Session-level effects of cognitive processing therapy and prolonged exposure on individual symptoms of posttraumatic stress disorder among U.S. veterans.

OBJECTIVE: To compare the course of change in individual posttraumatic stress disorder (PTSD) symptoms during prolonged exposure therapy (PE) and cognitive processing therapy (CPT). METHOD: We analyzed data from a previously published randomized clinical trial comparing PE and CPT among male and female U.S. military veterans with PTSD (Schnurr et al., 2022). Using data from a self-rated PTSD symptom measure administered before each therapy session, we evaluated individual symptom change from pretreatment to final therapy session (N = 802). Then, using network intervention analysis, we modeled session-by-session PTSD symptom networks that included treatment allocation (CPT vs. PE) as a node in the networks, allowing us to compare individual symptom change following each session in each treatment. RESULTS: Relative to CPT, PE was associated with greater reduction in 10 PTSD symptoms from first to final session of therapy. Numerous treatment-specific effects on individual symptoms emerged during the treatment period; these session-level effects occurred only in symptoms relatively specific to the diagnosis of PTSD (e.g., avoidance, hypervigilance). PE was associated with greater reduction in avoidance following the introduction and early weeks of imaginal exposure. The treatments yielded comparable effects on trauma-related blame and negative beliefs from pretreatment to final therapy session. However, there were differences in session-level change in these symptoms that may reflect differential timing of interventions that reduce distorted cognitions within each treatment. CONCLUSIONS: Findings may facilitate the shared decision-making process for patients choosing between CPT and PE. Session-level results provide direction for future research on the specific intervention components of CPT and PE. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Longitudinal PTSD network structure: measuring PTSD symptom networks over 5 years.

BACKGROUND: Network modeling has been applied in a range of trauma-exposed samples, yet results are limited by an over reliance on cross-sectional data. The current analyses used posttraumatic stress disorder (PTSD) symptom data collected over a 5-year period to estimate a more robust between-subject network and an associated symptom change network. METHODS: A PTSD symptom network is measured in a sample of military veterans across four time points (Ns = 1254, 1231, 1106, 925). The repeated measures permit isolating between-subject associations by limiting the effects of within-subject variability. The result is a highly reliable PTSD symptom network. A symptom slope network depicting covariation of symptom change over time is also estimated. RESULTS: Negative trauma-related emotions had particularly strong associations with the network. Trauma-related amnesia, sleep disturbance, and self-destructive behavior had weaker overall associations with other PTSD symptoms. CONCLUSIONS: PTSD's network structure appears stable over time. There is no single 'most important' node or node cluster. The relevance of self-destructive behavior, sleep disturbance, and trauma-related amnesia to the PTSD construct may deserve additional consideration.

Using electronic medical record diagnostic codes to identify veterans with posttraumatic stress disorder.

Researchers studying posttraumatic stress disorder (PTSD) often use diagnostic codes within electronic medical records (EMRs) to identify individuals with the disorder. This study evaluated the performance of algorithms for defining PTSD based on International Classification of Diseases (ICD) code use within EMR data. We used data from a registry of U.S. veterans for whom both structured interview data and Veterans Health Administration EMR data were available. Using interview-diagnosed PTSD as the reference criterion, we calculated diagnostic accuracy statistics for algorithms that required the presence of at least one and up to seven encounters in which a PTSD diagnosis was present in EMR data within any clinical source, mental health clinic, or specialty PTSD clinic. We evaluated algorithm accuracy in the total sample (N = 1,343; 64.1% with PTSD), within a subsample constrained to lower PTSD prevalence (n = 712; 32.3% with PTSD), and as a function of demographic characteristics. Algorithm accuracy was influenced by PTSD prevalence. Results indicated that higher thresholds for the operationalization of PTSD may be justified among samples in which PTSD prevalence is lower. Requiring three PTSD diagnoses from a mental health clinic or four diagnoses from any clinical source may be a suitable minimum standard for identifying individuals with PTSD in EMRs; however, accuracy may be optimized by requiring additional diagnoses. The performance of many algorithms differed as a function of educational attainment and age, suggesting that samples of individuals with PTSD developed based on EMR ICD codes may skew toward including older, less-educated veterans.

