The Relationship of Alprazolam Dose to Steady-State Plasma Concentrations
- 1 February 1990
- journal article
- research article
- Published by Wolters Kluwer Health in Journal of Clinical Psychopharmacology
- Vol. 10 (1), 27-32
- https://doi.org/10.1097/00004714-199002000-00005
Abstract
Alprazolam is a widely used antianxiety agent, yet relatively little is known about the relationship between chronic oral doses and steady-state plasma levels. This study examines the relationship over a wide range of therapeutic doses. We conducted a parallel, double-blind, placebo-controlled study in 36 patients with agoraphobia with panic attacks, or panic disorder with limited phobic avoidance based on DSM-III criteria. Patients received alprazolam (N = 25) or placebo (N = 11) beginning at 1 mg/day and increased weekly until either a maximum tolerated dose or 10 mg/day was achieved. Dosages were then gradually tapered according to a predetermined schedule. The entire study period lasted 14 weeks. Laboratory and clinical assessments were conducted weekly. Doses up to 6 mg/day were tolerated by 80% of patients on alprazolam and doses of 10 mg/day were tolerated by 40% of patients. Twenty-seven percent of the placebo patients reached 10 tablets/day. In the alprazolam group, the principal cause of intolerance was sedation. Throughout the study no significant changes in vital signs or laboratory parameters were observed. Steady state alprazolam, 4-hydroxy alprazolam, and .alpha.-hydroxy alprazolam plasma levels were linearly related to dose. A 1 mg dosage increment produced, on the average, a corresponding 10 ng/ml increase in steady state level of the parent drug. Significiant response was observed in subjects who achieved concentrations greater than 20 ng/ml, with a maximum of 81% of the samples classified as responders within the 60 ng/ml and above group. During taper, no severe withdrawal symptoms were noted; 12 of 25 alprazolam patients, however, reported rebound anxiety (anxiety rating scale scores higher than baseline), which occurred most commonly at the reduction from 1 mg to 0 mg.This publication has 12 references indexed in Scilit:
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