Background Lithium is well recognized as the first-line maintenance treatment for bipolar disorder (BD). However, besides therapeutic benefits attributed to lithium therapy, the associated side effects including endocrinological and renal disorders constitute important parameters in prescribing patterns and patient adherence. The objectives of this study is to (i) determine whether long-term lithium therapy is associated with a decrease in renal function, hyperparathyroidism and hypercalcemia and (ii) identify risk factors for lithium-induced chronic kidney disease (CKD). Methods We conducted a single-centered cohort study of adult patients (≥ 18 years) treated with lithium, who were enrolled at Rennes University Hospital in France between January 1, 2018 and June 1, 2020. Required data were collected from the patient’s medical records: demographics characteristics (age, sex, body mass index), biologic parameters (GFR, lithium blood level, PTH and calcium), medical comorbidities (hypertension and diabetes), lithium treatment duration and dosage, and length of hospitalization. Results A total of 248 patients were included (mean age: 60.2 ± 16.5 years). Duration of lithium treatment correlated with (i) deterioration of renal function estimated at − 2.9 mL/min/year (p < 0.0001) and (ii) the development of hyperparathyroidism (p < 0.01) and hypercalcemia (p < 0.01). We also noted that patients with lithium blood level > 0.8 mEq/mL had significantly lower GFR than patients with lithium blood level < 0.8 mEq/mL (61.8 mL/min versus 77.6 mL/min, respectively, p = 0.0134). Neither diabetes mellitus nor hypertension was associated with more rapid deterioration of renal function. Conclusion This study suggests that the duration of lithium treatment contribute to the deterioration of renal function, raising the question of reducing dosages in patients with a GFR < 60 mL/min. Overdoses has been identified as a risk factor for CKD, emphasizing the importance of regular re-evaluation of the lithium dose regimen. Also, long-term lithium therapy was associated with hyperparathyroidism and hypercalcemia. Particular vigilance is required on these points in order to limit the occurrence of endocrinological and renal lithium adverse effects.
BackgroundOxybutynin blocks the release of acetylcholine on the surface of the bladder’s muscle. This drug has two indications: urinary incontinence and symptoms of detrusor muscle hyperactivity in the paediatric population. Oxybutynin is a common paediatric prescription but only commercially available in tablet form, which is unsuitable for paediatric use. We developed oral suspensions but information is not available on the stability of oxybutynin in this form.PurposeThe aim of this study was to evaluate the physicochemical stability of 5 mg/mL oxybutynin oral suspension in commercial compounding excipient Syrspend.Material and methodsAn oral suspension was prepared using oxybutynin powder and Syrspend, packaged in amber vials, to protect from light, and stored at 25°C. Several parameters were studied on different days 0, 3, 5, 8, 10, 15, 30 and 60: microbiological stability (cultures at 36°C on agar), physical stability (macroscopic appearance, osmolality) and chemical stability (pH, concentration). We used a liquid chromatography high resolution mass spectrometer (Q Exactive ThermoFisherScientific). The chromatographic separation of the analytes was performed with an Accela pump equipped with a Thermo Fisher C18 Accucore column (100 × 2.1 mm, 2.6 μM). Data were acquired in targeted single ion monitoring (t-SIM) mode and quantification was performed by extracting the exact mass value of protonated oxybutynin (358.2376 m/z) using a 5 ppm mass window.ResultsNo culture growth was observed and macroscopic appearance was unchanged during the study period. Physical properties remained stable: pH (4.21–4.29) and osmolality (56–78 mOsm/L) during the 60 day period. The concentration of oxybutynin was 100.9% on day 8 and decreased significantly to 40.2% by day 30.ConclusionThese results indicate that microbiological stability and physical stability are acceptable but the concentration does not allow us to go beyond 8 days. Further study will be conducted to see whether the current findings can be replicated.References and/or AcknowledgementsEuropean PharmacopoeiaNo conflict of interest.
Introduction The efficacy and of current antidepressants is insufficient. Esketamine, a new antidepressant administered by nasal route, is available since 2019 in the management of resistant characterized depressive episodes. Objectives To evaluate the response profile of patients to Esketamine in our institution specialized in mental health. Methods We included all patients treated with Esketamine in our institution from November 2019 to September 2021.We collected efficacy and tolerability data using the computerized and paper patient record, prescribing support software, and nursing staff. Results Since 2019, we treated 11 patients with Esketamine in combination with an antidepressant as indicated in the MA. Two patients from the 11 were found resistant, three discontinued due to adverse events, four relapsed after an initial clinical response, and two were still ongoing at the end of the study. Conclusions Despite an initial and rapid response, our study does not highlight any long-term efficacy of Esketamine in resistant depressive disorder. This highlight the fact that its use in the acute phase of depression or earlier in the management strategy could be a good alternative because of its rapid onset of action. Esketamine was initiated as a last line therapy, which may represent a bias in the evaluation of the molecule, as the later the depression is treated, the lower the response rate. The place of Esketamine in the therapeutic strategy is not yet well determined due to a lack of hindsight, and the question of pharmacological tolerance and dependence on the molecule arises. Disclosure No significant relationships.
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