Fava 2005.

Methods	Twelve‐week randomised, double‐blind, multicentre study
Participants	Outpatients fulfilling DSM‐IV criteria for current major depression episode of at lest 2 weeks duration, Hamilton Rating Scale for Depression (HDRS) score at least 16. Age range: 18‐65 years Inclusion criteria: negative pregnancy test within 5 days before study start in women of childbearing potential, use of adequate contraception. Exclusion criteria: pregnancy, lactation, or non use of medically accepted contraception, current serious suicide or homicidal risk, serious or instable medical illness, history of seizure disorders, presence of any of the following diagnosis: organic mental disorder, substance use disorder, including alcohol, active within the last 6 months, schizophrenia, delusional disorder, psychotic disorders not elsewhere classified, bipolar disorder, antisocial personality disorder; history of multiple adverse drug reactions or allergy to the study drugs; mood congruent or mood incongruent psychotic features, concomitant use of other psychotropic drugs within 14 days before baseline, other investigational psychotropic drug within 40 days, fluoxetine within 40 days or any other investigational drug within 1 month, hypothyroidism; failure to respond during the course of current MDE to at least 2 adequate antidepressant trials; any other condition which, in the investigator judgement, may pose significant risk to the patient's health or may decrease the chances of obtaining reliable data to achieve the objectives of the study; mental condition rendering the patients unable to understand nature, scope and risk of the study; history or suspicion of unreality, poor cooperation, or non compliance with medical treatment.
Interventions	Fluoxetine: 47 participants St John's wort: 45 participants Fluoxetine dose: 20 mg/day St John's wort dose: 900 mg/day
Outcomes	Primary outcome: total score on the HDRS Secondary outcome: improvement on the Clinical Global Impression (CGI) scale and Beck Depression Inventory (BDI) score
Notes	Response: decrease of at least 50% in the HDRS total Remission: total score of maximum 8 on the HDRS at the endpoint Funding: by industry
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised, no further information
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Double blind, no further information
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double blind, no further information
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double blind, no further information
Incomplete outcome data (attrition bias) All outcomes	Low risk	Number and reasons for dropout reported. Primary and secondary endpoint scores reported
Selective reporting (reporting bias)	Low risk	Only most frequent (at least 10%) adverse events reported. Scores reported with standard deviations
Other bias	High risk	Quote: "the study was supported by a grant of Lichtwer Pharma AG (Berlin, Germany)", and this company produces St. John's wort