Delayed-onset posttraumatic stress disorder with response to methylphenidate / Trastorno por estrés postraumático de expresión retardada con respuesta a metilfenidato

Introduction: Posttraumatic stress disorder (PTSD) is extremely frequent in war veterans and has been widely studied. However, the efficacy of currently available pharmacological and psychotherapeutic treatments of war PTSD and other causes of PTSD is very limited. Method We present a case of war PTSD with delayed expression, with a good response to complementation with methylphenidate after a failed treatment with venlafaxine and risperidone. Results We review the role of dopamine in the pathophysiology of PTSD and the scarce studies in the treatment of PTSD with dopaminergic drugs that show an improvement in re-experimentation and in affective symptoms, especially anhedonia and cognitive impairment. Conclusions We conclude that the use of methylphenidate and other dopaminergic drugs can be a promising treatment for PTSD, a high prevalent disease with a high resistance to treatment, for which we encourage the use of large sample studies. (AU)

Introducción: El trastorno por estrés postraumático (TEPT) es extremadamente prevalente en veteranos de guerra y ha sido ampliamente estudiado. Sin embargo, la eficacia de los tratamientos farmacológicos y psicoterapéuticos disponibles es aún muy limitada, tanto en el TEPT de guerra como en el TEPT por otras causas. Método Presentamos un caso de TEPT de guerra con expresión retardada, con una buena respuesta al metilfenidato a su tratamiento con venlafaxina y risperidona, que había resultado ineficaz. Resultados Revisamos el rol de la dopamina en la psicopatología del TEPT y los pocos estudios del tratamiento del TEPT con fármacos dopaminérgicos, en los que se muestra una mejoría en los síntomas de reexperimentación y los síntomas afectivos, especialmente la anhedonia y los déficits cognitivos secundarios. Conclusiones Consideramos que el uso del metilfenidato y de otros fármacos dopaminérgicos podrían ser prometedores el tratamiento del TEPT, un trastorno altamente prevalente y con alta resistencia al tratamiento habitual. Por esto, animamos a realizar estudios con muestras amplias. (AU)

Novel Pharmacological Targets for Combat PTSD-Metabolism, Inflammation, The Gut Microbiome, and Mitochondrial Dysfunction.

INTRODUCTION: Current pharmacological treatments of post-traumatic stress disorder (PTSD) have limited efficacy. Although the diagnosis is based on psychopathological criteria, it is frequently accompanied by somatic comorbidities and perhaps "accelerated biological aging," suggesting widespread physical concomitants. Such physiological comorbidities may affect core PTSD symptoms but are rarely the focus of therapeutic trials. METHODS: To elucidate the potential involvement of metabolism, inflammation, and mitochondrial function in PTSD, we integrate findings and mechanistic models from the DOD-sponsored "Systems Biology of PTSD Study" with previous data on these topics. RESULTS: Data implicate inter-linked dysregulations in metabolism, inflammation, mitochondrial function, and perhaps the gut microbiome in PTSD. Several inadequately tested targets of pharmacological intervention are proposed, including insulin sensitizers, lipid regulators, anti-inflammatories, and mitochondrial biogenesis modulators. CONCLUSIONS: Systemic pathologies that are intricately involved in brain functioning and behavior may not only contribute to somatic comorbidities in PTSD, but may represent novel targets for treating core psychiatric symptoms.

Understanding the impact of complicated grief on combat related posttraumatic stress disorder, guilt, suicide, and functional impairment in a clinical trial of post-9/11 service members and veterans.

