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

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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.

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Author notes

  1. Joseph Junior Damba, Katie Bodenstein and Paola Lavin shared first-authorship.

Authors and Affiliations

  1. Geri-PARTy Research Group, Lady Davis Research Institute/Jewish General Hospital, McGill University, Montreal, QC, Canada

    Joseph Junior Damba, Katie Bodenstein, Paola Lavin, Jessica Drury, Harmehr Sekhon, Soham Rej & Kyle T. Greenway

  2. Department of Psychiatry, McGill University, Montreal, QC, Canada

    Jessica Drury, Soham Rej & Kyle T. Greenway

  3. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada

    Christel Renoux

  4. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada

    Christel Renoux

  5. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

    Christel Renoux

  6. Division of Nephrology, Department of Medicine, McGill University Health Center, Montreal, QC, Canada

    Emilie Trinh

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Funding

Charitable donations to the Jewish General Hospital Foundation, Fonds de recherche du Québec—Santé grant, and Canadian Institutes of Health Research grants #PJ8-169696 and #PJT-175191. No specific funding has been received for the conduct of this study and/or the preparation of this article.

Conflicts of interest/competing interests

KB received a Canada Graduate Scholarship Social Sciences and Humanities Research Council Master’s award, and McGill Faculty of Medicine Internal Studentship award. HS has a Canadian Institutes of Health Research fellowship award, Mitacs fellowship award, and an AGE-WELL award. SR receives a salary award from the Fonds de recherche du Québec - Santé, receives grant funding from Mitacs, is on a steering committee for AbbVie, and owns shares of Aifred Health. KTG has received payment for teaching from the Medical Doctor Psychotherapy Association of Canada and educational material preparation for psychedelic.support. JJD, PL, JD, CR, and ET report no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this review apart from those disclosed.

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Author contributions

SR and KTG initiated the project. JJD, KB, PL, JD, SR, and KTG developed the search protocol. JJD, KB, and PL conducted the search. JJD and KB conducted the risk of bias assessments. JJD, KB, and KTG extracted the data, which was reviewed by PL and SR. All authors developed the outline and refined the summaries of results. JJD and KTG prepared tables and prepared the first draft of the article and led revisions. All authors reviewed and provided intellectual contributions to the draft manuscript and its revisions. All authors have read and approved the final submitted manuscript, and agree to be accountable for the work.

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Damba, J.J., Bodenstein, K., Lavin, P. et al. Psychotropic Drugs and Adverse Kidney Effects: A Systematic Review of the Past Decade of Research. CNS Drugs 36, 1049–1077 (2022). https://doi.org/10.1007/s40263-022-00952-y

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