Acute-phase Cognitive Therapy Research Articles

Levels of depressed mood and low interest for two years after response to cognitive therapy for recurrent depression

BackgroundMajor depressive disorder (MDD) involves depressed mood (high negative affect, predominantly) and low interest/pleasure (low positive affect). In past research, negative affect has improved more than positive affect during acute-phase antidepressant medication or cognitive therapy (CT). We extended this literature by differentiating depressed mood and two dimensions of low interest (general and sexual), assessing persistence of symptom differences after acute-phase CT response, and testing whether continuation treatment acted differently on depressed mood versus low interest. MethodsWe analyzed data from two randomized controlled trials. Patients with recurrent MDD first received acute-phase CT. Then, responders were randomized to 8-month continuation treatments and assessed for 16-24 additional months. ResultsDepressed mood and low general interest improved more than low sexual interest during acute-phase CT. Among responders, these symptom differences persisted for at least 2 years and were not changed by continuation CT or antidepressant medication. LimitationsGeneralization of findings to other patient populations and treatments is uncertain. Depressed mood and low interest scales were constructed from standard symptom measures and overlapped empirically. ConclusionsLess improvement during CT, and persistent low sexual interest despite continuation treatment, highlights the need for MDD treatments more effectively targeting this positive affective symptom.

Does Symptom Linkage Density Predict Outcomes in Cognitive Therapy for Recurrent Depression?

Acute-phase cognitive therapy (CT) is an efficacious treatment for major depressive disorder (MDD), but how CT helps patients is incompletely understood. As a potential means to clarify CT mechanisms, we defined "symptom linkage density" (SLD) as a patient's mean time-lagged correlation among nine depressive symptoms across 13 weekly assessments. We hypothesized that patients with higher SLD during CT have better outcomes (treatment response, and fewer symptoms after response), and we explored whether SLD correlated with other possible CT processes (growth in social adjustment and CT skills). Data were drawn from two clinical trials of CT for adult outpatients with recurrent MDD (primary sample n = 475, replication sample n = 146). In both samples, patients and clinicians completed measures of depressive symptoms and social adjustment repeatedly during CT. In the primary sample, patients and cognitive therapists rated patients' CT skills. After CT, responders were assessed for 32 (primary sample) or 24 (replication sample) additional months to measure long-term depression outcomes. Higher SLD predicted increases in social adjustment (both samples) and CT skills (primary sample) during CT, CT response (both samples), and lower MDD severity for at least 2 years after CT response (both samples). Analyses controlled patient-level symptom means and variability to estimate SLD's incremental predictive validity. These novel findings from two independent samples with longitudinal follow-up require further replication and extension. SLD may reflect or facilitate generalization of CT skills, improvement in social functioning, or other processes responsible for CT's shorter and longer term benefits.

Quality of life after response to acute-phase cognitive therapy for recurrent depression

BackgroundAdults with major depressive disorder (MDD) often experience reduced quality of life (QOL). Efficacious acute-phase treatments, including cognitive therapy (CT) or medication, decrease depressive symptoms and, to a lesser degree, increase QOL. We tested longer-term changes in QOL after response to acute-phase CT, including the potential effects of continuation treatment for depression and time-lagged relations between QOL and depressive symptoms. MethodsResponders to acute-phase CT (N = 290) completed QOL and depressive symptom assessments repeatedly for 32 post-acute months. Higher-risk responders were randomized to 8 months of continuation treatment (CT, fluoxetine, or pill placebo) and then entered a 24-month follow-up. Lower-risk responders were only assessed for 32 months. ResultsOn average, large gains in QOL made during acute-phase CT response were maintained for 32 months. Continuation CT or fluoxetine did not improve QOL relative to pill placebo. Controlling for residual depressive symptoms, higher QOL after acute-phase CT response was a protective factor against MDD relapse and recurrence. Higher QOL predicted subsequent reductions in depressive symptom severity, but depressive symptom severity did not predict subsequent changes in QOL. LimitationsGeneralization of results to other patient populations, treatments, and measures is uncertain. The clinical trial was not designed to test relations between QOL and depression. Replication is needed before clinical application of these results. ConclusionsGains in QOL made during response to acute-phase CT are relatively stable and may help protect against relapse/recurrence. Continuation CT or fluoxetine may not further improve QOL among acute-phase CT responders.

Is sleep disturbance linked to short- and long-term outcomes following treatments for recurrent depression?

