Quality of life and posttraumatic stress disorder: a pilot study assessing changes in SF-36 scores before and after treatment in a placebo-controlled trial of fluoxetine.

In this small pilot study, we evaluated quality of life for 16 posttraumatic stress disorder (PTSD) patients by administering the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at baseline and endpoint during a 12-week double-blind trial of fluoxetine and placebo. At baseline, our subjects reported greater impairment relative to subjects with major depression or obsessive-compulsive disorder on several SF-36 domains. Significant effects of fluoxetine relative to placebo were observed for vitality, social functioning, and mental health. Overall, PTSD was associated with greatly reduced quality of life, but considerable improvement was achieved through treatment.

Demographics, treatment seeking, and diagnoses of anxiety support group participants.

Two peer-led anxiety disorder support groups were surveyed to ascertain characteristics of individuals seeking the services of these groups. Both groups had received information and consultation from the Anxiety Disorders Association of America. One hundred and eighty-four individuals were interviewed for diagnosis by structured clinical interview; demographics and treatment-seeking behaviors were ascertained by self-report questionnaires. Both groups surveyed were composed of more females than males and were predominantly Caucasian. Treatment was most frequently sought from psychiatrists, psychologists, and family doctors. One fourth of the sample had sought help for anxiety in a hospital emergency room. Eighty-eight subjects (94%) at the Dallas site and 57 subjects (61%) at the Durham site met criteria for at least one current anxiety or affective disorder. More than half of those who met criteria for current panic disorder with agoraphobia also met criteria for at least one other anxiety disorder, or for major depression. Approximately one third of each support group met criteria for current social phobia. Severity of social phobia symptoms was assessed by four scales. An increased risk of substance abuse was noted for individuals with a diagnosis of social phobia, as compared with diagnoses of other anxiety disorders.

Fluoxetine in post-traumatic stress disorder. Randomised, double-blind study.

BACKGROUND: Most pharmacotherapy trials in post-traumatic stress disorder (PTSD) have been conducted upon male combat veterans. Outcome studies relating to civilians are therefore needed. AIMS: To demonstrate that fluoxetine is more effective than placebo in treating PTSD. METHOD: Civilians with PTSD (n = 53) were treated for 12 weeks with fluoxetine (up to 60 mg/day) or placebo. Assessments of PTSD severity, disability, stress vulnerability, and high end-state function were obtained. RESULTS: Fluoxetine was more effective than placebo on most measures at week 12, including global improvement (much or very much improved: fluoxetine 85%, placebo 62%, difference 0.24, 95% CI 0.01-0.47; very much improved: fluoxetine 59%, placebo 19%, difference 0.40, 95% CI 0.16-0.64), and high end-state function (fluoxetine 41%, placebo 4%, difference 0.37, 95% CI 0.17-0.57). CONCLUSIONS: Fluoxetine was superior for measures of PTSD severity, disability, stress vulnerability, and high end-state function. The placebo-group response was low when viewed as a broad outcome based on a portfolio of ratings, but was higher with a traditional global rating criterion.

Discontinuation of clonazepam in the treatment of social phobia.

Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for longterm clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper.

Treatment of posttraumatic stress disorder with nefazodone.

Selective serotonin reuptake inhibitors are useful in the treatment of posttraumatic stress disorder (PTSD), but have a number of side-effects which limit their acceptability. A newer serotonergic compound, nefazodone, has a different side-effect profile, thus making it a potentially promising compound to study. Seventeen private practice patients with PTSD were treated with nefazodone up to 600 mg/day for a maximum total treatment period of 12 weeks. All subjects were civilians, and were monitored for efficacy and side-effects at weeks 1, 2, 4, 6, 8 and 12. Nefazodone was associated with statistically significant improvement in mean scores on all six rating scales used to assess change from baseline in PTSD symptoms. Additionally, statistically significant improvement from baseline were seen for the intrusive, avoidant/numbing, and hyperarousal clusters on a global PTSD scale. Early improvements in nightmares and general sleep disturbance were observed. Overall, there was a 43% response rate at endpoint, or 60% in treatment completers, by observer rating. Side-effects (assessed on the Medication Effects Scale) were generally benign. Nefazodone was associated with clinical improvement in this population, and now needs to be studied in double-blind, placebo controlled, protocols.

Response characteristics to antidepressants and placebo in post-traumatic stress disorder.

Characteristic response patterns are described for two antidepressant drugs and placebo in post-traumatic stress disorder. Early onset and steady improvement occurred on a global rating scale for both drugs and placebo in those who ultimately met responder criteria at the end of treatment. In certain cases, the magnitude of global response was greater for drug than for placebo. At weeks 2 or 4, the Clinical Global Impressions score for fluoxetine but not for amitriptyline, served as a good predictor of eventual response. In a review of numerous completed placebo-controlled trials, antidepressants were superior to placebo in seven out of eight comparisons using the Clinical Global Impressions, although specific effects on post-traumatic stress disorder scales were more variable. Drug response rates are similar for combat and civilian trauma samples, but placebo response rates may be higher in the latter. Effect sizes suggested a moderate-to-good effect for drug therapy.

Monoclonal antibodies against cardiac myosin heavy chain.

Three mouse IgG1 monoclonal antibodies (MAbs), named FA1, FA2, and FA3, against cardiac myosin heavy chain (MHC) with high specificity have been obtained. The immunogen used to generate these MAbs was the high-salt- and detergent-insoluble fraction of adult rat myocardial tissue. Western blots showed that these MAbs reacted with a 200 kD protein band, which comigrated with the heavy chain of purified rat cardiac myosin in SDS-PAGE. Immunofluorescence microscopy revealed that the antigen recognized by these MAbs was localized at the A-band of isolated myofibrils. The tissue-, species-, and isoform-specificities of these MAbs were examined by Western blots on various muscle samples. FA2 recognized fish, frog, chicken, rabbit, bovine, mouse and rat cardiac MHC, as well as rabbit skeletal and rat aorta smooth muscle MHC. This antibody reacted equally well with both alpha- and beta-isoforms of MHC. FA1 did not crossreact with any MHC tested so far but with rat cardiac MHC. It appeared to react only with alpha-isoform of MHC. FA3 recognized only rat, bovine and rabbit cardiac MHC with the specificity to bovine and rabbit atrial MHC. Elisa competition assay revealed that different epitopes on the antigen molecules were recognized by these three MAbs, although there was a partial overlap between the epitopes for FA1 and FA2. These anti-MHC MAbs will be most useful in investigating the expression of MHC during myocardial development.