Heightened healthcare utilization & risk of mental disorders among Veterans with comorbid opioid use disorder & posttraumatic stress disorder.

Although Veterans with posttraumatic stress disorder (PTSD) are vulnerable to opioid misuse, there is limited research evaluating the psychosocial and medical sequalae experienced by Veterans with comorbid PTSD and opioid use disorder (OUD). Using data from a nationwide, longitudinal registry of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) Veterans oversampled for PTSD with a 1:1 ratio of men to women, we identified Veterans with lifetime diagnoses of comorbid PTSD and OUD (n = 40), PTSD and non-opioid substance use disorder (SUD; n = 386), PTSD only (n = 901), and non-opioid SUD only (n = 52) using medical record data. We then compared these groups on Veterans Affairs emergency, urgent care, and inpatient healthcare utilization, suicide risk, functional impairment, and the presence of comorbid mental conditions in the following 1-2 years. Relative to all other groups, Veterans with comorbid OUD and PTSD had increased likelihood of emergency room and inpatient care, probable somatoform and major depressive disorders, and greater functional impairment. Both the PTSD/OUD group and PTSD/non-opioid SUD group demonstrated increased suicidality, urgent care utilization, and probable generalized anxiety disorder relative to Veterans with PTSD only or non-opioid SUD only. Results suggest that comorbid OUD and PTSD are associated with greater likelihood of negative psychiatric and healthcare related outcomes, even relative to PTSD comorbid with other types of SUDs. Findings support the importance of concentrated and sustained efforts to improve prevention and intervention strategies for Veterans struggling with PTSD symptoms and opioid misuse.

The 20-year course of posttraumatic stress disorder symptoms among veterans.

Although numerous longitudinal studies have examined heterogeneity in posttraumatic stress disorder (PTSD) symptom course, the long-term course of the disorder remains poorly understood. This study sought to understand and predict long-term PTSD symptom course among a nationwide sample of Operations Enduring Freedom and Iraqi Freedom veterans enrolled in Veterans Health Administration services. We assessed PTSD symptoms at 4 time points over approximately 4.5 years (M = 55.11 months, SD = 6.89). Participants (N = 1,353) with and without probable PTSD were sampled at a 3:1 ratio, and male and female veterans were sampled at a 1:1 ratio to fully explore the heterogeneity of PTSD symptom course and the effect of sex on symptom course. By coding time as years since index trauma, we estimated the course of PTSD symptoms over 20 years. Results indicate symptom course is most appropriately characterized by substantial heterogeneity. On average, veterans experienced initial PTSD symptom severity above the diagnostic threshold following trauma exposure, which was initially stable over time and later began to gradually improve. Although results indicate symptoms eventually began to decline, this effect was gradual; most participants continued to meet or exceed the PTSD provisional diagnostic threshold long after trauma exposure. We identified several predictors and correlates of symptom course, including Hispanic ethnicity, postdeployment social support, and co-occurring psychopathology. Results highlight the heterogeneous nature of PTSD symptom course following trauma exposure and the urgency of the need to ensure access to evidence-based care and to improve available treatments. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

