Current concepts in clinical therapeutics: anxiety disorders, Part 1.

The diagnosis, epidemiology, classification and clinical presentation, pathophysiology, and treatment of anxiety disorders are reviewed. Anxiety disorders, among the most common mental disorders, must be differentiated from medical diseases with anxious symptoms. A complete physical and mental status examination, as well as a thorough knowledge of the patient's medical, psychiatric, and drug history are required. Epidemiologic studies indicate an incidence of 4-8% in the United States. There are four categories of anxiety disorders: phobic disorders, anxiety states, posttraumatic stress disorders, and atypical anxiety disorders. Several psychoanalytic, behavioral, and cognitive theories have been advanced to explain the pathophysiologic mechanisms causing anxiety disorders. Of most interest are the biological theories involving the catecholamine neurotransmitter norepinephrine and the benzodiazepine receptor. Proper treatment for anxiety disorders involves nonpharmacologic and pharmacologic approaches. The benzodiazepines are widely used and are the mainstay of drug treatment for patients with situational anxiety and generalized anxiety disorder. However, problems with sedation, complications of drug withdrawal, and patients' fear of drug dependency may limit clinical usefulness. Buspirone is the first nonbenzodiazepine anxiolytic to be introduced in the United States in more than 25 years. Its unique role in treating anxiety, compared with the benzodiazepines, may include less sedation, minimal drug abuse potential, and fewer withdrawal symptoms upon drug discontinuation. Nonpharmacologic therapy is used extensively in the treatment of phobic disorders (simple and social phobia). Important advances in the diagnosis and treatment of anxiety disorders have been made. An accurate diagnosis is essential for optimal management. Unfortunately, many anxious patients do not seek treatment and some do not receive the most appropriate treatment.

Effect of estrogens on the dexamethasone suppression test in nondepressed women.

It is often suggested that estrogens may cause false-positive dexamethasone suppression test (DST) results. In this study of nine healthy, non-depressed women, DSTs were performed at baseline, immediately following administration of 21 days of oral contraceptives containing either 50 or 80 micrograms of mestranol (a synthetic estrogen) in combination with 1 mg of norethindrone (a synthetic progesterone), and 1 month after discontinuing the oral contraceptives. All subjects had post-dexamethasone cortisol levels less than or equal to 5 micrograms/dl during the study with the exception of two subjects in the mestranol 80 microgram group who had positive DSTs immediately following oral contraceptive administration; one of these subjects continued to have a positive DST 1 month later. DST results should be interpreted with caution if high dose estrogens are taken concurrently or have been recently discontinued.

Pharmacokinetics of bupropion and its major basic metabolites in normal subjects after a single dose.

The pharmacokinetics of bupropion (BUP) and its three major basic metabolites (the erythroamino alcohol [EB], the threoamino alcohol [TB], and the hydroxy [HB] metabolites) were characterized after a single, oral, 200 mg dose of BUP in six healthy men. Twenty-one sequential plasma samples for analysis by HPLC were drawn from each subject over the 56-hour period after dosing. Pharmacokinetic analyses were by noncompartmental methods. The mean elimination t1/2 values of BUP, TB, EB, and HB were 9.8, 19.8, 26.8, and 22.2 hours, respectively. The mean plasma AUCs of TB and HB were 2.4 and 10.3 times greater, respectively, than that for BUP. Because of the substantial presence of these metabolites in systemic circulation, further studies are recommended to understand further their roles in the clinical profile of this new antidepressant.

Buspirone: a new type of anxiolytic.

Buspirone is a member of a new class of agents known as azaspirodecanediones, and represents the first nonbenzodiazepine anxiolytic to be introduced in the U.S. in recent years. It does not resemble the benzodiazepines or older anxiolytics such as meprobamate and the barbiturates in pharmacologic profile. Buspirone lacks anticonvulsant activity, interacts minimally with central nervous system depressants such as alcohol, and does not cause muscle relaxation. The drug is reported to have minimal sedating effect, to cause no impairment of driving-related skills, and to have no euphoriant effect or addictive potential. With this low side-effect profile, buspirone should not require Drug Enforcement Agency scheduling controls. Clinical trials indicate buspirone is efficacious in the treatment of mild to moderate anxiety disorders. Answers to questions of possible side effects related to dopaminergic intractions must await post-marketing experience. Buspirone is a suitable addition to drug formularies as its pre-marketing data suggest several advantages compared with anxiolytics currently available.

The neuroendocrine and behavioral response to dextroamphetamine in normal individuals.

Dextroamphetamine 30 mg and placebo were administered by mouth in a double-blind randomized cross-over trial to ten subjects. Behavior was assessed and blood samples analyzed for growth hormone (GH), prolactin (PRL), homovanillic acid (HVA), and amphetamine. There was a statistically significant increase in well-being following d-amphetamine as compared to baseline and placebo on both the Amphetamine Interview Rating Scale and the Hopkins Mood Scale. No subject became psychotic. There was a statistically significant increase in GH from baseline to peak following d-amphetamine ingestion. When compared to placebo, the increase in GH was invariable and statistically significant for the 90-min sampling. PRL decreased from baseline following both d-amphetamine and placebo and there was no significant drug-placebo difference. Serum HVA was measured at baseline and 120 min, for eight subjects. Six subjects had an increase in HVA following d-amphetamine but there was no significant drug effect.