BackgroundPre-treatment sleep disturbance has been shown to predict antidepressant treatment outcomes. How changes in sleep disturbance during acute treatment affect longitudinal outcomes, or whether continuation-phase treatment further improves sleep disturbance, is unclear. MethodsWe assessed sleep disturbance repeatedly in: a) 523 adults with recurrent MDD who consented to 12–14 weeks of acute-phase cognitive therapy (A-CT) and b) 241 A-CT responders at elevated risk for depression relapse/recurrence who were randomized to 8 months of continuation-phase treatment (CCT vs. fluoxetine vs. matched pill placebo) and followed protocol-treatment-free for 24 months. Trajectories of change in sleep and depression during and after A-CT were evaluated with multilevel models; individual intercepts and slopes were retained and input into Cox regression models to predict remission, recovery, relapse, and recurrence of MDD. ResultsSleep disturbance improved over the course of A-CT, but most patients continued to report clinically significant sleep complaints. Response and remission were more likely in patients with less overall sleep disturbance and those with greater reduction in sleep disturbance during A-CT; these patients also achieved post-A-CT remission and recovery sooner. Sleep improvements endured throughout follow-up but were not enhanced by continuation-phase treatment. Sleep disturbance did not predict relapse or recurrence consistently. LimitationsObjective sleep disturbance was not assessed. Analyses were not specifically powered to use sleep changes to predict outcomes. ConclusionsImprovements in sleep disturbance during A-CT are linked to shorter times to remission and recovery, supporting consideration of monitoring and targeting sleep disturbance in adults with depression.

Estimating outcome probabilities from early symptom changes in cognitive therapy for recurrent depression.

Acute-phase cognitive therapy (CT) is an efficacious treatment for major depressive disorder (MDD) producing benefits comparable to pharmacotherapy, but not all patients respond or remit. The purpose of the current analyses was to estimate CT patients' probability of nonresponse and remission from symptom improvement early in treatment. Data from 2 clinical trials of acute-phase CT for recurrent depression were pooled for analysis (N = 679). Adult outpatients received 16- or 20-session CT protocols. Symptoms were measured repeatedly with the clinician-report Hamilton Rating Scale for Depression (HRSD) and Inventory of Depressive Symptomatology-Self-Report (IDS-SR). Outcomes at exit from CT were nonresponse (<50% reduction in HRSD scores) and remission (no MDD and HRSD score ≤6). The nonresponse rate was 45.7%, and the remission rate was 33.4%. In logistic regression models, improvements on the HRSD or IDS-SR from intake to CT Sessions 3, 5, 7, 9, or 11 significantly predicted both outcomes, with prediction gaining in accuracy in later sessions. Clinician and self-report assessments yielded similar results. Prediction of outcomes replicated across data sets. Patients with no symptom improvement by CT Session 9 (Week 5) had ≤10% probability of remission and >75% probability of nonresponse. Outcomes of CT for depression are predictable from early symptom changes. Clinicians may find nonresponse and remission probability estimates useful in the informed consent process and in choosing whether to continue, augment, or switch treatments for CT patients with recurrent MDD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Partner criticism during acute-phase cognitive therapy for recurrent major depressive disorder

Many patients with major depressive disorder (MDD) are married or in marriage-like relationships that could influence treatment process and outcomes. We clarified relations of patient-reported criticism from partners (perceived criticism) and criticism of partners with psychosocial functioning and changes in cognitive therapy (CT) for depression. Partnered outpatients (N = 219) received a 12-week CT protocol and completed measures repeatedly. As hypothesized, perceived criticism and criticism of partners correlated with personality (e.g., perceived criticism: trait mistrust, self-harm; criticism of partners: negative temperament, aggression), social-interpersonal problems (perceived criticism: cold and overly nurturant behavior; criticism of partners: vindictive and domineering behavior; both measures: poor adjustment in partnered and family relationships), cognitive content (both measures: negative failure attributions, dysfunctional attitudes), and depressive symptom intensity (both measures), although effect sizes were small-moderate. Both criticism measures decreased little during CT and remained elevated compared to community norms, despite the fact that relations between the criticism measures and depressive symptoms included both stable trait and more transient state components. From these findings, we speculate that some patients with MDD elicit or amplify criticism in ways that harm their relationships and psychosocial functioning and may benefit from additional or strategic treatment.

Could Treatment Matching Patients’ Beliefs About Depression Improve Outcomes?

