Toward Rational Pharmacotherapy for Posttraumatic Stress Disorder: Reprise

Results of a study of psychotropic prescribing patterns in a Veterans Affairs (VA) population with posttraumatic stress disorder (PTSD) are presented. VA prescription records were reviewed to identify veterans with PTSD at a large VA healthcare center and evaluate their medication regimens for conformance with a VA practice guideline that calls for the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as first-line therapies for PTSD; the VA guideline does not recommend second-generation antipsychotics (SGAs) and benzodiazepines for PTSD symptom control. The primary objective was to determine if veterans with PTSD who were receiving an SGA had first received SSRI or SNRI therapy in accordance with VA recommendations. Among 308 veterans who met the inclusion criteria, the average number of SSRI or SNRI agents prescribed prior to initiation of SGA therapy was 0.88. Only 19.8% of patients (n = 61) had been prescribed 2 SSRI or SNRI agents, with 48.4% of patients (n = 149) having received 1 agent. All evaluated courses of SSRI and SNRI therapy prior to SGA initiation were of sufficient duration (range, 5-30 months), and mean adherence rates were >80%. Current or past benzodiazepine use was documented in about 55% of patients (n = 170). SSRIs and SNRIs were under-utilized for the treatment of PTSD at the study site in patients receiving an SGA. The current use of benzodiazepines in these patients was lower than a reported national average for VA patients.

Cognitive Function and Dissociative Disorder Status Among Veteran Subjects With Chronic Posttraumatic Stress Disorder: A Preliminary Study

The authors' goal was to determine the levels of trauma and psychiatric symptoms in a randomly selected group of Cambodian refugees and to determine the relationship between the amount of trauma experienced and subsequent psychiatric symptoms. Data on traumatic experiences and symptoms of posttraumatic stress, dissociation, depression, and anxiety were collected on 50 randomly selected Cambodian refugees who had resettled in the United States. Subjects experienced multiple and severe traumas and showed high levels of all symptoms measured. Forty-three (86%) of the subjects met DSM-III-R criteria for posttraumatic stress disorder, 48 (96%) had high dissociation scores, and 40 (80%) could be classified as suffering from clinical depression. Correlations between trauma scores and symptom scores and among symptom scores were moderate to large. These results indicate that a high proportion of Cambodian refugees who are not psychiatric patients suffer from severe psychiatric symptoms and that there is a relationship between the amount of trauma they experienced and the severity of these symptoms.

BackgroundPosttraumatic stress disorder (PTSD) has a great impact on a patient’s quality of life (QoL). People in long-term contact with a person suffering from PTSD, such as family members, may also consequently develop various emotional problems.MethodsWe investigated whether chronic combat PTSD is related to lower QoL of veterans’ wives. The study included 164 veterans with PTSD, 281 PTSD veterans’ wives, 115 healthy non-veterans’ wives and 223 men without PTSD. All participants were assessed for psychiatric morbidity (Mini International Neuropsychiatric Interview) and measures of QoL (World Health Organization Quality of Life Questionnaire – short form). In veterans, the symptoms were evaluated using Clinician Administered PTSD Scale (CAPS).ResultsThe pattern of differences between the study groups was similar across all QoL domains. Men without PTSD had the highest scores, followed by women who were not married to PTSD patients (significantly different across all four QoL domains). PTSD veterans’ wives tended to had lower scores than either of these groups. Significant differences between PTSD veterans’ wives and women who were not married to PTSD patients were observed in three (out of four) QoL domains: psychological health, Z = 2.907, P = 0.022; social relationships, Z = 3.285, P = 0.006; and environmental domain, Z = 5.317, P < 0.001. The lowest scores were recorded in PTSD veterans (significantly lower than PTSD veterans’ wives in every domain except environmental). The wives who reported to be ill at the time tended to have lower scores across all four domains (P < 0.05) (low to moderate correlation; physical health, ρ = −0.56; psychological health, ρ = −0.42; social relationships, ρ = −0.30; environmental, ρ = −0.33), as well as those who sometimes in their lives they sought professional help due to having problems with their husband (P < 0.05) (very low to low correlation; physical health, ρ = −0.37; psychological health, ρ = −0.38; social relationships, ρ = −0.30; environmental, ρ = −0.15).ConclusionOur results indicate the negative impact of husband’s chronic PTSD on overall QoL, psychological health, social relations, and environmental area of QoL of veteran’s wives. Assessment of QoL may be important during the intervention and planning of specific treatment and rehabilitation programs for the families of war veterans.