BACKGROUND: Complicated grief (CG) is a bereavement-specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes. METHODS: To evaluate the impact of comorbid CG on PTSD treatment outcomes we analyzed data from a randomized trial comparing prolonged exposure, sertraline, and their combination in veterans with a primary diagnosis of combat-related PTSD (n = 194). Assessment of PTSD, trauma-related guilt, functional impairment, and suicidal ideation and behavior occurred at baseline and weeks 6, 12, and 24 during the 24-week trial. RESULTS: CG was associated with lower PTSD treatment response (odds ratio (OR) = 0.29, 95% confidence interval (CI) [0.12, 0.69], p = 0.005) and remission (OR = 0.28, 95% CI [0.11, 0.71], p = 0.007). Those with CG had greater severity of PTSD (p = 0.005) and trauma-related guilt (<0.001) at baseline and endpoint. In addition, those with CG were more likely to experience suicidal ideation during the study (CG: 35%, 14/40 vs. no CG 15%, 20/130; OR = 3.01, 95% CI [1.29, 7.02], p = 0.011). CONCLUSIONS: Comorbid CG is associated with elevated PTSD severity and independently associated with poorer endpoint treatment outcomes in veterans with combat-related PTSD, suggesting that screening and additional intervention for CG may be needed.

Enhancing Completion of Cognitive Processing Therapy for Posttraumatic Stress Disorder with Quetiapine in Veterans with Mild Traumatic Brain Injury: a Case Series.

To evaluate the outcomes of the antiarousal medications valproate, risperidone, and quetiapine on completion of treatment of cognitive processing therapy (CPT) for PTSD. A case series of fifty treatment-seeking adult (≥18 years) veterans with mild traumatic brain injury and combat-related PTSD who had unsuccessful trials of 2 or more first-line agents and previously declined treatment with trauma-focused therapy, seen at the psychiatric outpatient services of the local Polytrauma Rehabilitation Center from January 1, 2014, through December 31, 2017. Patients were prescribed valproate (n = 8), risperidone (n = 17), or quetiapine (n = 25) and were referred for individual weekly treatment with CPT. Outcome measurements of interest were measures of engagement and completion rate of CPT, PTSD Checklist total score (range, 0-80; higher scores indicate greater PTSD severity) and arousal subscale score (range, 0-24; higher scores indicate greater arousal severity), and clinical observations of sleep variables. Of the 50 patients included in the study, 48 (96%) were men; mean (SD) age was 36 (8) years. Eighteen (86%) patients initially receiving quetiapine and none taking valproate or risperidone became adequately engaged in and completed CPT. Among patients who completed CPT, the mean decrease in the PTSD Checklist score was 25 [95% CI, 30 to 20] and 9 (50%) patients no longer met criteria for PTSD. These preliminary findings support quetiapine as an adjunctive medication to facilitate CPT. A pragmatic trial is needed to evaluate the efficacy, safety, and feasibility of quetiapine to improve engagement in and completion rate of CPT.

Characterizing the Effects of Quetiapine in Military Post-Traumatic Stress Disorder.

Objectives: A previous randomized placebo-controlled trial in military veterans posttraumatic stress disorder (PTSD) found that quetiapine improved global PTSD symptoms severity, depression and anxiety as well as the re-experiencing and hypearousal clusters. However, it is not known if individual symptoms had a preferential response to this medication. The goal of this study was to analyze the individual symptom response in this group of patients. Methods: Data from a previous trial was re-analyzed. Each of the of the scale items was analyzed individually using Repeated Measures Analysis of Variance. Results: Compared to placebo, there was a significant decline in the Clinician-Administered PTSD Scale intrusive memories and insomnia questions. In the Davidson Trauma Scale, greater improvements were observed on irritability, difficulty concentrating, hyperstartle and a trend was observed on avoiding thoughts or feelings about the event. Greater improvements compared with placebo were noted on the Hamilton Depression (HAM-D) middle and late insomnia items. On the Hamilton Anxiety scale (HAM-A), the insomnia item was significantly improved. Conclusions: Quetiapine demonstrated greater effect than placebo on several symptoms. The strongest response was seen on insomnia, which the highest significance level on the CAPS. The insomnia items of both the HAM-D and HAM-A also demonstrated improvement with quetiapine. These finding indicate quetiapine improved sleep measure. Insomnia can be a difficult problem to treat in PTSD patients, therefore quetiapine should be considered in difficult cases.

Anticonvulsant Medication Use in Veterans With Posttraumatic Stress Disorder.

