ASSertID 2015.

Study characteristics
Methods	Study design Parallel RCT Study dates Duration of follow‐up: 6 months Study duration: not reported
Participants	Study characteristics Setting: multicentre (5 UK dialysis centres: the Lister Hospital in Stevenage, Hertfordshire, Southend Hospital in Essex, the Royal Free Hospital in London, and the Queen Elizabeth Hospital in Birmingham) Country: UK Inclusion criteria: aged 18 or over; BDI at least 16 and MADRS at least 18 (mild to moderate depression); receiving HD treatment for a minimum of 3 months; patients who speak and read English Exclusion criteria: treatment for anxiety or depression during the previous 3 months with either antidepressants or formal psychological therapy; planned living donor transplant within the period of the trial; pregnancy or childbearing potential without adequate birth control; contraindicated coexistent drug therapy (sertraline SmPC), including triptans, antipsychotics, dopamine antagonists, tramadol, linezolid, warfarin; hepatic impairment ‐ alanine transaminase more than twice the upper limit of normal and/or INR greater than 1.3; hepatitis; HIV/AIDS; Creutzfeldt‐Jakob disease; diagnosis of a severe major depressive disorder and those judged to be at moderate to severe risk of self‐harm who will be referred immediately for further psychiatric evaluation; other psychiatric conditions including substance dependency, psychosis, personality disorder, dementia or panic disorder, with the exception of other anxiety disorders Baseline characteristics Number (analysed/randomised): intervention group (8/15); control group (13/15) Mean age ± SD (years): intervention group (61.7 ± 13.2); control group (56.4 ± 14.4) Sex (M/F): overall (23/7); intervention group (11/4); control group (12/3) Dialysis type: HD Mean dialysis vintage ± SD (years): not reported Comorbidities CVD: not reported Diabetes: intervention group (6/15); control group (7/15) Hypertension: not reported Depression (clinician diagnosis): intervention group (5/15); control group (5/15)
Interventions	Intervention classification Pharmacological intervention Indication: study targeting fatigue Intervention group Sertraline hydrochloride: initial dose 50 mg with titration to 100 mg Control group Placebo: microcrystalline cellulose and magnesium stearate Co‐interventions Not reported
Outcomes	Outcomes reported Fatigue outcome measures used: validation data available Fatigue MFI‐20 assessed at baseline and at 6 months (Appendix 3) General fatigue Mental fatigue Physical fatigue Reduced motivation Reduced activity Depression symptoms BDI‐II: assessed at baseline and at 6 months PHQ‐9: assessed every month Change in MADRS: assessed at baseline and at 2, 4 and 6 months Change in BDI‐II: assessed at baseline and at 6 months Clinical Global Impression Severity scale: assessed at baseline and at 2, 4 and 6 months Improvement scale: assessed at baseline and at 2, 4 and 6 months HRQoL KDQoL: assessed at baseline and at 2, 4 and 6 months EQ‐5D: assessed at baseline and at 2, 4 and 6 months Adverse events: assessed every month Serious adverse events: assessed every month Biomedical and biochemical parameters: assessed every month Dialysis parameters: assessed every month Hospitalisation: assessed until end of treatment Withdrawal: assessed until end of treatment
Notes	Additional information Funding: National Institute for Health Research programme, Research for Patient Benefit programme (PB‐PG‐0110‐21073) Conflicts of interest/disclosures: none Trial registration identification number: ISRCTN06146268 A priori published protocol published FRiedli 2015 "A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from Friedli 2015 (protocol): "Randomisation will take place in blocks using pre‐prepared codes for each centre. These will be incorporated into a protected web based randomisation programme prepared by Norwich CTU." Comment: Sequence generation methods seemed to use a computer. No data were available to assess the possible imbalance between groups
Allocation concealment (selection bias)	Low risk	Quote from Friedli 2015 (protocol): "Randomisation will take place in blocks using pre‐prepared codes for each centre. These will be incorporated into a protected web based randomisation programme prepared by Norwich CTU. Only the research psychiatrist will have authorised access to the online randomisation programme. Following randomisation the relevant pharmacy will be informed of the allocation (treatment A or B) by automatically generated email. The pharmacist will be blind to the allocation. The CTU will hold the patient‐specific allocation data on a secure server. The CI and PI at each centre will have access to this data file only via a special log‐in should the need arise to un‐blind. No user identifiable data will stored in the randomisation database. Web traffic will be encrypted using standard secure sockets layer technology." Comment: A web‐based system is considered as low risk of bias. No data were available to assess the possible imbalance between groups
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote from Friedli 2017: "The patients, dispensing pharmacies, study psychiatrist, research nurses, all clinicians, trial manager, and study statistician were blind to the allocation of the study medication." Comment: A double‐blind study is considered as low risk of bias
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote from Chilcot 2017: "Fatigue was assessed using the MFI‐20." Comment: fatigue was assessed with an appropriate measure, without differences between groups. However, subjective measures were used, it was not stated whether outcomes were assessed without knowledge of treatment allocation, and knowledge of treatment assignment may have influenced reporting. Participant beliefs about the superiority/inferiority of either intervention could have influenced their assessment of the outcome, but there was no evidence that this was likely. However, objective and subjective outcomes were assessed
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Twenty‐one (70%) patients completed the trial: eight (53%) in the sertraline group and 13 (87%) in the placebo group (P=0.05). In the sertraline group, there were six dropouts within the first 2 months. One patient died of cardiac arrest having taken one tablet. Three patients withdrew because of adverse events (one after 3 days with nausea, another after 12 days with headaches and dizziness, and the third due to insomnia after 23 days). The fifth patient withdrew because of concern about side effects, having taken no study medication. The sixth patient was admitted for a prolonged hospital stay with leg ulcers shortly after randomisation and subsequently withdrawn without having taken any study medication. At 3 months, a seventh patient withdrew because of sweating and palpitations. In the placebo group, one patient withdrew after the baseline interview because of concern about taking additional medication, and a second decided against continuing after 3 months. The number of dropouts due to adverse or severe adverse events was greater in the sertraline group." Comment: overall, 21/30 participants completed the study (>5% lost to follow‐up, differences between groups). Some reasons for discontinuations could be related to the treatment assigned
Selective reporting (reporting bias)	High risk	Protocol was published. Trial registration number reported that fatigue should be assessed using MFI‐20 and SF‐36 energy/fatigue sub scale, but data were reported only using MFI‐20. It was unclear if the reported approach to analysing this outcome was pre‐specified or influenced by the results. Fatigue at the end of treatment was reported in a format that was not extractable for meta‐analysis. All outcomes that should be addressed (fatigue, cardiovascular disease, and death) were not reported
Other bias	Low risk	Similar baseline characteristics between groups were reported. Funding was unlikely to influence the data analysis and reporting and authors had no conflicts of interest