Lorenzo Lorenzo-Luaces

The Personalized Advantage Index: translating research on prediction into individualized treatment recommendations. A demonstration.

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 patients 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 patients 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.

Client Characteristics as Moderators of the Relation Between the Therapeutic Alliance and Outcome in Cognitive Therapy for Depression

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-O 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.

Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: A randomized, double-blind, parallel-group, prospective study

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.

Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate

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.

Heterogeneity in the prognosis of major depression: from the common cold to a highly debilitating and recurrent illness

Two different and seemingly competing views on the diagnosis of major depressive disorder (MDD) exist. The first is that the diagnosis conflates adaptive sadness reactions with pathological states of depressed mood and that MDD is overdiagnosed and overtreated. The second is that MDD is an underdiagnosed and undertreated disorder, and one that is best characterised by a severe, chronic, recurrent or treatment-resistant course. Existing research suggests that both views are valid and merit being integrated. Anywhere from 30 to 50% of individuals will meet criteria for MDD at some point in their life. About half of these episodes are of brief duration and unlikely to recur. However, a remaining half is either chronic or recurrent. Data on the outpatient diagnosis of depression support the view that depression is simultaneously underdiagnosed and undertreated as well as overdiagnosed and overtreated. About one-third of the patients who meet criteria for MDD and receive placebos experience clinically significant and long-lasting improvement. Many other patients, however, are unresponsive to one or multiple active treatments. Thus, the diagnosis of MDD likely applies to individuals who are experiencing either normal periods of sadness or single-episode afflictions that are mild, unlikely to recur, and are placebo responsive, as well as to individuals with more severe clinical profiles. More research is needed that can help ascertain what contextual or biopsychological variables help distinguish between individuals who may be experiencing adaptive states of negative affect and those who experience severe, chronic, recurrent or treatment-resistant depressions.

Cognitive-Behavioral Therapy: Nature and Relation to Non-Cognitive Behavioral Therapy

Since the introduction of Becks 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.

Racial and ethnic differences in risk factors associated with suicidal behavior among young adults in the USA.

Objective. The objectives of this study are to examine racial and ethnic differences in suicidal behaviour, its main risk factors, and the effect of the risk factors on suicidal behaviour in young adults in the United States. Design. Using nationally representative data (n = 10,585) from Add Health, we calculate the prevalence of suicidal behavior and associated risk factors for non-Hispanic White, non-Hispanic Black, and Hispanic youth (aged 18–26) using logistic regression models of suicidal ideation stratified by race. Results. Non-Hispanic White and Hispanic young adults have higher rates of suicidal ideation than their non-Hispanic Black counterparts, but racial/ethnic differences in attempts are not statistically significant. Non-Hispanic Whites and Hispanic young adults are more likely to possess key risk factors for suicide. With the exception of substance use variables (i.e. alcohol and marijuana use) which appear to be more conducive to suicidal ideation in non-Hispanic Black than in non-Hispanic White young adults, the effects of risk factors appear to be similar across race/ethnicity. Conclusion. The higher prevalence of suicidal ideation in non-Hispanic White and Hispanic young adults may be driven by their greater exposure to risk factors, as opposed to differences in the effects of these risk factors. More research is needed to uncover why non-Hispanic White and Hispanic young adults have higher rates of suicidal ideation than their non-Hispanic Black counterparts; yet, rates of suicide attempts are comparable and non-Hispanic White young adults have the highest rate of completed suicides.

Moderation of the Alliance-Outcome Association by Prior Depressive Episodes: Differential Effects in Cognitive-Behavioral Therapy and Short-Term Psychodynamic Supportive Psychotherapy

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.

Miles to Go Before We Sleep: Advancing the Understanding of Psychotherapy by Modeling Complex Processes

One of the main debates in the study of psychotherapy is whether specific techniques are best indicated for different problems or whether “common factors” better account for the efficacy of psychotherapy. Evidence for the superiority of specific techniques is mixed and limited to a handful of diagnoses. By contrast, evidence for the importance of common factors is riddled with methodological weaknesses and may be of limited clinical utility. The stagnation in this debate may reflect that the research methods heretofore employed have reached a plateau in their ability to advance knowledge regarding psychotherapy processes. The articles of the special issue move beyond simple bivariate relationship and attempt to model the real-world complexity involved in the process of psychotherapy. It is argued that these types of investigations, which model the interactions of patient characteristics as well as multiple specific and “common factors,” are the best way to advance the state of knowledge regarding psychotherapy processes.

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

To examine the safety and effectiveness of antidepressant versus mood stabilizer monotherapy in rapid versus non‐rapid cycling bipolar II disorder.