An Empirical Crosswalk for the PTSD Checklist: Translating DSM-IV to DSM-5 Using a Veteran Sample.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced numerous revisions to the fourth edition's (DSM-IV) criteria for posttraumatic stress disorder (PTSD), posing a challenge to clinicians and researchers who wish to assess PTSD symptoms continuously over time. The aim of this study was to develop a crosswalk between the DSM-IV and DSM-5 versions of the PTSD Checklist (PCL), a widely used self-rated measure of PTSD symptom severity. Participants were 1,003 U.S. veterans (58.7% with PTSD) who completed the PCL for DSM-IV (the PCL-C) and DSM-5 (the PCL-5) during their participation in an ongoing longitudinal registry study. In a randomly selected training sample (n = 800), we used equipercentile equating with loglinear smoothing to compute a "crosswalk" between PCL-C and PCL-5 scores. We evaluated the correspondence between the crosswalk-determined predicted scores and observed PCL-5 scores in the remaining validation sample (n = 203). The results showed strong correspondence between crosswalk-predicted PCL-5 scores and observed PCL-5 scores in the validation sample, ICC = .96. Predicted PCL-5 scores performed comparably to observed PCL-5 scores when examining their agreement with PTSD diagnosis ascertained by clinical interview: predicted PCL-5, κ = 0.57; observed PCL-5, κ = 0.59. Subsample comparisons indicated that the crosswalk's accuracy did not differ across characteristics including gender, age, racial minority status, and PTSD status. The results support the validity of this newly developed PCL-C to PCL-5 crosswalk in a veteran sample, providing a tool with which to interpret and translate scores across the two measures.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Un cruce empírico para la lista de verificación de TEPT: traducción de DSM-IV a DSM-5 utilizando una muestra de veteranos CRUCE PARA LA LISTA DE VERIFICACIÓN DEL TEPT La quinta edición del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5) introdujo numerosas revisiones a los criterios de la cuarta edición (DSM-IV) para el trastorno de estrés postraumático (TEPT), lo que representa un desafío para los médicos e investigadores que desean evaluar los síntomas de TEPT de manera continua a través del tiempo. El objetivo de este estudio fue desarrollar un cruce entre las versiones DSM-IV y DSM-5 de la Lista de verificación de TEPT (PCL en su sigla en inglés), una medida autoevaluada ampliamente utilizada de la gravedad de los síntomas de TEPT. Los participantes fueron 1.003 veteranos estadounidenses (58.7% con TEPT) que completaron el PCL para DSM-IV (PCL-C) y DSM-5 (PCL-5) durante su participación en un estudio de registro longitudinal en curso. En una muestra de entrenamiento seleccionada al azar (n = 800), utilizamos equipercentil equiparado con suavizado loglineal para calcular un "cruce" entre las puntuaciones PCL-C y PCL-5. Evaluamos la correspondencia entre las puntuaciones pronosticadas determinadas por el cruce y las puntuaciones PCL-5 observadas en la muestra de validación restante (n = 203). Los resultados mostraron una fuerte correspondencia entre los puntajes PCL-5 pronosticados para el cruce y los puntajes PCL-5 observados en la muestra de validación, ICC = .96. Los puntajes de PCL-5 pronosticados se compararon con los puntajes de PCL-5 observados al examinar su acuerdo con el diagnóstico de TEPT determinado por entrevista clínica: PCL-5 predicho, κ = 0.57; PCL-5 observado, κ = 0,59. Las comparaciones de submuestras indicaron que la precisión del cruce no difirió entre las características, incluidos el género, la edad, el estado de minoría racial y el estado de TEPT. Los resultados respaldan la validez de este paso de cruce recién desarrollado de PCL-C a PCL-5 en una muestra de veteranos, proporcionando una herramienta con la que interpretar y traducir las puntuaciones en las dos medidas.

A placebo-controlled randomized trial of D-cycloserine augmentation of cue exposure therapy for smoking cessation.

Recent studies underscore the importance of studying d-cycloserine (DCS) augmentation under conditions of adequate cue exposure treatment (CET) and protection from reconditioning experiences. In this randomized trial, we evaluated the efficacy of DCS for augmenting CET for smoking cessation under these conditions. Sixty-two smokers attained at least 18 hours abstinence following 4 weeks of smoking cessation treatment and were randomly assigned to receive a single dose of DCS (n=30) or placebo (n=32) prior to each of two sessions of CET. Mechanistic outcomes were self-reported cravings and physiologic reactivity to smoking cues. The primary clinical outcome was 6-week, biochemically-verified, continuous tobacco abstinence. DCS, relative to placebo, augmentation of CET resulted in lower self-reported craving to smoking pictorial and in vivo cues (d = 0.8 to 1.21) in a relevant subsample of participants who were reactive to cues and free from smoking-related reconditioning experiences. Select craving outcomes were correlated with smoking abstinence, and DCS augmentation was associated with a trend toward a higher continuous abstinence rate (33% vs. 13% for placebo augmentation). DCS augmentation of CET can significantly reduce cue-induced craving, supporting the therapeutic potential of DCS augmentation when applied under appropriate conditions for adequate extinction learning.

Examination of posttraumatic stress disorder symptom networks using clinician-rated and patient-rated data.

