Antidepressants for depression in stage 3–5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP)
Nephrology Dialysis Transplantation, 08/03/2012
Evidence Based Medicine
Nagler EV et al. – Dose reduction in chronic kidney disease 3 (CKD3) to CKD5 (CKD3–5) is necessary for selegiline, amitriptylinoxide, venlafaxine, desvenlafaxine, milnacipran, bupropion, reboxetine and tianeptine. The evidence on effectiveness of antidepressants versus placebo in patients with CKD3–5, and with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM–IV)–defined depression is insufficient, and in view of the high prevalence, a well–designed randomized controlled trial is greatly needed.Methods
- This is a systematic review of randomized clinical trials and observational studies examining antidepressants in patients with CKD3-5, regardless of whether or not patients are on dialysis.
- Through comprehensive searches of seven databases, the authors identified all studies examining pharmacokinetic properties or clinical outcomes in patients with CKD3-5.
- One author assessed studies for eligibility and quality and extracted all data.
- Antidepressant drugs were the studied intervention.
- The main outcomes were pharmacokinetic parameters, clinical outcomes such as response to treatment, reduction in depression severity and adverse events.
- The authors identified 28 studies evaluating pharmacokinetic parameters in CKD for 24 antidepressants.
- Sparse and heterogeneous data precluded informative meta-analysis.
- Drug clearance in CKD3-5 was markedly reduced for selegiline, amitriptylinoxide, venlafaxine, desvenlafaxine, milnacipran, bupropion, reboxetine and tianeptine.
- They identified one randomized controlled trial (RCT) in 14 patients on haemodialysis for fluoxetine versus placebo which showed no difference for efficacy and safety measures.
- One other RCT of escitalopram versus placebo in 62 patients on haemodialysis provided no efficacy data.
- There were nine non-randomized trials, all suggesting benefit for the antidepressant under investigation.
- Side-effects were common, but mild in most patients.
- The limitations of this review include the scarcity of randomized trial data, the small size of the observational studies and possibility of publication bias.
- In addition, study selection and data extraction were done by one reviewer only, increasing the risk for errors made in handling of the data.