Background
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What are the efficacy and safety of SJW in adults with MDD compared to placebo and active comparator?
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Is there a difference in effect, depending on the type of MDD (i.e., mild, moderate, severe)?
Methods
Search strategy
Eligibility criteria
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Participants: Studies in adults, male and female, 18 years of age and over, with a diagnosis of MDD were eligible for inclusion in the review. In studies not referring to a clinical diagnosis based on Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria, we applied a specified threshold on validated depression scales (see Additional file 3). Studies that enrolled individuals with other comorbid conditions, such as traumatic brain injury, were eligible for inclusion. Studies in participants in postnatal depression were included if the criteria were in accordance with DSM-V criteria for MDD (i.e., peripartum onset or 4 weeks following delivery). Studies in individuals with diagnoses of dysthymia, bipolar disorder, or schizophrenia, alone or in combination with major depression, were excluded in accordance with DSM-V criteria. Studies evaluating multiple psychiatric conditions were included if the data for patients with MDD were presented separately.
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Interventions: Studies that administered a supplement that contained a known amount of SJW, and the amount and type of active compounds contained in the SJW supplement that was specified (i.e., naphthodianthrones, hypericin, pseudohypericin, flavonoids, phloroglucinols, hyperforin, and adhyperforin), were eligible. SJW could be evaluated alone or in conjunction with pharmacologic and/or psychotherapy.
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Comparator: Studies comparing SJW with placebo or with active comparators, or against another amount or extract of SJW, were eligible.
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Outcomes: Studies that reported Hamilton clinical rating scale for depression (HAMD) scores or other validated depression scale scores were eligible for inclusion as well as studies that reported other changes in depressive symptoms (e.g., suicidal ideation) or the rate of treatment responders. Studies that reported the number of patients in remission or rates of depression relapse were also eligible. Studies that reported adverse events in adults taking SJW for MDD were included if adverse events were reported by study arm. Studies that reported on biomarkers alone without reporting efficacy for depression outcomes were excluded. Only studies that at least reported outcome assessments at baseline and at the end of treatment for both study arms were included. Studies of healthcare provider outcomes, acceptance, prevalence, use, costs, study design features, and intervention features not reporting patient health outcomes were excluded.
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Timing: Only studies with a treatment duration of 4 weeks or longer were eligible.
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Setting: Studies were not limited by setting (e.g., country, physical location of treatment).
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Study design: Included studies were limited to RCTs.
Inclusion screening
Data extraction
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Participants: MDD diagnostic criteria, baseline measure of depression symptoms, depression severity (mild, moderate, or severe) using the authors’ description, depression history (e.g., recurrent), comorbidities, mean age and age range, gender
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Interventions: details including amount and type of active compounds contained in the SJW supplement, dosage, co-intervention(s)
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Comparators: type and description of comparator
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Outcomes assessed: assessment measures and primary endpoint, method of data expression (e.g., mean difference), results (effect estimate, precision)
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Timing: time-points of outcome assessment, duration of intervention
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Setting: country
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Study design: aim of study, inclusion and exclusion criteria, sample size and reported power calculations, funding source.
Risk of bias
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Good: Comparable groups are initially assembled and maintained throughout the study with at least 80 % follow-up; reliable, valid measurement is used and applied equally to all groups; interventions are clearly described; all important outcomes are considered; appropriate attention is given to confounders in analysis; and ITT analysis is used.
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Fair: One or more of the following issues is found in the study: some though not major differences between groups exist at follow-up; measurement instruments are acceptable but not ideal, though are generally applied equally; some but not all important outcomes are considered; some but not all potential confounders are accounted for in analyses. ITT analysis must be done.
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Poor: One or more of the following “fatal flaws” is found in the study: initially assembled groups are not comparable or maintained throughout the study; unreliable or invalid measurements are used or applied unequally across groups; key confounders are given little to no attention in analyses; ITT analysis is not used.
Data synthesis
Quality of evidence
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High indicates that review authors are very confident that the effect estimate lies close to the true effect for a given outcome, as the body of evidence has few or no deficiencies. As such, the reviewers believe the findings are stable and further research is very unlikely to change confidence in the effect estimate.
