Journal Article Annotations
2022, 4th Quarter

Psychonephrology

Annotations by Sahil Munjal, MD
January, 2023

Psychotropic Drugs and Adverse Kidney Effects: A Systematic Review of the Past Decade of Research.

PUBLICATION #1 — Pyschonephrology

Psychotropic Drugs and Adverse Kidney Effects: A Systematic Review of the Past Decade of Research.

Joseph Junior Damba, Katie Bodenstein, Paola Lavin, Jessica Drury, Harmehr Sekhon, Christel Renoux, Emilie Trinh, Soham Rej, Kyle T Greenway,

Abstract: CNS Drugs. 2022 Oct;36(10):1049-1077. doi: 10.1007/s40263-022-00952-y. Epub 2022 Sep 26.

Abstract:

Background and objective:
Psychotropic drugs are a heterogenous group of treatments prescribed for many psychiatric disorders, often for long periods. Their effects on the kidney and its functioning are complex and a source of significant research and debate. This article aims to review recent evidence of the acute and chronic kidney adverse events of diverse psychotropes.

Methods:
A systematic search of randomized controlled trials and large observational studies (n ≥ 100) reporting the effects of psychotropic drugs on the kidney was conducted. The MEDLINE, PsycInfo, and EMBASE databases from 2011 to 2021, inclusive, were broadly searched with few restrictions and no prespecified outcomes. Two or more independent reviewers assessed and summarized all eligible studies, including risks of bias and levels of evidence.

Results:
In all, 1999 abstracts were screened for eligibility and 47 articles were included, which examined lithium (33), antiepileptics (10), antipsychotics (13), and antidepressants (9). No studies examining kidney adverse effects of other psychotropes, such as benzodiazepines, met inclusion criteria. Study populations were adult (8), geriatric (9), and mixed (30). Lithium was almost unanimously associated with (1) chronic kidney disease and (2) nephrogenic diabetes insipidus in methodologically diverse studies. The most supported risk factors for declining kidney functioning with lithium were advanced age, duration of lithium treatment, acute lithium toxicity, female sex, medications with known renal interactions, diabetes mellitus/hyperglycemia, and overall medical comorbidity. Supratherapeutic lithium concentrations are both the causes and consequences of acute kidney injury. Once significant chronic kidney disease has developed, four studies found that replacing lithium with other mood stabilizers does not slow progression, and the evolution to end-stage kidney disease is rare overall with modern practices. Compared to lithium, fewer studies examined antipsychotics and antiepileptics but found relatively less direct kidney harms. Antidepressants were not associated with acute or chronic kidney harms.

Conclusions:
Despite the heterogeneity of findings, owing to varying methodologies and research challenges, recent studies strongly suggest that lithium is associated with an increased risk of chronic kidney disease and nephrogenic diabetes insipidus, especially in older adults and long-term lithium users. Clinicians should balance the harms of lithium against its established benefits and ensure adequate monitoring and management of comorbidities in all patients. Weaker evidence suggests that antiepileptics such as valproate and antipsychotics result in comparatively less harm to the kidney than lithium, but warrant monitoring because of multiple direct and indirect mechanisms for potential kidney adverse events. Antidepressants do not have clear kidney adverse effects and appear safe (though potentially less effective) in the setting of kidney disease. Other classes of psychotropic drugs have received little research interest. Further research is warranted, particularly into specific antiepileptics and antipsychotics, and careful attention should be paid to mitigating important sources of bias such as confounding by indication.

Annotation

The finding:
This systematic review looks at 10 years of literature on the potential kidney adverse effects (AE) of psychotropic drugs. Lithium is strongly associated with CKD and nephrogenic diabetes insipidus (NDI). The strength of association and causal relationship to acute kidney insufficiency (AKI) was less clear. Antidepressants, in general, are associated with fewer kidney AE. Limited evidence exists on the renal risks of antiepileptics and antipsychotics. The authors share a helpful table with recommended kidney-related monitoring frequency in bipolar disorder on lithium, valproate, and antipsychotics.

Strength and weaknesses:
Authors included largest and methodologically sound studies with systematic evaluations of bias and levels of evidence. Majority of included studies were observational with significant heterogeneity. Most studies focused on lithium, with fewer studies examining antiepileptics, antipsychotics, and antidepressants. No studies evaluated the risks of psychostimulants and benzodiazepines. There may be multiple confounding variables including indication/severity of the illness, comorbidities, additional interacting medications, and dosage differences resulting in inconsistent results.

Relevance:
The findings pertaining to lithium and its association with CKD, AKI, and NDI are not surprising. Risk factors include advanced age, lithium duration, female sex, overall comorbidities, toxic lithium concentrations, and low eGFR when initiating lithium. Neither lithium nor antiepileptics were not observed to increase the risk of progression or the eventual development of end stage renal disease relative to discontinuing them. Evidence strongly supports the importance of regular monitoring, managing medical comorbidities, and avoiding drugs with potentially nephrotoxic lithium interactions such as thiazide diuretics and NSAIDs. Clinicians should keep this in mind while engaging in shared decision making.