Renal concentrating ability and glomerular filtration rate in lithium-treated patients

Background. Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium. Methods. 134 patients (>= 18 years of age) with a mood disorder treated with lithium were screened; Ioo patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA. Results. A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (U-osmol) 725 mOsmol/kg (SD: 153), and median eGFR 84 ml/min/1.73 m(2) (IQR: 68-95). Fifty patients (51%) had an impaired RCA and 17 patients (17%) had nephrogenic diabetes insipidus (U-osml 600-800 and <600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19%) had an eGFR Conclusions. RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease

Efficacy and Safety of Lamotrigine as Add-On Treatment to Lithium in Bipolar Depression: A Multicenter, Double-Blind, Placebo-Controlled Trial

Objective: Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy. This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression. Method: Outpatients (N = 124) aged 18 years and older with a DSM-lV bipolar I or 11 disorder and a major depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS] score ! 18 and Clinical Global Impressions-Bipolar Version [CGI-BP] severity of depression score ! 4) while receiving lithium treatment (0.6-1.2 mmol/L) were randomly assigned to 8 weeks of double-blind treatment with lamotrigine (titrated to 200 mg/d) or placebo. The primary outcome measure was mean change from baseline in total score on the MADRS at week 8. Secondary outcome measures were response (defined as a reduction of >= 50% on the MADRS and/or change of depression score on the CGI-BP of "much improved" or "very Much improved" compared to baseline) and switch to mania or hypomania (defined as a CGI-BP? severity of mania score of at least mildly ill at any visit). Patients were included in the study between August 2002 (Spain started in October 2003) and May 2005. Results: Endpoint mean change from baseline MADRS total score was -15.38 (SE = 1.32) points for lamotrigine and -11.03 (SE = 1.36) points for placebo (t = -2.29, df = 104, p =.024). Significantly more patients responded to lamotrigine than to placebo on the MADRS (51.6% vs. 31.7%, p = .030), but not on the CGI-BP change of depression (64.1% vs. 49.2%, p = .105). Switch to mania or hypomania occurred in 5 patients (7.8%) receiving lamotrigine and 2 patients (3.3%) receiving placebo (p = .441). Conclusion: Lamotrigine was found effective and safe as add-on treatment to lithium in the acute treatment of bipolar depression. Trial Registration: clinicaltrials.gov Identifier: NCT0022451