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Moderate indicates that the review authors are moderately confident that the effect estimate lies close to the true effect for a given outcome, as the body of evidence has some deficiencies. As such, the reviewers believe that the findings are likely to be stable, but further research may change confidence in the effect estimate and may even change the estimate.
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Low indicates that the review authors have limited confidence that the effect estimate lies close to the true effect for a given outcome, as the body of evidence has major or numerous (or both) deficiencies. As such, the reviewers believe that additional evidence is needed before concluding either that the findings are stable or that the effect estimate lies close to the true effect.
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Very low indicates that the review authors have very little confidence that the effect estimate lies close to the true effect for a given outcome, as the body of evidence has very major deficiencies. As such, the true effect is likely to be substantially different from the estimated effect; thus, any estimate of effect is very uncertain.
Results
Study ID | Recruitment method (random sequence generation) | Allocation concealment | Blinding of participants and personnel | Blinding of outcome assessment | Incomplete outcome data | Selective reporting of outcome data | Other: all receive TAU, only treatment group receives SJW (no placebo for controls) | Other: appropriate washout period or exclusion of individuals taking personal supplements | Other: baseline assessment, appropriate statistical analysis, COI) | USPSTF quality rating (good, fair, poor) |
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Behnke, 2002 [17] | Unclear risk | Unclear risk | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Poor |
Bernhardt, 1993 [16] | Unclear risk | Unclear risk | High risk | High risk | Unclear risk | Unclear risk | Low risk | NA | Unclear risk | Poor |
Bjerkenstedt, 2005 [18] | Unclear risk | Unclear risk | Low risk | Low risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Brenner, 2000 [19] | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Fava, 2005 [20] | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Poor |
Gastpar, 2005 [21] | Low risk | Unclear risk | Low risk | Unclear risk | Unclear risk | Unclear risk | Low risk | NA | Low risk | Poor |
Gastpar, 2006 [22] | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
HDTSG, 2002 [23] | Low risk | Low risk | Low risk | Low risk | Unclear risk | Low risk | Low risk | NA | Low risk | Fair |
Hangsen, 1994 [48] | Low risk | Low risk | Low risk | Unclear risk | Unclear risk | Unclear risk | Low risk | NA | Low risk | Poor |
Harrer, 1993 [24] | Low risk | Unclear risk | Low risk | Unclear risk | Unclear risk | Unclear risk | Low risk | NA | Low risk | Poor |
Harrer, 1999 [25] | Unclear risk | Unclear risk | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Kalb, 2001 [26] | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Kasper, 2006 [27] | Low risk | Low risk | Low risk | Low risk | Unclear risk | Low risk | Low risk | NA | Low risk | Fair |
Kasper, 2008 [28] | Low risk | Low risk | Low risk | Unclear risk | Low risk | Low risk | Low risk | Low risk | Low risk | Fair |
Laakmann, 1998 [29] | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Lecrubier, 2002 [30] | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Lenoir, 1999 [31] | Unclear risk | Low risk | Unclear risk | Unclear risk | Unclear risk | Unclear risk | Low risk | NA | Low risk | Poor |
Liu, 2010 [32] | High risk | Unclear risk | High risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Poor |
