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 1.7mg of prazosin (SD = 0.5) and 2.0mg 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 psycho-therapies might demonstrate further benefit. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVES: Although there have been important advances in the treatment of posttraumatic stress disorder (PTSD), many patients fail to respond to first-line pharmacotherapy. Limited evidence suggests that second generation antipsychotics may have a role to play as monotherapy in PTSD. METHODS: We undertook a randomized, placebo-controlled study using flexible-dose olanzapine monotherapy for 8 weeks in 28 adult male and female participants (mean age: 40.75 ± 11.59 years) with non-combat related chronic PTSD. Data were analysed with repeated measures analysis of variance, using an intention to treat, last observation carried forward approach. RESULTS: The olanzapine group (<i>n</i> = 14) demonstrated significantly greater improvement on the Clinician Administered PTSD Scale from baseline to endpoint than the placebo group (<i>n</i> = 14) (<i>F</i> = 5.71, <i>p</i> = 0.018). Olanzapine was generally well tolerated, with no serious adverse events recorded. Substantial weight gain (6–10 kg) was, however, reported in 6/14 participants in the olanzapine group. CONCLUSIONS: To our knowledge, this is the first controlled evidence of the efficacy of olanzapine monotherapy in an exclusively non-combat related chronic PTSD group. Despite the small sample size, these data suggest that olanzapine may have a role in the treatment of PTSD. These findings warrant replication in a larger sample. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
The wars in Iraq and Afghanistan are associated with high rates of post-traumatic stress disorder (PTSD) and comorbid alcohol use disorders. The pharmacotherapy of these comorbid conditions has received relatively little study. The current study compared the serotonin uptake inhibitor, paroxetine, to the norepinephrine uptake inhibitor, desipramine. It also evaluated the adjunctive efficacy of the Food and Drug Administration (FDA)-approved alcoholism pharmacotherapy, naltrexone, relative to placebo. Four groups of predominately male veterans (<i>n</i> = 88) meeting current diagnostic criteria for both alcohol dependence (AD) and PTSD were randomly assigned under double-blind conditions to one of four groups, paroxetine + naltrexone, paroxetine + placebo, desipramine + naltrexone; desipramine + placebo. Main outcome measures included standardized scales that assessed symptoms of PTSD and alcohol consumption. Paroxetine did not show statistical superiority to desipramine for the treatment of PTSD symptoms. However, desipramine was superior to paroxetine with respect to study retention and alcohol use outcomes. Naltrexone reduced alcohol craving relative to placebo, but it conferred no advantage on drinking use outcomes. Although the serotonin uptake inhibitors are the only FDA-approved medications for the treatment of PTSD, the current study suggests that norepinephrine uptake inhibitors may present clinical advantages when treating male veterans with PTSD and AD. However, naltrexone did not show evidence of efficacy in this population. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
BACKGROUND: Unlike civilian post-traumatic stress disorder (PTSD), the efficacy of sertraline for the treatment of combat-related PTSD has not yet been proven. The present study aimed to evaluate the clinical efficacy of sertraline against combat-related PTSD in a randomized, double-blind, placebo-controlled trial. METHOD: Seventy Iranian veterans of the Iran-Iraq war who met the DSM-IV criteria for diagnosis of PTSD were randomized to receive either flexibly dosed sertraline (50-200 mg/day) (<i>n</i> = 35, completers = 32) or placebo (<i>n</i> = 35, completers = 30) for 10 weeks. Efficacy was evaluated by the Impact of Event Scale—Revised (IES-R) and the Clinical Global Impression scale—Severity (CGI-S) and Improvement (CGI-I) ratings. Responder criteria were defined as a ≥30% reduction in the IES-R total score plus a CGI-I rating of 'much' or 'very much' improved. RESULTS: On both intention-to-treat (ITT) and per protocol (completer) methods of analysis, the mean reductions in the IES-R total and subscale (re-experiencing/intrusion, avoidance/numbing and hyperarousal) scores (<i>p</i> < 0.001) and also in the CGI-S score (<i>p</i> < 0.01) were significantly greater in the sertraline group than in the placebo group. For the CGI-I, the mean endpoint score was significantly lower in the sertraline group than in the placebo group (<i>p</i> ≤ 0.001). The number of responders in the sertraline group was significantly higher than in the placebo group (44% <i>v.</i> 3%, <i>p</i> ≤ 0.001). Sertraline was well tolerated, with a 6% discontinuation rate as a result of adverse reactions. CONCLUSIONS: The results of this study suggest that sertraline can be an effective, safe and tolerable treatment for combat-related PTSD in Iranian veterans. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
