Journal Article Annotations
2020, 4th Quarter

Pyschonephrology

Annotations by Sahil Munjal, MD
December, 2020

Association between selective serotonin reuptake inhibitors and kidney cancer risk: A nationwide population-based cohort study
Depression Screening Tools for Patients with Kidney Failure: A Systematic Review

PUBLICATION #1 — Pyschonephrology

Association between selective serotonin reuptake inhibitors and kidney cancer risk: A nationwide population-based cohort study

Min-Jing Lee, Chien-Wei Huang, Yi-Lung Chen, Yao-Hsu Yang, Vincent Chin-Hung Chen

Abstract: Int J Cancer. 2020 Sep 23. doi: 10.1002/ijc.33307. Online ahead of print.

The association between selective serotonin reuptake inhibitor (SSRI) exposure and cancer incidence has been investigated; however, no epidemiological study has investigated the association between exposure to individual SSRIs and kidney cancer incidence. The aim of this study is to examine whether SSRI use affected the risk of kidney cancer. We conducted a population-based retrospective cohort study using data from Taiwan’s National Health Insurance Research Database. After adjusting for sex, age, urbanization level, comorbidity and medication use through propensity score matching, we identified 222 024 SSRI users and 221 361 SSRI nonusers. A robust Cox proportional hazards model was used to examine the associations between use of individual SSRIs and the risk of kidney cancer with 1- and 2-year induction periods. The result showed that SSRI users tended to be associated with a lower risk of kidney cancer with a 2-year induction period than nonusers; however, the association was not statistically significant (adjusted hazards ratio [aHR] = 0.88, 95% confidence interval [CI] = 0.77-1.01). We further examined the effects of individual SSRIs and observed a significantly lower risk of kidney cancer associated with the use of citalopram (aHR = 0.67, 95% CI = 0.47-0.96) and paroxetine (aHR = 0.75, 95% CI = 0.58-0.97) with the 2-year induction period. These findings support that SSRIs are associated with decreased kidney cancer risk and indicate that citalopram and paroxetine have protective effects in depressed patients with kidney cancer.

Annotation

The finding:
This retrospective cohort study using a Taiwanese population-based database investigated the association between SSRIs and kidney cancer risk. Citalopram (aHR = 0.67,) and paroxetine (aHR= 0.75) were significantly associated with a lower risk of kidney cancer with a 2-year induction period. Any SSRI use tended to be associated with a lower but not statistically significant risk.

Strength and weaknesses:
The investigators specifically determined the effects of individual SSRIs on the risk of kidney cancer. Their sample was large and nationally representative with complete follow-up. Data were extracted to minimize recall and selection bias and used propensity score matching. Kidney cancer diagnosis is reliable given confirmation by a specialized clinician and tissue pathology.

The database lacked some crucial variables which may influence the risk of kidney cancer such as smoking status, diet pattern, occupation, and mortality. Adherence to SSRI treatment including duration may not be fully accounted for. The mechanism underlying the effects of citalopram or paroxetine on kidney cancer risk is unclear.

Relevance:
SSRIs have been suggested to exhibit antineoplastic effects in animal and human studies; a previous population-based study showed that SSRIs were associated with reduced risk of kidney cancer (Nayan et al 2017). This study showed significant associations of only citalopram and paroxetine with a reduced risk of kidney cancer. In addition, findings suggest cumulative exposure time is crucial to the antineoplastic effect of SSRIs. The study authors acknowledged the limited understanding of the mechanism underlying the antineoplastic effects of individual antidepressants in kidney cancer. Further research is needed but the authors do suggest that citalopram and paroxetine preferentially may be considered for the management of depressed patients with a high risk for kidney cancer.

Type of study (EBM guide):
Cohort study

PUBLICATION #2 — Pyschonephrology

Depression Screening Tools for Patients with Kidney Failure: A Systematic Review

Karli Kondo, Jennifer R Antick, Chelsea K Ayers, Devan Kansagara, Pavan Chopra

Abstract: Clin J Am Soc Nephrol. 2020 Dec 7;15(12):1785-1795. doi: 10.2215/CJN.05540420. Epub 2020 Nov 17.

Background and objectives:
Patients with kidney failure experience depression at rates higher than the general population. Despite the Centers for Medicare and Medicaid Services’ ESRD Quality Incentive Program requirements for routine depression screening for patients with kidney failure, no clear guidance exists.

Design, setting, participants, & measurements:
For this systematic review, we searched MEDLINE, PsycINFO, and other databases from inception to June 2020. Two investigators screened all abstracts and full text. We included studies assessing patients with kidney failure and compared a tool to a clinical interview or another validated tool (e.g., Beck Depression Inventory II). We abstracted data related to sensitivity and specificity, positive and negative predictive value, and the area under the curve. We evaluated the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2.

Results:
A total of 16 studies evaluated the performance characteristics of depression assessment tools for patients with kidney failure. The Beck Depression Inventory II was by far the best studied. A wide range of thresholds were reported. Shorter tools in the public domain such as the Patient Health Questionnaire 9 and Geriatric Depression Scale 15 (adults over 60) performed well but were not well studied. Short tools such as the Beck Depression Inventory-Fast Screen may be a good option for an initial screen.

Conclusions:
There is limited research evaluating the diagnostic accuracy of most screening tools for depression in patients with kidney failure, and existing studies may not be generalizable to US populations. Studies suffer from limitations related to methodology quality and/or reporting. Future research should target widely used, free tools such as the Patient Health Questionnaire 2 and the Patient Health Questionnaire 9.

Annotation

The finding:
This systematic review examined the performance characteristics of screening tools (and/or thresholds) in patients with kidney failure and comorbid depression, comparing them to the gold-standard clinical interview or another validated tool. They found BDI-II to have the strongest body of evidence and promising evidence for PHQ-9 and GDS-15, which are shorter instruments and in the public domain.

Strength and weaknesses:
Few studies had large sample sizes and examined specific tool thresholds. Many studies were conducted outside of the US. The definition of depression varied widely in the studies and the lack of methodology detail reported in many of the studies contributed to uncertainty about study processes and quality ratings. Very few studies included patients receiving peritoneal dialysis, and none were conducted exclusively in such patients.

Relevance:
It is well established that patients with kidney failure have high rates of major depressive disorder which in turn is associated with poor outcomes. Centers for Medicare and Medicaid Services’ ESRD Quality Incentive Program has set requirements for routine depression screening for patients with kidney failure. A major challenge remains differentiating the high burden of symptoms related to kidney disease versus major depression. The authors highlight the moderate positive predictive values of screening tools in this population and the need to validate positive screens before making treatment decisions that may introduce the possibility of harm. The authors do point out that even though BDI-II has the strongest evidence as a screening tool (which is in part due to scarcity of studies for other tools), it requires a per-use fee, is longer (21 items), and may be less informative for screening and assessment due to its reliance on somatic symptoms. There is a need for future research targeting free tools (e.g., PHQ-9, PHQ- 2, CES-D) that are widely used in US medical settings.

Type of study (EBM guide):
Systematic review or meta-analysis