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.

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.

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.

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.

Cognitive therapy and pharmacotherapy for depression. Singly and in combination.

Cognitive therapy and imipramine hydrochloride tricyclic pharmacotherapy, each singly and in combination, were compared in the treatment of nonpsychotic, nonbipolar depressed outpatients. One hundred seven patients were randomly assigned to 12 weeks of active treatment; 64 patients completed the full course of treatment. Rates of attrition were high but not differential. Cognitive therapy and pharmacotherapy did not differ in terms of symptomatic response, either in the primary analyses or in secondary analyses restricted to more severely depressed outpatients. Initial severity did predict response within pharmacotherapy alone, but not within cognitive therapy. Combining cognitive therapy with pharmacotherapy did not markedly improve response over that observed for either modality alone, although such nonsignificant differences as were evident did favor the combined treatment. Two patients died as a consequence of suicide attempts, both of which involved study medication.

Differential relapse following cognitive therapy and pharmacotherapy for depression.

Patients successfully treated during a 3-month period with either imipramine hydrochloride pharmacotherapy, cognitive therapy, or combined cognitive-pharmacotherapy were monitored during a 2-year posttreatment follow-up period. Half of the patients treated with pharmacotherapy alone continued to receive study medications for the first year of the follow-up. All other patients discontinued treatment at the end of the acute treatment phase. Patients treated with cognitive therapy (either alone or in combination with medication) evidenced less than half the rate of relapse shown by patients in the medication--no continuation condition, and their rate did not differ from that of patients provided with continuation medication. It appears that providing cognitive therapy during acute treatment prevents relapse. Whether this preventive effect extends to recurrence remains to be determined.

Response of depression to very high plasma levels of imipramine plus desipramine.

Forty-five depressed patients were treated with imipramine for 6 weeks. Seven of 7 patients (100%) who had plasma levels of imipramine plus desipramine greater than 500 ng/ml showed a 50% or greater improvement in Hamilton depression scores compared with 23 of 38 patients (60%) with plasma levels less than 500 ng/ml (p less than 0.057).

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.

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.

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.

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.

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.

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.

How does cognitive therapy work? Cognitive change and symptom change in cognitive therapy and pharmacotherapy for depression.

The effects of changes in depression-relevant cognition were examined in relation to subsequent change in depressive symptoms for outpatients with major depressive disorder randomly assigned to cognitive therapy (CT; n = 32) versus those assigned to pharmacotherapy only (NoCT; n = 32). Depression severity scores were obtained at the beginning, middle, and end of the 12-week treatment period, as were scores on 4 measures of cognition: Attributional Styles Questionnaire (ASQ), Automatic Thoughts Questionnaire (ATQ), Dysfunctional Attitudes Scale (DAS), and the Hopelessness Scale (HS). Change from pretreatment to midtreatment on the ASQ, DAS, and HS predicted change in depression from midtreatment to posttreatment in the CT group, but not in the NoCT group. It is concluded that cognitive phenomena play mediational roles in cognitive therapy. However, data do not support their status as sufficient mediators.

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.

Does 24-h urinary MHPG predict treatment response to antidepressants? II. Association between imipramine response and low MHPG.

Thirty depressed patients collected 24-h urine samples for a 3-methoxy-4-hydroxyphenylglycol (MHPG) determination prior to imipramine treatment. Patients responding to treatment had lower levels of MHPG than did non-responders.