OBJECTIVE: To evaluate the efficacy and tolerability of topiramate in patients with posttraumatic stress disorder (PTSD). METHOD: We conducted a 12-week double-blind, randomized, placebo-controlled study comparing topiramate to placebo. Men and women aged 18–62 years with diagnosis of PTSD according to DSM-IV were recruited from the outpatient clinic of the violence program of Federal University of São Paulo Hospital (Prove-UNIFESP), S˜ao Paulo City, between April 2006 and December 2009. Subjects were assessed for the Clinician-Administered Posttraumatic Stress Scale (CAPS), Clinical Global Impression, and Beck Depression Inventory (BDI). After 1-week period of washout, 35 patients were randomized to either group. The primary outcome measure was the CAPS total score changes from baseline to the endpoint. RESULTS: 82.35% of patients in the topiramate group exhibited improvements in PTSD symptoms. The efficacy analysis demonstrated that patients in the topiramate group exhibited significant improvements in reexperiencing symptoms: flashbacks, intrusive memories, and nightmares of the trauma (CAPS-B; <i>P</i> = 0.04) and in avoidance/numbing symptoms associated with the trauma, social isolation, and emotional numbing (CAPS-C; <i>P</i> = 0.0001). Furthermore, the experimental group demonstrated a significant difference in decrease in CAPS total score (topiramate −57.78; placebo −32.41; <i>P</i> = 0.0076). Mean topiramate dose was 102.94 mg/d. Topiramate was generally well tolerated. CONCLUSION: Topiramate was effective in improving reexperiencing and avoidance/ numbing symptom clusters in patients with PTSD. This study supports the use of anticonvulsants for the improvement of symptoms of PTSD. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
CONTEXT: Serotonin reuptake-inhibiting (SRI) antidepressants are the only FDA-approved pharmacotherapies for the treatment of posttraumatic stress disorder (PTSD). OBJECTIVE: To determine efficacy of the second-generation antipsychotic risperidone as an adjunct to ongoing pharmacologic and psychosocial treatments for veterans with chronic military-related PTSD. Design, Setting, and Participants: A 6-month, randomized, double-blind, placebo-controlled multicenter trial conducted between February 2007 and February 2010 at 23 Veterans Administration outpatient medical centers. Of the 367 patients screened, 296 were diagnosed with military-related PTSD and had ongoing symptoms despite at least 2 adequate SRI treatments, and 247 contributed to analysis of the primary outcome measure. Intervention: Risperidone (up to 4 mg once daily) or placebo. MAIN OUTCOME MEASURES: The Clinician-Administered PTSD Scale (CAPS) (range, 0-136). Other measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAMA), Clinical Global Impression scale (CGI), and Veterans RAND 36-Item Health Survey (SF-36V). RESULTS: Change in CAPS scores from baseline to 24 weeks in the risperidone group was −16.3 (95% CI, −19.7 to −12.9) and in the placebo group, −12.5 (95% CI, −15.7 to −9.4); the mean difference was 3.74 (95% CI, −0.86 to 8.35; <i>t</i> = 1.6; <i>P</i> = .11). Mixed model analysis of all time points also showed no significant difference in CAPS score (risperidone: mean, 64.43; 95% CI, 61.98 to 66.89, vs placebo: mean, 67.16; 95% CI, 64.71 to 69.62; mean difference, 2.73; 95% CI, −0.74 to 6.20; <i>P</i> = .12). Risperidone did not reduce symptoms of depression (MADRS mean difference, 1.19; 95% CI, −0.29 to 2.68; <i>P</i> = .11) or anxiety (HAMA mean difference, 1.16; 95% CI, −0.18 to 2.51; <i>P</i> = .09; patient-rated CGI mean difference, 0.20; 95% CI, −0.06 to 0.45; <i>P</i> = .14; observer-rated CGI mean difference, 0.18; 95% CI, 0.01 to 0.34; <i>P</i> = .04), or increase quality of life (SF-36V physical component mean difference, −1.13, 95% CI, −2.58 to 0.32; <i>P</i> = .13; SF-36V mental component mean difference, −0.26; 95% CI, −2.13 to 1.61; <i>P</i> = .79). Adverse events were more common with risperidone vs placebo, including self-reported weight gain (15.3% vs 2.3%), fatigue (13.7% vs 0.0%), somnolence (9.9% vs 1.5%), and hypersalivation (9.9% vs 0.8%), respectively. CONCLUSION: Among patients with military-related PTSD with SRI-resistant symptoms, 6-month treatment with risperidone compared with placebo did not reduce PTSD symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
