Owens 2008.

Methods	Eight‐week, prospective, multicentre, randomised, double‐blind, parallel‐group study.
Participants	Male and female patients (18–65 years) meeting diagnostic criteria for Major Depressive Disorder (MDD) were eligible (American Psychiatric Association, 1994). The diagnosis of MDD was made by the principal investigator using the Mini International Neuropsychiatric Interview (MINI) ‐ a structured diagnostic interview for DSM‐IV. A total score of >20 on the Montgomery and Asberg Depression Rating Scale (MADRS) was required at screening and baseline. Patients were excluded if they had a clinically predominant axis I disorder other than MDD. Other key exclusion criteria were: history of unresponsiveness to either paroxetine or venlafaxine or exhibited prior hypersensitivity/intolerance to either paroxetine CR or venlafaxine XR, substance abuse/dependence, prior non‐response to SSRIs, suicidal/homicidal risk, concurrent psychotherapy or psychotropic pharmacotherapy, or any serious medical condition or clinically significant finding in the screening or baseline evaluation that would preclude the administration of paroxetine CR or venlafaxine XR. Patients were excluded if they required concomitant therapy with psychoactive medication or patients who have taken other psychoactive medication within the time frames specified below prior to the screening visit: antidepressants other than MAOIs or fluoxetine (e.g., tricyclic antidepressants, SSRIs, and NSRIs), lithium and oral antipsychotics‐14 days; hypnotics, benzodiazepines, and all other sedatives (including chlorpheniramine and other sedating antihistamines)‐14 days; fluoxetine, MAOIs‐4 weeks; depot neuroleptics‐12 weeks; any CNS‐active herbal preparations/supplement (e.g., St John’s wort, kava kava, etc.)F‐14 days.
Interventions	Paroxetine: 42 participants. Venlafaxine XR: 44 participants. Paroxetine dose range: 12.5‐75 mg/day. Venlafaxine dose range: 75‐375 mg/day.
Outcomes	MADRS, Clinical Global Impression (CGI). Total dropout, dropout due to side‐effects. Number of patients experiencing at least one side effect.
Notes	Funding: paroxetine manufacturer.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "randomized (...) patients meeting eligibility criteria at baseline were randomized (1:1) to receive over‐encapsulated paroxetine or venlafaxine tables using a computer‐generated randomization list".
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "double blind (...) over‐encapsulated paroxetine or venlafaxine tables".
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "double blind".
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "all patients who were randomized, received at least one dose of study medication and had at least one post‐baseline efficacy assessment, were included in the modified intent‐to‐treat (ITT) efficacy analyses (...) Patients withdrawing before week 2 without MADRS assessments are not included in the analyses of the MADRS. The analyses on observed data were repeated using the Last Observation Carried Forward (LOCF) approach to impute missing values (...). Because five of the randomized patients did not have a post‐baseline efficacy assessment, the evaluable population (modified ITT) consisted of 81 patients". More than 20% of participants withdrew from the study prematurely.
Selective reporting (reporting bias)	Low risk	Outcomes data were reported.
Other bias	Unclear risk	Sponsorship bias cannot be ruled out.