Table 1.

Study characteristics.

Author	Recruitment site	Design	Study period		Sample size (Intervention/Control)		Intervention(s)	Comparison(s)	Measurement tools
			Breakdown	Total (for each participant)	Full analysis set	Per-protocol			Outcome	Compliance	Safety and tolerability
Woelk & Schlafke (2009)35 Germany	General practitioner’s clinics	Multi-centre, double-blind, randomised phase III study	1 week screening phase, 6 weeks treatment phase, 2 weeks discontinuation phase.	9 weeks	40/37	36/33	80 mg Silexan capsule + Lorazepam placebo once daily during 6-week treatment phase, and on day 43,45,47,50 and 53 during the discontinuation phase.	0.5 mg Lorazepam capsule + Silexan placebo once daily during 6-week treatment phase, and on day 43,45,47,50 and 53 during the discontinuation phase.	Hamilton Anxiety Rating Scale (HAMA total score)	Method was not reported	Adverse events (AE) reported, physical and ECG examinations, vital signs, routine laboratory measurements
Kasper et al. (2015)38 Germany	17 general and psychiatric practices	Randomized, double-blind trial	Single-blind screening and wash-out phase of 3–7 days, followed by 10 weeks treatment phase. Post-baseline efficacy and safety assessments performed every 2 weeks	11 weeks	86/84	73/65	80 mg Silexan capsule once daily	Placebo capsules with 1/1000 the amount of lavender oil in Silexan capsules (to match the smell of Silexan capsules) once daily	Hamilton Anxiety Rating Scale (HAMA total score)	Compared the number of unused capsules returned by the patients to the expected number assuming a fully protocol compliant intake	Adverse events (AE) reported spontaneously, physical and ECG examinations, vital signs, routine laboratory measurements
Kasper, et al. (2016)39 Germany	35 psychiatric practices	Double-blind, randomized, placebo-controlled, parallel-group multicentre trial	Screening period of 3–7 days, followed by 10 weeks treatment phase. Efficacy and safety assessments performed at 1 and 2 weeks ± 2 days, as well as at 4, 7 and 10 weeks ± 7 days after baseline	11 weeks	159/156	141/128	80 mg Silexan capsule once daily	Placebo capsules with 1/1000 the amount of lavender oil in Silexan capsules (to match the smell of Silexan capsules) once daily	Hamilton Anxiety Rating Scale (HAMA total score)	Assessed by counting of returned medication	Adverse events (AE) reported, physical and ECG examinations, vital signs, routine laboratory measurements
Kasper, et al. (2014)37 Germany	57 psychiatric and general practices	Randomized, double-blind, double-dummy, multi-centre trial with four parallel groups	Screening and wash-out phase of 3–7 days, followed by 10 weeks treatment phase. Efficacy and safety assessments performed after 2, 4, 6, 8 and 10 weeks. Treatment phase is followed by 1 week down-titration phase for paroxetine withdrawal	12 weeks	121 (Silexan 160 mg/d)/13 5 (Silexan 80 mg/d)/132 (paroxetine)/135 (placebo)	103 (Silexan 160 mg/d)/119 (Silexan 80 mg/d)/114 (paroxetine)/114 (placebo)	160 mg Silexan capsule once daily; 80 mg Silexan capsule once daily.	20 mg Paroxetine capsule; placebo capsule.	Hamilton Anxiety Rating Scale (HAMA total score)	Assessed by medication counting	Adverse events (AE) reported spontaneously, physical examinations, routine laboratory measurements. Withdrawal symptoms ascertained by administering the Physician Withdrawal Checklist (PWC-20) at the end of treatment phase and down-titration phase.
Kasper, et al. (2010)36 Germany	27 general and psychiatric primary care centres	Randomized, double-blind, placebo controlled, multi-centre trial	Single-blind placebo screening and wash-out phase of 3–7 days, followed by 10 weeks treatment phase. Post-baseline efficacy and safety assessments performed every 2 weeks	12 weeks	104/108	87/90	80 mg Silexan capsule daily	Placebo capsules with 1/1000 the amount of lavender oil in Silexan capsules (to match the smell of Silexan capsules) once daily	Hamilton Anxiety Rating Scale (HAMA total score)	Method was not reported	Adverse events (AE) reported, physical and ECG examinations, vital signs, routine laboratory measurements