Background
Methods
Search strategy
Selection criteria
Data abstraction and synthesis of results
Passionflower | Kava | St. John's wort | Lysine | Magnesium | All studies | |
---|---|---|---|---|---|---|
Patients (n)
| 278 | 1054 | 762 | 137 | 388 | 2619 |
Gender
| ||||||
Male
| 46 (17%) | 227 (22%) | 246 (32%) | 83 (61%) | 130 (34%) | 732 (28%) |
Female
| 50 (18%) | 759 (72%) | 516 (68%) | 54 (39%) | 258 (66%) | 1637 (63%) |
Not Reported
| 182 (65%) | 68 (6%) | - | - | - | 250 (9%) |
Age range (years)
| 19-47 | 18-75 | 18-65 | 20-59 | 18-82 | 18-82 |
Race/Ethnicity
| ||||||
Asian
| - | 2 (< 1%) | - | 108 (79%) | - | 110 (4%) |
Caucasian
| - | 401 (38%) | 83 (11%) | 29 (21%) | - | 513 (20%) |
African American
| - | 14 (1%) | - | - | 14 (1%) | |
Hispanic
| - | 7 (< 1%) | - | - | 7 (< 1%) | |
Native American
| - | 7 (< 1%) | - | - | 7 (< 1%) | |
Not Reported
| 278 (100%) | 623 (59%) | 679 (89%) | 316 (100%) | 1896 (72%) |
Reference | Study Design | Sample Population | Intervention | Control | Length of Treatment | Outcomes | Direction of Evidence | Reported Adverse Events |
---|---|---|---|---|---|---|---|---|
Bourin (1997) [34] | Randomized; Double-blind; Parallel Group | 182 outpatients with adjustment disorder with anxious mood | Euphytose1; 2 tablets, 3 times a day | Placebo tablets | 28 days | Significant reduction in HAMA scores (from D7 to D28) in favour of Euphytose treatment | + | No serious AEs. Dry mouth Headache Constipation Drowsiness |
Akhondzadeh (2001) [32] | Randomized; Double-blind; Parallel group | 36 outpatients with DSM-IV for GAD for at least 6 months | 45 drops/day of Passiflora extract plus placebo tablet | Oxazepam 30 mg/day plus placebo drops | 4 weeks | Decrease in HAMA for both treatments2; overall no significant difference in efficacy between treatments | + | Higher impairment of job performance in oxazepam group; overall no significant difference in total side effects3
|
Movafegh (2008) [33] | Randomized; Double-blind; Parallel Group | 60 patients undergoing inguinal herniorrhaphy | Oral Passiflora incarnata (500 mg, Passipy™ IranDarouk) | Placebo | Given as pre-medication 90 minutes before surgery | NRS anxiety scores were significantly lower in the passiflora group | + | Not reported |
Reference | Study Design | Sample Population | Intervention | Control | Length of Treatment | Outcomes | Direction of Evidence | Reported Adverse Events |
---|---|---|---|---|---|---|---|---|
Volz (1997) [42] | Randomized; Double-blind; Parallel Group | 101 outpatients with anxiety of non-psychotic origin1
| Kava-kava extract WS 1490 (90- 110 mg dry extract = 70 mg kl per capsule) | Placebo | 24 weeks | Significant reduction in anxiety (HAMA, CGI, SCL-90-R, AMS) in favour of kava-kava treatment. | + | Excellent tolerability, similar to placebo; no clinically relevant changes in laboratory results. Stomach upset. |
Scherer (1998)* [48] | Open-label; Uncontrolled Observational study | 52 outpatients with nonpsychotic anxiety | Kava preparation (no dose reported in abstract) | N/A | Not reported in abstract | 42 patients (80.8%) rated kava treatment as "very good" or "good". | + | Rare |
Malsch (2001) [45] | Randomized; Double-blind; Parallel group | 40 adult outpatients with non-psychotic nervous anxiety, tension and restlessness, impairing work performance, normal social activities and relationships2
| Pre-treatment with benodiazepines (tapered off over two weeks) followed by capsules of 50 mg/day of dry extract standardized to 35 mg kava lactone for three weeks | Pre-treatment with benodiazepines (tapered off over two weeks) followed by placebo for three weeks | 5 weeks | Significant reduction in anxiety (HAMA, Bf-S, EAAS, CGI) in kava-treated group. | + | No serious adverse events |
Watkins (2001) [44] | Randomized; Double-blind; Parallel Group | 13 patients with GAD | Kava 280 mg/day (standardized to 30% kavalactones) | Placebo | 4 weeks | Significant improvement in baroreflex control of heart rate in kava-treated group; respiratory sinus arrhythmia did not respond to kava treatment. | + | Not reported |