BackgroundPrazosin is significantly effective to reduce sleep disturbance and trauma nightmare in patients with post-traumatic stress disorder (PTSD); however, results of different studies were evaluated.ObjectivesThe current randomized clinical trial aimed to assess the effects of prazosin on sleep parameters and nightmares among veterans with chronic PTSD.Materials and MethodsThirty-two veterans with chronic war-induced PTSD and distressing nightmares were randomized into prazosin and placebo groups for eight weeks. The main symptoms were qualified using the recurrent distressing dreams item of the clinician administered PTSD scale (CAPS) and the daytime symptom severity was measured by PTSD checklist (PCL) and the objective sleep quality assessment by actigraphy.ResultsCompared with placebo, prazosin had no significant effects on reduction of daytime symptoms (P = 0.69) and frequency and intensity of trauma-related nightmares. Also, there were no significant differences between pre- and post-treatment actigraphy measurements (P > 0.05).ConclusionsThe study findings showed that prazosin had no significant effect on reduction of PTSD symptoms as well as nightmares among veterans with chronic PTSD. Further clinical trials are needed to define the effect of prazosin on sleep physiology and whether such effects regarding the therapeutic response.

Cognitive-behavioral therapies (CBTs) emphasizing exposure have been the most widely studied and empirically validated psychotherapeutic treatments for posttraumatic stress disorder (PTSD). Prolonged exposure, which was recently endorsedby the InstituteofMedicine as theonlyPTSD therapy forwhich there is adequate evidenceof effectiveness, has a hypothesized mechanism of action consistent with the animal models of fear activation and extinction that form the basis for understanding PTSD from a neurobiological perspective.At the same time, it is known that interpersonal traumas are the most frequently occurring and potent precipitants of PTSD, that the avoidant and numbing symptoms of PTSD adversely affect one’s current relationships, and that social support reduces the risk of chronic PTSD after trauma. These facts suggest that for patients entering PTSD treatment, their current interpersonal relations are problematic and that improving themcould improve symptoms and overall functioning. Against this backdrop, Markowitz and colleagues (1) tested the efficacy of interpersonal psychotherapy (IPT)—an evidence-based, present-oriented psychotherapy with established efficacy for depression—for patients with PTSD. Based on Bowlby’s attachment theories (2), IPT initially focuses on helping patients understand their emotional responses as they arise in the context of their current relationships (“affective attunement”) and uses this understanding, along with behavioral methods such as problem solving and role playing, to improve and strengthen interpersonal relationships (3, 4). Current interpersonal problems are broadly defined as grief, disputes, life transitions,andinterpersonaldeficits.Byclarifying and resolving these problems in the here and now, symptoms may begin to improve, even if the origin of the symptoms lies in experiences in thepast.Thehighrateofcomorbiddepression in patients with PTSD provided an added rationale for exploring the efficacy of this treatment in PTSD. The three-arm randomized controlled trial compared IPT to both prolonged exposure, the gold standard for PTSD, and relaxation therapy, an active psychotherapy control that has known, but limited, anxiolytic effects. The authors hypothesized that both IPT and prolonged exposure would be superior to relaxation therapy and, more importantly, that IPT would be no more than “minimally inferior” to prolonged exposure. This last andmost crucial hypothesis wasmeant to demonstrate that IPT could serve as a viable alternative to prolonged exposure for PTSD patients who prefer an interpersonal approach. The study recruited 110 seriously ill patients with PTSD, 90% of whom had some kind of interpersonal trauma and many of whom had a history of multiple traumas (including childhood trauma in 36%). Over half had chronic PTSD, 50% had comorbid major depression, 50% had a comorbid axis II diagnosis, and most had limited social support (84% were single, and less than 50% were employed) and a history of unsuccessful community psychotherapy (75%) and pharmacotherapy (50%). Use of medication was not allowed, which may limit the generalizability of the study but may also have provided a more stringent test of the efficacy of the therapies. Therapies were delivered by experts over 14 weeks and were balanced for total therapy time and for therapist age and gender. Assessments used state-of-the-art instruments at baseline and at 7 and 14 weeks. The outcomes of the trial are potentially practice changing. Both IPT and prolonged exposure showed superiority to relaxation therapy on multiple PTSD, depression, and functional status outcome measures, and IPT was no more than minimally inferior to prolonged exposure, with a difference of 5.5 points on the Clinician-Administered PTSD Scale (CAPS), much smaller than the accepted 15-point CAPS difference required to demonstrate superiority between treatments. Only prolonged exposure was superior to relaxation therapy on the CAPS, with IPT showing an advantage that fell short of statistical significance (p,0.10), while only IPT was superior to relaxation therapy inmeeting thecriterion for response (a 30% reduction in PTSD symptoms) (response rates, 63% compared with 38%; prolongedexposure fell in between,with a response rate of 47%). Remission rates were relatively low and were similar in all three groups (26%, 23%, 22%). Both IPT and prolonged exposure were superior to relaxation therapy on the Posttraumatic Stress Scale–Self-Report, the Hamilton Depression Rating Scale, measures of quality of life and social functioning, and the Inventoryof InterpersonalProblems.The analysis indicated that the effects of prolonged exposure relative to IPT were greater at 7 weeks than at 14 weeks—that is, prolonged exposure appeared to be superior to IPT early on, This study reminds us that there may be multiple therapeutic routes to achieve the same beneficial outcome.

