Lithium Treatments: Single and Multiple Daily Dosing

Ljubičić, Đulijano; Letica-Crepulja, Marina; Vitezić, Dinko; Bistrović, Ivana Ljubičić; Ljubičić, Rudolf

doi:10.1177/070674370805300507

Cited by 21 publications

(19 citation statements)

References 34 publications

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“…When lithium is administered, patients may experience adverse effects that correlate with the peak serum concentrations of the drug, such as gastrointestinal disturbances. 9 Historically, it was believed that administering MDD of lithium would reduce the peak serum levels and therefore minimize these effects. Other proposed benefits of MDD and of SR preparations include maintaining a more consistent serum level of lithium, theorized to improve prophylactic efficacy by preventing subtherapeutic trough levels.…”

Section: Limitationsmentioning

confidence: 99%

An Updated Review of the Optimal Lithium Dosage Regimen for Renal Protection

2013

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Objective: Despite several decades of research, there is still uncertainty regarding the optimal lithium dosage regimen associated with a decreased risk of renal effects, such as polyuria, in patients with bipolar affective disorder. We present an updated review of the literature to provide an informed dosing regimen recommendation for prescribers. Method:Major databases MEDLINE and Embase were searched using terms, such as lithium, drug administration schedule, dose-response relationship, once daily, twice daily, and sustained release. In addition, the bibliographies of related publications were manually searched.Results: A total of 20 trials were included. Some trials showed a reduction in urine volume with single daily dosing (SDD), while others showed no change. The only trial evaluating patients newly started on lithium found a reduction in urinary frequency with SDD after 21 days. Trials examining renal biopsy results found that multiple daily doses were associated with more pathologic damage to the kidneys. SDD regimens were generally well tolerated, and no reduction in efficacy was noted in any of the trials. Conclusions:The available evidence is contradictory as to whether SDD of lithium reduces polyuria; however, no trial has demonstrated any downfall of SDD in terms of prophylactic efficacy or adverse effects. Given the added benefits of SDD, such as improved compliance, we recommend patients newly started on lithium should be converted to a SDD of lithium at bedtime once an appropriate daily dose is determined. W W WUne revue mise à jour de la posologie optimale du lithium pour la protection rénale Objectif : Malgré plusieurs décennies de recherche, il y a encore de l'incertitude concernant la posologie optimale du lithium associée au risque réduit d'effets rénaux, comme la polyurie, chez les patients souffrant du trouble bipolaire affectif. Nous présentons une revue mise à jour de la littérature afin d'offrir aux prescripteurs une recommandation éclairée de régime posologique.Méthode : Cette recherche a été menée à partir des grandes bases de données MEDLINE et Embase à l'aide de termes comme : lithium, horaire d'administration des médicaments, relation dose-réponse, une fois par jour, deux fois par jour, et libération prolongée. En outre, les bibliographies de publications connexes ont fait l'objet d'une recherche manuelle.Résultats : Un total de 20 essais ont été inclus. Certains essais montraient une réduction du volume d'urine avec une dose unique quotidienne (DUQ), alors que d'autres n'indiquaient aucun changement. Le seul essai qui évaluait les patients qui commençaient le lithium a observé une réduction de la fréquence urinaire avec la DUQ après 21 jours. Les essais examinant les résultats de biopsie rénale ont constaté que les doses multiples quotidiennes étaient associées à plus de dommages pathologiques aux reins. Les posologies de DUQ étaient généralement bien tolérées, et aucune réduction d'efficacité n'a été notée dans tous les essais. Conclusions :Les données probantes disponibles sont...