Connor (2002) [52] | Randomized; Double-blind; Parallel Group | 38 adults with DSM-IV GAD3
| Kava (standardized to 70 mg kavalactones [kl]). Treatment initiated at 149 mg kl/day and increased to 280 mg kl/day for the next 3 weeks. | Placebo | 4 weeks | No significant difference to placebo4
| - | Well tolerated. No evidence of withdrawal or sexual side effects. |
Boerner (2003) [43] | Randomized; Double-blind; Parallel Group | 129 outpatients diagnosed with GAD (GAD; ICD-10: F41.1) | 400 mg/day Kava extract LI 150 (standardized to 30% kavapyrones, extraction solvent 96% ethanol in water, drug-extract ratio 13-20:1) | (1) 10 mg/day Buspirone or (2) 100 mg/day Opipramol | 8 weeks | Kava was shown to be as effective as reference treatments; 75% of patients responded (50% reduction of HAMA score). | + | 1 treatment-related adverse event. No systematic difference between treatments. No liver toxicity reported5. |
Cagnacci (2003) [46] | Randomized; Open; Parallel Groups (3) | 80 peri-menopausal women | Calcium (1 g/day) plus: (1) Kava-Kava,100 mg/day (55% of kavaina; Natural Bradel, Milano, Italy) (2) Kava-Kava, 200 mg/day | Calcium (1 g/day) | 3 months | Significant reduction in STAI scores in favour of combination treatment. | + | Mild/moderate: Nausea Gastric pain. No liver toxicity. |
Gastpar (2003) [50] | Randomized; Double-blind; Parallel Group | 141 adult outpatients diagnosed with neurotic anxiety6
| 150 mg/day kava special extract WS 1490 (standardized to 35 mg kl) | Placebo | 4 weeks | Pronounced decrease in ASI score for the kava group; however not statistically significant overall; however an exploratory analysis of variance across the differences between treatment end and baseline, with center as a second factor, showed superiority of kava over placebo. | - | Increased tiredness. No liver toxicity |
Jacobs (2005) [53] | Randomized; Double-blind; Parallel Group (3) | 391 healthy volunteers with anxiety7 and insomnia | (1) 100 mg kl/day kava (30% total kavalactones in extract) with valerian placebo (2) 6.4 mg/day valerian (1% valerenic acid in extract) with kava placebo | Double placebo | 28 days | Greater reductions in placebo group, but not statistically significant (STAI-State substest). | - | Similar frequency between treatments and placebo. No reports of liver toxicity |
Sarris (2009) [47] | Randomized; Double-blind; Crossover | 41 adult participants with 1 month or more of elevated generalized anxiety | Kava tablets (250 mg/day kavalactones) | Placebo | 3 weeks | Highly significant reduction in anxiety (HAMA, BAI, MADRS) in kava-treated group. | + | No serious adverse events. Mild dizziness, nausea. No liver toxicity. |
Sarris (2009) [51] | Randomized; Double-blind; Crossover | 28 adults with MDD and co-occurring anxiety | Hypericum perforatum8
(1 × 1.8 g tablet, three times/day); Kava rhizome aqueous extract9
(1 × 2.66 g tablet, 3 times/day) | Placebo | 4 weeks | Combination treatment had no significant effects on anxiety (BDI-II). | - | No serious adverse events. Mild gastrointestinal upset. No liver toxicity |
Reference | Study Design | Sample Population | Intervention | Control | Length of Treatment | Outcomes | Direction of Evidence | Reported Adverse Events |
---|---|---|---|---|---|---|---|---|
Taylor (2000) [63] | Open-label; Uncontrolled; Observational | 13 subjects with a primary DSM-IV diagnosis of OCD of at least 12 month duration | Fixed dose of 900 mg/day of 0.3% hypericin (a psychoactive compound in Hypericum) | N/A | 12 weeks | Significant improvement in Y-BOCS scores in SJW group (comparable to those seen in clinical trials with SSRIs). | + | Diarrhea Restless sleep |
Volz (2002) [61] | Randomized; Double-blind; Parallel Group | 149 outpatients diagnosed with somatization Disorder2, undifferentiated somatoformDisorder3, or somatoform autonomic Dysfunctions4
