Maintenance therapy with fluoxetine in posttraumatic stress disorder: a placebo-controlled discontinuation study

The effect of fluoxetine (FLU) in posttraumatic stress disorder was studied in a one-year trial. Subjects received open-label treatment for 6 months, followed by double-blind randomized treatment with FLU or placebo (PBO) for 6 months. Rates of relapse were compared using the Clinical Global Impressions of Improvement. One hundred twenty-three subjects entered open-label treatment, of whom 114 returned at least once. Sixty-two subjects were randomized to receive FLU or PBO, of whom 57 returned at least once and were analyzed. The dose of FLU ranged from 10 to 60 mg/d; at randomization, mean doses were 48.6 and 42.1 mg for FLU and PBO groups. Rates of relapse were 22% for FLU versus 50% for PBO (P = 0.02), and time to relapse on FLU was longer than for PBO (P = 0.02, log-rank statistic). The odds ratio for relapse on PBO relative to FLU was 3.50. No significant differences were found on other measures. Fluoxetine was well tolerated during double-blind treatment.     

A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study

Nefazodone is a unique serotonergic antidepressant that acts as both a presynaptic serotonin reuptake inhibitor and a postsynaptic 5-hydroxytryptamine 2A receptor antagonist. Based on the positive results of open-label trials of nefazodone, including one from our group, we tested nefazodone's efficacy in the treatment of posttraumatic stress disorder (PTSD) under placebo-controlled conditions. Forty-one patients with chronic PTSD, predominantly male combat veterans, were enrolled in a randomized, double-blind, placebo-controlled 12-week trial of nefazodone. The primary outcome measure was the Clinician-Administered PTSD Scale. Fifteen patients were randomized to placebo and 26 were randomized to nefazodone. In a repeated-measures analysis of variance with last observation carried forward, patients on nefazodone showed a significant improvement in the percentage change of Clinician-Administered PTSD Scale Total score from baseline compared with those on placebo (P = 0.04; effect size = 0.6). Sample size was not powered to test group differences in the Clinician-Administered PTSD Scale criterion B, C, or D subscale. However, the criterion D subscale showed significant improvement in patients treated with nefazodone compared with those treated with placebo (P = 0.007). In addition, the Hamilton Rating Scale for Depression showed significant improvement compared with placebo (P = 0.008). The nefazodone group also reported an improvement on the PTSD Checklist (self-report scale; P = 0.08) and the Clinician-Administered Dissociative States Scale (P = 0.06). This pilot study supports the efficacy of nefazodone for the treatment of PTSD. However, larger placebo-controlled studies in more diverse patient population are warranted.     

Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder

The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of "much" or "very much" improved. The baseline CAPS-2 total severity score was 94.3 +/- 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 +/- 0.3 for sertraline and 3.4 +/- 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (chi2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (>or=30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (chi2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response.     

Failed efficacy of fluoxetine in the treatment of posttraumatic stress disorder: results of a fixed-dose, placebo-controlled study

A multicenter, double-blind, 12-week, placebo-controlled trial of 411 randomized patients, predominantly women diagnosed with posttraumatic stress disorder, failed to show a difference between either dose of fluoxetine treatment and placebo. The mean changes from baseline (SD) measured by the Clinician-Administered PTSD Scale scores were -42.9 (23.1), -42.8 (27.9), and -36.6 (25.7) in the 20-mg fluoxetine, 40-mg fluoxetine, and placebo arms, respectively. Placebo response rate was substantially higher in this study than in a previously published fluoxetine trial of posttraumatic stress disorder.     

Resilience as a predictor of treatment response in patients with posttraumatic stress disorder treated with venlafaxine extended release or placebo

This post-hoc analysis evaluated resilience as a predictor of treatment response in patients with posttraumatic stress disorder (PTSD). Data were pooled from two randomized, double-blind studies conducted with adult outpatients treated with flexible doses of venlafaxine extended release (ER) 37.5 to 300 mg/day or placebo. The 17-item Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS-SX(17)) was the primary outcome measure. Baseline Connor-Davidson Resilience Scale (CD-RISC) scores for the 25-, 10-, and 2-item versions were used to predict changes in PTSD symptom severity at week 12 and symptomatic remission (CAPS-SX(17) ≤ 20). Analyses were conducted for the overall population and separately for the individual treatment groups. In total, pretreatment resilience predicted a positive treatment response. For the overall population, all versions of the CD-RISC predicted CAPS-SX(17) change scores and remission after controlling for variables such as treatment group and baseline symptom severity. For venlafaxine ER-treated patients, all versions of the CD-RISC were predictive of remission, but only the 10-item version was predictive of CAPS-SX(17) change score. Our results suggest that higher pretreatment resilience is generally associated with a positive treatment response. Future research may be warranted to explore the relationship between response to active treatment and the spectrum of resiliency.     

