Table 1.

Valeriana spp. as a Single Herb.

	First Author	Study design	Intervention and measures	Outcomes	Adverse events	*
Hydroalcoholic extract
1	Roh D 201934	Randomized, placebo-controlled, double-blind. Population: nonclinical volunteers suffering psychological stress (n=52)	Intervention: V. officinalis 70%EtOH extract capsule 300 mg (0.8% valerenic acid) per day (100 mg t.i.d.) for 4 weeks. Measures: 1. Psychiatric variables (HAM-A, HAM-D, PSQI). 2. Functional brain connectivity changes (EEG) Summary measures for meta-analysis: difference in means	1. Improvement in both treatment and control groups. No statistically significant difference between the groups. 2. Greater increases in frontal brain region alpha coherence in valerian group, which was correlated with anxiolysis	No moderate or serious adverse reaction. Two adverse effects (one from each group): atypical chest pain (unrelated to the medication) in treatment group and gastrointestinal problems in the placebo group.	(1) PSQI (2) HAM-A (3) 5
2	Taibi DM 200954	Randomized, placebo-controlled, single-blind, pilot study. Population: Arthritis patients with mild sleep disturbance (n=15)	Intervention: V. officinalis 70%EtOH extract (0.8% valerenic acid) 600 mg for 5 nights Measures: Sleep outcomes (sleep diaries and wrist actigraphy) Summary measures for meta-analysis: difference in means	No significant difference between the groups.	Dizziness and sleepiness	(1) Self-rated (2) n/a (3) 5
3	Taibi DM 200953	Randomized, placebo-controlled, double-blind, cross-over Population: Older women with insomnia (n=16)	Intervention: V. officinalis 70% extract 300 mg (0.8% valerenic acid), 30 min before bedtime for 2 weeks Measures: (1) polysomnography (PSG); (2) self-rated sleep Summary measures for meta-analysis: difference in means	No significant difference between the groups in sleep latency, wake after sleep onset, sleep efficiency, and self-rated sleep quality.	No severe adverse events. No difference between valerian and placebo	(1) Self-rated (2) n/a (3) 5
4	Oxman AD 200752	Randomized, placebo-controlled, double-blind (Web-based trial) Population: Volunteers with insomnia without treatment (n=405)	Intervention: V. officinalis 60%EtOH extract 600 mg per day, 1 h before bedtime for 14 days. Measures: Sleep diary (sleep onset latency, number of night awakenings, sleep duration, sleep quality, energy level the following day). Summary measures for meta-analysis: odds ratio	Global self-assessment of change was better for valerian group (p=0.04). Similar trends favoring the treatment group for sleep quality, night awakenings, and sleep duration.	No serious adverse events. No statistically significant differences in minor adverse events between the groups.	(1) Self-rated (2) n/a (3) 5
5	Koetter U 200765	Randomized, placebo-controlled, double-blind Population: Patients suffering from non-organic sleep disorders (n=27)	Intervention: V. officinalis 45%MeOH extract 500 mg compared to placebo. For 4 weeks. Measures: (1) the reduction of the initially prolonged sleep latency; (2) WASO, sleep efficiency, relative proportion of the sleep stages, REM latency and CGI	No significant difference between valerian extract and placebo.	No adverse events.	(1) n/a (2) n/a (3) 3
6	Diaper A 200450	Randomized, placebo-controlled, double-blind, cross-over Population: Sleep-disturbed, but otherwise normal subjects (n=16)	Intervention: (1) V. officinalis 70%EtOH extract (LI 156) 300 mg; (2) V. officinalis 70%EtOH extract 600 mg; (3) placebo. Single dose, separated by 6 days washout. Measures: Sleep EEG, CFF, CRT, SMT, LARS, LSEQ, STDI, and STAI Summary measures for meta-analysis: difference in means	No significant differences between the 3 groups.	Mild or moderate adverse events: Drowsiness was 4 under 600 mg valerian, 12 under 300 mg valerian, and 8 in placebo.	(1) n/a (2) STAI (3) 3
