Savadi Oskouie 2012.

Methods	Study type: interventional (clinical trial) Primary purpose: treatment
Participants	144 participants Country: Islamic Republic of Iran Setting: inpatient At randomisation number allocated: N = 144; citalopram (n = 72); placebo (n = 72) % male at baseline: citalopram n = unclear; placebo n = unclear Age at baseline: citalopram (n = unclear); placebo (n = unclear) Subtype of stroke at baseline: unclear Severity of stroke at baseline: unclear Time since stroke onset: within 7 days Inclusion criteria: Acute ischaemic stroke No previous use of citalopram or other antidepressants in the month prior to stroke onset Pre‐stroke NIHSS < 20 No depression MADRS > 18 Exclusion criteria: Request of patients to leave the study Previous chronic disease likely to interfere with assessment of effects of citalopram including: chronic infections, liver or kidney failure, cancer Previous stroke‐related disability Pregnancy or breastfeeding or any conditions that makes follow‐up impossible Severe loss of consciousness Thrombolytic therapy Endarterectomy Depression (MADRS > 18) Withdrawal criteria: not stated
Interventions	Experimental: oral citalopram 20 mg once daily Comparator: placebo
Outcomes	Primary outcome 50% reduction in NIHSS score at 3 months compared to baseline Secondary outcome mRS score at 3 months 50% reduction in NIHSS (motor) score at 3 months compared to baseline 50% reduction in NIHSS (language) score at 3 months compared to baseline Mortality
Funding source	Neurosciences Research Center (NSRC) of Tabriz University of Medical Sciences
Notes	IRCT201203192150N2 Baseline demographic and clinical characteristics for each group not presented, rather the baseline demographic and clinical characteristics for those completing the trial (i.e. a subset of all those randomised at baseline) are presented. Dates study conducted: May 2012 to January 2014 Declarations of Interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A total of 144 patients were randomized through an allocation sequence based on 2 blocks with size of 72, generated with a computer random number generator."
Allocation concealment (selection bias)	Low risk	Quote: "Allocation was concealed using the sequentially numbered black envelopes."
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not explicitly stated that key study personnel and care providers were blinded, although implied by Quote: "The blinding code remained confidential until the end of the study." Quote: "placebo of the same shape and full packaging during the first day after hospital admission."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not explicitly stated that outcome assessors were blinded, although perhaps implied by the fact Quote: "The blinding code remained confidential until the end of the study."
Incomplete outcome data (attrition bias) All outcomes	High risk	Primary outcome data were available for 58 (81%) of the citalopram group and 50 (69%) of the placebo group. Reasons for attrition are reported but there are differences between groups: number of participants in the placebo group (n = 11) dead compared to the citalopram group (n = 4). 3 times the number of participants in the placebo group were depressed (n = 6) compared to the citalopram group (n = 2). Did not want to continue (placebo group (n = 5), citalopram group (n = 8). Intention‐to‐treat analyses were carried out (suppl table) assuming that 1. those lost to follow‐up had a poor outcome (i.e. did not improve their NIHSS scores from baseline) and 2. those participants in the placebo group who did not want to continue had a good outcome. Overall loss of > 5%
Selective reporting (reporting bias)	Low risk	The study protocol is available and all the study's prespecified (primary outcomes and secondary outcomes) that are of interest in the review have been reported in the prespecified way
Other bias	High risk	The baseline data presented in table 1: comparison of demographic and baseline variables and not true baseline characteristics (i.e. at randomisation). The data presented in table 1 are the characteristics of the full analysis set at 3 months which is a subgroup of all participants randomised. We cannot tell if there is whether there were any baseline imbalance in important demographic or clinical characteristics. However, given that approximately 3 times the number of participants in the placebo group (n = 11) died compared to the citalopram (n = 4) and 3 times the number of participants in the placebo group were depressed (n = 6) compared to the citalopram group (n = 2), this suggests that there may have been important group differences in clinical characteristics at baseline