive and neurotoxicity symptomatology improved after cure (p&lt;0.01). HCV-patients showed a reduced volume in a right latero-occipital area compared to controls (CWP&lt;0.005) in both BL and FU12. This difference was smaller between FU12 and controls. LGI was higher in FU12-HCV compared to BL-HCV. fMRI connectivity showed a high association between insula and occipital/parietal territories in patients than controls, being higher among BL-HCV and controls. Differences were limited to occipital areas among FU12-HCV and controls.ConclusionsNeuropsychiatric symptomatology improved after cure. Left insula is altered among HCV-patients in structured and connectivity (mainly occipital areas). After cure differences with controls were reduced, suggesting a partial restoration of brain connectivity.

Early symptomatic improvements as a predictor of response to repeated-dose intravenous ketamine: Results from the Canadian Rapid Treatment Center of Excellence

BackgroundEarly symptomatic improvement with monoamine-based antidepressants is predictive of treatment response. The objective of this study was to determine if early symptomatic improvements with intravenous (IV) ketamine predicted treatment response to an acute course of four infusions. Method134 adults with treatment resistant depression (TRD) received four ketamine infusions over one to two weeks. Depressive symptoms were measured using the Quick Inventory for Depressive Symptomatology Self-Report16 (QIDS-SR16) at baseline and post-infusions 1, 2, 3, and 4. Early improvement was defined as ≥20% reduction in QIDS-SR16 scores after the first or second infusion. Linear models were used to determine whether early improvement was associated with post-infusion 4 QIDS-SR16 scores after controlling for baseline characteristics. ResultsEarly improvement post-infusion 1 (β = −3.52, 95% BCa CI [−5.40, −1.78]) and 2 (β = −3.16, 95% BCa CI [−5.75, −1.59]) both significantly predicted QIDS-SR16 scores post-infusion 4. Early improvers had significantly lower QIDS-SR16 scores at post-infusion 4 (post-infusion 1 improvers: M = 9.8, SD = 4.5; post-infusion 2 improvers: M = 10.6, SD = 5.7) compared to non-early improvers (post-infusion 1 non-improvers: M = 13.7, SD = 5.8; post-infusion 2 non-improvers: M = 14.1, SD = 5.3) when controlling for baseline characteristics. The majority (58%) of individuals who did not improve post-infusions 1 or 2 still experienced an antidepressant response or partial response (≥20% reduction in QIDS-SR16) post-infusion 4. LimitationsThis is a post-hoc analysis of an open-label study. ConclusionEarly improvement was associated with greater antidepressant effects following a course of four ketamine infusions. However, individuals who did not show early improvements still had a high likelihood of experiencing clinically significant symptom reduction after the fourth infusion, suggesting that completing four infusions, regardless of early symptom changes, is appropriate and merited.

Overcoming a Poor Early Response with Cognitive Behavioral Therapy Skills

Early response to treatment is a robust predictor of outcome in cognitive behavioral therapy (CBT) for depression. When clients show a poor early response, therapists may understandably be concerned. We examine how early CBT skill development might be used to help inform therapists about patients’ prognoses in such circumstances. In a sample of 95 clients participating in CBT for depression, we examine the role of the development of CBT skills by asking whether a client’s prognosis depends not only on early response, but on its interaction with CBT skill development. We found support for the hypothesized interaction in predicting posttreatment depression and anxiety symptoms. For those who experienced modest early CBT skill improvements, early symptom improvement was strongly predictive of posttreatment outcome. However, for those who experienced more substantial early CBT skill improvements, early symptom change was not as strongly related to their posttreatment symptoms. Our findings extend the literature on early response predicting outcome by showing that when clients experience more limited early symptom change, outcome depends considerably on the degree to which they are learning CBT skills. For clients with greater CBT skill improvements, a relatively positive treatment outcome is still common.

Early predictors of treatment outcome in a partial hospital program for adolescent anorexia nervosa.

Previous research supports the relevance of early symptom change in eating disorder (ED) treatment; however, few studies have distinguished early weight change from early change in ED psychopathology, particularly in higher levels of care. Thus, the present study examined whether early change in weight and ED psychopathology predicted outcome for adolescents with anorexia nervosa (AN) in a partial hospitalization program. Adolescents with AN (n = 99) completed assessments at admission, 1-month after treatment admission, discharge, and 6-month follow-up. Higher admission percent expected body weight (%EBW), greater early change in %EBW, longer duration of treatment, shorter length of illness, and earlier age of onset predicted greater change in %EBW at discharge, but not follow-up. Greater ED psychopathology at admission and greater early change in ED psychopathology predicted later change in ED symptoms at discharge, but not follow-up. Neither early change in %EBW nor ED psychopathology predicted likelihood of remission at discharge and follow-up. Results support the importance of early change in predicting later change in the same ED outcome variables and suggest that early change in both %EBW and ED psychopathology in adolescents may be an important area for future research.