Effects of venlafaxine extended release on resilience in posttraumatic stress disorder: an item analysis of the Connor-Davidson Resilience Scale

The aim was to evaluate the efficacy of venlafaxine extended release (ER) on characteristics of resilience, measured by the Connor-Davidson Resilience Scale, in patients with posttraumatic stress disorder (PTSD). Data were evaluated from a randomized, 6-month, international, multicenter study of adult outpatients with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PTSD for >or=6 months, and 17-item Clinician-Administered PTSD Scale score >or=60. Patients were assigned randomly to treatment with flexible-dose venlafaxine ER (37.5-300 mg/day) or placebo. Changes from baseline scores and effect sizes of response to treatment with venlafaxine ER compared with placebo were computed for each item, as well as for the newly developed 2-item and 10-item subscales. Effect sizes across items ranged from 0.41 (moderate) to 0.08 (very weak). The effect size for the Resilience Scale-2 (2-item subscale) was 0.32, which was comparable to the effect sizes of 0.35 for the 25-item full scale and 0.34 for the 10-item subscale. Venlafaxine ER improved resilience on individual Connor-Davidson Resilience Scale items that reflect four factors (hardiness, persistence/tenacity, social support, and faith in a benevolent or meaningful world), to varying degrees in patients with PTSD. The findings suggest that assessment of treatment response might be enhanced by routine evaluation of resilience.     

Divalproex in the treatment of posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial in a veteran population

OBJECTIVE: To evaluate the efficacy of divalproex for the treatment of posttraumatic stress disorder (PTSD) hyperarousal symptom cluster. METHOD: Under double-blind conditions, 85 US military veterans with PTSD were randomized to treatment with divalproex or placebo for 8 weeks. All patients who received at least 1 dose of medication and 1 postbaseline assessment (n = 82) were included in the efficacy population. The primary outcome measure was the hyperarousal subscale of the Clinician-Administered PTSD Scale. RESULT: There were no significant intergroup differences in primary or secondary end points. The final mean (SD) divalproex dose and serum valproic acid level were 2309 +/- 507 mg/d and 82 +/- 30 mg/L, respectively. CONCLUSIONS: Divalproex monotherapy was not effective in the treatment of chronic PTSD in predominantly older male combat veterans. Further study is needed to determine the efficacy of divalproex in the management of PTSD in women or civilians or in combination with antidepressants.     

A placebo-controlled trial of guanfacine for the treatment of posttraumatic stress disorder in veterans

Preclinical and clinical studies demonstrate a hyperactivity of the norepinephrine system in patients with posttraumatic stress disorder (PTSD). a(2) adrenergic agonists have been shown to ameliorate symptoms of PTSD, likely because of their ability to dampen noradrenergic tone. This study tests the ability of the a(2) adrenergic agonist, guanfacine, to reduce the symptoms of PTSD. Experimental Design: Patients with chronic PTSD were randomized (1:1) to an 8-week double-blind, placebo-controlled treatment of guanfacine followed by a 2 month open label extension phase. Patients were maintained on their stable doses of allowed antidepressants during the trial. Efficacy was measured by the following assessment scales: Clinician Administered PTSD Scale (CAPS), Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Davidson Trauma Scale (DTS, self-report). Principal Observations: There were no significant differences in the drug versus placebo responses for the clinician-administered or patient self-report outcome measures in this small sample of predominantly male combat veterans with PTSD. However, the medication was well tolerated. Similar to previous findings, this small pilot study failed to show differences in the response to guanfacine versus placebo in a small sample of predominantly male combat veterans with PTSD.     

A placebo-controlled trial of bupropion SR in the treatment of chronic posttraumatic stress disorder

