Dominique Elie

Molecular mechanisms in lithium-associated renal disease: a systematic review

PurposeLithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease.MethodsWe conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium’s effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers.ResultsFrom a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD.DiscussionFuture studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium’s biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events.

Statins in the prevention of lithium-associated diabetes insipidus: preliminary findings

Dalia El-Gamal, Saša Frank, Seth Hallström and Gunther Marsche Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria; Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria and Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria Correspondence: Gunther Marsche, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, Graz 8010, Austria. E-mail: gunther.marsche@medunigraz.at

Health Canada Warning on Citalopram and Escitalopram—Its Effects on Prescribing in Consultation-Liaison Psychiatry

BACKGROUND Reports have suggested that citalopram and escitalopram may prolong the QTc interval, leading Health Canada to issue a warning to limit their dosages in 2012. Little is known about the effects of this warning and similar ones (e.g., by the Food and Drug Administration) on antidepressant prescribing in inpatients with acute medical illness, who are theoretically at high risk of QTc prolongation. The main objective of our study is to examine the effect of the Health Canada warning on citalopram/escitalopram prescribing patterns in the consultation-liaison (C-L) psychiatry setting. METHODS We performed a retrospective cohort study including 275 randomly selected inpatients with medical illness assessed by the psychiatric C-L team of a large Canadian academic hospital between 2008 and 2014. We grouped patients based on whether they were assessed by the C-L team before or after the citalopram Health Canada warning. Our primary outcome was change in citalopram/escitalopram prescribing patterns. RESULTS We found that of patients seen before the Health Canada warning, a significantly higher number were prescribed citalopram/escitalopram (44.1% vs. 22.3%, χ(2) = 14.835, p < 0.001), even after controlling for confounders. However, the percentage of patients using a citalopram/escitalopram dose exceeding those recommended by the Health Canada warning was similar in both groups (8.9% vs. 12.1%, χ(2) = 0.233, p = 0.63). CONCLUSIONS Overall, C-L psychiatrists were less likely to prescribe citalopram/escitalopram following the Health Canada warning, which did not translate into safer dosing. Clinicians should not avoid prescribing citalopram/escitalopram appropriately in medically vulnerable inpatients when benefits outweigh disadvantages.

Can Geriatric Psychiatry Patients Complete Symptoms Self-Reports Using Tablets? A Randomized Study

Background With our aging population and limited number of geriatric psychiatrists, innovations must be made in order to meet the growing demands for geriatric psychiatry services. Emerging technologies could greatly improve access to care and systematic data collection. Methods This randomized study compared completion rates and time to completion (primary outcomes) when using iPad technology vs. traditional paper forms to complete self-report psychiatric symptoms. Geriatric psychiatry outpatients (n = 72) and adult psychiatry inpatients (n = 50) were recruited to complete the Brief Symptom Inventory (BSI-53), the Activities of Daily Living (ADL), and Patient Health Questionnaire (PHQ-9) questionnaires. Results Geriatric psychiatry outpatients completed the iPad and paper questionnaires at similar rates (91.7% vs. 97.2%, Fisher’s Exact p = .61). In two-way ANOVA, including patients aged ≥ 60 (n = 85), outpatient status (F(1,81) = 4.48, p = .037) and iPad format (F (1,81) = 8.96, p = .04) were associated with a shorter time to completion. The effect of questionnaire formats was especially prominent in the inpatient group on time to completion. Conclusions Older adults with mental illness demonstrate a similar ability to complete self-report questionnaires whether iPads or paper forms. iPad questionnaires may even require less time to complete in geriatric psychiatry inpatients. Patients also found iPad questionnaires to be easy to use and read. Tablets could potentially be used for psychiatric symptom assessment for clinical, research, and population health purposes.

Citalopram and escitalopram: adverse cardiac outcomes in medically ill inpatients

Serotonin selective reuptake inhibitors (SSRIs) have widely replaced older tricyclic antidepressants (TCAs) in the treatment of depression and anxiety over the years, given their safer cardiac profile [Glassman, 1998]. Even at therapeutic doses, TCAs commonly cause a slowing of intraventricular conduction through their sodium-channel blocking properties, leading to prolonged PR, QRS and QT intervals [Pacher and Kecskemeti, 2004]. Similarly, in vitro and animal studies have shown that citalopram and escitalopram, through their cardiotoxic metabolite, didesmethylcitalopram, can delay ventricular repolarization, prolong QT, and increase the risk of torsade de pointes by directly blocking potassium-hERG channels in cardiomyocytes [Overa, 1989; Witchel et al. 2002]. In 2011–2012, the US Food and Drug Administration (FDA) released a safety communication regarding citalopram and escitalopram and their increased risk for QTc prolongation and cardiac outcomes, especially in elderly and patients with comorbid medical illnesses [FDA, 2012]. The new FDA recommendations state that citalopram should not be used at doses greater than 40 mg per day in healthy adults, and not exceed 20 mg per day in the elderly, patients with hepatic impairment, or patients taking a CYP2C19 inhibitor. Health Canada released a similar warning for escitalopram in 2012, stating that doses greater than 10 mg should be avoided in these latter high-risk populations [Health Canada, 2012]. A retrospective cross-sectional study in elderly surgical patients published in 2014 showed no association between citalopram and escitalopram and cardiac outcomes in this vulnerable population [van Haelst et al. 2014]. However, this association has never been assessed in a sample of acutely medically ill inpatients, another highly vulnerable population.

Selective Serotonin Re-Uptake Inhibitors and Hyponatremia in Acutely Medically-Ill Inpatients

BACKGROUND Selective Serotonin Reuptake Inhibitors (SSRIs) have become the mainstay of treatment for depression, anxiety, and many other conditions. However, they have been associated with an increased risk of hyponatremia. Little is known about the risk of SSRI-associated hyponatremia in certain potentially at-risk populations, such as patients with acute medical illnesses. OBJECTIVE The main objective of this study was to examine the effect of SSRIs on serum sodium levels in medically-ill inpatients. METHOD We performed a retrospective cohort study of 239 medically-ill inpatients assessed by the psychiatric consultation-liaison team of a large Canadian academic hospital between 2008 and 2014. We grouped patients based on whether they were exposed to an SSRI, a non-SSRI antidepressant, or no antidepressant at all. Our primary outcome was the maximum decrease in serum sodium level observed within 30 days of antidepressant exposure in the inpatient setting. Our secondary outcome was the incidence of hyponatremia (serum sodium level <135 mEq/L) or severe hyponatremia (sodium level <130 mEq/L) within the same time frame. RESULTS The maximum decrease in sodium serum level from baseline did not differ between the 3 groups studied (SSRIs - 3.31 mEq/L vs non-SSRI antidepressants -3.41 mEq/L vs no antidepressants -3.13 mEq/L, F (2) = 0.79, p= 0.92). The incidence of hyponatremia and severe hyponatremia did not differ between groups either. This remained the case after controlling for covariates. CONCLUSION SSRIs do not appear to be associated with an increased risk of hyponatremia in medically-ill inpatients. Clinicians should not avoid prescribing SSRIs in this population based solely on the assumption of hyponatremia risk.