The PTSD Psychopharmacology Working Group: Two Suggestions

Sleep disturbances are common among veterans with chronic military-related posttraumatic stress disorder (PTSD). This article reports the results of a multicenter clinical trial that explored the clinical correlates of reported sleep impairment in these veterans and tested the impact of the second-generation antipsychotic risperidone upon these symptoms. This article reports secondary analyses of a 24-week multicenter randomized placebo-controlled trial of adjunctive risperidone in patients with chronic military-related PTSD symptoms (n = 267, 97% male) who were symptomatic despite treatment with antidepressants and other medications. The study was conducted between February 2007 and February 2010. DSM-IV PTSD diagnoses were made by using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Nonpatient Edition. Sleep disturbances were assessed principally by using the Pittsburgh Sleep Quality Index (PSQI) (primary outcome measure). Analyses were conducted using bivariate correlations and longitudinal mixed model regressions. Eighty-eight percent of the patients in this study had clinically significantly impaired sleep on the PSQI. Severity of sleep disturbances correlated with PTSD symptom severity as measured by the Clinician-Administered PTSD Scale (CAPS) and reductions in multiple measures of quality of life (Veterans RAND 36-item Health Survey [SF-36 V] subscales, Boston Life Satisfaction Index). Risperidone produced small but statistically significant effects on total PSQI scores (main effect of drug: F1,228 = 4.57, P = .034; drug-by-time interaction: F2,421 = 4.32, P = .014) and severity of nightmares as assessed by the CAPS (main effect of drug: F1,248 = 4.60, P = .033). The improvements in sleep quality produced by risperidone correlated with reductions in PTSD symptom severity and improvement in the mental health subscale of the SF-36 V. This study highlighted the near universality and significant negative impact of severe disturbances in sleep quality in veterans with chronic military-related PTSD who were partial responders to standard pharmacotherapies. The modest improvements in sleep quality produced by adjunctive risperidone were correlated with limited reductions in PTSD severity and improvements in quality of life. ClinicalTrials.gov identifier: NCT00099983.