Mannel, 2010 [33] | Low risk | Low risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Montgomery, 2000 [34] | Unclear risk | Unclear risk | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Unclear risk | Poor |
Moreno, 2005 [35] | Unclear risk | Unclear risk | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Pakseresht, 2012 [36] | Unclear risk | Unclear risk | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Philipp, 1999 [37] | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Rahman, 2008 [38] | Low risk | Low risk | Low risk | Unclear risk | Unclear risk | Unclear risk | Low risk | NA | Low risk | Poor |
Schrader, 1998 [40] | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Schrader, 2000 [39] | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Shelton, 2001 [41] | Low risk | Low risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Szegedi, 2005 [42] | Low risk | Low risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Uebelhack, 2004 [43] | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Volz, 2000 [50] | Unclear risk | Low risk | Low risk | Low risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Vorbach, 1997 [44] | Low risk | Unclear risk | Low risk | Unclear risk | Unclear risk | Unclear risk | Low risk | NA | Low risk | Poor |
Wheatley, 1997 [45] | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Witte. 1995 [49] | Unclear risk | Low risk | Low risk | High risk | Low risk | Unclear risk | Low risk | NA | Low risk | Good |
Woelk, 2000 [46] | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
van Gurp, 2002 [47] | Low risk | Low risk | Low risk | Low risk | Low risk | Unclear risk | Low risk | NA | Low risk | Fair |
Study Details | Participants | Intervention |
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Behnke, 2002 [17], Country: NR Funding: unclear, industry author, provided SJW | Number of participants: 70 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: mild-moderate Age (years, M (SD)): 18–73 overall; 51.4 (10.9) SJW; 48.0 (12.6) fluoxetine, gender (% male): 29 % SJW; 34 % fluoxetine; (1 participant missing from SJW group) | Extract: Hypericum perforatum Dosage: 150 mg (0.450–0.495 mg total hypericin), 6 weeks Comparator: fluoxetine Follow-up time: 6 weeks |
Bernhardt, 1993 [16], Country: Germany Funding: unclear, not reported | Number of participants: 55 Diagnosis: clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): 54.5 (11.6), gender (% male): 29 % | Extract: hypericin Dosage: 0.25 mg extract/3 times per day (morning/noon/night), 4 weeks; Comparator: 0.25 mg extract/3 times per day (2 in the morning, 1 at noon) Follow-up time: 4 weeks |
Bjerkenstedt, 2005 [18], Country: Sweden Funding: no industry funding | Number of participants: 174 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): 49.1 (12.0) SJW; 50.4 (11.6) fluoxetine; 51.4 (11.8) placebo; gender (% male): SJW 20 %; fluoxetine 24 %: placebo 18 % | Extract: hypericum LI 160 Dosage: 300 mg, 3 times per day, daily, 4 weeks Comparator: fluoxetine, placebo Follow-up time: 4 weeks |
Brenner, 2000 [19], Country: USA Funding: no industry funding | Number of participants: 30 Diagnosis: MDD (DSM) and clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): 45; gender (% male): 37 % | Extract: LI 160 Dosage: 600 mg per day during week 1, followed by 900 mg per day for the remainder of the trial Comparator: sertraline Follow-up time: 7 weeks |
Fava, 2005 [20], Country: USA Funding: no industry funding | Number of participants: 135 Diagnosis: MDD (DSM), clinical rating scale for depression, other diagnosis, SCID Severity: moderate Age (years, M (SD)): 37.3 (11.0) Gender (% male): 43 % | Extract: LI 160 Dosage: 300 mg, 3 times a day Comparator: fluoxetine, placebo Follow-up time: 12 weeks |
