BACKGROUND: Etizolam is an anxiolytic drug with a pharmacologic profile similar 
to that of the classic benzodiazepines. Neurochemical research suggests that 
etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type 
A receptors associated with anxiety (ie, alpha1, beta2, gamma2). This property, 
plus its characterization as a ligand with fewer of the adverse events typical 
of full agonists (impaired cognitive function, tolerance, and dependence), led 
to its selection for this study.
OBJECTIVES: The primary aim of this study was to test for the noninferiority of 
etizolam 0.5 mg BID versus placebo in affecting cognitive function in patients 
with mild to moderate anxiety disorder of recent onset (<1 month). Anxiety 
measures and tolerability were also assessed.
METHODS: Patients between the ages of 18 and 65 years were eligible for 
enrollment. This double-blind, placebo-controlled study was performed in 5 
centers in Italy using a 2-treatment, 3-period crossover design. Patients were 
randomized to 3-week sequences of either etizolam-placebo-placebo or 
placebo-etizolam-etizolam. They were evaluated at 4 scheduled visits (screening 
and days 7, 14, and 21). Cognitive function was assessed using scores from the 
Wechsler Adult Intelligence Scale (WAIS) Digit Span test (total forward and 
backward scores and the time required to perform the test). Anxiety was measured 
using the Hamilton Anxiety Rating Scale (HAM-A) and the State-Trait Anxiety 
Inventory (STAI) for screening and to monitor adequacy of therapy. Blood 
pressure, heart rate, weight, and adverse events were also recorded.
RESULTS: A total of 77 white patients were enrolled (mean age, 33.3 years 
[range, 22-60 years]; 62.3% female; mean weight, 65.2 kg). With a power of 0.80, 
the difference between the effects of etizolam and placebo on WAIS Digit Span 
performance was not significant for total score (0.102 [90% CI, -0.130 to 
0.335]) or time required for completion (0.029 second [90% CI, -0.574 to 
0.632]). Anxiety, as measured using the HAM-A and STAI instruments, did not 
differ significantly between groups. No significant differences were found 
between etizolam 0.5 mg BID and placebo for cardiovascular events, weight 
changes, or adverse events. Mild or moderate somnolence was reported by 7 of 77 
patients (9.1% [3 patients while receiving etizolam and 4 patients while 
receiving etizolam and placebo]).
CONCLUSIONS: No significant differences between etizolam 0.5 mg BID and placebo 
were found for cognitive function or anxiety measures in these patients with 
anxiety. Etizolam was well tolerated.