An open-label, 12-week clinical and sleep EEG study of nefazodone in chronic combat-related posttraumatic stress disorder.

BACKGROUND: We examined the effects of nefazodone on polysomnographic sleep measures and subjective reports of sleep quality and nightmares. as well as other symptoms, in patients with chronic combat-related posttraumatic stress disorder (PTSD) during a 12-week, open-label clinical trial. To our knowledge, this is the first polysomnographic study of treatment in patients with PTSD. METHOD: The subjects were 12 male veterans (mean age = 54 years) who met DSM-IV diagnostic criteria for PTSD (mean duration = 30 years). All but I patient also met DSM-IV criteria for major depressive disorder. Patients were evaluated weekly with clinical ratings in an open-label clinical trial. Polysomnographic recordings for 2 consecutive nights were obtained before treatment and at 2, 4, 8, and 12 weeks. The dose of nefazodone was adjusted according to individual clinical needs. Final mean daily dose was 441 mg. RESULTS: The patients reported significantly fewer nightmares and sleep problems during treatment. Nevertheless, contrary to studies in depressed patients, nefazodone did not significantly affect polysomnographic sleep measures compared with baseline. In addition, the patients showed significant improvement in the Clinical Global Impressions of PTSD symptoms (global score, hyperarousals and intrusions subscales), the Clinician-Administered PTSD Scale (global, hyperarousal, and intrusions subscales), the Hamilton Rating Scale for Depression (HAM-D). and the Beck Depression Inventory (BDI). CONCLUSION: These patients with chronic, treatment-resistant, combat-related PTSD showed significant improvement of subjective symptoms of nightmares and sleep disturbance, as well as depression and PTSD symptoms. in this 12-week open-label clinical trial. Nevertheless, objective polysomnographic sleep measures did not change. Further studies, including double-blind. placebo-controlled trials, are needed to extend these findings and to understand the relationships between the physiology of sleep and symptoms of poor sleep and nightmares.

Nefazodone in patients with treatment-refractory posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a highly prevalent and often chronic disorder among combat veterans, persisting in as many as 15% of Vietnam veterans for at least 20 years. Treatment response in veterans with combat-related PTSD has been disappointing. Although anxiolytics, anticonvulsants, antipsychotics, and antidepressants have been tried, none has been consistently associated with improvement in all primary symptom domains (i.e., intrusive recollections, avoidance/numbing, and hyperarousal). This open-label study evaluated the use of nefazodone in a group of Vietnam veterans with chronic, treatment-refractory symptoms of PTSD. METHOD: Male outpatients with DSM-IV PTSD who had failed a minimum of 3 previous medication trials were eligible for the study. Nineteen Vietnam combat veterans entered the study and were treated with nefazodone, 100-600 mg/day, for 12 weeks. PTSD symptoms, anxiety, depression, sleep, sexual functioning, and adverse events were assessed weekly. RESULTS: Severity of depression lessened, as did PTSD symptoms of intrusive recollections, avoidance, and hyperarousal. Depressive symptom severity as measured by the Beck Depression Inventory decreased by a mean of 30%. Similarly, there was an overall drop in the intensity of PTSD symptoms as measured by the Clinician Administered PTSD Scale of 32% with a 26% improvement for symptoms of intrusion, 33% for avoidance, and 28% for arousal. In addition, improvements in sleep and sexual functioning were reported. The mean daily dose of nefazodone after 12 weeks was 430 mg (range, 200-600 mg/day). The most frequently reported side effects were headaches (53%), dry mouth (42%), and diarrhea (42%), but side effects tended to be mild and transient. CONCLUSION: In this group of Vietnam veterans with chronic treatment-refractory PTSD and multiple comorbid Axis I psychiatric disorders, nefazodone was well tolerated and effective. Larger, controlled studies are warranted.

Mammary hypertrophy is not associated with increased estrogen receptors.

Estrogen promotes secondary female sex characteristics, including breast enlargement. Since excessive breast hypertrophy is unrelated to elevated serum estrogen levels, it has been postulated that the enlarged breast is a hypersensitive "target organ." At the cellular level, estrogen crosses the cell membrane, is bound to a cytoplasmic estrogen receptor (ER), and induces the formation of specific anabolic proteins. In breast cancer, this estrogen receptor is regarded as a measure of the sensitivity of the cell to estrogen. To determine if mammary hypertrophy is related to an increase in the number of estrogen receptors, we assayed breast tissue, not fat, from 25 consecutive breast reductions. The median age of patients was 26 years (17 to 77 years), with 752 gm per breast removed on average. Twenty-four percent of the patients were taking estrogens, primarily birth control bills. Cellular estrogen-receptor status was measured by a standardized cytosol extraction radioactive estradiol technique. Estrogen receptors were undetectable (less than 3 fmol/mg cytosol protein) in all patients. We conclude that estrogen receptors alone, and hence estrogen, are not a determinant in mammary hypertrophy. If the enlarged breast is a "target organ," it is by another mechanism.

Nodular bleomycin toxicity.

Pulmonary interstitial fibrosis, a well-known toxic effect of bleomycin therapy, usually presents radiographically as diffuse reticularity. The authors report an unusual case of biopsy-proven bleomycin toxicity that presented as pulmonary nodules mimicking metastatic tumor. The histologic findings resembled those seen in the diffuse form of toxicity but notably also included foci of bronchiolitis obliterans.