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Background: Anxiety symptoms are common in bipolar disorder. We explored the effect of anxiety on the outcome of acute and continuation pharmacotherapy of bipolar II depression.Methods: Data were derived from a randomized double-blind 12-week acute (N = 129) and 6-month continuation (N = 55) comparison of venlafaxine versus lithium monotherapy in bipolar II depression in adults. We distinguished between the items of the Hamilton Rating Scale for Depression (HRSD) that capture depression vs. anxiety (i.e., psychomotor agitation, psychic anxiety, somatic anxiety, hypochondriasis, and obsessive-compulsive concerns) and examined the effect of treatment on depression and anxiety. Additionally, we explored whether baseline anxiety or depression predicted changes over time in depression and anxiety ratings or moderated treatment outcomes. We also explored whether residual depressive and anxious symptoms predicted relapse during continuation therapy.Results: Venlafaxine was superior to lithium in reducing both depression and anxiety, though its effects on anxiety were more modest than those on depression. Baseline anxiety predicted change over time in anxiety, but not depression. By contrast, baseline depression did not predict change over time in depression or anxiety. Residual anxiety, specifically uncontrollable worry, was a stronger predictor of relapse than residual depression.Conclusion: Successful treatment of symptoms of anxiety in bipolar depression may protect against depressive relapse. [ABSTRACT FROM AUTHOR]

Prior studies have suggested that the association between the alliance and depression improvement varies as a function of prior history of depression. We sought to replicate these findings and extend them to short-term psychodynamic supportive psychotherapy (SPSP) in a sample of patients who were randomized to one of these treatments and were administered the Helping Alliance Questionnaire (N=282) at Week 5 of treatment. Overall, the alliance was a predictor of symptom change (d=0.33). In SPSP, the alliance was a modest but robust predictor of change, irrespective of prior episodes (d=0.25-0.33). By contrast, in CBT, the effects of the alliance on symptom change were large for patients with 0 prior episodes (d=0.86), moderate for those with 1 prior episode (d=0.49), and small for those with 2+ prior episodes (d=0.12). These findings suggest a complex interaction between patient features and common vs. specific therapy processes. In CBT, the alliance relates to change for patients with less recurrent depression whereas other CBT-specific processes may account for change for patients with more recurrent depression. [ABSTRACT FROM AUTHOR]

Background: Prognostic indices (PIs) combining variables to predict future depression risk may help guide the selection of treatments that differ in intensity. We develop a PI and show its promise in guiding treatment decisions between treatment as usual (TAU), treatment starting with a low-intensity treatment (brief therapy (BT)), or treatment starting with a high-intensity treatment intervention (cognitive-behavioral therapy (CBT)).Methods: We utilized data from depressed patients (N=622) who participated in a randomized comparison of TAU, BT, and CBT in which no statistically significant differences in the primary outcomes emerged between the three treatments. We developed a PI by predicting depression risk at follow-up using a LASSO-style bootstrap variable selection procedure. We then examined between-treatment differences in outcome as a function of the PI.Results: Unemployment, depression severity, hostility, sleep problems, and lower positive emotionality at baseline predicted a lower likelihood of recovery across treatments. The PI incorporating these variables produced a fair classification accuracy (c=0.73). Among patients with a high PI (75% percent of the sample), recovery rates were high and did not differ between treatments (79-86%). Among the patients with the poorest prognosis, recovery rates were substantially higher in the CBT condition (60%) than in TAU (39%) or BT (44%).Limitations: No information on additional treatment sought. Prospective tests needed.Conclusion: Replicable PIs may aid treatment selection and help streamline stepped models of care. Differences between treatments for depression that differ in intensity may only emerge for patients with the poorest prognosis. [ABSTRACT FROM AUTHOR]

