Table 3. Combination Therapy for Insomnia.

Scientific name (common name)	Part (extract)	Study design	Jadud score	Intervention	Patients	Duration	Result	Mechanism	Reference
Valeriana officinalis + Humulus lupulus	-Dormeasan®: 460 mg of V. officinalis+ 460 mg H. lupulus -1: 12 dissolved in 61% ethanol	Double-Blind, Randomized, Placebo-Controlled	3	2 ml dissolved in 50 ml of honey flavored water and administrated orally 15 min before EEG(n=20) -placebo(n=22)	44 patients (30-70y) reporting on having a poor sleep for 2 weeks without neurological complications and any organic disease	2nights(reference night and medication night).	-Led to deeper sleep. -↑sleep quantity in the treatment group	no mechanism of action presented	30
V. officinalis + H. lupulus	Ze 91019: 500 mg valerian extract siccum + 120 mg hops extract siccum _45% methanol m/m with a drug extract ratio of 5.3:1 (valerian) and 6.6:1 (hops)	Randomized, Double-Blind, Placebo- Controlled	2	-Valerian Ze 911 (n=10) - Valerian/hops Ze 91019 (n=10) -placebo (n=10)	30 patients (≥18 years) suffering from non-organic sleep disorders (ICD 10, F 51.0–51.2)	4weeks	-No significant differences across groups in NREM -↑significantly sleep latency for Ze91019 -single valerian is not superior to placebo in sleep latency (=plausibility for adding hops extract to the valerian Extract)	decreasing excitatory neurotransmission in the central nervous system	31
Hypericum perforatun (St. Johns Wort) + V. officinalis + Passiflora Incarnata (passionflower)	Neurapas balance: 60mg St. John’s wort+28mg valerian+ 35mg passion flower	Double-blind randomized cross-over study		3 tablets twice a day	20 healthy subjects	3days	-↓ wakefulness, REM latency, NREM sleep in the first sleep cycle -↑NREM- sleep in the second cycle -↑subjective mood and subjective sleep evaluation -no difference in cognitive performance	no mechanism of action presented	32
Valeriana officinali + Humuluslupulus	Dormeasan®:460 mg of fresh V. officinalis; radix (root) rec. Tinct. 1:10 and H. lupulus, strobulus (fruit) rec. tinct. 1:12 dissolved in 61% ethanol	Double-blind, randomized, placebo-controlled	3	-2ml of the formulation was dissolved in 50 mL of honey-flavored water and then administered orally(n=20 -placebo (n=22)	42 healthy (Mean age of female 50.2 and males 48.2) having poor sleep within the previous 2weeks period	2 consecutive nights (reference nd medication night)	-↑sleep time and deeper sleep time Significantly	May: 1.inhibit central catabolism of GABA 2.bind directly to GABA-A receptors and stimulate the release and reuptake of GABA	33
Piper methysticum (kava) / Valeriana officinali		crossover trial, not double-blind	0	First treated for 6 weeks with kava 120 mg daily(n=24) This was followed by 2 weeks off treatment and then, 5 having dropped out, 19 received valerian 600mg daily for another 6 weeks (n=19)	24 patients suffering from stress-induced insomnia ( 23-65y)	6 weeks for each drug with washout period of 2weeks between	-↓Total stress severity by both -valerian: no sig effect on inducing sleep but good effect on quality -stress problems and the severity of the resulting insomnia were rapidly relieved by kava -improvements achieved with kava were then maintained by valerian	no mechanism of action presented	34