OBJECTIVE: Although selective serotonin reuptake inhibitors have been the most empirically studied pharmacotherapy for posttraumatic stress disorder (PTSD), a need remains for the investigation of additional pharmacological agents in the treatment of PTSD. The present study examined the use of bupropion sustained release (SR) as compared with placebo for symptom reduction in patients with PTSD: approximately half who were already prescribed an selective serotonin reuptake inhibitor and half who were not. METHOD: Thirty patients (mean age, 50 years) with civilian- or military-related PTSD enrolled in an 8-week evaluation of bupropion SR versus placebo assigned in a 2:1 ratio in addition to their usual pharmacological care. Statistical tests included analyzing both study completers and using an intent-to-treat analysis, as well as post hoc examination of responders versus nonresponders. RESULTS: Although no between-group differences were detected, both groups reported a reduction in PTSD symptoms. In a hypothesis-generating post hoc analysis of responders versus nonresponders in the bupropion SR condition (defined as a Clinician Global Improvement score of at least minimally improved), it seemed that younger patients not currently on another antidepressant were more likely to benefit from bupropion. CONCLUSIONS: Bupropion SR in the treatment of PTSD had no significant effect in the current sample. Factors contributing to the absence of an effect need further study. Our analysis points to the inclusion of age and concomitant antidepressant treatment as important variables in any future larger-scale study.     

A placebo-controlled dose-response study of felodipine extended release in hypertensive patients

This placebo-controlled study assessed antihypertensive effect and tolerability of two dose levels of an extended release (ER) formulation of felodipine (Plendil), given once daily to patients in primary health care. The patients had mild to moderate hypertension and were randomized to receive felodipine ER (FER) 20 mg (n = 50), FER 10 mg (n = 50), or placebo (n = 51) in a 4-week, double-blind, parallel-group multicenter study. After 4 weeks, the 24-h reduction in supine diastolic BP (DBP) was greater (p less than 0.01) in both FER groups (7 +/- 6 and 8 +/- 5 mm Hg) than in the placebo group (4 +/- 6 mm Hg). The 24-h reduction in supine systolic BP (SBP) was greater (p less than 0.01) in the FER 20-mg group (14 +/- 11 mm Hg), but not in the FER 10-mg group, than in the placebo group (8 +/- 11 mm Hg). No significant difference in blood pressure (BP) was found between FER 10 and 20 mg. Heart rate (HR) did not differ between any of the groups, nor did body weight or routine laboratory parameters. During felodipine treatment, 17 patients (12 receiving FER 20 mg) were withdrawn mostly because of vasodilatory side effects such as headache and ankle edema. We conclude that FER 10 mg and 20 mg once daily had an antihypertensive 24-h effect and that FER 10 mg may be more suitable as initial dose.     

文拉法辛缓释剂与米氮平治疗难治性抑郁症的对照研究

目的:探讨文拉法辛缓释剂与米氮平治疗难治性抑郁症(TRD)的疗效、安全性及不良反应。方法:对68例TRD病人以简单随机抽样方法分成2组,分别给予文拉法辛与米氮平治疗8 wk,用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、临床疗效总评量表病情严重程度(CGI-SI)评定疗效。结果:文拉法辛组治疗剂量为(196±s 48)mg·d~(-1),显效时间(8±3)d,有效率68%,米氮平组分别为(32±11)mg·d~(-1)、(12±6)d、65%。2组疗效量表评定结果均较治疗前有显著下降,特别是文拉法辛组wk 1和wk 4的HAMA减分率为(33±3)%和(50±3)%,米氮平组为(14±3)%和(31.0±2.3)%,前者下降更为明显。结论:文拉法辛缓释剂和米氮平治疗TRD疗效均较好、安全性高、不良反应少,文拉法辛缓释剂起效更快速,其抗焦虑作用更快、更佳。     

文拉法辛缓释片治疗功能性消化不良的疗效

目的探讨文拉法辛缓释片治疗功能性消化不良的疗效及安全性。方法将60例功能新消化不良患者随机分为两组各30例,均给予内科常规治疗,研究组联用博乐欣治疗,疗程4周,采用CG I、及HAMD在治疗前、治疗2周末、4周末评定临床疗效。结果研究组在第4周末CG I及HAMD评分均显著低于同期对照组,两组比较差异有统计学意义(P<0.05)。结论功能性消化不良与精神心理因素相关,文拉法辛缓释片治疗疗效显著,安全性好。     

Duloxetine in military posttraumatic stress disorder

The objective of this prospective study was to assess the efficacy and tolerability of duloxetine in the treatment of in military veterans with posttraumatic stress disorder (PTSD).Twenty subjects were enrolled in this 12-week, open-label trial. Diagnosis and symptom severity were assessed with the Clinician Administered PTSD Scale (CAPS). Depressive symptoms were assessed the Hamilton Depression Rating Scale. All subjects had a CAPS score of at least 60 at baseline. Subjects with lifetime history of psychotic disorders or bipolar illness were excluded. Fifteen participants completed 12 weeks of treatment, five dropped-out from the trial, 3 due to side effects. For patients who discontinued, missing values were estimated using "the last observation carried forward" method. Significant improvements were seen on: CAPS total and all subscales, depression and sleep measures. Most of the improvement was observed by week 2 of treatment. Nine participants (45%) were classified as responders, defined by 20% or greater improvement on CAPS total score. The mean daily dose of duloxetine was 81 mg. The most common side effects were constipation (20%) diarrhea (25%) and nausea (20%). Two subjects developed tachycardia, one withdrew from the trial due to this problem. Duloxetine had a fast onset of action and was effective in about half of the subjects, it was well tolerated in most subjects. These preliminary results in a difficult to treat population warrant the conduction of a double blind, placebo-controlled study of duloxetine in PTSD.     