Objectives We examined differences in treatment outcome between Diagnostic and Statistical Manual Fourth Edition (DSM-IV)-defined rapid cycling and average lifetime-defined rapid cycling in subjects with bipolar II disorder. We hypothesized that, compared with the DSM-IV definition, the average lifetime definition of rapid cycling may better identify subjects with a history of more mood lability and a greater likelihood of hypomanic symptom induction during long-term treatment. Methods Subjects ≥18 years old with a bipolar II major depressive episode (n=129) were categorized into DSM-IV- and average lifetime-defined rapid cycling and prospectively treated with either venlafaxine or lithium monotherapy for 12 weeks. Responders (n=59) received continuation monotherapy for six additional months. Results These exploratory analyses found moderate agreement between the two rapid-cycling definitions (κ=0.56). The lifetime definition captured subjects with more chronic courses of bipolar II depression, whereas the DSM-IV definition captured subjects with more acute symptoms of hypomania. There was no difference between rapid-cycling definitions with respect to the response to acute venlafaxine or lithium monotherapy. However, the lifetime definition was slightly superior to the DSM-IV definition in identifying subjects who went on to experience hypomanic symptoms during continuation therapy. Conclusions Although sample sizes were limited, the findings suggest that the lifetime definition of rapid cycling may identify individuals with a chronic rapid-cycling course and may also be slightly superior to the DSM-IV definition in identifying individuals with hypomania during relapse-prevention therapy. These findings are preliminary in nature and need replication in larger, prospective, bipolar II studies. [ABSTRACT FROM AUTHOR]

Since the introduction of Beck's cognitive theory of emotional disorders, and their treatment with psychotherapy, cognitive-behavioral approaches have become the most extensively researched psychological treatment for a wide variety of disorders. Despite this, the relative contribution of cognitive to behavioral approaches to treatment are poorly understood and the mechanistic role of cognitive change in therapy is widely debated. We critically review this literature, focusing on the mechanistic role of cognitive change across cognitive and behavioral therapies for depressive and anxiety disorders. [ABSTRACT FROM AUTHOR]

Objective This study examined the relationship between the number of prior antidepressant treatment trials and step-wise increase in pharmacodynamic tolerance (or progressive loss of effectiveness) in subjects with bipolar II depression. Methods 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 After controlling for baseline covariates of prior medications, there was a 25% reduction in the likelihood of response to treatment with each increase in the number of prior antidepressant trials (odds ratio [ OR]=0.75, unstandardized coefficient [B]=−0.29, standard error ( SE)=0.12; χ2=5.70, P<.02], as well as a 32% reduction in the likelihood of remission with each prior antidepressant trial ( OR=0.68, B=−0.39, SE=0.13; χ2=9.71, P=.002). This step-wise increase in pharmacodynamic tolerance occurred in both treatment conditions. Prior selective serotonin reuptake inhibitor ( SSRI) therapy was specifically associated with a step-wise increase in tolerance, whereas other prior antidepressants or mood stabilizers were not associated with pharmacodynamic tolerance. Neither the number of prior antidepressants, nor the number of prior SSRIs, or mood stabilizers, were associated with an increase in relapse during continuation therapy. Conclusions The odds of responding or remitting during venlafaxine or lithium monotherapy were reduced by 25% and 32%, respectively, with each increase in the number of prior antidepressant treatment trials. There was no relationship between prior antidepressant exposure and depressive relapse during continuation therapy of bipolar II disorder. [ABSTRACT FROM AUTHOR]

Background: Controversy exists over antidepressant use in bipolar II depression.Aims: To compare the safety and effectiveness of antidepressantv.mood stabiliser monotherapy for bipolar type II major depressive episodes.Method: Randomised, double-blind, parallel-group, 12-week comparison of venlafaxine (n= 65)v.lithium (n= 64) monotherapy in adult out-patients (trial registration numberNCT00602537).Results: Primary outcome - venlafaxine produced a greater response rate (67.7%)v lithium (34.4%,P<0.001). Secondary outcomes - venlafaxine produced a greater remission rate (58.5%v 28.1%,P<0.001); greater decline in depression symptom scores over time (β = -5.32, s.e. = 1.16, χ(2)= 21.19,P<0.001); greater reduction in global severity scores over time (β = -1.05, s.e. = 0.22, w(2)= 22.33,P<0.001); and greater improvement in global change scores (β = -1.31, s.e. = 0.32, χ(2)= 16.95,P<0.001) relative to lithium. No statistically significant or clinically meaningful differences in hypomanic symptoms were observed between treatments.Conclusions: These findings suggest that short-term venlafaxine monotherapy may provide effective antidepressant treatment for bipolar II depression without a statistically significant increase in hypomanic symptoms relative to lithium. [ABSTRACT FROM AUTHOR]