Network theory, which conceptualizes psychiatric disorders as networks of interacting symptoms, may provide a useful framework for understanding psychopathology. However, questions have arisen regarding the stability and generalizability of network analytic methods, with some researchers arguing that symptom networks have limited replicability. The aim of this study was to evaluate assessment modality as one possible source of instability in the estimation of posttraumatic stress disorder (PTSD) symptom networks. We estimated two cross-sectional DSM-5 PTSD symptom networks in 378 U.S. veterans: one using data from a clinician-rated assessment instrument (Clinician-Administered PTSD Scale for DSM-5; CAPS-5) and one using data from a self-rated questionnaire (the PTSD Checklist for DSM-5; PCL-5). We calculated centrality indices, conducted community structure analyses, and compared the strength and structure of the networks. The CAPS-5 and PCL-5 symptom networks were highly similar, challenging the notion that network methods produce unreliable results due to estimations consisting primarily of measurement error. Furthermore, each network contained distinct symptom communities that only partially overlapped with the DSM-5 PTSD symptom clusters. These findings may provide guidance for future revisions of the DSM, suggest hypotheses about how PTSD symptoms interact, and inform recent debate about replicability of psychopathology symptom networks. (PsycINFO Database Record

Behavioral activation treatment for major depression: A randomized trial of the efficacy of augmentation with cognitive control training.

BACKGROUND: Major depressive disorder (MDD) is associated with hypoactivation of the dorsolateral prefrontal cortex, a brain region involved in emotion regulation and basic cognitive control processes. Recent studies have indicated that computerized interventions designed to activate this region may reduce depressive and ruminative symptoms. In this double-blind randomized controlled trial, we tested whether one such program, called Cognitive Control Training (CCT), enhanced treatment outcomes when used in adjunct to brief behavior therapy for MDD. METHODS: Thirty-four adults with MDD were randomly assigned to complete four sessions of either computerized CCT or a control task, concurrently with four sessions of Brief Behavioral Activation Therapy for Depression (BATD). Post-treatment and one-month follow-up assessments were conducted, with self-reported depressive symptoms as the primary outcome and clinician-rated depressive symptoms and self-reported rumination as secondary outcomes. RESULTS: In both intent-to-treat and completer analyses, depressive symptoms and rumination decreased significantly over the course of treatment in both treatment conditions. There were no significant differences in treatment outcome depending on the augmentation condition. LIMITATIONS: The sample size was small, hindering secondary analyses and identification of potential predictors or moderators of treatment effect. CONCLUSIONS: Results demonstrate substantial clinical benefit following four sessions of BATD; however, adjunctive CCT did not enhance outcomes. This study and other recent research suggest that the effects of CCT may not be as robust as previously indicated, highlighting the need for continued investigation of the conditions under which CCT may be effective.

No site unseen: predicting the failure to control problematic Internet use among young adults.

Problematic Internet use has been associated with the neglect of valued activities such as work, exercise, social activities, and relationships. In the present study, we expanded the understanding of problematic Internet use by identifying an important predictor of the inability to curb Internet use despite the desire to do so. Specifically, in a college student sample reporting a mean of 27.8 h of recreational Internet use in the past week, we investigated the role of distress intolerance (DI)-an individual difference variable that refers to the inability of an individual to tolerate emotional discomfort and to engage in goal-directed behavior when distressed-to predict the failure to meet personal restrictions on Internet use. Consistent with hypotheses, DI emerged as a significant predictor of the failure to meet self-control goals in both bivariate and multivariate models, indicating that DI offers unique prediction of self-control failure with problematic Internet use. Given that DI is a modifiable trait, these results encourage consideration of DI-focused early intervention strategies.

Anxiety Sensitivity Uniquely Predicts Exercise Behaviors in Young Adults Seeking to Increase Physical Activity.

Individuals with elevated levels of anxiety sensitivity (AS) may be motivated to avoid aversive emotional or physical states, and therefore may have greater difficulty achieving healthy behavioral change. This may be particularly true for exercise, which produces many of the somatic sensations within the domain of AS concerns. Cross-sectional studies show a negative association between AS and exercise. However, little is known about how AS may prospectively affect attempts at behavior change in individuals who are motivated to increase their exercise. We recruited 145 young adults who self-identified as having a desire to increase their exercise behavior. Participants completed a web survey assessing AS and additional variables identified as important for behavior change-impulsivity, grit, perceived behavioral control, and action planning-and set a specific goal for exercising in the next week. One week later, a second survey assessed participants' success in meeting their exercise goals. We hypothesized that individuals with higher AS would choose lower exercise goals and would complete less exercise at the second survey. AS was not significantly associated with exercise goal level, but significantly and negatively predicted exercise at Time 2 and was the only variable to offer significant prediction beyond consideration of baseline exercise levels. These results underscore the importance of considering AS in relation to health behavior intentions. This is particularly apt given the absence of prediction offered by other traditional predictors of behavior change.