Patients’ beliefs about depression and expectations for treatment can influence outcomes of major depressive disorder (MDD) treatments. We hypothesized that patients with weaker biological beliefs (less endorsement of [a] biochemical causes and [b] need for medication) and more optimistic treatment expectations (greater improvement and shorter time to improvement), have better outcomes in cognitive therapy (CT). Outpatients with recurrent MDD who received acute-phase CT (N = 152), and a subset of partial or unstable responders (N = 51) randomized to 8 months of continuation CT or fluoxetine with clinical management, completed repeated measures of beliefs, expectations, and depression. As hypothesized, patients with weaker biological beliefs about depression, and patients who expected a shorter time to improvement, experienced greater change in depressive symptoms and more frequent response to acute-phase CT. Moreover, responders who received continuation treatment better matched to their biological beliefs (i.e., responders with weaker biological beliefs about depression who received continuation CT, or responders with stronger biological beliefs about depression who received continuation fluoxetine) had fewer depressive symptoms and less relapse/recurrence by 32 months after acute-phase CT than did responders who received mismatched continuation treatment. Specific screening and/or intervention targeting patients’ biological beliefs about depression could increase CT efficacy.

The Role of Dyadic Discord in Outcomes in Acute Phase Cognitive Therapy for Adults With Recurrent Major Depressive Disorder

Major depressive disorder (MDD) and relationship discord between cohabiting partners frequently co-occur, with bidirectional effects established. As relationship quality influences understanding and treatment of MDD, the current analyses clarified the relations of pretreatment dyadic discord with outcomes during and at the end of acute phase cognitive therapy (CT) for adults with recurrent MDD. Married or cohabiting patients (n = 219) completed the Dyadic Adjustment Scale (DYS) before and after a 16–20 session, 12–14 week CT protocol. Lower levels of dyadic adjustment indicated higher levels of dyadic discord. Response to CT was defined as the absence of a major depressive episode and ≤ 12 on the 17-item Hamilton Rating Scale for Depression. Pretreatment dyadic discord, whether defined as a continuous or categorical variable (using DYS cutoff score of 97), was not associated with treatment completion or response but was positively associated with levels of depressive symptoms at the end of acute phase CT. Furthermore, CT was associated with declines in dyadic discord, with 23.3% of initially discordant couples moving to nondiscordant status at the end of CT. Depressive symptoms did not significantly mediate changes in dyadic discord. Finally, pre- (but not mid-) treatment dyadic discord was associated with subsequent changes in depressive symptoms, suggesting limited mediation. These findings replicate prior research indicating that individual CT is associated with reductions in depressive symptoms and dyadic discord while clarifying that lower pre-treatment dyadic discord may predict initial improvement in depressive symptoms.

A prognostic index for long-term outcome after successful acute phase cognitive therapy and interpersonal psychotherapy for major depressive disorder.

BackgroundMajor depressive disorder (MDD) has a highly recurrent nature. After successful treatment, it is important to identify individuals who are at risk of an unfavorable long‐term course. Despite extensive research, there is no consensus yet on the clinically relevant predictors of long‐term outcome in MDD, and no prediction models are implemented in clinical practice. The aim of this study was to create a prognostic index (PI) to estimate long‐term depression severity after successful and high quality acute treatment for MDD.MethodsData come from responders to cognitive therapy (CT) and interpersonal psychotherapy (IPT) in a randomized clinical trial (n = 85; CT = 45, IPT = 40). Primary outcome was depression severity, assessed with the Beck Depression Inventory II, measured throughout a 17‐month follow‐up phase. We examined 29 variables as potential predictors, using a model‐based recursive partitioning method and bootstrap resampling in conjunction with backwards elimination. The selected predictors were combined into a PI. Individual PI scores were estimated using a cross‐validation approach.ResultsA total of three post‐treatment predictors were identified: depression severity, hopelessness, and self‐esteem. Cross‐validated PI scores evidenced a strong correlation (r = 0.60) with follow‐up depression severity.ConclusionLong‐term predictions of MDD are multifactorial, involving a combination of variables that each has a small prognostic effect. If replicated and validated, the PI can be implemented to predict follow‐up depression severity for each individual after acute treatment response, and to personalize long‐term treatment strategies.

Relations of Shared and Unique Components of Personality and Psychosocial Functioning to Depressive Symptoms.

