One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a retrospective analysis of a monitoring database.

OBJECTIVES: Lithium is a mainstay of bipolar disorder treatment, however, there are still differences in opinion on the effects of lithium use on renal function. The aim of this analysis was to determine if there is an association between short-term exposure to various elevated lithium levels and estimated-glomerular filtration rate (eGFR) at ≤3 months, 6 months (±3 months) and 1 year (±3 months) follow-up. SETTING: Norfolk-wide (UK) lithium register and database. PARTICIPANTS: 699 patients from the Norfolk database. PRIMARY OUTCOME MEASURES: eGFR change from baseline at ≤3 months, 6 months (±3 months) and 1 year (±3 months) after exposure to a lithium level within these ranges: 0.81-1.0 mmol/L (group 2), 1.01-1.2 mmol/L (group 3) and 1.21-2.0 mmol/L (group 4). The reference group was patients whose lithium levels never exceeded 0.8 mmol/L. RESULTS: Compared to the reference group, groups 3 and 4 showed a significant decrease in eGFR in the first 3 months after exposure (p=0.047 and p=0.040). At 6 months (±3 months) postexposure group 4 still showed a decline in eGFR, however, this result was not significant (p=0.298). CONCLUSIONS: These results show for the first time that a single incident of a lithium level >1.0 mmol/L is associated with a significant decrease in eGFR in the following 3 months when compared to patients whose lithium levels never exceeded 0.8 mmol/L. It is still not known whether the kidneys can recover this lost function and the impact that more than a single exposure to a level within these ranges can have on renal function. These results suggest that lithium level monitoring should be undertaken at least every 3 months, in line with current UK guidelines and not be reduced further until the impact of more than one exposure to these lithium levels has been fully established.

A naturalistic evaluation and audit database of agomelatine: clinical outcome at 12 weeks.

OBJECTIVE: To determine the effectiveness of agomelatine in routine clinical practice and explore factors associated with response and continuation. METHOD: Consecutive patients prescribed agomelatine in participating psychiatric services were included. Patient demographic and outcome data were collected at treatment initiation and then at weeks 4, 8 and 12. Outcomes were analysed with respect to clinical and demographic factors. RESULTS: A total of 110 patients from nine NHS trusts were followed through 12 weeks of treatment. Agomelatine was largely used in difficult-to-treat or refractory patients: 83 (75%) had failed to respond to, or relapsed on, prior antidepressants. There were high rates of physical (54.5%) and psychiatric (50.0%) comorbidity. At 12 weeks of treatment, 68 (62%) continued agomelatine treatment. Overall, 69 subjects (62.7%) improved by at least one point of the Clinical Global Impression (severity) scale. Of 42 who discontinued, 23 (56%) discontinued because of lack of efficacy and 10 (24%) due to an adverse event. Of all variables examined, only a history of more than five episodes of depression significantly predicted discontinuation of treatment (OR continuation - 0.36, 95% CI 0.14, 0.95). CONCLUSION: Agomelatine was effective and generally well tolerated in a cohort of difficult-to-treat patients in clinical practice.

The use of antidepressants in clinical practice: focus on agomelatine.

OBJECTIVE: Agomelatine (Valdoxan) is licensed by the European Medicines Agency for the treatment of major depressive episodes in adults. The objective of this review was to consider how the drug should be used in clinical practice in particular starting, stopping and switching to and from the drug. METHODS: The existing clinical evidence was reviewed. RESULTS: Data suggest that when switching to agomelatine from other antidepressants consideration should be given to tapering the previous antidepressant in order to minimize the risk of the original drug causing discontinuation/withdrawal symptoms. The risk of pharmacological interactions between most antidepressants and agomelatine is low and so tapering the previous antidepressant can usually be done after agomelatine has been started. An exception is fluvoxamine which should not be concurrently prescribed with agomelatine. As agomelatine appears to cause no significant discontinuation symptoms, it can probably be stopped abruptly when treatment is completed or when switching to another antidepressant. CONCLUSIONS: While this guidance may change as clinical evidence and experience grows, currently agomelatine appears to have a good tolerability profile and is relatively easy to use, though prescribers should note the requirement to conduct liver function tests (LFTs) in accordance with the Summary of Product Characteristics (SPC).

Sudden death associated with switching monoamine oxidase inhibitors.

A drug-free interval is often recommended when switching monoamine oxidase inhibitors, although the evidence firmly supporting this caution has been minimal. A case is reported where an abrupt change in monoamine oxidase inhibitor was followed by the death of a patient.