The Development of a Novel Measure to Assess Motives for Compensatory Eating in Response to Exercise: The CEMQ.

Compensatory eating in response to exercise may be an obstacle to achieving weight-loss and fitness goals. In this study we develop and conduct a preliminary examination of the psychometric properties of the Compensatory Eating Motives Questionnaire (CEMQ), a self-report questionnaire of motives for compensatory eating. Development and testing of the CEMQ was conducted in two student samples. Of respondents, 75% reported engaging in compensatory eating. Factor analysis yielded factors representing three domains of motives for compensatory eating: Eating for Reward, Eating for Recovery, and Eating for Relief. Internal consistency of the factors was adequate, and the factor structure was replicated. Correlations between the CEMQ subscales and trait questionnaires supported hypotheses for convergent and divergent validity. These results encourage further investigation of compensatory eating as a potential obstacle to weight loss, and support the continued assessment of the CEMQ as a tool to measure three conceptually distinct motives for compensatory eating.

Treatment Outcome and Predictors of Internet Guided Self-Help for Obsessive-Compulsive Disorder.

Internet-guided self-help (iGSH) has amassed significant empirical support for a variety of psychiatric conditions; however, it is not known who responds best to these treatments. This open trial examined the clinical outcomes and predictors of a 17-week iGSH program for obsessive-compulsive disorder (OCD). Therapist support was provided either in person or by phone 9 times for an average of 13minutes per session. Twenty-four patients initiated treatment, and 17 of these (70.8%) completed. Results of the intent-to-treat sample indicated statistically significant improvements at posttreatment with large treatment effects for OCD symptoms as assessed by the Yale Brown Obsessive-Compulsive Scale (d=0.87), and small to moderate improvements in depression (d=0.19), functioning (d=0.53), and quality of life (d=-0.18). These outcomes were largely maintained over a 6-month follow-up. Readiness to reduce avoidance of OCD triggers and attendance to therapist sessions were moderately associated with posttreatment response, and correctly classified the responder status (defined as clinically significant change) of nearly 9 out of 10 patients at posttreatment. These same variables did not predict responder status at 6-month follow-up. These results lend further empirical support to iGSH as a treatment for OCD and provide direction on the development of predictor models to identify patients who are and are not likely to acutely respond to iGSH.

De novo fear conditioning across diagnostic groups in the affective disorders: evidence for learning impairments.

De novo fear conditioning paradigms have served as a model for how clinical anxiety may be acquired and maintained. To further examine variable findings in the acquisition and extinction of fear responses between clinical and nonclinical samples, we assessed de novo fear conditioning outcomes in outpatients with either anxiety disorders or depression and healthy subjects recruited from the community. Overall, we found evidence for attenuated fear conditioning, as measured by skin conductance, among the patient sample, with significantly lower fear acquisition among patients with depression and posttraumatic stress disorder. These acquisition deficits were evident in both the simple (considering the CS+only) and differential (evaluating the CS+in relation to the CS-) paradigms. Examination of extinction outcomes were hampered by the low numbers of patients who achieved adequate conditioning, but the available data indicated slower extinction among the patient, primarily panic disorder, sample. Results are interpreted in the context of the cognitive deficits that are common to the anxiety and mood disorders, with attention to a range of potential factors, including mood comorbidity, higher-and lower-order cognitive processes and deficits, and medication use, that may modulate outcomes in fear conditioning studies, and, potentially, in exposure-based cognitive behavioral therapy.

Impulsivity as a moderator of the intention-behavior relationship for illicit drug use in patients undergoing treatment.