Gastpar, 2005 [21] Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 241 Diagnosis: MDD (DSM), clinical rating scale for depression, MDD (ICD) Severity: moderate Age (years, M (SD)): 48.3 (12.7) SJW; 49.5 (13.8) sertraline Gender (% male): SJW 21 %; sertraline 31 % | Extract: STW3 Dosage: 612 mg/day/12 weeks Comparator: sertraline Follow-up time: 24 weeks |
Gastpar, 2006 [22], Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 388 Diagnosis: MDD (DSM), clinical rating scale for depression, MDD (ICD) Severity: moderate Age (years, M (SD)): SJW 50.8 (12.1); citalopram 49.3 (10.7); placebo 49.4 (12.7) Gender (% male): SJW 34 %, citalopram 35 %, placebo 27 % | Extract: STW3-VI Dosage: 900 mg/day/6 weeks Comparator: citalopram, placebo Follow-up time: 6 weeks |
HDTSG, 2002 [23], Country: USA Funding: no industry funding | Number of participants: 338 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: not reported Age (years, M (SD)): SJW 43.1 (13.5); sertraline 43.9 (13.9); placebo 40.1 (12.2) Gender (% male): SJW 35 %; sertraline 33 %; placebo 34 % | Extract: LI 160 Dosage: 300 mg/3 times a day/8 weeks Comparator: sertraline, placebo Follow-up time: 8 weeks |
Hangsen, 1994 [48], Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 108 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: not reported Age (years, M (SD)): 53.0 (7.5) SJW; 53.5 (10.3) placebo Gender (% male): SJW 42 %; placebo 32 % | Extract: LI 160 Dosage: 300 mg/3 times a day/6 weeks Comparator: placebo Follow-up time: 5 and 6 weeks |
Harrer, 1994 [24], Country: Germany Funding: unclear, not reported | Number of participants: 102 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: moderate Age (years, M (SD)): SJW 43.8 (13.4); maprotiline 47.6 (10.9) Gender (% male): SJW 25 %; maprotiline 31 % | Extract: LI 160 Dosage: 300 mg/3 times a day/4 weeks Comparator: maprotiline Follow-up time: 4 weeks |
Harrer, 1999 [25], Country: NR Funding: unclear, not reported | Number of participants: 228 Diagnosis: MDD (ICD) Severity: mild-moderate Age (years, M (SD)): SJW 68.4; fluoxetine 69.1 Gender (% male): 13 % | Extract: LoHyp-57 Dosage: 400 mg/two times a day/6 weeks Comparator: fluoxetine Follow-up time: 6 weeks |
Kalb, 2001 [26], Country: Germany Funding: industry funding | Number of participants: 72 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): SJW 48 (11); placebo 49 (10) Gender (% male): SJW 30 %; placebo 37 % | Extract: WS 5572 Dosage: 300 mg/3 times a day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Kasper, 2006 [27], Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 332 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): SJW 600 mg 46.3 (11.5); SJW 1200 mg 46.1 (10.7); placebo 46.9 (11.8) Gender (% male): SJW 600 mg 44 %; SJW 1200 mg 34 %; placebo 31 % | Extract: WS 5570 Dosage: 600 or 1200 mg/day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Kasper, 2008 [28], Countries: Germany and Sweden Funding: industry funding | Number of participants: 570 Diagnosis: MDD (DSM), clinical rating scale for depression, MDD (ICD) Severity: mild Age (years, M (SD)): 47.5 (10.7); placebo 47.4 (11.8) Gender (% male): SJW 27 %; placebo 24 % | Extract: WS 5570 Dosage: 300 mg/3 times a day/26 weeks Comparator: placebo Follow-up time: 32 weeks |
Laakmann, 1998 [29], Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 196 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): SJW WS 5572 47.3 (11.8); SJW WS 5573 48.7 (11.8); placebo 51.0 (12.7) Gender (% male): SJW WS 5572 18 %; SJW WS 5573 14 %; placebo 29 % | Extract: WS 5572; WS 5573 Dosage: 3 × 300 mg/day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Lecrubier, 2002 [30], Country: France Funding: industry funding | Number of participants: 375 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): SJW 40.2 (11.7); placebo 41.2 (11.4) Gender (% male): SJW 24 %; placebo 23 % | Extract: WS 5570 Dosage: 300 mg/3 times a day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Lenoir, 1999 [31], Countries: Switzerland and Germany Funding: unclear, industry author, provided SJW | Number of participants: 348 Diagnosis: MDD (ICD) Severity: mild-moderate Age (years, M (SD)): 19–94 (range) Gender (% male): 26 % | Extract: hypericin Dosage: 0.17 mg, 0.33 mg, or 1 mg/day (divided into 3 doses)/6 weeks Comparator: other doses of SJW |