7	Donovan JL 200469	Open-label, fixed treatment, cross-over Population: Healthy volunteers (n=12)	Intervention: V. officinalis 70%EtOH extract 1000 mg (containing 11.02 mg valerenic acid) nightly for 14 days. Measures: CYP2D6 and CYP3A4 activities	V. officinalis has a moderate effect on CYP3A4 (increase in maximum probe drug concentration), however there were no significant differences in other pharmacokinetic parameters.	No treatment-associated adverse events	(1) n/a (2) n/a (3) n/a
8	Hallam KT 200347	Placebo-controlled, double-blind, cross-over Population: Healthy volunteers (n=9)	Intervention: Single doses of V. officinalis 70%EtOH extract (0.25% valerenic acids) 500 mg or 1000 mg. Compared to triazolam 0.25 mg. Measures: Cognitive and psychomotor performance (CFF, CRT, DSST, SST, DST) and mood (VAS). Summary measures for meta-analysis: difference in means	Single doses of valerian were without effect on either cognitive or psychomotor performance, while triazolam had detrimental effects on cognitive processes, in healthy volunteers. Although not statistically significant, valerian 500 mg may have tranquilizing / calming effect.		(1) n/a (2) Self-rated calming effect (3) 3
9	Ziegler G 200244	Randomized, double-blind, comparative Population: Non-organic insomnia outpatients (n=202)	Intervention: V. officinalis 70%EtOH extract (LI 156 sedonium) 600 mg for 6 weeks. Compared with oxazepam Measures: Sleep questionnaire	Both Valerian and oxazepam improved sleep quality.	Mild or moderate adverse events in both oxazepam (36%) and valerian (28%) groups.	(1) n/a (2) n/a (3) 2
10	Herrera-Arellano A 200142	Randomized, controlled, double-blind, cross-over Population: Outpatients with clinical insomnia (n=20)	Intervention: Single doses of (1) V. officinalis hydroalcoholic extract 450 mg or (2) V. edulis (hydroalcoholic extract) 450 mg. Prior to lights out. Compared to basal levels. Measures: Hypnotic effects (polysomnography), anterograde memory (measured by D. Wechsler Memory Scale)	V. officinalis and V. edulis increased the REM sleep (better improved by V. officinalis), and morning sleepiness. V. edulis reduced the number of awaking episodes.	Slight dyspepsia (2 for V. officinalis and one for V. edulis)	(1) n/a (2) n/a (3) 2
11	Donath F 200036	Randomized, placebo-controlled, double-blind, cross-over Population: Patients suffering from psychophysiological insomnia (n=16)	Intervention: V. officinalis 70%EtOH extract (Sedonium) 600 mg, 1 h before bedtime. (1) Single dose, (2) 14 days. Measures: Objective sleep efficiency (SE) and sleep onset latency (SOL). NREM, REM, and slow wave sleep SWS). Subjective sleep quality (VAS) Summary measures for meta-analysis: difference in means	(1) There was no significant effect after a single dose. (2) SE was significantly higher in both groups at the end of the trial periods. SWS latency was significantly shorter and SWS increased in valerian group. A tendency toward reduced subjective sleep latency was observed despite there was no significant difference in objective SOL between the groups.	Fewer adverse events for Valerian group than placebo.	(1) Self-rated (2) n/a (3) 2
12	Kuhlmann J 199937	Randomized, placebo-controlled, double-blind Population: Healthy volunteers (n=102)	Intervention: V. officinalis 70%EtOH extract (600 mg, LI 156). Single dose in the evening (compared to placebo and Flunitrazepam (FNZ)), and repeated evening administration for 2 weeks (compared to placebo). Measures: (1) Sleep quality and latency (self-assessment). (2) Reaction time (Vienna Determination Test), alertness, and concentration (2-handed co-ordination) at next morning.	(1) Sleep quality and latency improved after single doses of valerian and FNZ. After 2 weeks with Valerian, sleep quality had a trend toward improvement, compared to placebo. (2) Neither single dose nor repeated administrations of valerian extract had a negative impact on reaction time, alertness, and concentration.	No serious adverse events. Headache and weakness were most frequently reported, which had not inter-group difference (no causal relationship to valerian). Note: Single dose of FNZ caused hangover effect in 59.4%, while only 32.4% of placebo and 30.3% of valerian-treated groups reported this effect.	(1) n/a (2) n/a (3) 3