Consistent with theories of depression, several personality (e.g., high neuroticism, low extraversion) and psychosocial (e.g., interpersonal problems, cognitive content) variables predict depressive symptoms substantively. In this extended replication, we clarified whether 13 theoretically relevant personality and psychosocial variables were unique versus overlapping predictors of symptoms among 351 adult outpatients with recurrent major depressive disorder who received acute-phase cognitive therapy (CT). Using factor analysis and regression methods, we partitioned the measures' variance into general components common across the two types of measures (psychosocial and personality), within-type components shared only with other measures of the same type, and scale-specific components. From early to late in CT, and from late in CT through 8 months after response, the general components were the strongest (median r = .23)-and scale-specific components the weakest (median r = .01)-forward predictors of symptoms. We discuss implications for measurement and treatment of depression.

Initial Steps to inform selection of continuation cognitive therapy or fluoxetine for higher risk responders to cognitive therapy for recurrent major depressive disorder

Responders to acute-phase cognitive therapy (A-CT) for major depressive disorder (MDD) often relapse or recur, but continuation-phase cognitive therapy (C-CT) or fluoxetine reduces risks for some patients. We tested composite moderators of C-CT versus fluoxetine's preventive effects to inform continuation treatment selection. Responders to A-CT for MDD judged to be at higher risk for relapse due to unstable or partial remission (N=172) were randomized to 8 months of C-CT or fluoxetine with clinical management and assessed, free from protocol treatment, for 24 additional months. Pre-continuation-treatment characteristics that in survival analyses moderated treatments’ effects on relapse over 8 months of continuation-phase treatment (residual symptoms and negative temperament) and on relapse/recurrence over the full observation period's 32 months (residual symptoms and age) were combined to estimate the potential advantage of C-CT versus fluoxetine for individual patients. Assigning patients to optimal continuation treatment (i.e., to C-CT or fluoxetine, depending on patients’ pre-continuation-treatment characteristics) resulted in absolute reduction of relapse or recurrence risk by 16–21% compared to the other non-optimal treatment. Although these novel results require replication before clinical application, selecting optimal continuation treatment (i.e., personalizing treatment) for higher risk A-CT responders may decrease risks of MDD relapse and recurrence substantively.

Defined symptom-change trajectories during acute-phase cognitive therapy for depression predict better longitudinal outcomes

BackgroundAcute-phase cognitive therapy (CT) is an efficacious treatment for major depressive disorder (MDD), but responders experience varying post-acute outcomes (e.g., relapse vs. recovery). Responders' symptom-change trajectories during response to acute-phase CT may predict longer term outcomes. MethodWe studied adult outpatients (N = 220) with recurrent MDD who responded to CT but had residual symptoms. Responders with linear (steady improvement), log-linear (quicker improvement earlier and slower later), one-step (a single, relatively large, stable improvement between adjacent assessments), or undefined (not linear, log-linear, or one-step) symptom trajectories were assessed every 4 months for 32 additional months. ResultsDefined (linear, log-linear, one-step) versus undefined acute-phase trajectories predicted lower depressive symptoms (d = 0.36), lower weekly probability of being in a major depressive episode (OR = 0.46), higher weekly probabilities of remission (OR = 1.93) and recovery (OR = 2.35), less hopelessness (d = 0.41), fewer dysfunctional attitudes (d = 0.31), and better social adjustment (d = 0.32) for 32 months after acute-phase CT. Differences among defined trajectory groups were nonsignificant. ConclusionsResponding to acute-phase CT with a defined trajectory (orderly pattern) of symptom reduction predicts better longer term outcomes, but which defined trajectory (linear, log-linear, or one-step) appears unimportant. Frequent measurement of depressive symptoms to identify un/defined CT response trajectories may clarify need for continued clinical monitoring and treatment.

Longitudinal social-interpersonal functioning among higher-risk responders to acute-phase cognitive therapy for recurrent major depressive disorder