Liu, 2010 [32], Country: China Funding: no industry funding | Number of participants: 170 Diagnosis: clinical rating scale for depression, other diagnosis, ISFC and WHO criteria Severity: not reported Age (years, M (SD)): SJW 67 (2.7); Deanxit 68 (2.8); psychotherapy 68 (3.0); placebo 67 (2.5) Gender (% male): 50 % | Extract: NA Dosage: 300 mg/3 times a day/12 weeks Comparator: Deanxit 10.5 mg/daily, cognitive therapy, suggestion therapy, supportive therapy and rational emotive therapy/twice per week, placebo (oryzanol 20 mg)/3 times a day Follow-up time: 12 weeks |
Mannel, 2010 [33], Country: Germany Funding: industry funding | Number of participants: 201 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: mild-moderate Age (years, M (SD)): SJW 47.0 (13.1); placebo 46.6 (13.8) Gender (% male): 17 % | Extract: LI 160 Dosage: 300 g/2 times a day/8 weeks Comparator: placebo Follow-up time: 8 weeks |
Montgomery, 2000 [34], Country: UK Funding: unclear, not reported | Number of participants: 248 Diagnosis: MDD (DSM) Severity: mild-moderate Age (years, M (SD)): NA Gender (% male): NA | Extract: LI 160 Dosage: 300 mg/3 times a day/12 weeks Comparator: placebo Follow-up time: 6 weeks |
Moreno, 2005 [35], Country: Brazil Funding: industry funding | Number of participants: 66 Diagnosis: clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): 40.5 (10.7) Gender (% male): 17 % | Extract: NA Dosage: 300 mg/3 times a day/8 weeks Comparator: fluoxetine, placebo Follow-up time: 8 weeks |
Pakseresht, 2012 [36], Country: Iran Funding: no industry funding | Number of participants: 40 Diagnosis: clinical rating scale for depression, other diagnosis, diagnosed depression, method unspecified Severity: mild-moderate Age (years, M (SD)): SJW 29.8 (6.2); placebo 30 (16.6) Gender (% male): SJW 50 %; placebo 45 % | Extract: NA Dosage: 300 mcg/3 times a day/6 weeks Comparator: nortriptyline 75–100 mg, imipramine 100–150 mg, amitriptyline 100–150 mg/daily, placebo/daily Follow-up time: 6 weeks |
Philipp, 1999 [37], Country: Germany Funding: industry funding | Number of participants: 263 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: not reported Age (years, M (SD)): 47 (12) Gender (% male): 25 % | Extract: STEI 300 Dosage: 350 mg/3 times day/8 weeks Comparator: imipramine, placebo Follow-up time: 8 weeks |
Rahman, 2008 [38], Country: Pakistan Funding: industry funding | Number of participants: 225 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: mild-moderate Age (years, M (SD)): SJW 33.89 (10.884); placebo 36.29 (12.478) Gender (% male): SJW 23 %; placebo 21 % | Extract: NA Dosage: 300 mg/3 times a day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Schrader, 1998 [40] Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 162 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: mild-moderate Age (years, M (SD)): SJW 47 (32–59.25, 25–75 % range); placebo 39 (30–59.25, 25–75 % range) Gender (% male): SJW 28 %; placebo 38 % | Extract: ZE117 Dosage: 250 mg/2 times a day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Schrader, 2000 [39] Country: Germany Funding: industry funding | Number of participants: 240 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: mild-moderate Age (years, M (SD)): SJW 46 (19); fluoxetine 47 (17) Gender (% male): SJW 29 %; fluoxetine 41 % | Extract: Ze 117 Dosage: 250 mg/2 times a day/6 weeks Comparator: fluoxetine Follow-up time: 6 weeks |