Aqueous extract
13	Pakseresht S 201155	Randomized, placebo-controlled, double-blind Population: Obsessive-Compulsive Disorder (OCD) patients (n=31)	Intervention: V. officinalis aqueous extract 750 mg per day (250 mg t.i.d.) for 8 weeks Measures: Yale-Brown scale for OCD (Y-BOCS)	Significantly reduced Y-BOCS score in the treatment group compared to placebo.	No significant difference in observed side effects, however increased somnolence in the treatment group (53.3% in treatment group and 18.75% in placebo group)	(1) n/a (2) n/a (3) 5
14	Schulz H 199438	Randomized, placebo-controlled, double-blind Population: Elderly poor sleepers (n=14)	Intervention: V. officinalis aqueous alkaline extract (Valdispert forte): (1) 405 mg single administration 1 h before sleep recording; (2) 405 mg t.i.d. for 7 days. Measures: Objective (polysomnography)	(1) Acute administration had no effect. (2) V. officinalis increased SWS and K-complex density, and decreased sleep stage 1. (SWS increased in each single subject on valerian.) No effect on sleep onset time, time awake after sleep onset, or self-rated sleep quality.	Not noted.	(1) n/a (2) n/a (3) 2
15	Balderer G 198540	Randomized, placebo-controlled, double-blind, cross-over Population: Healthy young volunteers (n=18)	Intervention: Single doses of V. officinalis aqueous extract (450 or 900 mg) or placebo 30 min before bedtime. At home (n=10) and in the laboratory (n=8). Measures: Subjective: sleep questionnaires, self-rating scale, night-time motor activity (n=18). Objective: polysomnography (n=8).	Home: V. officinalis dose-dependently reduced subjective sleep latency and wake time after sleep onset. Self-rating of subjective quality showed no difference (data not shown). Laboratory: No statistically significant difference between valerian and placebo.		(1) n/a (2) n/a (3) 2
16	Leathwood PD 198241	Randomized, placebo-controlled, blinded Population: Volunteers. Self-reported habitually good sleeper, habitually poor or irregular sleepers (n=128)	Intervention: Single doses of (1) V. officinalis aqueous extract 400 mg; (2) over-the-counter preparation containing valerian and hops (Hova, Zyma S.A.); (3) placebo. 1 h before bedtime. Each treatment 3 times, randomly on non-consecutive nights. Measures: Sleep latency and quality, dream recall, night awakenings, somnolence the next morning (sleep questionnaire).	V. officinalis produced significant decrease in subjective sleep latency and improved sleep quality. Sleep quality improvement was most notable among poor or irregular sleepers and smokers. Proprietary preparation produced ‘hangover effect’ the next morning, which was absent after valerian intake.	No notable side effects	(1) n/a (2) n/a (3) 5
Unknown extract
17	Farah GJ 201933	Randomized, split-mouth, controlled, double-blind, cross-over Population: anxious patients undergoing osteotomy and odontosection (n=20)	Intervention: V. officinalis extract 100 mg. Control drug: midazolam 15 mg. Both in an identical-looking capsules). 60 min before the surgical procedures. Measures: Oxygen saturation, HR, systolic and diastolic BP, RR, sedation (Ramsay scale). Self-assessment of anterograde amnesia.	More patients with valerian were rated as calm. No difference between valerian and midazolam (benzodiazepine) in oxygen saturation. HR and BP were lower with midazolam. Midazolam caused somnolence and anterograde amnesia, while valerian did not.	The most commonly reported side effect was somnolence. No statistically significant difference between the 2 drugs.	(1) n/a (2) n/a (3) 5
