Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches.

BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.

Role of age, gender and marital status in prognosis for adults with depression: An individual patient data meta-analysis.

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials.

BACKGROUND: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. METHOD: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. RESULTS: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. CONCLUSION: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

[Cognitive therapy and interpersonal psychotherapy for major depressive disorder: how do they work, how long, and for whom?] / Cognitieve therapie en interpersoonlijke psychotherapie voor depressie: hoe werken ze, hoe lang en voor wie?

BACKGROUND: Although the effectiveness of cognitive therapy (ct) and interpersonal psychotherapy (ipt) for depression has been well established, little is known about how, how long and for whom they work.
AIM: To summarize findings from a large rct to the (differential) effects and mechanisms of change of ct/ipt for depression.
METHOD: 182 adult depressed outpatients were randomized to ct (n = 76), ipt (n = 75), or a two-month wait-list-control condition (n = 31). Primary outcome was depression severity (bdi-ii). Other outcomes were quality of life, social and general psychological functioning and various potential process measures. Interventions were compared at the end of treatment, and up to 17 months follow-up.
RESULTS: Overall, ct and ipt were both superior to the wait-list, but did not differ significantly from one another. However, the pathway through which therapeutic change occurred appeared to be different for ct and ipt, and many patients were predicted to have a clinically meaningful advantage in one of the two interventions. We did not find empirical support for the theoretical models of change.
CONCLUSION: (Long-term) outcomes of ct and ipt appear to not differ significantly. The field would benefit from further refinement of research methods to disentangle mechanisms of change, and from advances in the field of personalized medicine.

Rapid versus non-rapid cycling bipolar II depression: response to venlafaxine and lithium and hypomanic risk.

OBJECTIVE: To examine the safety and effectiveness of antidepressant versus mood stabilizer monotherapy in rapid versus non-rapid cycling bipolar II disorder. METHOD: Subjects ≥18 years old with bipolar II depression (n = 129) were randomized to double-blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n = 59) received continuation monotherapy for six additional months. RESULTS: Rapid cycling did not affect frequency of response or change over time in depressive symptoms. Rapid cycling status did not affect frequency of depressive relapse or sustained treatment response. Rapid cyclers were more likely to experience hypomanic symptoms (P = 0.005) during continuation monotherapy; however, rates were similar in venlafaxine (17.6%) and lithium (42.9%) (P = 0.31). CONCLUSION: Rapid cycling status may not be associated with an increased risk of diminished response or greater depressive relapse during venlafaxine, relative to lithium monotherapy, in bipolar II subjects. Additional randomized studies are needed to confirm these findings.

Dysfunctional cognitions in personality pathology: the structure and validity of the Personality Belief Questionnaire.

BACKGROUND: This study examines the structure of the Personality Belief Questionnaire (PBQ), a self-report instrument designed to assess dysfunctional beliefs associated with personality pathology, as proposed by the cognitive theory of personality dysfunction. METHOD: The PBQ was examined using exploratory factor analysis (EFA) with responses from 438 depressed out-patients, and confirmatory factor analysis (CFA) with responses from 683 treatment-seeking psychiatric out-patients. All participants were assessed for personality disorder (PD) using a standard clinical interview. The validity of the resulting factor structure was assessed in the combined sample (n=1121) by examining PBQ scores for patients with and without PD diagnoses. RESULTS: Exploratory and confirmatory analyses converged to indicate that the PBQ is best described by seven empirically identified factors: six assess dysfunctional beliefs associated with forms of personality pathology recognized in DSM-IV. Validity analyses revealed that those diagnosed with a PD evidenced a higher average score on all factors, relative to those without these disorders. Subsets of patients diagnosed with specific DSM-IV PDs scored higher, on average, on the factor associated with their respective diagnosis, relative to all other factors. CONCLUSIONS: The pattern of results has implications for the conceptualization of personality pathology. To our knowledge, no formal diagnostic or assessment system has yet systematically incorporated the role of dysfunctional beliefs into its description of personality pathology. The identification of dysfunctional beliefs may not only aid in case conceptualization but also may provide unique targets for psychological treatment. Recommendations for future personality pathology assessment systems are provided.

