The effects of menstrual cycle phases and gender on alprazolam pharmacokinetics were evaluated in normal volunteers. Alprazolam (1 mg) was administered to seven women during the late follicular and luteal phases of the menstrual cycle and to eight men on one occasion. No difference in alprazolam pharmacokinetic parameters was observed during the menstrual cycle phases. Mean alprazolam clearance (+/- SD) was 0.0037 +/- 0.0009 ml/hr during the follicular phase and 0.0036 +/- 0.001 ml/hr during the luteal phase (p greater than 0.05, difference not significant). With use of weight as a covariant, there was no difference in alprazolam pharmacokinetic parameters between women and men. Mean alprazolam clearance (+/- SD) was 0.0036 +/- 0.0009 ml/hr in women compared with 0.0041 +/- 0.0006 ml/hr in men (p greater than 0.05, difference not significant). Although alprazolam metabolism was similar on the 2 days tested, alterations may occur at other times during the menstrual cycle. Further investigation is needed to understand the effects of menstrual cycle phases and gender on drug metabolism.

Studies evaluating the antianxiety and antipanic properties of beta-blockers do not support their routine use in treating either generalized anxiety disorder or panic disorder. The use of propranolol for anxiety disorders accompanied by physical symptoms, especially cardiovascular complaints, may be effective in some patients when combined with benzodiazepines or perhaps in some non-responders to conventional treatment. Better designed studies are needed to evaluate the exact role of beta-blocking agents in treating anxiety. The efficacy of propranolol in patients with panic disorder has not been widely researched, but preliminary results have not been encouraging. Propranolol may provide symptomatic relief in some patients with residual somatic complaints (i.e., palpitations and tachycardia), when combined with the patient's ongoing drug regimen. Because beta-blockers may induce depression, they should be used cautiously--if at all--in panic patients with concurrent depressive illness.

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In the 1960s, several studies reported that propranolol and other beta‐blocking drugs appeared especially useful in patients with physical symptoms of anxiety. However, subsequent reports produced conflicting findings, and at this time the efficacy of propranolol in anxiety disorders is not clearly established. Propranolol's utility in anxiety states may be entirely restricted to those anxiety patients whose physical symptoms have not adequately responded to benzodiazepine therapy. This places the beta‐blockers among the least useful drugs in treating anxiety disorders. A major problem in assessing propranolol's antianxiety properties has been a virtual lack of well‐designed studies addressing the issue; the studies reviewed here contained a surprising number of study design problems. Several guidelines regarding study design are included to assist the reader in evaluating studies of antianxiety agents. High dose (e.g., 2,000 mg) propranolol may have a role as an alternative to traditional antipsychotic therapy in neuroleptic‐resistant patients. During the last decade a number of studies have demonstrated symptomatic improvement in schizophrenic patients using propranolol alone or combined with neuroleptics. However, four recent double‐blind reports have failed to replicate this finding. Future research should focus on possible identification of propranolol‐responsive patients and their characteristics. The use of propranolol and other beta‐blockers in schizophrenia should remain in the research or medical center setting.

In the 1960s, several studies reported that propranolol and other beta‐blocking drugs appeared especially useful in patients with physical symptoms of anxiety. However, subsequent reports produced conflicting findings, and at this time the efficacy of propranolol in anxiety disorders is not clearly established. Propranolol's utility in anxiety states may be entirely restricted to those anxiety patients whose physical symptoms have not adequately responded to benzodiazepine therapy. This places the beta‐blockers among the least useful drugs in treating anxiety disorders. A major problem in assessing propranolol's antianxiety properties has been a virtual lack of well‐designed studies addressing the issue; the studies reviewed here contained a surprising number of study design problems. Several guidelines regarding study design are included to assist the reader in evaluating studies of antianxiety agents. High dose (e.g., 2,000 mg) propranolol may have a role as an alternative to traditional antipsychotic therapy in neuroleptic‐resistant patients. During the last decade a number of studies have demonstrated symptomatic improvement in schizophrenic patients using propranolol alone or combined with neuroleptics. However, four recent double‐blind reports have failed to replicate this finding. Future research should focus on possible identification of propranolol‐responsive patients and their characteristics. The use of propranolol and other beta‐blockers in schizophrenia should remain in the research or medical center setting.

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