18	Mineo L 201731	Randomized, placebo-controlled, double-blind, cross-over. Population: Healthy volunteers (n=15)	Intervention: Single dose of V. officinalis extract capsule (300 mg with 0.8% valerenic acid) Measures: Cortical excitability (TMS)	Significant reduction in intracortical facilitation (ICF) at 1 h after Valerian extract intake, without affecting other TMS parameters. ICF returned to normal at 6 h.	No adverse events	(1) n/a (2) n/a (3) 4
19	Behboodi Moghadam Z 201663	Randomized, placebo-controlled, double-blind Population: Female students having premenstrual syndrome (n=100)	Intervention: V. officinalis extract 630 mg twice daily, in the last 7 days of menstrual period for 3 cycles. Measures: Severity of emotional, behavioral, and physical premenstrual symptoms (questionnaire) Summary measures for meta-analysis: difference in means	Valerian improved emotional, behavioral, and physical premenstrual symptom severity, whole placebo had no effects.	Not noted	(1) n/a (2) self-rated emotional state (3) 5
20	Jacobs BP 200551	Randomized, placebo-controlled, double-blind (internet-based) Population: Volunteers with anxiety and insomnia (n=391). Recruited via e-mail and banner advertisements on websites	Intervention: (1) V. officinalis extract (6.4 mg (1%) valerenic acid); (2) Piper methysticum extract (100 mg total (30%) kavalactones); (3) placebo. For 28 days Measures: Anxiety (STAI) and insomnia (ISI) Summary measures for meta-analysis: difference in means	Similar decrease in anxiety and insomnia symptoms among the 3 groups.	Diarrhea (valerian 18%, Kava 11%, control 8%)	(1) ISI (2) STAI (3) 5
21	Gurley BJ 200568	Cross-over Population: Healthy volunteers (n=12)	Intervention: (1) V. officinalis extract (125 mg 3 times daily); (2) Hydrastis canadensis (900 mg 3 times daily); (3) Piper methysticum (100 mg twice daily); (4) Cimicifuga racemosa (1090 mg twice daily). For 28 days separated by 30 days washout. Measures: CYP1A2, CYP2D6, CYP2E1 and CYP3A4/5 phenotypes	No significant changes in phenotypic ratios were observed for V. officinalis. (H. canadensis inhibited CYO2D6 and CYP3A4/5, P. methysticum reduced CYP2E1, and C. racemosa inhibited CYP2D6.)	No serious adverse events	(1) n/a (2) n/a (3) n/a
22	Gutierrez S 200449	Randomized, placebo-controlled, double-blind, cross-over Population: Healthy volunteers (n=10)	Intervention: Single doses of V. officinalis standardized extract 600, 1200, and 1800 mg Measures: Subjective mood (including sedation by ARCI) and psychomotor performance (DSST) Summary measures for meta-analysis: difference in means	No significant difference from placebo.		(1) n/a (2) self-rated sedation (3) 4
23	Coxeter PD 200348	Randomized, placebo-controlled, double-blind, n-of-1 Population: Patients with chronic insomnia (n=24)	Intervention: V. officinalis extract 450 mg equivalent to 2000 mg dry root / rhizome (5.88 mg valerenic acids, 0.96 mg valerenal, and 2.46 mg valtrates), 30 min before bed for 3 weeks. 5 days wash-out. Measures: Sleep diary	Fair response for energy level in the previous day, but only modest response for other variables.	There was no significant difference in the number, distribution, or severity of side effects between valerian and placebo.	(1) n/a (2) n/a (3) 5
24	Cropley M 200243	Randomized, controlled Population: Young healthy volunteers (n=54)	Intervention: (1) V. officinalis standardized extract 600 mg (Lichtwer-Pharma UK Ltd); (2) Piper methysticum (120 mg) For 7 days. Compared to non-placebo control. Measures: Blood pressure, heart rate, and subjective ratings of pressure in response to standardized mental stress task-induced psychological stress were assessed.	V. officinalis (and Piper methysticum) reduced psychological pressure and systolic blood pressure responsivity during stress task. V. officinalis reduced heart rate reaction to mental stress.		(1) n/a (2) n/a (3) 1