| Hypericum extract LI 160 (600 mg/day) | Placebo | 6 weeks | Significant reduction in anxiety (HAMA-SOM, CGI, HAMA-T, HAMA-PSY, HDS, SCL-90-R, SCL-90-R-ANX) in favour of SJW treatment. | + | Verywell tolerated. Mild/moderate: Abdominal pain Arthritis Arrythmia Bronchitis Cystitis Headache Neuralgia |
Muller (2003) [62] | Open-label; uncontrolled observational | 500 patients diagnosed with depression comorbid with anxiety | (1) 500 mg valerian extract5 and 600 mg/day St John's Wort6(2) 1,000 mg valerian extract7 and 600 mg/day St John's wort6
| N/A | 6 weeks | Significant reduction in anxiety disorder symptoms (HAMA) in both treatment groups. Higher dosage results in greater improvements. | + | Allergy Bad dreams Sleep disorders Dysphoria |
Kobak (2005) [60] | Randomized; Double-blind;Parallel Group | 40 subjects with GAD | St John's wort8; flexible dose (600-1800 mg/day), mean dose at week 12 was 1676 mg/day | Placebo | 12 weeks | No significant difference to placebo (LSAS) | - | Similar to placebo. Mild/moderate: Gastrointestinal upset Dizziness Insomnia Fatigue |
Kobak (2005) [59] | Randomized; Double-blind; Parallel Group | 60 outpatients with primary diagnosis of OCD | St John's wort LI 1608; flexible dose (600-1800 mg/day), mean dose at week 12 was 1663 mg/day | Placebo | 12 weeks | No significant difference to placebo (Y-BOCS) | - | Similar to placebo9. Mild/moderate: Headache Gastrointestinal symptoms Fatigue Agitation Sleep disturbance |
Sarris (2009) [51] | Randomized; Double-blind; Crossover | 28 adults with MDD and co-occurring anxiety | Hypericum perforatum10
(1 × 1.8 g tablet, three times/day); Kava rhizome aqueous extract11(1 × 2.66 g tablet, 3 times/day) | Placebo | 4 weeks | Combination treatment had no significant effects on anxiety (BDI-II). | - | No serious adverse events. Mild gastrointestinal upset. No liver toxicity |
Reference | Study Design | Sample Population | Intervention | Control | Length of Treatment | Outcomes | Direction of Evidence | Reported Adverse Events |
---|---|---|---|---|---|---|---|---|
Jezova (2005) [67] | Randomized; Double-blind; Parallel Group | 29 healthy male subjects at the upper limit of the normal range of a trait anxiety scale1
| Mixture of L-lysine and L-arginine (3 g each/day) | Placebo | 10 days | AMino acid treatment enhanced adrenocorticotropic hormone, cortisol, adrenaline and noradrenaline levels and galvanic skin responses during stress; no effect on heart rate and blood pressure. |
+
| None |
Smriga (2007) [68] | Randomized; Double-blind; Parallel Group | 108 healthy Japanese adults | Oral L-lysine (2.64 g/day) and L-arginine (2.64 g/day) | Placebo | 1 week | L-lysine/L-arginine treatment significantly reduced trait and state anxiety; also decreased basal levels of salivary cortisol and chromogranin-A in male subjects |
+
| None |
Reference | Study Design | Sample Population | Intervention | Control | Length of Treatment | Outcomes | Direction of Evidence | Reported Adverse Events |
---|---|---|---|---|---|---|---|---|
Carroll (2000) [75] | Randomized; Double-blind; Parallel Group | 80 healthy males | Berocca: oral multivitamin1
| Placebo | 28 days | Multivitamin treatment significantly reduced anxiety as measured by GHQ-28, HADS and PSS. | + | Not reported |
De Souza (2000) [76] | Randomized; Double-blind; Crossover (4) | 44 women with adverse premenstrual symptoms but otherwise in good health | (1) 200 mg Mg, (2) 50 mg vitamin B6, (3) 200 mg Mg + 50 mg vitamin B6 per day | Placebo | One menstrual cycle | 200 mg/day Mg + 50 mg/day vitamin B6 significantly reduced anxiety-related premenstrual symptoms | + | Participants were not specifically asked, but none were reported spontaneously |
Hanus (2004) [77] | Randomized; Double-blind; Parallel Group | 264 patients with generalized anxiety (DSM-III-R) of mild-to-moderate intensity2
| Sympathyl: extracts of crataegus oxyacantha and eschscholtzia californica plus magnesium | Placebo | 3 months | Significant clinical improvement in anxiety3 in favour of the combination treatment | + | No serious AEs related to treatment4
|