Using prefrontal and midline right frontal EEG-derived theta cordance and depressive symptoms to predict the differential response or remission to antidepressant treatment in major depressive disorder

There is a growing need for optimizing treatment selection and response prediction in individuals with major depressive disorder (MDD). Prior investigations have shown that changes in electroencephalographic (EEG)-based measures precede symptom improvement and could serve as biomarkers of treatment outcome. One such method is cordance, a computation of regional brain activity based on a combination of absolute and relative resting EEG activity. Specifically, early reduction in prefrontal (PF) and midline right frontal (MRF) theta (4-8Hz) cordance has been shown to predict response to various antidepressants, though replication is required. Thus, this study examined early changes (baseline to week 1) in PF and MRF cordance in 47 MDD patients undergoing antidepressant treatment. Early changes in cordance and in Montgomery Åsberg Depression Rating Scale (MADRS) scores were assessed alone, and in combination, to predict eventual (by week 12) treatment response and remission. Models combining early changes in theta cordance (PF and MRF) and depressive symptoms were most predictive of response to treatment at week 12; remission models (cordance, MADRS, and their combination) were weaker, though provided modest prediction values. These results suggest that antidepressant response may be optimally predicted by combining both EEG and symptom-based measures after one week of treatment.

Prospective testing of a neurophysiologic biomarker for treatment decisions in major depressive disorder: The PRISE-MD trial

Management of Major Depressive Disorder (MDD) might be improved by a biomarker to predict whether a selected medication is likely to lead to remission. We previously reported on a quantitative electroencephalogram-based biomarker, the Antidepressant Treatment Response (ATR) index, that integrated recordings at baseline and after one week of treatment. The present study prospectively tested whether treatment directed by the biomarker increased the likelihood of remission; we hypothesized that continued treatment with a drug predicted to lead to remission (i.e., high ATR values) would be associated with better outcomes than if the drug was predicted not to lead to remission (i.e., low ATR values). We enrolled 180 adult outpatients with unipolar MDD from the community. After one week of escitalopram treatment to determine the biomarker, stratified randomization (high vs. low ATR) was used to assign subjects to either continued escitalopram or a switch to bupropion as a blinded control condition, for seven additional weeks. For the 73 evaluable subjects assigned to continued escitalopram treatment, the remission rate was significantly higher for those in whom ATR had predicted remission versus non-remission (60.4% vs. 30.0%, respectively, p = 0.01). Accuracy was enhanced by combining 1-week depressive symptom change with ATR (68.6% vs 28.9%). This prospective validation study supports further development of the ATR biomarker, alone or together with early symptom change, to improve care by identifying individuals unlikely to remit with their current treatment, and support the decision to change treatment after one week rather than after failing a full, prolonged course of medication.

Association between treatment-related early changes in psychological factors and development of postherpetic neuralgia.

To examine the association between catastrophizing and pain intensity with acute herpes zoster, and the association of treatment-related early changes in depressive symptoms, anxiety, and catastrophizing with postherpetic neuralgia (PHN) development, independent of acute pain intensity. We analyzed 44 outpatient participants with acute herpes zoster who completed a 6-month follow-up. Participants completed a self-reported questionnaire with a Visual Analog Scale (VAS), the Pain Catastrophizing Scale (PCS), and the Hospital Anxiety and Depression Scale (HADS) at first visit, and 3 and 6months, thereafter. We assessed associations between acute pain intensity and analyzed factors using univariate regression analyses. Univariate and bivariate logistic regression models were constructed to assess associations of variables at the first visit and early changes in psychological factors with PHN development. Sex, severe skin rash at first visit, PCS, and HADS depression were associated with acute pain intensity {standardized regression coefficient, 0.46 [95% confidence interval (CI) 0.12-0.74], 0.36 (95% CI 0.07-0.65), 0.33 (95% CI 0.03-0.62), 0.47 (95% CI 0.19-0.74), respectively}. Acute pain intensity and early change in pain intensity were associated with PHN development [odds ratio (OR) 1.08 (95% CI 1.02-1.14) OR 2.38 (95% CI 1.10-5.16), respectively]. Decreased PCS was associated with decreased risk of PHN development, independent of acute pain intensity [OR 0.31 (95% CI: 0.12-0.80)]. Catastrophizing was associated with acute pain intensity, and lower pain-related catastrophizing among patients with acute herpes zoster was associated with less risk of PHN development, independent of acute pain intensity.