The Finding:
This pharmacoepidemiologic study looked at the association between the initiation of higher (citalopram or escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, or sertraline) QT-prolonging–potential SSRIs and the 1-year risk of sudden cardiac death among individuals receiving maintenance hemodialysis (HD) (primary outcome). Study participants included HD patients with Medicare coverage (Parts A, B, and D) who newly initiated SSRI therapy from the study period after a 180-day washout period free of documented SSRI use.  They used CredibleMeds website to identify the QT-prolonging potential of SSRIs marketed in the USA during the study period. The study found that initiation of a SSRI with higher vs lower QT-prolonging potential was associated with higher risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31). Also, the association may be more pronounced among elderly individuals, females, patients with conduction disorders, and those treated with other non- SSRI QT-prolonging medications.

Strength and weaknesses:

Strengths-
Large-scale safety study (65,000 HD pts), new-user study design, multiple sensitivity analyses.

Weaknesses-
Apart from residual confounding, outcome misclassification may have occurred. Information on laboratory parameters, including serum electrolytes, and patient-reported medication ineffectiveness or side effects were not available.

Relevance:
About a third of patients with end-stage renal disease who are receiving maintenance HD have depressive symptoms. In 2015, 20% of United States HD patients filled a SSRI prescription given it being first line for medication management of depressive symptoms. Also, according to ESRD Death Notification forms, 30% of all HD patient deaths in 2014–2016 were primarily due to cardiac arrest or arrhythmia. Even with the extensive use of SSRIs in this population (and the high mortality due to cardiovascular causes), there is paucity of evidence linking them to adverse cardiac outcomes. These patients are particularly susceptible to lethal cardiac consequences of drug-induced QT prolongation. They have a substantial cardiovascular disease burden, high level of polypharmacy and are recurrently exposed to electrolyte shifts during HD. This study has important clinical implications for CL psychiatrists highlighting SSRI’s with higher QT prolonging potential had a higher risk of sudden cardiac death which was more pronounced among elderly individuals, females, those with conduction disorders, and those taking other non-SSRI QT-prolonging medications. The study also makes the case for individualized SSRI therapy selection, especially in patients with high risk for drug-induced QT prolongation. If citalopram or escitalopram therapy is unavoidable in a high-risk patient, clinicians should recommend serial ECG monitoring throughout the course of therapy.

Type of study:
Retrospective cohort study

Findings:
The study looked at bipolar disorder(BD) patients without prior nephropathy, for onset of kidney diseases (KDs) (of moderate or high severity) following psychopharmacotherapy (lithium, mood stabilizing anticonvulsants [MSAs], antipsychotics, antidepressants), or “No drug”. It found most of the studied pharmacotherapies were associated with significantly increased risk of KDs over the drug-free regimen which were significantly higher for complex combinations. Lithium-containing treatment options were associated with up to 2.50-fold higher risk of all KDs, and up to 5.30- fold higher risk of severe KDs, compared to the no drug regimen. Monotherapy with MAOI antidepressants had the highest risk of all KDs. As for monotherapy with antidepressants such as SSRI, SNRI, and noradrenergic and specific serotonergic antidepressants, the risk of KDs was not found to be statistically significant when compared with no drug.

Strength and weaknesses: 

Strengths-
It compared the largest number of BD drug regimens used in the US to date, cohort was restricted to only patients with BD, included patients without previously documented KDs. They controlled for multiple baseline patient-related covariates.

Weaknesses-
Clinical records or lab results were not available to verify the assignments to classify them into the moderate or high severity group. Mono-class therapies with FGAs, SSRIs, SNRIs, MAOIs, or tri-and tetracyclic antidepressants did not distinguish between monotherapy and polypharmacy within the respective class.

Relevance:
This study addresses a major evidence gap on comprehensive comparison of multidrug psychotropic regimens for kidney safety in patients with BD. No BD psychopharmacotherapy had significantly lower risk of “all” or “severe” KDs, compared to the “No drug” regimen. Psychotropic polypharmacy is a common mode of BD pharmacologic treatment, and is often associated with higher risk of KDs compared to monotherapies. Lithium was associated with significantly higher risk of any KD compared to the “No drug” regimen, and HR estimates were even higher when it was combined with other drugs. MAOIs mono-class therapy stood out relatively to other studied drug regimens by markedly high KD risk estimates. Other mono-class antidepressant therapies were not associated with additional risk of KDs. Cardiovascular and metabolic disturbances prior to the initiation of psychopharmacotherapy are risk factors for subsequent KDs occurrence in patients with BD.

The study highlights that clinicians should consider monitoring renal function for BD patients not only treated with lithium, but also other regimens regardless of choice of psychopharmacotherapy.

Type of study- Retrospective observation study.