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Section: Limitationsmentioning

confidence: 99%

An Updated Review of the Optimal Lithium Dosage Regimen for Renal Protection

2013

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“…[37] Interestingly, it has been recently suggested that the administration of a single daily dose may be a viable option that in fact confers advantages with respect to achieving greater compliance and staving off long-term renal damage. [55] Therefore, current plasma lithium concentration recommendations for initiating treatment and prophylaxis, although overlapping, differ significantly (figure 1) and optimal dosing remains a contentious issue.…”

Section: Lithium Dosingmentioning

confidence: 99%

Optimal Frequency of Lithium Administration in the Treatment of Bipolar Disorder

2011

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Bipolar disorder is a recurrent chronic illness distinguished by periods of mania and depression. Lithium has been used for about 60 years as a 'mood stabilizer' for bipolar disorder with proven efficacy in preventing relapse of both mania and depression. Despite its long history and ongoing use in current management of bipolar disorder, the optimal dosing of lithium is still the subject of ongoing debate. This article aims to evaluate different dosing schedules, in the light of the unique pharmacokinetic and pharmacodynamic properties of lithium, as well as its adverse-effect and toxicity profiles. This is all the more important given the narrow therapeutic index of lithium. Current recommendations mostly advocate that lithium be administered in multiple daily doses. However, single daily or alternate daily schedules may be viable options for administration. Multiple daily schedules are thought to be advantageous in maintaining more constant plasma lithium concentrations than single daily regimens, which are associated with significant fluctuations throughout the day. When comparing these two schedules with respect to plasma lithium concentrations, adverse-effect profiles and recurrence of symptoms, there are no significant differences between the two regimens. In fact, a single daily regimen may have added advantages in reducing the risk of long-term renal damage and increasing compliance. The evidence for alternate daily dosing is somewhat varied with regard to symptom recurrence; however, this schedule has been shown to be associated with decreased adverse effects, and further research into this issue is therefore warranted. Presently, therefore, clinicians should consider single daily administration of lithium to potentially minimize adverse effects and enhance compliance.

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“…Lithium can be given as a single daily dose, usually shortly before bedtime or alternatively every 8-12 h. There has been a recent shift toward SDD, because it may increase compliance and minimize renal adverse effects [105,110]. While in theory SDD could lead to breakthrough symptoms prior to the next dose and result in increased adverse effects due to transient higher peak plasma concentrations compared with multiple daily dosing (MDD), which creates more constant plasma concentrations [105], there is little evidence to support these notions.…”

Section: Dosing and Duration Of Treatment Dosingmentioning

confidence: 99%

“…MDD was associated with significantly more urinary frequency than SDD at day 21 (p = 0.008) and 42 (p = 0.017) [111]. Recent reviews have not demonstrated reduced efficacy or increased adverse effects with SDD versus MDD, however, most evidence comes from small retrospective studies [103,110]. There is a need for a large, prospective long-term trial comparing SDD and MDD.…”

Section: Dosing and Duration Of Treatment Dosingmentioning

confidence: 99%

“…Lithium's usefulness can be limited by its relatively slower onset of action [32], the need for regular blood tests, its narrow therapeutic index [111] and adverse effects including thyroid and parathyroid abnormalities, reduced urine concentrating ability, weight gain and renal impairment [92]. More recently, there has been a shift toward SDD [105,110] and increasing discussion of routinely monitoring serum calcium levels to improve detection of lithium-associated hypercalcemia [92,95].…”

Section: Expert Commentarymentioning

confidence: 99%

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Lithium for bipolar disorder: a review of the recent literature

Curran

Ravindran

2014

Expert Review of Neurotherapeutics

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Lithium is a commonly prescribed treatment for bipolar disorder. Many early studies on which its use has been historically based no longer meet current research standards. A large number of studies with more modern designs have been recently published warranting a review. New research adds to the evidence for lithium's efficacy in mania and maintenance. There is also additional evidence, albeit less robust, to support its benefit in bipolar depression and mixed episodes. Meta-analyses of mainly observational data have found reduced suicidal behavior in bipolar patients taking lithium. Careful monitoring and prescribing can reduce the risk of adverse effects.

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Lithium Treatments: Single and Multiple Daily Dosing

Cited by 21 publications

References 34 publications

An Updated Review of the Optimal Lithium Dosage Regimen for Renal Protection

An Updated Review of the Optimal Lithium Dosage Regimen for Renal Protection

Optimal Frequency of Lithium Administration in the Treatment of Bipolar Disorder

Lithium for bipolar disorder: a review of the recent literature

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