Many clinicians continue to prescribe lithium carbonate immediate-release rather than the extended-release (or controlled-release) preparation. I only prescribe extended-release preparations of lithium because they are believed to have various advantages over immediate-release preparations (Girardi et al., 2016) and the price difference is small. The potential advantages are:
1. More consistent serum lithium concentrations
2. Fewer adverse events
3, Improved convenience
4. Improved adherence to treatment (Lavantes et al., 1999)
Sustained-release preparations and adverse effects
It is believed that some adverse effects of lithium are related to the rate of increase of serum lithium (Bowden, 1998). The combination of the slower rate of increase in serum lithium concentration and lower peak concentration with extended-release preparations of lithium are probably why some adverse effects may be less common and/or less severe with extended-release preparations of lithium (Girardi et al., 2016). These may include tremor, upper gastrointestinal cramping, nausea, rash, cognitive dulling, urinary frequency, and neuromuscular slowing (Bowden, 1998), even though this has not been clearly proven.
Note: There is an ongoing study (https://clinicaltrials.gov/ct2/show/NCT03210480) that aims to assess the tolerability, efficacy and safety of a new lithium sulphate prolonged release formulation (Lithiofor®) in patients affected by Bipolar Disorder poor tolerant to lithium immediate-release treatment in terms of lithium-induced tremor when switched from therapy with a lithium carbonate immediate release formulation (Carbolithium®) to a new lithium sulphate prolonged release formulation (Lithiofor®).
Question from a Member: Can you discuss the kidney-sparing effects of regular versus ER lithium?
Is either the immediate-release or extended-release less harmful to the kidney? The short answer is that we don’t know.
While there is at least one study that suggested that the sustained-release preparation is less likely to impair the kidney’s ability to concentrate the urine (Wallin and Alling, 1979), that study did not control for key variables like serum lithium and duration of treatment (Vestergaard, 1980).
Does the extended-release preparation have any potential disadvantages other than slightly increased cost? Lower gastrointestinal problems like diarrhea may be worse with the extended-release preparation of lithium carbonate (Bowden, 1998).
Cost and availability
In the US, lithium carbonate extended-release is available in 300 mg and 450 mg strengths. The 150 mg strength of lithium carbonate is only available as an immediate-release capsule.
Ninety capsules of lithium carbonate immediate-release 300 mg cost only about $8. Ninety capsules of lithium carbonate extended-release 300 mg cost about $20.
Bowden CL. Key treatment studies of lithium in manic-depressive illness: efficacy and side effects. J Clin Psychiatry. 1998;59 Suppl 6:13-9; discussion 20. Review. PubMed PMID: 9674932.
Girardi P, Brugnoli R, Manfredi G, Sani G. Lithium in Bipolar Disorder: Optimizing Therapy Using Prolonged-Release Formulations. Drugs R D. 2016 Dec;16(4):293-302. Review. PubMed PMID: 27770296; PubMed Central PMCID: PMC5114200.
Lavantes B, Senimon F, Bayle FJ. [Compliance with and tolerance of sustained-release lithium carbonate]. Encephale. 1999 Mar-Apr;25(2):152-7. French. PubMed PMID: 10370888.
Vestergaard P. Sustained-release lithium tablets and renal function. Br Med J. 1980 Jan 12;280(6207):113. PubMed PMID: 7353112; PubMed Central PMCID: PMC1600195.
Wallin L, Alling C. Effect of sustained-release lithium tablets on renal function. Br Med J. 1979 Nov 24;2(6201):1332. PubMed PMID: 519437; PubMed Central PMCID: PMC1597327.
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