Can pharmacotherapists be too supportive? A process study of active medication and placebo in the treatment of depression.

BACKGROUND: This study examined therapist-patient interactions during clinical management with antidepressant medication and pill-placebo. METHOD: The sample consisted of 80 patients on active medication and 40 patients in a pill-placebo condition from a randomized controlled trial for moderate to severe depression. Pharmacotherapist-patient interactions were characterized using observer ratings of the therapeutic alliance, pharmacotherapist-offered facilitative conditions, pharmacotherapist adherence to clinical management treatment guidelines and pharmacotherapist competence. Patients, therapists and raters were blind to treatment condition and outcome. RESULTS: Provision of greater non-specific support (facilitative conditions) in early sessions predicted less subsequent improvement in depressive symptoms for patients receiving pill-placebo but not those receiving active medications, for which none of the process ratings predicted subsequent change. Early symptom change predicted later alliance and adherence in both conditions and therapist competence in the active condition. CONCLUSIONS: Higher levels of support in early sessions predict poorer subsequent response among placebo patients. It remains unclear whether patients who are likely to be refractory elicit greater non-specific support or whether the provision of such support has a deleterious effect in unmedicated patients. Differences in treatment process variables between conditions late in treatment are likely to be largely a consequence of symptom relief produced by active medications.

Response to cognitive therapy in depression: the role of maladaptive beliefs and personality disorders.

This study examined whether personality disorder status and beliefs that characterize personality disorders affect response to cognitive therapy. In a naturalistic study, 162 depressed outpatients with and without a personality disorder were followed over the course of cognitive therapy. As would be hypothesized by cognitive theory (A. T. Beck & A. Freeman, 1990), it was not personality disorder status but rather maladaptive avoidant and paranoid beliefs that predicted variance in outcome. However, pre- to posttherapy comparisons suggested that although patients with or without comorbidity respond comparably to "real-world" cognitive therapy, they report more severe depressive symptomatology at intake and more residual symptoms at termination.

The factor structure of the working alliance inventory in cognitive-behavioral therapy.

Studies of the therapeutic alliance in cognitive-behavioral therapy (CBT) have varied in their results, necessitating a deeper understanding of this construct. Through an exploratory factor analysis of the alliance in CBT, as measured by the Working Alliance Inventory (shortened, observer-rated version), the authors found a two-factor structure of alliance that challenges the commonly accepted one general factor of alliance. The results suggest that the relationship between therapist and client (Relationship) may be largely independent of the client's agreement with and confidence in the therapist and CBT (Agreement/ Confidence), necessitating independent measures of these two factors, not one measure of a general alliance factor.

Change in compensatory skills in cognitive therapy for depression.

The Ways of Responding (WOR) was developed to assess change in compensatory or metacognitive skills taught by cognitive therapists. Thus, one would expect WOR scores to change during cognitive therapy (CT) and to be associated with change in depression level. Twenty-seven patients with a DSM-III-R diagnosis of major depression who had received CT filled out the WOR and other measures of cognition. After 12 weeks of CT, the patients exhibited change in the WOR, the Attributional Style Questionnaire, the Dysfunctional Attitude Scale, and the Self-Control Scale. Furthermore, there were indications that change in depression was associated with changes in these measures of cognition, including the WOR. The WOR appears to be a sensitive measure of change during CT that covaries with change in depression. It remains to be tested whether change on the WOR is specific to CT.

Determining the pertinence of psychotherapy outcome research findings for clinical practice: comment on Westen and Morrison (2001).

D. Westen and K. Morrison's (2001) article is a challenge to advocates of empirically supported therapies (ESTs) and to the research enterprise that has determined which therapies are given the EST designation. Their concern that the long-term effects of ESTs are understudied and, apparently, weak is valid. However, their pessimistic conclusions about the generalizability of the results from outcome studies of ESTs are based on a serious logical error. The authors of the present article described an alternative research method that can address important and appropriate questions about the generalizability of ESTs. Continued dialogue between proponents and opponents of contemporary trends in psychotherapy outcome research is encouraged.

Sudden gains and critical sessions in cognitive-behavioral therapy for depression.