OBJECTIVE: Anticonvulsants have been studied for many indications, including posttraumatic stress disorder (PTSD). The limited efficacy research on anticonvulsants for PTSD is mixed. However, anticonvulsants are prescribed widely to veterans with PTSD. Our objective was to measure trends and factors associated with anticonvulsant prescriptions among veterans with PTSD. METHODS: We obtained administrative and pharmacy data for veterans who initiated PTSD treatment in the US Department of Veterans Affairs (VA) between 2004 and 2013 (N = 731,520). We identified those who received anticonvulsants during the year following their initial clinical PTSD diagnosis and examined common indications for anticonvulsant use, patient characteristics, and service use characteristics. Using logistic regression, we determined the predictors of anticonvulsant initiation among those without an indication. RESULTS: Although 24.9% of patients in the cohort received an anticonvulsant during their initial year of PTSD treatment, 94.6% had an indication unrelated to PTSD and 51.2% initiated anticonvulsant use before their PTSD diagnosis. While there was growth in anticonvulsant initiation over the 10-year period, this was explained both by growth in indications unrelated to PTSD and by increased use of anticonvulsants for these indications. The rate of anticonvulsant initiation without an indication was stable at approximately 5% throughout the period, with patient and service use characteristics driving the selection of individual agents. CONCLUSIONS: A large and increasing proportion of veterans with PTSD receives anticonvulsant prescriptions. However, this may be appropriate use driven by increased prevalence of comorbid conditions that may be an indication for anticonvulsant use, including pain and headache disorders.

Effect of Rivastigmine Augmentation in Treatment of Male Patients With Combat-Related Chronic Posttraumatic Stress Disorder: A Randomized Controlled Trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) is one of the chronic and disabling psychiatric disorders, particularly in combat veterans. In a case series, rivastigmine was suggested to be an effective augmentation in treatment of PTSD. The aim of the present study was to evaluate this finding in a randomized controlled trial. METHOD: A 12-week, double-blind, placebo-controlled clinical trial was performed on 36 male patients (aged 42-60 years) diagnosed with chronic, combat-related PTSD. Subjects were screened for apparent cognitive deficits by means of Mini-Mental State Examination. All patients received selective serotonin reuptake inhibitors plus sodium valproate for 4 weeks and then reevaluated. Subjects who did not show adequate response were randomly assigned into 3 groups receiving rivastigmine (up to 6 mg/d), placebo, or the prior treatment regimen. Efficacy of medication was measured by administering PTSD Check List-Military Version at baseline and weeks 2, 4, 8, and 12. Collected data were analyzed by analysis of variance and repeated measurement. Reported differences were considered significant at the level of 0.05 or less. RESULTS: The 3 groups showed statistically significant reductions in the total PTSD Check List-Military Version, avoidance subscale, and the reexperience subscale but not in the hyperarousal subscale. No significant differences were found between the 3 groups. CONCLUSIONS: In contrast to the previous case series, findings of the current study did not support the efficacy of adjunctive rivastigmine in treatment of PTSD. This hypothetically could be due to the fact that all the study's subjects scored higher than 25 on Mini-Mental State Examination.

Facilitating Fear-Based Memory Extinction With Dexamethasone: A Randomized Controlled Trial in Male Veterans With Combat-Related PTSD.

OBJECTIVE: Animal and preliminary human studies have demonstrated that glucocorticoids enhance the extinction of fear memories. Impaired extinction of fear memories is a critical component in the development and maintenance of posttraumatic stress disorder (PTSD). The purpose of this translational study was to determine the effectiveness of pairing a glucocorticoid with trauma memory reactivation as a novel intervention to treat PTSD and to measure the duration of the effect. METHOD: A total of 54 male veterans with combat-related PTSD in this double-blind, randomized, placebo-controlled trial received either four weekly glucocorticoid (dexamethasone [DEX]) or placebo administrations paired with a 45-second trauma memory reactivation task. PTSD and depressive symptom severity were assessed at baseline and at one three, and six months. RESULTS: Trauma memory activation paired with DEX versus trauma memory activation paired with placebo demonstrated a significantly greater reduction of PTSD symptoms for DEX at the one-month (p = .037) and three-month (p = .036) posttreatment assessments, but the difference was no longer evident at six months. DEX showed a nonsignificantly greater reduction of PTSD symptoms than placebo over the course of the study (p = .067). Significantly more veterans in the DEX group lost their diagnosis of PTSD at one month posttreatment compared to the placebo group, but the difference was not maintained at three or six months. DEX had no effect on depression symptoms. CONCLUSIONS: Despite insufficient power to test differences in PTSD symptom reduction, findings suggest that this novel intervention may have potential for treatment of combat-related PTSD.

