Figure 1.

Schematic workflow of balanced Williams crossover design comparing etifoxine (150 mg/d) with alprazolam (1.5 mg/d) and placebo (three “treatments”). Fifty-four men were screened as study prospects for eligibility. Thirty-six of them met inclusion criteria and were randomized into two latin squares of six sequences with six participants each. Three sequential periods are described as timepoints T1, T2, und T3 with an initial baseline measurement (T0) as reference. This Williams design is therefore a 3-treatments, 3-periods and 6-sequences balanced crossover design. Treatments lasted for 5 days followed by 9 days of wash-out. Microbiome was sampled on the last day of treatment. Participants were between 20 and 50 years old (mean = 27.7, SD = 6.9).