BackgroundSocial-interpersonal dysfunction increases disability in major depressive disorder (MDD). Here we clarified the durability of improvements in social-interpersonal functioning made during acute-phase cognitive therapy (CT), whether continuation CT (C-CT) or fluoxetine (FLX) further improved functioning, and relations of functioning with depressive symptoms and relapse/recurrence. MethodAdult outpatients (N=241) with recurrent MDD who responded to acute-phase CT with higher risk of relapse (due to unstable or partial remission) were randomized to 8 months of C-CT, FLX, or pill placebo plus clinical management (PBO) and followed 24 additional months. We analyzed repeated measures of patients’ social adjustment, interpersonal problems, dyadic adjustment, depressive symptoms, and major depressive relapse/recurrence. ResultsLarge improvements in social-interpersonal functioning occurring during acute-phase CT (median d=1.4) were maintained, with many patients (median=66%) scoring in normal ranges for 32 months. Social-interpersonal functioning did not differ significantly among C-CT, FLX, and PBO arms. Beyond concurrently measured residual symptoms, deterioration in social-interpersonal functioning preceded and predicted upticks in depressive symptoms and major depressive relapse/recurrence. LimitationsResults may not generalize to other patient populations, treatment protocols, or measures of social-interpersonal functioning. Mechanisms of risk connecting poorer social-interpersonal functioning with depression were not studied. ConclusionsAverage improvements in social-interpersonal functioning among higher-risk responders to acute phase CT are durable for 32 months. After acute-phase CT, C-CT or FLX may not further improve social-interpersonal functioning. Among acute-phase CT responders, deteriorating social-interpersonal functioning provides a clear, measurable signal of risk for impending major depressive relapse/recurrence and opportunity for preemptive intervention.

Assessing cognitive therapy skills comprehension, acquisition, and use by means of an independent observer version of the Skills of Cognitive Therapy (SoCT-IO).

The purposes of this study were (a) to describe the adaptation and psychometric properties of the Skills for Cognitive Therapy (SoCT) measure for use by an independent observer (SoCT-IO) who rates the cognitive therapy (CT) skill acquisition, comprehension, and use by depressed adults and (b) to compare ratings of CT skill comprehension, acquisition, and use by independent observers to those by patients and therapists. Like the other SoCT versions, the SoCT-IO consists of 8 items that assess patients' comprehension, acquisition, and use of cognitive and behavioral skills for managing depressive symptoms, using a 5-point Likert-type scale. Four experienced raters (2 doctoral-level CT therapists and 2 bachelor-level nontherapists) used the SoCT-IO to rate 80 CT videotapes from both mid and later sessions in acute-phase CT from a randomized controlled trial for outpatients with recurrent major depression. The SoCT-IO ratings showed excellent internal consistency reliability and moderately high interrater reliability. Concurrent validity was demonstrated by convergence of the SoCT-IO with 2 other versions of the SoCT, 1 completed by therapists (SoCT-O) and the other by patients (SoCT-P). SoCT-IO ratings evidenced good predictive validity: Independent observers' ratings of patient CT skills midphase in therapy predicted treatment response even when the predictive effects of SoCT ratings by therapists and patients were controlled. The SoCT-IO is a psychometrically sound measure of CT skill comprehension, acquisition and use for rating outpatients with recurrent depression. The clinical utility and implications for using the SoCT-IO as a measure of CT skills acquisition are discussed. (PsycINFO Database Record

Quantifying and qualifying the preventive effects of acute-phase cognitive therapy: Pathways to personalizing care.

To determine the extent to which prospectively identified responders to cognitive therapy (CT) for recurrent major depressive disorder (MDD) hypothesized to be lower risk show significantly less relapse or recurrence than treated higher risk counterparts across 32 months. Outpatients (N = 523), aged 18-70, with recurrent MDD received 12-14 weeks of CT. The last 7 consecutive scores from the Hamilton Rating Scale for Depression (HRSD-17) were used to stratify or define responders (n = 290) into lower (7 HRSD-17 scores of less than or equal to 6; n = 49; 17%) and higher risk (n = 241; 83%). The lower risk patients entered the 32-month follow-up. Higher risk patients were randomized to 8 months of continuation-phase CT or clinical management plus double-blind fluoxetine or pill placebo, with a 24-month follow-up. Lower risk patients were significantly less likely to relapse over the first 8 months compared to higher risk patients (Kaplan-Meier [KM] estimates; i.e., 4.9% = lower risk; 22.1% = higher risk; log-rank χ2 = 6.83, p = .009). This increased risk was attenuated, but not completely neutralized, by active continuation-phase therapy. Over the subsequent 24 months, the lower and higher risk groups did not differ in relapse or recurrence risk. Rapid and sustained acute-phase CT remission identifies responders who do not require continuation-phase treatment to prevent relapse (i.e., return of an index episode). To prevent recurrence (i.e., new episodes), however, strategic allocation and more frequent "dosing" of CT and/or targeted maintenance-phase treatments may be required. Longitudinal follow-up is recommended.