Higher Pretreatment Blood Pressure Is Associated With Greater Posttraumatic Stress Disorder Symptom Reduction in Soldiers Treated With Prazosin.

BACKGROUND: In a previously reported positive randomized controlled trial of the α1-adrenoreceptor (α1AR) antagonist prazosin for combat posttraumatic stress disorder (PTSD) in 67 active duty soldiers, baseline symptoms did not predict therapeutic response. If increased brain α1AR activation in PTSD is the target of prazosin treatment action, higher brain α1AR activation should predict greater prazosin efficacy. Although brain α1AR activation is not measurable, coregulated peripheral α1AR activation could provide an estimate of brain α1AR activation. Standing blood pressure (BP) is an accessible biological parameter regulated by norepinephrine activation of α1ARs on peripheral arterioles. METHODS: Effects of baseline standing systolic and other BP parameters on PTSD outcome measures from the previously reported randomized controlled trial were analyzed using linear mixed-effects models. Prazosin participants (n = 32) and placebo participants (n = 35) were analyzed separately. RESULTS: In prazosin participants, each 10-mm Hg higher baseline standing systolic BP increment resulted in an additional 14-point reduction (improvement) of Clinician-Administered PTSD Scale total score at end point (p = .002). All other combinations of baseline BP parameters and PTSD outcome measures were similarly significant or demonstrated trends in the predicted direction. In placebo participants, there was no signal for a baseline BP effect on PTSD outcome measures. CONCLUSIONS: These findings suggest that higher standing BP is a biomarker that helps identify persons with combat PTSD who are likely to benefit from prazosin. These results also are consistent with α1AR activation contributing to PTSD pathophysiology in a subgroup of patients.

Sleep disturbance in chronic military-related PTSD: clinical impact and response to adjunctive risperidone in the Veterans Affairs cooperative study #504.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00099983.

Amphetamine-Type Stimulants: The Early History of Their Medical and Non-Medical Uses.

Amphetamine was discovered as a drug in the late 1920s, and its pharmacological effects on attention and cognition, emotions, and appetite were explored thoroughly in the 1930s and 1940s. By the late 1940s, it had achieved medical and market success as an antidepressant and was quickly gaining such success as a diet medication. In contrast, both careful testing and extensive military experience had left the impression that the drugs' benefits for attention and cognition were more subjective than real and that any objective benefits were explained mainly by the drug's mood-elevating effects. Because of its unpatentable status, methamphetamine had been introduced for all the same uses by drug firms competing with the holder of the amphetamine patent. The drugs were being widely used nonmedically and their abuse potential was becoming recognized by medicine, eventually leading to their strict control internationally around 1970.

Effects of Pharmacotherapy on Combat-Related PTSD, Anxiety, and Depression: A Systematic Review and Meta-Regression Analysis.

