Dunner 2007.

Methods	Parallel group RCT
Participants	Country: US Setting: Outpatients N randomised: 64 (n = 31 (50.8%) female (of 61 included in analyses)) Age: Mean 44 years (SD 11) Inclusion: Adult outpatients aged 21 to 65 years meeting DSM‐IV criteria for MDD and MADRS total score ≥ 20 Exclusion: Current DSM‐IV diagnosis of any psychotic disorder, post‐traumatic stress disorder, panic disorder, or obsessive‐compulsive disorder; DSM‐IV substance abuse or dependence disorder in the past 3 months; history of treatment with an atypical antipsychotic agent; treatment with fluoxetine, a monoamine oxidase inhibitor, or electroconvulsive therapy during the 6 weeks prior to study entry; any clinically significant abnormality on electrocardiogram (ECG); current therapy with medications known to prolong the corrected QT interval; any acute or unstable medical illness; pregnancy or breast feeding
Interventions	Group 1: Augmentation of sertraline with ziprasidone (160 mg) for eight weeks Group 2: Augmentation of sertraline with ziprasidone (80 mg) for eight weeks Group 3: Sertraline for eight weeks
Outcomes	Post‐treatment assessment (8 weeks): 1. Depressive symptoms, continuous (MADRS, HAM‐D) 2. Dropouts 3. Response, dichotomous (≥ 50% decrease from baseline MADRS score) 4. Remission, dichotomous (MADRS score ≤ 10) 5. Adverse events
Definition of TRD	Nonresponse to at least 1 course of treatment of at least 4 weeks’ duration with a clinically appropriate dose of an SSRI or non‐SSRI antidepressant. Also confirmed prospectively by a failure to achieve at least a 30% decrease in MADRS score and a CGI‐S score ≥ 4 following a 6‐week open‐label sertraline (100 to 200 mg/d) treatment period
Notes	Funding: Study funded by Pfizer Inc
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised but no information given about how the randomisation sequence was generated. "Subjects who continued to meet TRD criteria at the conclusion of the 6‐week sertraline lead‐in period were randomly assigned, in a 1:1:1 ratio".
Allocation concealment (selection bias)	Unclear risk	Insufficient information to make a judgment. "Subjects who continued to meet TRD criteria at the conclusion of the 6‐week sertraline lead‐in period were randomly assigned, in a 1:1:1 ratio".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label trial so likely that participants and those delivering the intervention knew their treatment allocation. "After completion of the 6‐week lead‐in study, nonresponders were randomized to open‐label treatment with 8 weeks of …"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded to participants' treatment assignment. ''The clinician who rated efficacy was blind to the subject's treatment assignment, and, whenever possible, the rater who conducted a subject's baseline assessments rated that subject at end point."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Three randomised participants discontinued prior to taking the study drug and were not included in the analyses. LOCF used to account for missing data for the remaining participants. Minor discrepancy between the text and the table with regards to numbers of participants (text stated 61 but table reported data for 60 participants)
Selective reporting (reporting bias)	Unclear risk	No study protocol available. All outcomes detailed in the methods are reported in the study results.
Other bias	Low risk	No other concerns identified