In this study of cognitive-behavioral therapy for depression, many patients experienced large symptom improvements in a single between-sessions interval. These sudden gains' average magnitude was 11 Beck Depression Inventory points, accounting for 50% of these patients' total improvement. Patients who experienced sudden gains were less depressed than the other patients at posttreatment, and they remained so 18 months later. Substantial cognitive changes were observed in the therapy sessions preceding sudden gains, but few cognitive changes were observed in control sessions, suggesting that cognitive change in the pregain sessions triggered the sudden gains. Improved therapeutic alliances were also observed in the therapy sessions immediately after the sudden gains, as were additional cognitive changes, suggesting a three-stage model for these patients' recovery: preparation-->critical session/sudden gain-->upward spiral.

The temporal relation of adherence and alliance to symptom change in cognitive therapy for depression.

This study attempted to replicate an earlier study (R. J. DeRubeis & M. Feeley, 1990) of the prediction of symptom change from process variables in cognitive therapy for depressed outpatients. Measures of in-session therapist behavior and therapist-patient interactions were correlated with prior and subsequent symptom change. One of the positive findings was confirmed, but the other received only marginal support. A "concrete" subset of theory-specified therapist actions, measured early in treatment, predicted subsequent change in depression. The therapeutic alliance was predicted by prior symptom change in 1 of the 2 later assessments, but only at a trend level. Several negative findings were similar to those obtained in the earlier study. Specifically, the alliance, an "abstract" subset of theory-specified therapist actions, and facilitative conditions did not predict subsequent change. Implications for causal inferences in psychotherapy process research are discussed.

Medications versus cognitive behavior therapy for severely depressed outpatients: mega-analysis of four randomized comparisons.

OBJECTIVE: The purpose of this study was to compare the acute outcomes of antidepressant medication and cognitive behavior therapy in the severely depressed outpatient subgroups of four major randomized trials. A secondary objective was to compare the results obtained in the National Institute of Mental Health Treatment of Depression Collaborative Research Program, upon which treatment guidelines have been based, with those obtained in the other three studies. METHOD: Outcomes of antidepressant medication and cognitive behavior therapy were compared within each of the four studies separately and for patients aggregated across the four studies. In addition, the outcomes in the antidepressant medication and cognitive behavior therapy conditions of the Treatment of Depression Collaborative Research Program were compared with those obtained in the other three studies. RESULTS: The overall effect sizes comparing antidepressant medication to cognitive behavior therapy favored cognitive behavior therapy, but tests comparing the two modalities did not reveal a significant advantage for either modality overall. CONCLUSIONS: Cognitive behavior therapy has fared as well as antidepressant medication with severely depressed outpatients in four major comparisons. Until findings emerge from current or future comparative trials, antidepressant medication should not be considered, on the basis of empirical evidence, to be superior to cognitive behavior therapy for the acute treatment of severely depressed outpatients.

Empirically supported individual and group psychological treatments for adult mental disorders.

The experimental literature on individual and group psychological treatments for adult disorders is reviewed. For each of the 11 disorders or problems covered, treatments that fall into the following categories, as defined by D.L. Chambless and S. D. Hollon (1998), are identified: efficacious and specific, efficacious, and possibly efficacious. Behavioral and cognitive-behavioral treatments dominate the lists, especially in the anxiety disorders, with notable exceptions. Reasons for the hegemony of the behavioral and cognitive modalities are discussed, and some limitations of the empirically supported treatment concept are addressed. Continued research is recommended on Aptitude x Treatment interactions, cost-benefit ratios, and generalization of treatments to a variety of patient populations, therapists, and treatment settings.

Reliability and validity of a daily diary for premenstrual syndrome.

Daily ratings of symptoms are essential to confirm a diagnosis of premenstrual syndrome (PMS). The 17-item Daily Symptom Report (DSR) is relatively brief and appropriate for clinical and primary care settings. We report the reliability, factor structure and relationships with other standard mood measures of the DSR as a measure of PMS. The sample includes 170 women who sought medical treatment for severe PMS and a non-clinical comparison group of 54 healthy women in the same age range. Cronbach's coefficient alpha was 0.92 for the premenstrual DSR scores, indicating very high internal consistency for the 17 symptoms. Factor analysis yielded four factors describing mood, behavioral items, pain, and physical symptoms. In the PMS sample, there were moderate correlations between the DSR and the Hamilton Rating Scale for Depression, the Profile of Mood States, and the Premenstrual Assessment Form. The moderate correlations of the DSR with other standard symptom measures add to the evidence that PMS overlaps with other mood disorders at the premenstrual time but is not simply a brief depression or a truncated anxiety disorder.