25	Wheatley D 200166	Observational, cross-over Population: Outpatients suffering from stress-induced insomnia (n=19)	Intervention: (1) Piper methysticum 120 mg; (2) V. officinalis 600 mg (Lichtwer-Pharma UK Ltd). For 6 weeks. 2 weeks wash-out. Piper methysticum first. Measures: Severity of stress (VAS) and sleep disturbance (subjective).	Severity of stress: Significant reduction during the first weeks on P. methysticum. There was no further change during the second 6 weeks on V. officinalis. Severity of insomnia: Score fell after he first 6 weeks on P. methysticum, and further fell after the final 6 weeks on V. officinalis.	1. Vivid dreams, daytime drowsiness, heavy sleep and depression for V. officinalis. 2. Dry mouth, gastric disturbance, diarrhea, dizziness, craving for trial drug, and depression for P. methysticum.	(1) n/a (2) n/a (3) n/a
26	Kohnen 198839	Randomized, placebo-controlled, double-blind Population: Healthy volunteers (n=48)	Intervention: Single doses of (1) Valerian extract 100 mg, (2) propranolol (20 mg), (3) placebo, and (4) valerian + propranolol Measures: Pulse frequency, test performance, psychological strain, and somatic arousal under stress conditions after intervention	Valerian induced a slight improvement in the concentration task, while propranolol and valerian-propranolol combination reduced the performance values. Valerian reduced the feelings of somatic arousal. Valerian had no effect on psychological strain.	Not noted	(1) n/a (2) n/a (3) 2
Whole root
27	Samaei A 201832	Randomized, placebo-controlled, double-blind, cross over Population: haemodialysis patients (n=39)	Intervention: V. officinalis root/rhizome 530 mg, 60 min before bedtime for 1 month. Measures: Cognitive brain functions (Mini-Mental State Examination: MMSE) and EEG	Valerian significantly improved cognitive status (MMSE), although no significant changes were observed in EEG.	Not noted.	(1) n/a (2) n/a (3) 4
28	Ahmadi M 201735	Randomized, placebo-controlled, double-blind. Population: HIV-positive patients receiving efavirenz (n=51)	Intervention: V. officinalis root/rhizome 530 mg (> 0.05% valerenic acid), nightly 1 h before sleep for 4 weeks Measures: Neuropsychiatric status (HAM-D, HAM-A, PANSS, PANSI, and PSQI) Summary measures for meta-analysis: difference in means	Sleep and anxiety significantly improved in Valerian treatment group.	There was no significant difference between the groups.	(1) PSQI (2) HAM-A (3) 3
29	Jenabi E 201764	Randomized, placebo-controlled, triple-blind Population: postmenopausal women with hot flashes (n=60, all women)	Intervention: V. officinalis root/rhizome 225 mg 3 times per day for 8 weeks Measures: Severity and frequency of hot flashes (Kupperman index)	Significantly lower severity after 1 and 2 months and reduced frequency after 2 months in V. officinalis treatment group	No side effects	(1) n/a (2) n/a (3) 4
30	Thomas K 201662	Randomized, placebo-controlled, double-blind, cross-over Population: Healthy volunteers (n=40)	Intervention: Single dose of V. officinalis root/rhizome 1600 mg (containing 0.8% valerenic acid) Measures: SVRT, subjective sleepiness scales (Karolinska Sleepiness Scale), SFST performance scores, driving simulator performance	There were no significant differences in SVRT, sleepiness scales, SFST, and driving simulator performance		(1) n/a (2) n/a (3) 5
31	Hassani S 201561	Randomized, placebo-controlled, double-blind Population: Coronary artery bypass graft (CABG) surgery patients (n=61)	Intervention: V. officinalis root/rhizome 1,060 mg per day (530 mg twice daily, every 12 h) for 8 weeks Measures: Cognitive brain function (MMSE test)	MMSE score was restored on the 60th day in valerian treatment group, whereas reduced in placebo group.		(1) n/a (2) n/a (3)5