INTRODUCTION: Evident across clinical practice and clinical trials is a divergence between stated intentions and subsequent drug-related behaviors in substance abuse treatment settings. Impulsivity, itself related to drug abuse, may be one variable which may moderate the degree of disconnect in the intention-behavior relationship. The present study examines the relationship between self-stated desire to quit, impulsivity, and drug use in a group of outpatients receiving methadone maintenance treatment. In particular, we examined the direct and moderating influence of different facets of impulsivity (urgency, lack of premeditation, sensation seeking, and lack of perseverance) on drug use in the context of a stated desire to abstain from drugs. METHOD: 84 opioid-dependent individuals undergoing counseling and methadone maintenance treatment completed a battery of self-report questionnaires including measures of impulsivity (UPPS Impulsivity Scale), stated desire to quit, and past 30-day drug use. We hypothesized that two facets of impulsivity, urgency and (lack of) premeditation, would moderate the relationship between desire to quit and past 30-day drug use, such that the relationship between intention and behavior would be weaker in those with high levels of these facets of impulsivity. RESULTS: Consistent with the disconnect between intentions and drug-use behaviors typical of treatment settings, desire to quit was not directly associated with self-reported past month drug use. However, in separate regression analyses, 2 facets of impulsivity, premeditation and sensation seeking, moderated the relationship between desire to quit and past month use. Whereas there was not a significant relationship between desire to quit and drug use in individuals high in sensation-seeking or lack of premeditation, the relationship between intention and drug use behaviors was preserved in those low in these facets of impulsivity. CONCLUSION: These findings indicate that the relationship between desire to quit and self-reported past-month drug use is weak for those high in sensation seeking or low in premeditation. These results are discussed in the context of current interventions for substance dependence.

The role of perceived belongingness to a drug subculture among opioid-dependent patients.

Illicit drug use frequently occurs in a context of a drug subculture characterized by social ties with other drug users, feelings of excitement and effectiveness deriving from illicit activities, and alienation from mainstream society. Identification with this subculture is recognized anecdotally as a barrier to recovery, but clear quantification of individual differences in perceived belongingness to the drug subculture has been absent from the literature. The purpose of this study was to describe the development and psychometric properties of a brief self-report measure designed to assess this construct, the Belongingness to Drug Culture Questionnaire (BDCQ). Ninety-six opioid-dependent, methadone-maintained participants completed the BDCQ, related self-report measures, and assessment of drug use patterns. The BDCQ demonstrated high internal consistency (α = .88) and was significantly associated with self-reported days of drug use in the past 30 days, desire to quit, impulsivity, psychopathy, and social, enhancement, and coping drug use motives. These findings encourage continued psychometric evaluation of the BDCQ and study of the role of belongingness in the development and maintenance of substance use disorders.

Memory dysfunction in panic disorder: an investigation of the role of chronic benzodiazepine use.

BACKGROUND: Studies of the neurocognitive effects of long-term benzodiazepine use have been confounded by the presence of neurocognitive deficits characterizing the clinical conditions for which these medications are taken. Similarly, studies of the neurocognitive effects of anxiety disorders have been confounded by the inclusion of chronically benzodiazepine-medicated patients. This study was designed to tease apart the potentially confounding effects of long-term benzodiazepine use and panic disorder (PD) on memory and visuoconstructive abilities. METHODS: Twenty chronically benzodiazepine-medicated and 20 benzodiazepine-free patients with PD with agoraphobia were compared with a group of 20 normal control participants, group-matched for age, education, and gender on a battery of neuropsychological tests assessing short-term, episodic long-term, and semantic memory, as well as visuoconstructive abilities. RESULTS: Results indicated that benzodiazepine-free panic patients were relatively impaired in nonverbal short-term and nonverbal episodic long-term memory and visuoconstructive abilities, whereas verbal short-term and verbal episodic memory and semantic memory were preserved. Only limited evidence was found for more pronounced impairments in chronically benzodiazepine-medicated PD patients. CONCLUSIONS: This study provides evidence that patients with PD are characterized by relative impairments in nonverbal memory and visuoconstructive abilities, independent of benzodiazepine use. Nonetheless, we found evidence that chronic treatment with benzodiazepines is associated with intensification of select relative impairments in this realm. Documentation of these deficits raises questions about the broader etiology of neurocognitive impairment in PD as well as its impact on daily functioning.