The substance P-neurokinin-1 receptor (SP-NK1R) system has been extensively studied in experimental models of stress, fear, and reward. Elevated cerebrospinal fluid (CSF) SP levels were reported previously in combat-related PTSD. No medication specifically targeting this system has been tested in PTSD. This proof-of-concept randomized, double-blind, placebo-controlled trial evaluated the selective NK1R antagonist GR205171 in predominately civilian PTSD. Following a 2-week placebo lead-in, 39 outpatients with chronic PTSD and a Clinician-Administered PTSD Scale (CAPS) score ≥ 50 were randomized to a fixed dose of GR205171 (<i>N</i> =20) or placebo (<i>N</i> =19) for 8weeks. The primary endpoint was mean change from baseline to endpoint in the total CAPS score. Response rate (≥ 50% reduction in baseline CAPS) and safety/tolerability were secondary endpoints. CSF SP concentrations were measured in a subgroup of patients prior to randomization. There was significant improvement in the mean CAPS total score across all patients over time, but no significant difference was found between GR205171 and placebo. Likewise, there was no significant effect of drug on the proportion of responders [40% GR205171 versus 21% placebo (<i>p</i> =0.30)]. An exploratory analysis showed that GR205171 treatment was associated with significant improvement compared to placebo on the CAPS hyperarousal symptom cluster. GR205171 was well-tolerated, with no discontinuations due to adverse events. CSF SP concentrations were positively correlated with baseline CAPS severity. The selective NK₁R antagonist GR205171 had fewer adverse effects but was not significantly superior to placebo in the short-term treatment of chronic PTSD. (ClinicalTrials.gov Identifier: NCT 00211861, NCT 00383786). (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Background: Posttraumatic stress disorder (PTSD) is a debilitating and disabling mental disorder that afflicts at least 25% of Veterans who have suffered life-threatening war zone trauma. Trauma-related nightmares and sleep disturbance are among the most treatment-resistant PTSD symptoms in Veterans. Increased responsiveness to central nervous system (CNS) norepinephrine (NE) contributes to the pathophysiology of overall PTSD and treatment-resistant nighttime symptoms. Placebo-controlled pilot studies demonstrate that the generically available CNS-active alpha-1 adrenoreceptor antagonist prazosin substantially reduces PTSD trauma nightmares and sleep disturbance and improves global clinical status (sense of well being and ability to function) in Veterans.
Objective: The primary objective is to demonstrate in a large multi-site placebo-controlled trial in Veterans with war zone trauma-induced PTSD that prazosin is efficacious for PTSD trauma nightmares, sleep disturbance, and global clinical status. A secondary objective is to demonstrate prazosin effectiveness for these outcome measures during clinically meaningful long-term (26 week) maintenance treatment of PTSD. The investigators will also address prazosin efficacy and long-term effectiveness for improving total PTSD symptoms, comorbid depression, quality of life, and physical functioning.
Methods: This 26 week randomized double-blind placebo-controlled study is designed to demonstrate both short term efficacy and long term effectiveness of prazosin for PTSD. The research design encompasses a shorter-term, more tightly controlled efficacy component and a longer-term, more .real world. effectiveness component. Three hundred twenty-six Veterans with war zone -related PTSD and persistent trauma nightmares will be randomized 1:1 to prazosin or placebo. Study drug will be increased using a flexible dose titration schedule based on clinical response and adverse effects to an optimum maintenance dose (1-20 mg/day). During the first 10 weeks of the study, participants will be randomized to prazosin or placebo. Previous psychotropic medications and/or psychotherapy will be maintained constant. Short term efficacy will be determined during the first 10 weeks. During the remaining 16 weeks of the 26 week trial, subjects will continue to receive stable-dose double-blind prazosin or placebo, but will have the option to receive additional psychotropic medications and/or psychotherapeutic interventions, as needed, per the judgment of the study Clinician Prescriber. It is hypothesized that prazosin will remain more clinically effective than placebo at the end of the 26-week trial, demonstrating that prazosin adds benefit over-and-above other treatments that are naturalistically administered by providers in a .real world. clinical setting.
Prazosin will be judged efficacious at 10 weeks if superior to placebo on all three primary outcome measures assessing trauma nightmares, sleep disturbance, and global clinical status: the Recurrent Distressing Dreams item of the Clinician Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index (PSQI), and the Clinical Global Impression of Change (CGIC). Secondary outcome measures will assess prazosin effects on total PTSD symptoms, depression, physical functioning, and quality of life. Adverse effects and cardiovascular measures, including supine and standing blood pressure (BP) and heart rate (HR) will be assessed.