32	Pinheiro ML 201460	Randomized, placebo-controlled, double-blind, split-mouth Population: Dental surgery patients (n=20)	Intervention: V. officinalis comminuted root/rhizome 100 mg, 1 h prior to each surgical procedure Measures: Anxiety (assessed by surgeons and researchers) and physical parameters Summary measures for meta-analysis: odds ratio	Valerian significantly reduced anxiety. Valerian was effective in maintaining systolic blood pressure and heart rate after surgery.	There was no significant difference between the groups.	(1) n/a (2) Surgeon-assessed anxiety (3) 5
33	Mirabi P 201359	Randomized, placebo-controlled, double-blind Population: Menopausal women with the chief complaint of hot flash (n=68)	Intervention: V. officinalis root/rhizome 675 mg per day (225 mg t.i.d), for 8 weeks Measures: Severity and frequency of hot flashes	Valerian reduced the severity and frequency of hot flashes	–	(1) n/a (2) n/a (3) 4
34	Mirabi P 201158	Randomized, placebo-controlled, double-blind Population: Female students experiencing moderate-severe dysmenorrhoea (n=100)	Intervention: V. officinalis root/rhizome 675 mg per day (225 mg t.i.d) for 3 days from the first day of menstruation, continued for 2 menstrual cycles. Measures: Pain severity (VAS, 3 times per day), the severity of associated systemic symptoms (fatigue, diarrhea, syncope, nausea and vomiting, lack of energy, headache, and mood swings)	The pain severity was reduced in both groups, but the extent of the reduction was larger in the treatment group. There was no difference between the groups in the total scores of associated systemic manifestations, except for syncope (improvement in V. officinalis treatment group)	No adverse effects	(1) n/a (2) n/a (3) 5
35	Taavoni S 201157	Randomized, placebo-controlled, triple-blind Population: Postmenopausal women with self-reported insomnia (n=100)	Intervention: V. officinalis root/rhizome 530 mg (Sedamin) twice daily for 4 weeks Measures: PSQI Summary measures for meta-analysis: difference in means	Significant improvement in PSQI score and improved percentage in the intervention group compared to placebo.	No reported adverse effects.	(1) PSQI (2) n/a (3) 4
36	Barton DL 201156	Randomized, placebo-controlled, double-blind Population: Cancer patients (n=227)	Intervention: V. officinalis root/rhizome 450 mg (containing 0.8% valerenic acid) 1 h before bedtime for 8 weeks Measures: (1) PSQI. (2) Functional outcomes of sleep questionnaire, fatigue (BFI), and mood (POMS). (3) Toxicity Summary measures for meta-analysis: difference in means	(1) No difference in PSQI score. (2) Significantly better fatigue end points (BFI and POMS), less trouble with sleep, and less drowsiness in the treatment group over control.	No difference in toxicities, except for alkaline phosphatase increase (slightly more common in the placebo group).	(1) PSQI (2) n/a (3) 4
37	Cuellar NG 200930	Randomized, placebo-controlled, triple-blind Population: Restless legs syndrome (RLS) patients (n=37)	Intervention: V. officinalis root/rhizome 800 mg (containing 1.16 mg valerenic acid) per day 60 min before bedtime for 8 weeks Measures: Sleep disturbances (PSQI and ESS) and severity of RLS Summary measures for meta-analysis: difference in means	Although there was no statistically significant difference valerian group showed a greater improvement in the majority of sleep quality and RLS scores. The most obvious changes were seen in participants with ESS score of ≥10.	GI disturbances, fatigue, vivid dreams, agitation/restlessness, headache, dizziness, rash	(1) PSQI (2) n/a (3) 5
38	Glass JR 200345	Randomized, placebo-controlled, double-blind, cross-over. Population: Healthy elderly volunteers (n=14)	Intervention: Single doses of V. officinalis root/rhizome 400 or 800 mg (containing 0.683% valerenic acids). Compared to temazepam, diphenhydramine, and placebo. Measures: Psychomotor performance (Manual Tracking Test, DSST, manual tracking and digit symbol substitution test); sedation and mood (VAS)	Valerian was not different from placebo on any measure of psychomotor performance, while temazepam and diphenhydramine caused psychomotor impairment. No sedation or any side effects as a result of valerian treatment.		(1) n/a (2) n/a (3) 2