Eszopiclone for the treatment of posttraumatic stress disorder and associated insomnia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The development of novel strategies for the treatment of posttraumatic stress disorder (PTSD) represents a critical public health need. We present the first prospective, randomized, double-blind, placebo-controlled trial of a non-benzodiazepine hypnotic agent for the treatment of PTSD and associated insomnia. METHOD: Twenty-four patients with PTSD by DSM-IV criteria and sleep disturbance were treated in a randomized, double-blind, placebo-controlled crossover study of 3 weeks of eszopiclone 3 mg at bedtime compared to placebo. The primary outcome measures were changes in scores on the Short PTSD Rating Interview (SPRINT) and the Pittsburgh Sleep Quality Index (PSQI). The data were collected from April 2006 to June 2008. RESULTS: Three weeks of eszopiclone pharmacotherapy was associated with significantly greater improvement than placebo on PTSD symptom measures including the SPRINT (P = .032) and the Clinician-Administered PTSD Scale (P = .003), as well as on measures of sleep including the PSQI (P = .011) and sleep latency (P = .044). Greater improvement with eszopiclone on PTSD measures was present even when specific sleep-related items were excluded. Adverse events were consistent with the known profile of the drug. CONCLUSIONS: This study provides initial evidence that pharmacotherapy with eszopiclone may be associated with short-term improvement in overall PTSD severity as well as associated sleep disturbance. Longer, more definitive study of eszopiclone in PTSD is warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00120250.

Duloxetine for the treatment of generalized social anxiety disorder: a preliminary randomized trial of increased dose to optimize response.

OBJECTIVE: This is the first trial examining duloxetine for generalized social anxiety disorder (GSAD) and the effect of increased dose for those without early remission. METHODS: Individuals (n=39) with GSAD received 6 weeks of open-label duloxetine 60 mg/day; those with a Liebowitz Social Anxiety Disorder Scale (LSAS) score >30 at week 6 were randomized in double-blind fashion to an additional 18 weeks of continued duloxetine 60 mg/day or to duloxetine 120 mg/day. RESULTS: Duloxetine was associated with a significant LSAS reduction at week 6 (91.3 [17.7] to 69.8 [28.5], paired t [df]=5.2 [38], P<.0001), and randomized participants overall continued to improve at week 24 (74.6 [23.9] to 60.3 [29.7]; paired t [df]=3.3 [27], P=.0026). Though the increased dose strategy was associated with a moderate effect size (Cohen's d=.57), there was no significant difference at week 24 endpoint in LSAS reduction (20.5 [26.0] versus 7.3 [17.2], t [df]=1.6 [26], P=.13) nor remission (33% versus 8%) for duloxetine with dose increased to 120 mg/day compared to duloxetine continued at 60 mg/day. Overall, 44% (17/39) discontinued prior to week 24. CONCLUSIONS: Though with limited power, these data provide preliminary support for the efficacy of duloxetine for GSAD, and suggest continued improvement but limited remission overall at 24 weeks for individuals remaining symptomatic at week 6. These observations warrant further controlled study.

Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial.

BACKGROUND: More data are needed to guide next-step interventions for panic disorder refractory to initial intervention. METHOD: This 24-week randomized clinical trial (RCT) enrolled 46 patients with DSM-IV-defined panic disorder from November 2000 to April 2005 and consisted of 3 phases. Patients who failed to meet remission criteria were eligible for randomization in the next treatment phase. Phase 1 was a 6-week lead-in with open-label sertraline flexibly dosed to 100 mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 was a 6-week double-blind RCT of (1) increased-dose selective serotonin reuptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 was a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to "medication optimization" with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent-to-treat sample in each phase. RESULTS: In phase 1, 20.5% (8/39) of the patients achieved remission, and only baseline severity predicted endpoint PDSS score (beta [SE] = 1.04 [0.15], t = 6.76, P < .001). In phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n = 2] vs increased dose 9% [n = 1]: Fisher exact test P = NS). In phase 3, remission was minimal (medication optimization = 11% [n = 1]; CBT = 10% [n = 1]), with a lack of group difference in PDSS score reduction (t(17) = 0.51, P > .60) consistent with a small effect size (d = 0.24). CONCLUSIONS: Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in nonremitted panic after 12 weeks of an SSRI did not differ, suggesting that both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest that better predictors of response to specific treatments over time and additional interventions are needed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00118417.