OBJECTIVES: To estimate the effect of pharmacotherapy on PTSD, anxiety, and depression among combat veterans; to determine whether the effects varied according to patient and intervention characteristics; and to examine differential effects of pharmacotherapy on outcomes. MATERIALS AND METHODS: Google Scholar, PILOTS, PsycINFO, PubMed, and Web of Science databases were searched through November 2014. Searches resulted in eighteen double-blind, placebo controlled trials of 773 combat veterans diagnosed with PTSD and included only validated pre- and post-intervention PTSD and anxiety or depression measures. Authors extracted data on effect sizes, moderators, and study quality. Hedges' d effect sizes were computed and random effects models estimated sampling error and population variance. The Johnson-Neyman procedure identified the critical points in significant interactions to define regions of significance. RESULTS: Pharmacotherapy significantly reduced (Δ, 95%CI) PTSD (0.38, 0.23-0.52), anxiety (0.42, 0.30-0.54), and depressive symptoms (0.52, 0.35-0.70). The effects of SSRIs and tricyclic antidepressants on PTSD were greater than other medications independent of treatment duration. The effect of SSRIs and tricyclic antidepressants were greater than other medications up to 5.2 and 13.6 weeks for anxiety and depression, respectively. The magnitude of the effect of pharmacotherapy on concurrently-measured PTSD, anxiety, and depression did not significantly differ. CONCLUSIONS: Pharmacotherapy reduced PTSD, anxiety, and depressive symptoms in combat veterans. The effects of SSRIs and tricyclic antidepressants were greater for PTSD and occurred quicker for anxiety and depression than other medications.

Antipsychotic prescriptions in Iraq and Afghanistan veterans with posttraumatic stress disorder in Department of Veterans Affairs healthcare, 2007-2012.

OBJECTIVE: Antipsychotic medications have been increasingly prescribed for off-label uses, including treatment of posttraumatic stress disorder (PTSD). Given limited knowledge about their use in returning Iraq and Afghanistan veterans with PTSD, we explored rates of antipsychotic use in this population and correlations with sociodemographic, military service, and psychiatric factors. METHOD: Iraq and Afghanistan veterans with a PTSD diagnosis based on ICD-9-CM codes enrolled in Veterans Administration care between January 1, 2007, and September 30, 2011, were followed through September 30, 2012. Patients with a comorbid diagnosis of schizophrenia or bipolar disorder were excluded. Poisson regression models evaluated factors associated with prescriptions for antipsychotic versus other psychiatric medications (primary outcome). RESULTS: The mean age of our study population was 29.3 years, and 9.4% were women. Of 186,460 veterans with PTSD diagnoses examined, 19.9% received no psychiatric medications, and the remainder received psychiatric medications that excluded (61.2%) or included (18.9%) antipsychotics. In adjusted models, several factors were independently associated with antipsychotic use, including male sex (adjusted relative risk = 1.25; 95% CI, 1.20-1.30) and enlisted rank (1.44; 95% CI, 1.35-1.53). Increased likelihood of antipsychotic prescribing was associated with suicidal ideation (4.77; 95% CI, 4.59-4.95) and comorbid psychiatric diagnoses including personality disorder (4.27; 95% CI, 4.09-4.46), drug use disorder (3.56; 95% CI, 3.43-3.69), and alcohol use disorder (2.75; 95% CI, 2.65-2.84). CONCLUSIONS: A substantial minority of Iraq and Afghanistan veterans diagnosed with PTSD received antipsychotics. Male veterans, those of enlisted rank, and those with suicidal ideation and psychiatric comorbidities were more likely to receive antipsychotics than other types of psychiatric medications. Providers should be cautious about antipsychotic use, given their known metabolic risks and questionable benefits for PTSD.

Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies.

Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the ß-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.

Effect of pregabalin augmentation in treatment of patients with combat-related chronic posttraumatic stress disorder: a randomized controlled trial.

OBJECTIVE: It has been suggested that the anticonvulsant drug pregabalin may be useful in some anxiety disorders. The goal of this study was to evaluate the effectiveness of pregabalin augmentation of standard treatment (selective serotonin reuptake inhibitors and sodium valproate) for patients with chronic posttraumatic stress disorder (PTSD). METHODS: This doubleblind, placebo-controlled clinical trial was conducted at Ibn-E-Sina Psychiatric Hospital (Mashhad, Iran) in 2013. Thirty-seven male patients diagnosed with combat-related PTSD based on DSM-IV-TR criteria were randomly assigned to two groups: 18 patients, the case group, received pregabalin (300 mg/day) while 19 patients, the control group, received placebo for 6 weeks. Assessments were done at baseline and at 2, 4, and 6 weeks after the onset of treatment, using the PTSD Check List-Military Version (PCL-M), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Spitzer Quality of Life Index. RESULTS: Pregabalin was just significantly effective in improving PCL-M scores (p=0.045) in comparison to placebo. Although depression and anxiety scores diminished significantly in both groups (p=0.001 and 0.0001, respectively), comparison of the efficacy of pregabalin and placebo did not show significant differences in depression, anxiety, and quality of life scores (p=0.614, 0.144, and 0.076, respectively). CONCLUSION: Pregabalin effectively reduced the severity of PTSD symptoms but it was not effective in improving the severity of depression, anxiety, and quality of life. Further investigations are required to confirm or refute these findings.