Supplemental Material for Quantifying and Qualifying the Preventive Effects of Acute-Phase Cognitive Therapy: Pathways to Personalizing Care

Supplemental Material for Quantifying and Qualifying the Preventive Effects of Acute-Phase Cognitive Therapy: Pathways to Personalizing Care

Improved cognitive content endures for 2 years among unstable responders to acute-phase cognitive therapy for recurrent major depressive disorder.

The cognitive model of depression suggests that cognitive therapy (CT) improves major depressive disorder (MDD) in part by changing depressive cognitive content (e.g. dysfunctional attitudes, hopelessness). The current analyses clarified: (1) the durability of improvements in cognitive content made by acute-phase CT responders; (2) whether continuation-phase CT (C-CT) or fluoxetine (FLX) further improves cognitive content; and (3) the extent to which cognitive content mediates continuation treatments' effects on depressive symptoms and major depressive relapse/recurrence. Out-patients with recurrent MDD who responded to acute-phase CT (n = 241) were randomized to 8 months of C-CT, FLX or pill placebo (PBO) and followed for an 24 additional months. Cognitive content was assessed approximately every 4 months using five standard patient-report measures. Large improvements in cognitive content made during acute-phase CT were maintained for 32 months, with 78-90% of patients scoring in normal ranges, on average. Cognitive content varied little between C-CT, FLX and PBO arms, overall. Small, transient improvements in cognitive content in C-CT or FLX compared with PBO patients did not clearly mediate the treatments' effects on depressive symptoms or on major depressive relapse/recurrence. Outpatients with recurrent MDD who respond to acute-phase CT show durable improvements in cognitive content. C-CT or FLX may not continue to improve patient-reported cognitive content substantively, and thus may treat recurrent MDD by other paths.

Predictors of longitudinal outcomes after unstable response to acute-phase cognitive therapy for major depressive disorder.

After patients with major depressive disorder (MDD) respond to acute-phase cognitive therapy (CT), continuation-phase treatments may be applied to improve long-term outcomes. We clarified which CT responders experience remission, recovery, relapse, and recurrence by testing baseline demographic, clinical, and personality variables. The sample of CT responders at higher risk of relapse (N = 241) was randomized to 8 months of continuation-phase CT, double-blinded fluoxetine, or pill placebo, and followed 24 months (Jarrett & Thase, 2010). Patients with lower positive emotionality and behavioral activation at the end of acute-phase CT showed increased risk for relapse/recurrence of MDD. In addition, patients with lower positive emotionality and behavioral activation, as well as higher residual depression (including emotional, cognitive, and social facets), showed decreased probability of remission (≥6 continuous weeks of minimal or absent symptoms) after acute-phase CT. Finally, patients with greater residual depression, as well as younger age and earlier MDD onset, showed decreased probability of recovery (≥35 continuous weeks of minimal or absent symptoms) after acute-phase CT. Moderator analyses did not reveal differential prediction across the continuation phase treatment arms. These results may help clinicians gauge the prognoses and need for continuation treatment among MDD patients who respond to acute-phase CT.

Supplemental Material for Predictors of Longitudinal Outcomes After Unstable Response to Acute-Phase Cognitive Therapy for Major Depressive Disorder

Supplemental Material for Predictors of Longitudinal Outcomes After Unstable Response to Acute-Phase Cognitive Therapy for Major Depressive Disorder

Are Improvements in Cognitive Content and Depressive Symptoms Correlates or Mediators during Acute-Phase Cognitive Therapy for Recurrent Major Depressive Disorder?

The cognitive model of depression posits that cognitive therapy's (CT) effect on depressive symptoms is mediated by changes in cognitive content (e.g., automatic negative thoughts dysfunctional attitudes, failure attributions). We tested improvement and normalization of cognitive content among outpatients (N = 523) with recurrent major depressive disorder treated with acute-phase CT (Jarrett & Thase, 2010; Jarrett et al., 2013). We also tested whether improvement in cognitive content accounted for subsequent changes in depressive symptoms and vice versa. Five measures of content improved substantively from pre- to post-CT (median d = 0.96), and the proportions of patients scoring in "healthy" ranges increased (median 45% to 82%). Evidence for cognitive mediation of symptom reduction was limited (median r = .06), as was evidence for symptom mediation of cognitive content improvement (median r = .07). We discuss measurement and design issues relevant to detection of mediators and consider alternative theories of change.