39	Francis AJ 200246	Randomized, placebo-controlled, double-blind, cross-over Population: Children with intellectual deficit (ID) and primary sleep problems (n=5)	Intervention: Valeriana edulis (dried and crushed whole root, containing 1.1% of valtrate/isovaltrate) 20mg/kg body weight, nightly 1 h before bedtime for 2 weeks. Wash-out 7 days. Measures: Sleep latency, time spent awake during the night, and sleep quality (VAS).	V. edulis treatment significantly reduced sleep latencies and nocturnal time awake, lengthened total sleep time, and improved sleep quality. The treatment was most effective in children with hyperactivity.	No significant adverse effects.	(1) n/a (2) n/a (3) 5
40	Dominguez RA 200067	Observational Population: Hispanic outpatients receiving mental health services and complaining of insufficient sleep (n=20)	Intervention: V. officinalis root/rhizome (Nature’s Way) 470 mg each night 30-60 min prior to retiring (possibly increased up to max. 1410 mg after 1 week) for 4 weeks. Measures: Sleep questionnaire	Week 1: 16 patients rated moderately improved. Week 2: 15 patients rated more than moderately improved. Global improvement at week 2 was significantly better at week 2 than week 1.		(1) n/a (2) n/a (3) n/a
Isolates
41	Andreatini R 200271	Randomized, placebo-controlled, double-blind Population: Outpatients with generalized anxiety disorders (n=36)	Intervention: (1) Valepotriates (80% dihydrovaltrate, 15% valtrate, and 5% acevaltrate) (average dose: 81.3mg/day); (2) placebo; (3) diazepam (average dose:6.5mg/day). Flexible doses according to the patient’s therapeutic response. 4 weeks. Measures: Anxiety (HAM-A and STAI).	Total HAM-A score: significant reduction in all 3 groups. (No significant difference among the 3 groups.) Psychological factor of HAM-A: Reduced in valepotriates and diazepam groups.	No moderate or serious adverse reaction was observed.	(1) n/a (2) n/a (3) 5
42	Poyares DR 200270	Randomized, placebo-controlled, double-blind Population: (A) Primary insomnia patients with poor sleep despite chronic use of BZDs (n=19); (B) Healthy individuals (n=18)	Intervention: valepotriates: 80% didrovaltrate, 15% valtrate, and 5% acevaltrate (from Valeriana wallichii root). Three times daily in 100 mg doses for 15 days. After BZD withdrawal (over 2 weeks + 48 h without BZD). Measures: Sleep diaries and sleep parameters (sleep latency, total sleep time, sleep efficiency, number of arousals, WASO, REM and NREM; sleep EGG	Valerian group reported significantly better sleep quality than placebo during the second week of treatment. Sleep EEG data showed a significant increase in alpha count during Sleep stage 3 and 4 NREM in valerian group. Valerian group showed a significant decrease in WASO compared to placebo, while placebo group presented shorter sleep latency.	Gastrointestinal symptoms (diarrhea, stomachache, and bitter taste in their mouth) in the first week of valerian treatment.	(1) n/a (2) n/a (3) 3

* (1) data included in meta-analysis for sleep quality; (2) data included in meta-analysis for anxiety; (3) Jadad scale.

Abbreviations: ARCI-Addiction Research Center Inventory, CFF-Critical Flicker Fusion, CRT-Choice Reaction Time, DSST-Digit Symbol Substitution Test, DST-Digit Span Test, EEG-Electroencephalogram, HAM-A-Hamilton Anxiety Rating Scale, HAM-D-Hamilton Depression Rating Scale, ISI-Insomnia Severity Index, LARS-Line Analogue Rating Scales, LSEQ-Leeds Sleep Evaluation Questionnaire, MMSE-Mini-Mental State Examination, PANSS-Positive and Negative Syndrome Scale, PANSI-The Positive and Negative Suicide Ideation, PSQI-Pittsburgh Sleep Quality Index, SFST-Standardized Field Sobriety Test, SMT-Short term Memory Test, SST-Symbol Search Test, STDI-State Trait Depression Inventory, SVRT-Simple Visual Reaction Test, WASO-Wake Time After Sleep Onset.