Katarzyna Wyka

D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial.

Viewing post-traumatic stress disorder (PTSD) as a disorder of emotional learning, this study used a cognitive enhancer synergistically with virtual reality exposure (VRE) therapy for the treatment of PTSD. The main objective was to determine if a novel pharmacotherapy, D-cycloserine (DCS), enhanced the efficacy of the psychotherapy. Pre-clinical studies suggest that when fear extinction occurs during DCS administration, neuroplasticity may be enhanced. VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning, as sensory fear cues are standardized across patients. In a pilot randomized, double-blind, placebo-controlled trial, 100 mg of DCS or placebo was administered 90 min before each weekly VRE session, to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Beck Depression Inventory-II and the State-Trait Anger Expression Inventory-2. Assessments occurred at pre-treatment, following sessions 3, 6, 10, post-treatment, and at 6 months. The difference in CAPS between the VRE-DCS (n=13) and VRE-placebo (n=12) groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later (d=0.68 and d=1.13, respectively). A similar pattern was observed for depression, anger expression, and sleep. PTSD remission rates were significantly greater for the VRE-DCS group (46% vs 8% at post-treatment; 69% vs 17% at 6 months). Patients in the VRE-DCS group showed earlier and greater improvement in PTSD symptoms compared with the VRE-placebo group. These results suggest a promising new treatment for PTSD.

The nature and course of subthreshold PTSD

This study investigated rates of subthreshold PTSD and associated impairment in comparison to no PTSD and full PTSD and prospectively followed the course of subthreshold symptoms over 3 years. 3360 workers dispatched to the WTC site following 9/11 completed clinician interviews and self-report measures at three time points each one year apart. At Time 1, 9.7% of individuals met criteria for subthreshold PTSD. The no PTSD, subthreshold PTSD, and full PTSD groups exhibited significantly different levels of impairment, rates of current MDD diagnosis, and self-reported symptoms of depression. At Time 2, 29% of the initial sample with subthreshold PTSD continued to meet criteria for subthreshold or full PTSD; at Time 3, this was true for 24.5% of the initial sample. The study lends credence to the clinical significance of subthreshold PTSD and emphasizes that associated impairment may be significant and longstanding. It also confirms clinical differences between subthreshold and full PTSD.

Psychosocial Intervention Improves Depression, Quality of Life, and Fluid Adherence in Hemodialysis

Patients with ESRD have high rates of depression, which is associated with diminished quality of life and survival. We determined whether individual cognitive behavioral therapy (CBT) reduces depression in hemodialysis patients with elevated depressive affect in a randomized crossover trial. Of 65 participants enrolled from two dialysis centers in New York, 59 completed the study and were assigned to the treatment-first group (n=33) or the wait-list control group (n=26). In the intervention phase, CBT was administered chairside during dialysis treatments for 3 months; participants were assessed 3 and 6 months after randomization. Compared with the wait-list group, the treatment-first group achieved significantly larger reductions in Beck Depression Inventory II (self-reported, P=0.03) and Hamilton Depression Rating Scale (clinician-reported, P<0.001) scores after intervention. Mean scores for the treatment-first group did not change significantly at the 3-month follow-up. Among participants with depression diagnosed at baseline, 89% in the treatment-first group were not depressed at the end of treatment compared with 38% in the wait-list group (Fishers exact test, P=0.01). Furthermore, the treatment-first group experienced greater improvements in quality of life, assessed with the Kidney Disease Quality of Life Short Form (P=0.04), and interdialytic weight gain (P=0.002) than the wait-list group, although no effect on compliance was evident at follow-up. In summary, CBT led to significant improvements in depression, quality of life, and prescription compliance in this trial, and studies should be undertaken to assess the long-term effects of CBT on morbidity and mortality in patients with ESRD.

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data

Importance Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, −3.62; 95% CI, −0.81 to −6.43; P = .01; d = −0.25) but not from pretreatment to midtreatment (mean difference, −1.66; 95% CI, −4.92 to 1.60; P = .32; d = −0.14) or from pretreatment to follow-up (mean difference, −2.98, 95% CI, −5.99 to 0.03; P = .05; d = −0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

The longitudinal course of PTSD among disaster workers deployed to the World Trade Center following the attacks of September 11th

This study examined the long-term mental health outcomes of 2,960 nonrescue disaster workers deployed to the World Trade Center site in New York City following the September 11, 2001 (9/11) terrorist attacks. Semistructured interviews and standardized self-report measures were used to assess the prevalence of posttraumatic stress disorder (PTSD) and other psychopathology 4 and 6 years after the attacks. Clinician-measured rates of PTSD and partial PTSD 4-years posttrauma were 8.4% and 8.9%, respectively, in a subsample of 727 individuals. Rates decreased to 5.8% and 7.7% for full and partial PTSD 6 years posttrauma. For the larger sample, self-report scores revealed probable PTSD and partial PTSD prevalence to be 4.8% and 3.6% at 4 years, and 2.4% and 1.8% at 6 years. Approximately 70% of workers never met criteria for PTSD. Although PTSD rates decreased significantly over time, many workers remained symptomatic, with others showing delayed-onset PTSD. The strongest predictors of ongoing PTSD 6 years following 9/11 were trauma history (odds ratio (OR) = 2.27, 95% confidence interval (CI) [1.06, 4.85]); the presence of major depressive disorder 1-2 years following the trauma (OR = 2.80, 95% CI [1.17, 6.71]); and extent of occupational exposure (OR = 1.31, 95% CI [1.13, 1.51]). The implications of the findings for both screening and treatment of disaster workers are discussed.