Psychotic features and illness severity in combat veterans with chronic posttraumatic stress disorder

The symptom overlap between posttraumatic stress disorder (PTSD) and other pharmacotherapy-responsive disorders suggests that pharmacotherapy might be effective. Nevertheless, of the eight published placebo-controlled trials investigating the pharmacotherapy of PTSD, only four found statistically significant efficacy for the treatment being studied. This literature possesses a number of methodologic limitations, including the fact that most studies have been conducted with war veterans, who may constitute a more treatment-refractory population. Several open trials and one controlled trial with selective serotonin reuptake inhibitors have reported improvement in some or all core PTSD symptoms (reexperiencing, avoidance, numbing, and hyperarousal). The authors hypothesized that paroxetine might be effective in PTSD, based on findings of its particular efficacy for anxiety and agitation in studies of depressed patients. The study presented here summarizes a 12-week, open-label trial of paroxetine among patients with noncombat-related, chronic PTSD. Outcome was assessed by an independent evaluator, the treating physician, and the patient, with the use of established rating scales for depression, anxiety, general symptoms, and PTSD core symptoms. A repeated-measures analysis of variance revealed highly significant improvement in all three symptom clusters, as well as in associated anxiety, depressive, and dissociative symptoms, with 11 of 17 (65%) patients rated as much or very much improved. The mean reduction in PTSD symptom scores was 48%. Exploratory analyses revealed that cumulative childhood trauma was negatively correlated with pharmacotherapy response (r = -0.52, p = 0.03). There was also significant variation in the time course of response across symptom clusters, which is suggestive of multiple mechanisms of response. Because paroxetine seems a highly promising treatment for all three symptom clusters of PTSD, a placebo-controlled clinical trial is warranted.

Patients with post‐traumatic stress disorder (PTSD) are at significantly higher risk of developing hypertension and cardiovascular disease. Low‐grade inflammation and overactive sympathetic nervous system (SNS) activity are suggested as contributing mechanisms. Our prior studies showed that while SNS reactivity during stress is heightened in PTSD, resting MSNA and inflammation was not elevated in young combat Veterans with PTSD as a group; however, prior results did not take into account the potential influence of PTSD symptom severity on neural cardiovascular function. The aim of the current study was to determine if PTSD patients with greater PTSD symptoms measured via the gold‐standard clinician administered PTSD scale (CAPS) have higher SNS activity and inflammation compared to PTSD patients with less severe symptoms. To answer this question, we recruited 21 veterans clinically diagnosed with PTSD (mean CAPS score, 68±4). We measured muscle sympathetic nerve activity (MSNA) via microneurography and blood pressure using standard technique. We collected blood samples to measure serum levels of two inflammatory biomarkers: highly sensitive C‐reactive protein (hsCRP) and interleukin‐6 (IL‐6). For data analysis, the participants were grouped based on the median CAPS score of 70, with the low CAPS group (L‐CAPS) having a score ≤ 70 and the high CAPS group (H‐CAPS) having a score &gt; 70. The two groups (L‐CAPS, n=11; H‐CAPS, n=10) were matched for age, body mass index (BMI) and selective serotonin reuptake inhibitor (SSRI) prescription. Resting blood pressure and heart rate were similar between the two groups. However, the H‐CAPS group had a significantly greater MSNA at baseline when quantified as both burst frequency (26±5 vs 13±2 bursts/min, p= 0.011) and burst incidence (35±6 vs 21±3 bursts/100hb, p= 0.022) compared to the L‐CAPS group. Similarly, hsCRP (2.02±0.71 vs 0.74±0.18, p= 0.036) and IL‐6 (5.44±1.86 vs 2.35±0.73, p= 0.055) levels were higher in the H‐CAPS group compared to the L‐CAPS group. Furthermore, the levels of hsCRP (r= 0.766, p&lt; 0.001) and IL‐6 (r= 0.594, p=0.007) were positively correlated with MSNA. When the groups were analyzed separately, the correlation between MSNA and hsCRP was stronger in the H‐CAPS group (r=0.822, p=0.012) than the L‐CAPS group (r=0.604, p=0.065). These results suggest that the severity of PTSD is associated with chronically increased MSNA and inflammation, and SNS overactivity may be mechanistically linked to inflammation in severe PTSD.Support or Funding InformationSupported by NIH HL‐098744, NIH DK‐00756, VA Merit I01CX001065, AHA 15CSA24340001This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Efficacy of ECT in Chronic, Severe, Antidepressant- and CBT-Refractory PTSD: An Open, Prospective Study

