Journal Article Annotations
2024, 1st Quarter


Annotations by Shivali Patel, MD, Sahil Munjal, MD.
April, 2024

  1. Comparative Safety of Antidepressants in Adults with CKD.

PUBLICATION #1 — Psychonephrology

Comparative Safety of Antidepressants in Adults with CKD.
Nanbo Zhu, Hong Xu, Tyra Lagerberg, Kristina Johnell, Juan Jesús Carrero, Zheng Chang


The finding:
This study aimed to assess the safety of antidepressants in patients with depression and non-dialysis dependent chronic kidney disease (CKD) stages III-V.  Antidepressant initiation was associated with a non-statistically significant increased risk of hip fractures and upper GI bleed but not associated with all-cause mortality, major adverse cardiovascular events, CKD progression, or suicidal behavior.  Additionally, initiation of SSRIs at approximately 50% of the standard dose was associated with a non-statistically significant reduced risk of CKD progression and upper GI bleeding but a higher risk of cardiac arrest. Finally, mirtazapine was associated with a lower risk of upper GI bleed but a higher risk of mortality compared to SSRIs.

Strength and weaknesses:
Authors emulated the analyses of target trials (initiating versus not initiating antidepressant treatment, initiating mirtazapine versus SSRI treatment, and initiating SSRI treatment with a lower dose versus a standard dose) to reduce confounding and bias. Additionally, a large population was examined for this study, with a good covariate balance. However, given the limited power of this study, it is difficult to disentangle the impact of antidepressants on short-term and long-term outcomes from those of moderating variables, including age, comorbid medical pathologies, concomitant medications, and substance use.  Moreover, the study did not focus on antidepressant efficacy in this population and did not report the specific SSRIs used, making it difficult to contextualize if the benefits of antidepressant initiation outweighed risks. Apart from mirtazapine, the study also did not examine the safety of other non-SSRI antidepressants in patients with CKD and depression, including SNRIs and bupropion, or the safety of augmenting agents like atypical antipsychotics. Finally, given that the study population was residents from Stockholm, Sweden, results may not be generalizable to the general population.

As up to 25% of patients with CKD are affected by depression, it is important for C-L psychiatrists treating this population to consider the short-term and long-term risks of antidepressant initiation. Though antidepressants were not associated with long-term renal, cardiovascular, or mortality outcomes, given associated short-term bleeding and fracture risks, initiating antidepressants at lower than standard doses and gradual titration is recommended. However, further studies are needed given the non-statistically significant findings.