Shelton, 2001 [41], Country: USA Funding: unrestricted grant/industry funding but no conflict | Number of participants: 200 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: Mild-moderate Age (years, M (SD)): SJW 41.4 (12.5); placebo 43.3 (13.7) Gender (% male): SJW 35 %; placebo 37 % | Extract: NA Dosage: 300 mg/a day/8 weeks Comparator: placebo Follow-up time: 8 weeks |
Szegedi, 2005 [42], Country: Germany Funding: industry funding | Number of participants: 251 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: moderate-severe Age (years, M (SD)): SJW 49.0 (11.0); Paroxetine 45.5 (11.5) Gender (% male): SJW 30 %; paroxetine 32 % | Extract: WS 5570 Dosage: 300 mg–600 mg/3 time a day/6 weeks Comparator: paroxetine Follow-up time: 6 weeks |
Uebelhack, 2004 [43], Country: Germany Funding: unclear, not reported | Number of participants: 140 Diagnosis: MDD (DSM), clinical rating scale for depression, MDD (ICD) Severity: not reported Age (years, M (SD)): SJW 46.4 (12.5); placebo 43.3 (12.6) Gender (% male): SJW 30 %; placebo 36 % | Extract: STW 3-VI Dosage: 900 mg/day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Volz, 2000 [50], Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 140 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: mild-moderate Age (years, M (SD)): 47 Gender (% male): 19 % | Extract: D-0496 (hypericin) Dosage: 250 mg/twice a day/6 weeks Comparator: placebo Follow-up time: 6–8 weeks |
Vorbach, 1997 [44], Country: Germany Funding: unclear, industry author, provided SJW | Number of participants: 209 Diagnosis: MDD (ICD) Severity: not reported Age (years, M (SD)): SJW 48.8 (12.0); imipramine 50.1 (11.8) Gender (% male): SJW 27 %; imipramine 25 % | Extract: LI 160 Dosage: 3 × 600 mg/day/6 weeks Comparator: imipramine Follow-up time: 6 weeks |
Wheatley, 1997 [45], Country: UK Funding: unclear, not reported | Number of participants: 165 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: Mild-moderate Age (years, M (SD)): SJW 42 (range: 20–64); Amitriptyline 38 (range: 24–65) Gender (% male): SJW 16 %; Amitriptyline 23 % | Extract: LI 160 Dosage: 300 mg/3 times a day/6 weeks Comparator: Amitriptyline Follow-up time: 6 weeks |
Witte, 1995 [49], Country: Germany Funding: unclear, not reported | Number of participants: 97 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: Not reported Age (years, M (SD)): 44.7 (10.9) SJW; 41.6 (12.5) placebo Gender (% male): SJW 31 %; placebo 37 % | Extract: psychotonin forte Dosage: 100–120 mg/2 times a day/6 weeks Comparator: placebo Follow-up time: 6 weeks |
Woelk, 2000 [46], Country: Germany Funding: unrestricted grant/industry funding but no conflict | Number of participants: 324 Diagnosis: clinical rating scale for depression, MDD (ICD) Severity: mild-moderate Age (years, M (SD)): SJW 46.5 (12.7); imipramine 45.4 (12.8) Gender (% male): SJW 29 %; imipramine 29 % | Extract: Ze 117 Dosage: 250 mg/2 times a day/6 weeks Comparator: imipramine Follow-up time: 6 weeks |
van Gurp, 2002 [47], Country: Canada Funding: unrestricted grant/industry funding but no conflict | Number of participants: 90 Diagnosis: MDD (DSM), clinical rating scale for depression Severity: not reported Age (years, M (SD)): SJW 40.9 (11.6); sertraline 39.1 (10.2) Gender (% male): SJW 36 %; sertraline 42 % | Extract: NR Dosage: 1–2 300 mg/3 times a day/12 weeks Comparator: sertraline Follow-up time: 12 weeks |
Outcome | Study design: number of studies, number of participants | Findings: direction and magnitude of effect | GRADE |
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Comparison: SJW vs. placebo | |||
Depression, number of treatment responders | 18 RCTs, N = 2922 | RR 1.53 (1.19, 1.97), favors SJW | Moderatea |
Depression scale score | 16 RCTs, N = 2888 | SMD 0.49 (0.23, 0.74), favors SJW | Moderatea |
Depression remission | 9 RCTs, N = 1419 | RR 1.69 (0.63, 4.55), n.s. | Lowa,b |