BackgroundWar, as a stressor event, has a variety of acute and chronic negative consequences, such as posttraumatic stress disorder (PTSD). In this context, early maladaptive schema-based problems in PTSD have recently become an important research area. The aim of this study was to assess early maladaptive schemas in patients with acute and chronic PTSD.MethodUsing available sampling methods and diagnostic criteria, 30 patients with chronic PTSD, 30 patients with acute PTSD, and 30 normal military personnel who were matched in terms of age and wartime experience were selected and assessed with the Young Schema Questionnaire-Long Form, Beck Depression Inventory second version (BDI-II), the Beck Anxiety Inventory (BAI), and the Impact of Events Scale (IES).ResultsBoth acute and chronic PTSD patients, when compared with normal military personnel, had higher scores for all early maladaptive schemas. Additionally, veterans suffering from chronic PTSD, as compared with veterans suffering from acute PTSD and veterans without PTSD, reported more impaired schemas related, for instance, to Self-Control, Social Isolation, and Vulnerability to Harm and Illness.DiscussionThe results of the present study have significant preventative, diagnostic, clinical, research, and educational implications with respect to PTSD.

Background: Coronavirus disease (COVID-19) hospitalization has been related to Post-Traumatic Stress Disorder (PTSD). Available information is limited by insufficient follow-up and lack of longitudinal studies. Baseline factors (e.g., sex; obesity) have been related to PTSD, but post-hospitalization factors have not been studied. Objective: This study aimed to analyse prevalence, baseline, post-discharge factors and possible clinical courses of PTSD after hospitalization for COVID-19. Method: 109 patients (94.7% of the original sample) completed a programme of three follow-up telephone assessments during the year following hospitalization. Data included clinical and sociodemographic factors as well as psychometric tools assessing PTSD, social support, and perception of threat to life (PTL). Mixture model analysis was performed to study the longitudinal course of PTSD symptoms. Chronic (>6 months) PTSD predictors were also analysed. Results: 1-year PTSD period prevalence was 23.9%, peaking at six months; 11% of the patients suffered chronic PTSD. Pre- and post-hospitalization factors influenced the onset and course of PTSD over time. These included working status, PTL, and lack of social support. Interestingly, obesity, pulmonary diseases and family cluster infection seem specifically related to PTSD following COVID-19. Inversely, clinical interventions, older age and male gender were protective. Conclusions: PTSD following COVID-19 hospitalization is common. The analysed demographic, social, clinical, and psychological factors predict PTSD symptomatology over time and can modify odds of a chronic course. Clinicians could better identify cases at risk of a chronic PTSD course. Finally, treatment as usual appeared related to a better outcome and should be proposed to patients with PTSD.

Exposure to trauma reminders has been considered imperative in psychotherapy for posttraumatic stress disorder (PTSD). The authors tested interpersonal psychotherapy (IPT), which has demonstrated antidepressant efficacy and shown promise in pilot PTSD research as a non-exposure-based non-cognitive-behavioral PTSD treatment. The authors conducted a randomized 14-week trial comparing IPT, prolonged exposure (an exposure-based exemplar), and relaxation therapy (an active control psychotherapy) in 110 unmedicated patients who had chronic PTSD and a score >50 on the Clinician-Administered PTSD Scale (CAPS). Randomization stratified for comorbid major depression. The authors hypothesized that IPT would be no more than minimally inferior (a difference <12.5 points in CAPS score) to prolonged exposure. All therapies had large within-group effect sizes (d values, 1.32-1.88). Rates of response, defined as an improvement of >30% in CAPS score, were 63% for IPT, 47% for prolonged exposure, and 38% for relaxation therapy (not significantly different between groups). CAPS outcomes for IPT and prolonged exposure differed by 5.5 points (not significant), and the null hypothesis of more than minimal IPT inferiority was rejected (p=0.035). Patients with comorbid major depression were nine times more likely than nondepressed patients to drop out of prolonged exposure therapy. IPT and prolonged exposure improved quality of life and social functioning more than relaxation therapy. This study demonstrated noninferiority of individual IPT for PTSD compared with the gold-standard treatment. IPT had (nonsignificantly) lower attrition and higher response rates than prolonged exposure. Contrary to widespread clinical belief, PTSD treatment may not require cognitive-behavioral exposure to trauma reminders. Moreover, patients with comorbid major depression may fare better with IPT than with prolonged exposure.