Frank J. Farach

Pharmacological treatment of anxiety disorders: Current treatments and future directions

Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey two broad approaches to the development of innovative anxiety treatments:the continued development of drugs based on specific neuroreceptors and the pharmacological manipulation of fear-related memory. We highlight directions for future research, as neither of these approaches is ready for routine clinical use.

Enhancing Extinction Learning in Posttraumatic Stress Disorder With Brief Daily Imaginal Exposure and Methylene Blue: A Randomized Controlled Trial

OBJECTIVE The memory-enhancing drug methylene blue (MB) administered after extinction training improves fear extinction retention in rats and humans with claustrophobia. Robust findings from animal research, in combination with established safety and data showing MB-enhanced extinction in humans, provide a foundation to extend this work to extinction-based therapies for posttraumatic stress disorder (PTSD) such as prolonged exposure (PE). METHODS Patients with chronic PTSD (DSM-IV-TR; N = 42) were randomly assigned to imaginal exposure plus MB (IE + MB), imaginal exposure plus placebo (IE + PBO), or waitlist (WL/standard PE) from September 2011 to April 2013. Following 5 daily, 50-minute imaginal exposure sessions, 260 mg of MB or PBO was administered. Waitlist controls received PE following 1-month follow-up. Patients were assessed using the independent evaluator-rated PTSD Symptom Scale-Interview version (primary outcome), patient-rated PTSD, trauma-related psychopathology, and functioning through 3-month follow-up. RESULTS Both IE + MB and IE + PBO showed strong clinical gains that did not differ from standard PE at 3-month follow-up. MB-augmented exposure specifically enhanced independent evaluator-rated treatment response (number needed to treat = 7.5) and quality of life compared to placebo (effect size d = 0.58). Rate of change for IE + MB showed a delayed initial response followed by accelerated recovery, which differed from the linear pattern seen in IE + PBO. MB effects were facilitated by better working memory but not by changes in beliefs. CONCLUSIONS The findings provide preliminary efficacy for a brief IE treatment for PTSD and point to the potential utility of MB for enhancing outcome. Brief interventions and better tailoring of MB augmentation strategies, adjusting for observed patterns, may have the potential to reduce dropout, accelerate change, and improve outcomes. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01188694.

Effects of induced and naturalistic mood on the temporal allocation of attention to emotional information

Building upon recent findings that affective states can influence the allocation of spatial attention, we investigate how state, trait and induced mood are related to the temporal allocation of attention to emotional information. In the present study, 125 unscreened undergraduates completed a modified rapid serial visual presentation task designed to assess the time course of attention to positive and negative information, comparing a neutral baseline mood induction to either a positive or negative mood induction. Induced negative mood facilitated attentional engagement to positive information while decreasing attentional engagement to negative information. Greater naturally occurring negative state mood was associated with faster or more efficient disengagement of attention from negative information in the presence of manipulated negative mood, relative to baseline. The engagement findings were inconsistent with our mood-congruence hypotheses and may be better explained by mood repair or affective counter-regulation theories. In contrast, the disengagement findings for state mood were somewhat consistent with our mood-congruence hypotheses. The relationship between mood and attention to emotional information may differ depending on the combination of attentional mechanism (engagement versus disengagement), aspect of mood (state, trait or induced), stimulus valence (positive versus negative) and timescale (early versus late) under investigation.

Understanding heterogeneity in PTSD

Fear, dysphoria, and distress are prominent components in the conceptualization of posttraumatic stress disorder (PTSD). However, because our diagnostic categories are open concepts, relying on observed patterns of symptoms for classification, it is unclear whether these components represent core or auxiliary features of the disorder. Convergence across multiple indices is critical for this understanding. In this paper, we examine these components of PTSD across observed symptom patterns, broader theoretical conceptualizations, underlying information processing mechanisms of attention and memory, and underlying learning and neurobiological mechanisms. For each, evidence for similarity or distinctiveness of PTSD with other anxiety disorders and depression is examined. Throughout the review, key points of similarity to the anxiety disorders and divergence with depression argue for a distinction between core fear symptoms and auxiliary dysphoria and distress symptoms. Implications are discussed, noting that, as heterogeneity increases, core characteristics will become more diffused and ancillary constructs will gain an inflated degree of importance.

UNDERSTANDING HETEROGENEITY IN PTSD: FEAR, DYSPHORIA, AND DISTRESS: Review: Heterogeniety in PTSD

Fear, dysphoria, and distress are prominent components in the conceptualization of posttraumatic stress disorder (PTSD). However, because our diagnostic categories are open concepts, relying on observed patterns of symptoms for classification, it is unclear whether these components represent core or auxiliary features of the disorder. Convergence across multiple indices is critical for this understanding. In this paper, we examine these components of PTSD across observed symptom patterns, broader theoretical conceptualizations, underlying information processing mechanisms of attention and memory, and underlying learning and neurobiological mechanisms. For each, evidence for similarity or distinctiveness of PTSD with other anxiety disorders and depression is examined. Throughout the review, key points of similarity to the anxiety disorders and divergence with depression argue for a distinction between core fear symptoms and auxiliary dysphoria and distress symptoms. Implications are discussed, noting that, as heterogeneity increases, core characteristics will become more diffused and ancillary constructs will gain an inflated degree of importance.