Objective Compare the safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for preventing depressive relapse in bipolar II disorder. Methods Subjects ≥18 years old with bipolar II depression ( n =129) were randomized to double-blind venlafaxine or lithium monotherapy for 12 weeks. Responders with a ≥50% reduction in depression score were continued for an additional 6 months of relapse-prevention monotherapy. Primary outcome was depressive relapse during continuation monotherapy. Secondary outcomes included sustained response rate from initiation of treatment to study end-point, relapse hazard, time to relapse, change in mania ratings, and frequency of treatment-emergent sub-syndromal hypomania and/or depressive episodes. Results Venlafaxine produced greater sustained response rate versus lithium ( p <0.0001); however, there was no difference in relapse rate for venlafaxine (7.5%) versus lithium (26.7%) ( p =0.079); relapse hazard ( p =0.073), or time to relapse ( p =0.090) between treatment conditions during continuation monotherapy. There were no group differences in mania rating scores over time and no difference in frequency or duration of syndromal or sub-syndromal hypomanic episodes. There were more sub-syndromal depressive episodes during lithium monotherapy ( p =0.03). Limitations Sample size was limited by the lower sustained response rate for lithium versus venlafaxine; study was not specifically powered to detect differences in treatment-emergent hypomanic or depressive episodes between groups. Conclusion Results suggest that continuation venlafaxine monotherapy may provide similar prophylactic effectiveness relative to lithium, with no difference in treatment-emergent hypomanic episodes and without the need for frequent serum lithium level and metabolic monitoring. Larger, prospective trials are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the variability of the alliance-outcome correlation across identifiable client subsets. This question was explored in a sample of 60 clients receiving cognitive therapy for depression, from which an overall correlation of .23 was observed between alliance ratings and subsequent symptom change. Method: We examined interactions between the observer-rated version of the Working Alliance Inventory-Short Observer-Rated version (WAI-O; Tracey & Kokotovic, 1989) and client demographics, features of depression, personality, and other clinical features in predicting subsequent symptom change. Results: After correcting for multiple comparisons, interactions between the WAI-0 and the number of prior depressive episodes, as well as the severity of baseline anxiety symptoms, were significant predictors of symptom change. When both interactions were controlled for, number of prior depressive episodes emerged as a statistically significant moderator. The alliance predicted outcome in the subgroup of clients with 0-2 prior episodes (r = .52), but not in those with 3 or more prior episodes (r = -.02). These findings were obtained despite similar univariate distributions on the alliance and symptom change in the 2 subgroups. Discussion: Differences that were observed in the predictive relation of alliance to outcome as a function of number of prior episodes suggest that different therapy processes may account for change in these subgroups. If the pattern observed in the present study is replicated, it would suggest that the alliance-outcome association has been both under-and overestimated. [ABSTRACT FROM AUTHOR]

Background: Advances in personalized medicine require the identification of variables that predict differential response to treatments as well as the development and refinement of methods to transform predictive information into actionable recommendations. Objective: To illustrate and test a new method for integrating predictive information to aid in treatment selection, using data from a randomized treatment comparison. Method: Data from a trial of antidepressant medications (N = 104) versus cognitive behavioral therapy (N = 50) for Major Depressive Disorder were used to produce predictions of post-treatment scores on the Hamilton Rating Scale for Depression (HRSD) in each of the two treatments for each of the 154 patients. The patient's own data were not used in the models that yielded these predictions. Five pre-randomization variables that predicted differential response (marital status, employment status, life events, comorbid personality disorder, and prior medication trials) were included in regression models, permitting the calculation of each patient's Personalized Advantage Index (PAI), in HRSD units. Results: For 60% of the sample a clinically meaningful advantage (PAI≥3) was predicted for one of the treatments, relative to the other. When these patients were divided into those randomly assigned to their “Optimal” treatment versus those assigned to their “Non-optimal” treatment, outcomes in the former group were superior (d = 0.58, 95% CI .17—1.01). Conclusions: This approach to treatment selection, implemented in the context of two equally effective treatments, yielded effects that, if obtained prospectively, would rival those routinely observed in comparisons of active versus control treatments. [ABSTRACT FROM AUTHOR]