Faculty Bibliography

To evaluate the possibility that abnormal regulation of benzodiazepine receptor (BZR) function may relate to the pathophysiology of anxiety disorders, two doses of the BZR antagonist flumazenil (Ro 15-1788) and placebo were administered to panic disorder patients in a double-blind, randomized, crossover design. All 11 patients received flumazenil (600 mg). Ten of the 11 also received flumazenil (200 mg), and 8 of the 11 were given matching placebo capsules orally on separate test days. Neither dose of flumazenil showed significant anxiolytic effects or significantly altered heart rate, blood pressure, or levels of plasma cortisol or 3-methoxy-4-hydroxyphenylglycol in comparison to placebo. On 200 mg days, anxiety ratings on a visual analog scale significantly increased compared to placebo at 30 min and then returned to baseline levels. Panic attacks occurred on placebo, 200 mg, and 600 mg days in 0/8, 4/10, and 0/11, respectively. Failure to observe anxiolytic effects suggests that flumazenil at these doses does not antagonize a tonic increased interaction of BZRs with an endogenous BZR inverse agonist in panic patients.

Posttraumatic stress disorder (PTSD) may develop after exposure to severe stress, such as combat, accidents, assaults, and natural disasters. Pharmacotherapy can be a useful adjunct in the comprehensive treatment of these patients. The presence of comorbid conditions, including depression, panic disorder, substance abuse, and traumatic brain injury, should be carefully evaluated. Symptoms of PTSD that are associated with central nervous system hyperarousal or reexperiencing of the traumatic event appear to be the most responsive to pharmacotherapy. Social withdrawal and dulled responsiveness have not been shown to be alleviated through standard pharmacologic interventions. A therapeutic strategy is proposed that is based on the patient's symptoms and initial response to medication.

Issues related to the epidemiology, nosology, and differential diagnosis of organic aggressive disorders in the elderly are discussed. Rating and monitoring of aggressive events using the Overt Aggression Scale are reviewed. The management of acute aggression with antipsychotic agents and benzodiazepines is presented, as well as an approach for using beta-blockers, anticonvulsant agents, and serotonin-specific antidepressants and an antianxiety agent for the treatment of chronic aggression.