Factors in Outcomes of Short-Term Dynamic Psychotherapy for Chronic vs. Nonchronic Major Depression.

The benefits, and variables influencing the benefits, of short-term dynamic psychotherapy for chronic major depression versus nonchronic major depression were examined for 49 patients. The two diagnostic groups started at the same level on the Beck Depression Inventory (BDI) and Global Assessment of Functioning Scale (GAF) and benefited similarly. The bases for the benefits were examined by linear models explaining 35% of termination BDI variance and 47% of termination GAF scores. By far the largest contributor to outcome was initial GAF, followed by presence of more than one comorbid Axis I diagnosis. Initial level of depression on the BDI was not a significant predictor of termination BDI. The chronic/ nonchronic distinction accounted for less than 1% of explained variance, and little was added by personality disorder, age, or gender.

High self-esteem, hardiness and affective stability are associated with higher basal pituitary-adrenal hormone levels.

Whereas much is known about the function of the hypothalamic-pituitary-adrenal (HPA) axis during environmental stress and in psychiatric disorders, little is known about the relation of individual differences in basal HPA-functioning to individual differences in healthy psychological functioning. In the present study, we recruited 37 healthy young men and examined the relations of hardiness, self-esteem and hypomanic personality--dispositions that moderate the effects of psychosocial stress on depressive reactions and health--to circulating levels of cortisol and beta-endorphin at rest. High self-esteem, hardiness and affective stability were associated with higher plasma cortisol levels and less psychological distress. Additionally, affective stability was associated with higher levels of beta-endorphin. The present findings suggest that individual differences in basal HPA-function are associated with individual differences in psychological functioning following stress.

Reduced cytokine levels and T-cell function in healthy males: relation to individual differences in subclinical anxiety.

Previous studies of psychopathological populations and populations challenged by significant life events have shown that high levels of anxiety and depression are associated with impaired cellular immunity. However, less is known about the sources and psychoimmunological relevance of subclinical variations in distress in healthy populations faced with typical levels of life stress. In the present study, we examined the relations of state distress to T-cell function and in vivo cytokine levels in 40 male college freshmen on two occasions. In addition, we assessed the possible contribution of dispositional determinants of distress to immune-related differences in mood. Relative to characteristically less anxious subjects, subjects who were characteristically more anxious (but subclinically anxious) had more anxious mood and had significantly lower lymphocyte proliferative responses to the mitogen concanavalin A (Con A) as well as lower levels of circulating interleukin-1 beta. In addition, subjects with more negative attributional styles for bad events exhibited reduced Con A-stimulated T-cell responses and lower levels of circulating interleukin-2. Finally, subjects who were more depressed (but subclinically depressed) also had reduced blastogenic responses. Individual differences in cortisol and beta-endorphin were not shown to mediate these relationships. The present study provides evidence that dispositionally related variations in distress in psychiatrically healthy, relatively unstressed college males have immunological correlates that suggest altered T-cell and macrophage activity.

Do depressed patients with higher pretreatment stress levels respond better to cognitive therapy than imipramine?

Forty-eight unipolar depressed patients were randomly assigned to 12 weeks of treatment with either imipramine (IMI) (n = 32) or cognitive therapy (CT) (n = 16). Prior to treatment assignment, all patients were rated for severity of a variety of psychosocial stressors. The interaction effect between pretreatment stress and type of treatment, CT or IMI, on symptom improvement was evaluated. We hypothesized that patients with greater pretreatment stress would respond better to cognitive therapy. Patients treated with either CT or IMI showed equivalent reductions of depressive symptoms. There was no interaction effect between pretreatment stress and type of treatment on improvement of depressive symptoms. Based on this preliminary study it does not appear that depressed patients with higher pretreatment levels of stress respond better to cognitive therapy than they do to imipramine.