Numbing symptoms as predictors of unremitting posttraumatic stress disorder

This prospective longitudinal study examined the ability of re-experiencing, avoidance, numbing, and hyperarousal symptoms to predict persistence of posttraumatic stress disorder (PTSD) in disaster workers followed for 2 years. Cluster analyses suggested that overall severity was the best predictor of PTSD at follow up, but for groups with PTSD of moderate severity, numbing symptoms were also associated with PTSD at the 2-year follow up. Regression analyses with all four symptom groups as independent variables found that only numbing and re-experiencing symptoms predicted PTSD at the 1 year follow up, and only numbing symptoms predicted PTSD at the 2-year follow up. Findings suggest that numbing symptom severity could be used as a risk index of very chronic PTSD, especially when the overall PTSD severity falls in the moderate range.

Posttraumatic stress symptoms in older adults hospitalized for fall injury

OBJECTIVE Although unintentional falls may pose a threat of death or injury, few studies have investigated their psychological impact on older adults. This study sought to gather data on early posttraumatic stress symptoms in older adults in the hospital setting after a fall. METHOD Participants in this study were 100 adults age 65 years or older admitted to a large urban hospital in New York City because of a fall. Men and women were represented approximately equally in the sample; most were interviewed within days of the fall event. The studys bedside interview included the Posttraumatic Stress Symptom Scale, which inquires about the presence and severity of 17 trauma-related symptoms. RESULTS Twenty-seven participants reported substantial posttraumatic stress symptoms (moderate or higher severity). Exploratory bivariate analyses suggested an association between posttraumatic stress symptom severity and female gender, lower level of education, unemployment, number of medical conditions, and back/chest injury. CONCLUSIONS A significant percentage of older patients hospitalized after a fall suffer substantial posttraumatic stress. Future investigations are needed to assess the association between the psychiatric impact of a fall and short-term inpatient outcomes as well as longer-term functional outcomes.

The treatment of posttraumatic stress disorder and related psychosocial consequences of burn injury: a pilot study

Burn injuries are unique in their medical and psychological impact, yet there has been little exploration of psychiatric treatment for this population. This uncontrolled pilot study assessed feasibility, acceptability, and preliminary efficacy of a treatment protocol designed to address posttraumatic stress disorder, depression, coping with scarring, and community integration among adult burn survivors. A 14-session, manualized treatment protocol was created using cognitive-behavioral interventions including imaginal exposure, behavioral activation, cognitive restructuring, modeling, and in vivo exposure. Responses were measured using the Clinician Administered PTSD Scale, Beck Depression Index, Community Integration Questionnaire, Oswestry Disability Questionnaire, and Burn Specific Health Scale. Nine of 10 enrolled patients (60% women; mean = 42 years old) completed treatment. Burn size was 0.5% to 65%; mechanism of injury included flame (4), scald (5), and contact (1) burns. Mean acute hospitalization was 30.1 days (range = 13–87); mean time from injury to treatment was 3.2 months (range = 1–7). Baseline mean posttraumatic stress score was 68 on the Clinician Administered PTSD Scale (severe); scores decreased by 36% to a mean of 45.3 at posttreatment, with a large effect size. Baseline self-reported depression was 21 (moderate) on the Beck Depression Index, decreasing by 47% to a mean of 12 posttreatment (nonclinical). Change in community reintegration score was significant and large, and body image showed significant improvement. The protocol showed promise in the treatment of posttraumatic stress disorder, depression, self-image, and community reintegration following burn injury. These findings suggest that coping may improve with treatment and symptoms should not be dismissed as unavoidable consequences of burn injury.

The effect of albendazole treatment on seizure outcomes in patients with symptomatic neurocysticercosis

BACKGROUND Randomized controlled trials have found an inconsistent effect of anthelmintic treatment on long-term seizure outcomes in neurocysticercosis. The objective of this study was to further explore the effect of albendazole treatment on long-term seizure outcomes and to determine if there is evidence for a differential effect by seizure type. METHODS In this trial, 178 patients with active or transitional neurocysticercosis cysts and new-onset symptoms were randomized to 8 days of treatment with albendazole (n=88) or placebo (n=90), both with prednisone, and followed for 24 months. We used negative binomial regression and logistic regression models to determine the effect of albendazole on the number of seizures and probability of recurrent or new-onset seizures, respectively, over follow-up. RESULTS Treatment with albendazole was associated with a reduction in the number of seizures during 24 months of follow-up, but this was only significant for generalized seizures during months 1-12 (unadjusted rate ratio [RR] 0.19; 95% CI: 0.04-0.91) and months 1-24 (unadjusted RR 0.06; 95% CI: 0.01-0.57). We did not detect a significant effect of albendazole on reducing the number of focal seizures or on the probability of having a seizure, regardless of seizure type or time period. CONCLUSIONS Albendazole treatment may be associated with some symptomatic improvement; however, this association seems to be specific to generalized seizures. Future research is needed to identify strategies to better reduce long-term seizure burden in patients with neurocysticercosis.

Is a Successful High-K Fitness Strategy Associated with Better Mental Health?

This study examined the associations between a high-K fitness strategy and mental health. These associations were tested on a sample of 1400 disaster workers who had exposure to a singular traumatic event and who underwent psychological evaluations. The results showed that high-K was an important negative predictor of psychopathology, accounting for significant variance in PTSD, general psychopathology, functional disability, anger, and sleep disturbances. Implications of the results are discussed.