Lydiatt 2013.

Study characteristics
Methods	Study design: randomised (2‐arm parallel randomised controlled clinical trial) Sample size: 298 Method of randomisation: 1:1 ratio according to a randomisation table prepared by the study statistician Method of concealment: centralised Blinding: double‐blind Analysis: per protocol Date the study was conducted: January 2008 ‐ December 2011
Participants	Location: USA Total N randomised: 148 Intervention n: 74 (80 % male; age M = 63, SD = 11) Control n: 74 (80 % male; age M = 63, SD = 13) Inclusion criteria: > 18 years; newly diagnosed or recurrent stage II to IV epidermoid cancer of the head and neck Diagnostic criteria ‐ long‐term physical condition: newly diagnosed or recurrent stage II to IV epidermoid cancer of the head and neck (no assessment specified) Diagnostic criteria ‐ depression: depression diagnosis assessed by the MINI depression and suicide modules; clinician version of the QIDS (QIDS‐C): QIDS‐SR cut‐off score ≥ 11 Exclusion criteria: cognitively impaired; advanced cancer or other conditions that limited life expectancy to less than 6 months; met diagnostic criteria for psychosis, schizophrenia, or major depressive disorder; receiving treatment for depression or anxiety; persistent inability to verbally communicate; uncontrolled pain; currently participating in another research study involving a therapeutic intervention; were females of childbearing age who were pregnant, nursing, or not practicing a reliable method of birth control History of depression: no information specified
Interventions	Intervention: escitalopram ≤ 1 week: daily dose of 10 mg weeks 1‐15: daily dose of 20 mg week 16: daily dose of 10 mg Control: matched placebo Duration of treatment: 16 weeks Length of follow‐up: 28 weeks (baseline, at 2, 4, 6, 8, 10, 12, 16, 20, 24, and 28 weeks) Other study arms: no
Outcomes	Primary outcome: incidence of depression ‐ diagnosis: N/A adverse events: total number of drop‐outs due to adverse events Secondary outcome: incidence of depression ‐ cut‐off: QIDS‐SR cut‐off score ≥ 11 severity of depression: N/A cost‐effectiveness: N/A cost‐utility: N/A
Notes	Language: English Funding: grant R01 MH079420 from the National Institute of Mental Health additional support was provided by a research support fund grant from the Nebraska Medical Center and the UNMC Declaration of interest: Dr Lydiatt is on the head and neck panel for guideline development for the National Comprehensive Cancer Network but does not receive honorarium for participation in guideline development. Dr Burke has received grant support for his institution from Forest Research Institute and has served as a consultant to Forest and on their speakers’ bureau.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"...patients were randomised by a pharmacist with no involvement in the evaluation in a 1:1 ratio to either escitalopram or matching placebo according to a randomisation table prepared by the study statistician" (p. 680)
Allocation concealment (selection bias)	Low risk	"patients were randomised by a pharmacist with no involvement in the evaluation ..." (p. 680)
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	no information specified except for headline saying "...double‐blind ..."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	no information specified except for headline saying "...double‐blind ..."
Incomplete outcome data (attrition bias) All outcomes	High risk	numbers randomised: escitalopram: n = 74; placebo: n = 74; total: N = 148 number of drop‐outs at 28 weeks: escitalopram: n = 38; placebo: n = 30; total: N = 68 numbers analysed post‐intervention: escitalopram: n = 36; placebo: n = 44; total: N = 80 reasons for drop‐out (p. 681, fig. 1) escitalopram: non‐evaluable (only baseline visit): adverse events, withdrew consent, need to take lorazepam, fear of adverse events, surgical complications evaluable: adverse events, withdrew consent, unable to take medication in nursing home, recommendation to stop study by primary physician, death placebo: non‐evaluable (only baseline visit): adverse events, withdrew consent, did not want to take medication evaluable: adverse events, withdrew consent, unable to take medication in nursing home, need to take lorazepam, wants to continue to take antidepressant
Selective reporting (reporting bias)	Unclear risk	no protocol available
Other bias	Unclear risk	"patients were stratified by site (UNMC or NMCC), sex, stage (early [stage II] vs advanced [stage III/IV]), and primary modality of treatment (radiation with or without chemotherapy vs surgery [not biopsy] with or without radiation)" (p. 679)