Eicosapentaenoic acid in serum lipids could be inversely correlated with severity of clinical symptomatology in Croatian war veterans with posttraumatic stress disorder.

AIM: To explore the association between plasma fatty acids composition and the severity of clinical symptoms in Croatian war veterans with posttraumatic stress disorder (PTSD). METHODS: This cross-sectional study included 62 men diagnosed with PTSD caused by combat activities during the War in Croatia 1991-1995. Clinician-Administered PTSD Scale (CAPS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D-17) were used. Plasma fatty acids composition was determined by gas chromatography. Data about life-style habits were collected by a structured interview. To evaluate the association between plasma fatty acid levels and PTSD severity scales, multivariate general linear models (GLM) were applied while controlling for different confounders. RESULTS: Significant negative correlations were found between plasma eicosapentaenoic acid (EPA, 20:5n-3) level and the scores on psychological scales (τ = -0.326, P<0.001 for CAPS; τ-0.304, P =0 .001 for HAM-A; and τ = -0.345, P<0.001 for HAM-D-17). GLM confirmed that PTSD severity was affected by EPA (Wilks'Λ = 0.763-0.805, P = 0.006-0.018, ηp 0.195-0.237), arachidonic acid (AA)/EPA (Wilks'Λ = 0.699-0.757, P = 0.004, ηp 0.243-0.301), and dairy products consumption (Wilks'Λ = 0.760-0.791, P = 0.045-0.088, ηp 0.128-0.111). No other fatty acid or dietary/lifestyle variable was significant ( P = 0.362-0.633). CONCLUSION: The study suggests that lower EPA levels are associated with the severity of clinical symptoms in PTSD.

Symptom structure and severity: a comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia.

OBJECTIVES: To describe and compare the structure and relative severity of symptoms in clinical trial patients diagnosed with Post Traumatic Stress Disorder (PTSD) or schizophrenia using the Positive and Negative Syndrome Scale (PANSS), developed originally to evaluate symptoms of schizophrenia. METHOD: This secondary data analysis used baseline PANSS symptom ratings (n=267) from a six-month multicenter randomized placebo-controlled trial of adjunctive risperidone in patients with chronic military-related PTSD. First, using a split-half design, Exploratory Factor Analysis (EFA) was employed to identify independent factors which were then compared to published factor structures for schizophrenia. Next, Confirmatory Factor Analysis (CFA) was applied to the second half of the sample to compare the results of the EFA and published factor structures. Finally, T-tests were used to compare the severity of factor scores between the PTSD sample and the baseline PANSS ratings from the Clinical Antipsychotic Trial for Intervention Effectiveness (CATIE) schizophrenia sample (n=1460). RESULTS: EFA suggested five factors similar to those identified in a summary of 29 schizophrenia studies by Wallwork (Schizophrenia Research, 137:246-250). CFA showed that the five factor Wallwork model fit the data better than the EFA, although both had relatively high goodness of fit. T-tests showed that the PTSD sample had more severe symptoms on the Depressive factor, and the schizophrenia sample on the Positive, Negative, and Disorganized factors, with no significant difference on the Excited factor. CONCLUSION: Veterans with PTSD had similar symptom structure to patients with schizophrenia on the PANSS, but were less symptomatic on psychosis-related factors and more symptomatic on depression. Dimensional symptom factors can be virtually the same across diagnoses.

A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan.

OBJECTIVE: The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan. METHOD: Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire-9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant. RESULTS: Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups. CONCLUSIONS: Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.