Depression relapse | 1 RCT, N = 426 | RR 0.70 (0.49, 1.02), n.s. | Very lowa,b |
Quality of life—mental | 2 RCTs, N = 358 | SMD 0.48 (0.24, 0.73), favors SJW | Lowb |
Quality of life—physical | 2 RCTs, N = 358 | SMD 0.28 (−1.03, 0.47), n.s. | Very lowa,b |
Number of patients with adverse events | 13 RCTs, N = 2600 | OR 0.83 (0.62, 1.13), n.s. | Moderateb |
Serious adverse events | 6 RCTs, N = 1358 | OR 0.26 (0.04, 1.23), n.s. | Moderatea |
Gastrointestinal/metabolic/nutritional adverse events | 16 RCTs, N = 2490 | OR 1.06 (0.83, 1.41), n.s. | Lowa,b |
Neurologic/nervous system adverse events | 14 RCTs, N = 2404 | OR 1.56 (1.08, 3.32) SJW more AE | Lowa,b |
Skin/musculoskeletal adverse events | 10 RCTs, N = 1978 | OR 1.47 (0.98, 2.21), n.s. | Very lowa,b |
Photosensitivity | 4 RCTs, N = 1054 | OR 1.10 (0.36, 3.56), n.s. | Lowa,b |
Respiratory/infectious adverse events | 7 RCTs, N = 1081 | OR 1.48 (0.95, 2.33), n.s. | Lowa,b |
Other organ system (eye, ear, liver, renal, reproductive) adverse events | 5 RCTs, N = 1054 | OR 1.87 (1.08, 3.32), SJW more AE | Lowa,b |
Cardiovascular adverse events | 4 RCTs, N = 759 | OR 6.81 (0.92, 304.08), n.s. | Very lowa,b,d |
Psychiatric adverse events | 3 RCTs, N = 608 | OR 1.61 (0.34, 10.21), n.s. | Very lowa,b,d |
Sexual dysfunction adverse events | 2 RCTs, N = 428 | OR 1.92 (0.94, 4.00), n.s. | Very lowa,b,d |
Comparison: SJW vs. antidepressant | |||
Depression, number of treatment responders | 17 RCTs, N = 2776 | RR 1.01 (0.90, 1.14), n.s. | Moderateb |
Depression scale score | 14 RCTs, N = 2248 | SMD 0.03 (−0.15, 0.21), n.s. | Moderateb |
Depression remission | 7 RCTs, N = 787 | RR 1.17 (0.84, 1.62), n.s. | Lowb |
Depression relapse | 1 RCT, N = 241 | RR 4.17 (0.47, 33.33), n.s. | Very lowa,b |
Quality of life—mental | 1 RCT, N = 216 | SMD −0.11 (−0.15, 0.38), n.s. | Very lowa,b |
Quality of life—physical | 1 RCT, N = 153 | SMD 0.35 (0.01, 0.70), favors SJW | Very lowa,b |
Number of patients with adverse events | 11 RCTs, N = 1946 | OR 0.67 (0.56, 0.81), favors SJW | Moderatea |
Serious adverse events | 4 RCTs, N = 805 | OR 0.62 (0.05, 5.46) n.s. | Lowa,b |
Gastrointestinal/metabolic/nutritional adverse events | 15 RCTs, N = 2491 | OR 0.43 (0.34, 0.55) favors SJW | Lowa,b |
Neurologic/nervous system adverse events | 15 RCTs, N = 2492 | OR 0.29 (0.24, 0.36) favors SJW | Lowa,b |
Skin/musculoskeletal adverse events | 10 RCTs, N = 1587 | OR 1.18 (0.79, 1.78) n.s. | Lowa,b |
Respiratory/infectious adverse events | 2 RCTs, N = 352 | OR 1.25 (0.70, 2.25) n.s. | Very lowa,b |
Other organ system (eye, ear, liver, renal, reproductive) adverse events | 4 RCTs, N = 761 | OR 0.85 (0.52, 1.38), n.s. | Lowa,b |
Cardiovascular adverse events | 5 RCTs, N = 750 | OR 0.55 (0.26, 1.16), n.s. | Lowa,b |
Psychiatric adverse events | 4 RCTs, N = 552 | OR 0.41 (0.19, 0.87) favors SJW | Very lowa,b |
Sexual dysfunction adverse events | 2 RCTs, N = 301 | OR 0.51 (0.30, 0.88) favors SJW | Lowa,b |
Effect of depression severity | |||
Depression, treatment responders | 18 RCTs, N = 2922 | Meta-regression did not suggest differences between patient subgroups (p = 0.798) | Very lowa,c |
Depression scale score | 16 RCTs, N = 2888 | Meta-regression did not suggest differences between patient subgroups (p = 0.365) | Very lowa,c |
Depression remission | 9 RCTs, N = 1507 | Meta-regression did not suggest differences between patient subgroups (p = 0.159) | Very lowa,c |
Number of patients with adverse events | 13 RCTs, N = 2600 | Meta-regression did not suggest differences between patient subgroups (p = 0.480) | Very lowa,c |
Review question 1: What are the efficacy and safety of SJW in adults with MDD compared to placebo or active comparator?
SJW vs. placebo
SJW vs. antidepressants
Other results
Review question 2: Is there a difference in effect, depending on the type of MDD (i.e. mild, moderate, severe)?