Dexmethylphenidate extended release: in attention-deficit hyperactivity disorder

Dexmethylphenidate extended release (XR) is an orally administered, bimodal release, capsule formulation of the active d-enantiomer of methylphenidate (MPH), which inhibits dopamine and norepinephrine (noradrenaline) reuptake to increase their concentration in the extraneuronal space. A single dose of dexmethylphenidate XR mimics the pharmacokinetic profile of two doses of dexmethylphenidate immediate-release formulation administered 4 hours apart, albeit with less fluctuation in plasma concentration. Once-daily dexmethylphenidate XR was more effective than placebo in reducing attention-deficit hyperactivity disorder (ADHD) symptom scores in children, adolescents and adults with ADHD in four randomised, double-blind, placebo-controlled trials of up to 7 weeks' duration. In crossover trials in children (aged 6-12 years), dexmethylphenidate XR 20 mg/day reduced mean ADHD symptom scores 1 hour after administration (by 43% in one trial) and was significantly better than placebo for up to 12 hours. Dexmethylphenidate XR 5-30 mg/day reduced mean ADHD symptom scores by 49%, while scores declined by 16% with placebo in a 7-week trial in children and adolescents (aged 6-17 years). Dexmethylphenidate XR 20, 30 or 40 mg/day reduced ADHD symptom scores by 36-46% versus a 21% reduction with placebo in a 5-week trial in adults (aged 18-60 years). Dexmethylphenidate XR was generally well tolerated in children, adolescents and adults with ADHD, with an adverse-event profile typical of MPH.     

一氧化氮:创伤后应激障碍研究的新靶点

创伤后应激障碍(PTSD)是当机体遭受生命威胁或者强烈精神创伤后发生的疾病。近年来研究发现,一氧化氮可能通过损伤海马神经元、参与创伤记忆的形成和影响海马神经元再生参与PTSD的发生,该文就此进行综述。     

Immediate antecedents of cigarette smoking in smokers with and without posttraumatic stress disorder: a preliminary study

Using ambulatory methods for 1 day of monitoring, the authors of this study investigated the association between smoking and situational cues in 63 smokers with posttraumatic stress disorder (PTSD) and 32 smokers without PTSD. Generalized estimating equations contrasted 682 smoking and 444 nonsmoking situations by group status. Smoking was strongly related to craving, positive and negative affect, PTSD symptoms, restlessness, and several situational variables among PTSD smokers. For non-PTSD smokers, the only significant antecedent variables for smoking were craving, drinking coffee, being alone, not being with family, not working, and being around others who were smoking. These results are consistent with previous ambulatory findings regarding mood in smokers but also underscore that, in certain populations, mood and symptom variables may be significantly associated with ad lib smoking.     

文拉法辛缓释剂(24例)与氯米帕明(25例)治疗广泛性焦虑症的比较

目的 :比较文拉法辛缓释剂与氯米帕明治疗广泛性焦虑症的疗效和安全性。方法 :文拉法辛缓释剂组 (文拉法辛组 ) 2 4例 ,年龄为 (36±s1 2 )a,1 8～ 55a;氯米帕明组 2 5例 ,年龄为 (35± 1 2 )a,2 0～55a。文拉法辛用量 75～ 2 2 5mg·d-1 ,po,qd,氯米帕明用量 50～ 2 50mg·d-1 ,po,bid。共 6wk。疗效评定采用HAMA减分率。安全性评价应用TESS、体检和实验室检查。结果 :经过 6wk的治疗 ,文拉法辛组痊愈率为 2 7% ,有效率为 59%。氯米帕明组痊愈率为 33 % ,有效率为 62 % ,P >0 .0 5。另外 ,文拉法辛组的抗焦虑起效时间与氯米帕明组相近 ,不良反应较氯米帕明组少。结论 :文拉法辛缓释剂治疗广泛性焦虑症疗效与氯米帕明相似 ,可用于广泛性焦虑症的治疗