A critical appraisal of lithium’s efficacy and effectiveness: the last 60 years

Grof, Paul; Müller‐Oerlinghausen, B.

doi:10.1111/j.1399-5618.2009.00707.x

Cited by 84 publications

(55 citation statements)

References 72 publications

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“…This episodic recurrent form of BD is known to be associated with an increased rate of recurrent mood disorders, but not schizophrenia in relatives, and a high response rate to long-term lithium, estimated at 80%. 13,14 A recent large prospective study 15 of patients with classical BD reported that the morbidity index in lithium-treated patients remained stable for up to 20 years. Moreover, lithium response was found to cluster in affected members.…”

Section: Natural History and Heterogeneity Of Bipolar Disordermentioning

confidence: 99%

Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

Duffy

2014

Can J Psychiatry

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Objectives: To describe key findings relating to the natural history and heterogeneity of bipolar disorder (BD) relevant to the development of a unitary clinical staging model. Currently proposed staging models are briefly discussed, highlighting complementary findings, and a comprehensive staging model of BD is proposed integrating the relevant evidence.Method: A selective review of key published findings addressing the natural history, heterogeneity, and clinical staging models of BD are discussed. Results:The concept of BD has broadened, resulting in an increased spectrum of disorders subsumed under this diagnostic category. Different staging models for BD have been proposed based on the early psychosis literature, studies of patients with established BD, and prospective studies of the offspring of parents with BD. The overarching finding is that there are identifiable sequential clinical phases in the development of BD that differ in important ways between classical episodic and psychotic spectrum subtypes. In addition, in the context of familial risk, early risk syndromes add important predictive value and inform the staging model for BD. Conclusions:A comprehensive clinical staging model of BD can be derived from the available evidence and should consider the natural history of BD and the heterogeneity of subtypes. This model will advance both early intervention efforts and neurobiological research. W W WVers un modèle complet de staification clinique du trouble bipolaire : intégrant l'évidence Objectifs : Décrire les principaux résultats concernant l'histoire naturelle et l'hétérogénéité du trouble bipolaire (TB) qui se rapportent à l'élaboration d'un modèle unitaire de stades cliniques. Les modèles de staification présentement proposés sont brièvement présentés, de même que les résultats complémentaires, et un modèle complet de staification du TB est proposé qui intègre les données probantes pertinentes.Méthode : Est présentée une revue sélective des principaux résultats publiés sur l'histoire naturelle, l'hétérogénéité, et les modèles de staification clinique du TB.Résultats : Le concept du TB s'est élargi, ce qui a donné un spectre accru de troubles classés dans cette catégorie diagnostique. Différents modèles de staification du TB ont été proposés d'après la littérature sur la psychose précoce, les études de patients souffrant d'un TB établi, et les études prospectives des enfants de parents souffrant de TB. Le résultat déterminant est qu'il y a des phases cliniques séquentielles identifiables dans le développement du TB qui diffèrent de manière importante entre les sous-types épisodiques classiques et ceux du spectre psychotique. En outre, dans le contexte du risque familial, les syndromes de risque précoce ajoutent une valeur prédictive importante et éclairent le modèle de stadification du TB.Conclusions : Un modèle complet de stadification clinique du TB peut être déduit des données probantes disponibles et devrait tenir compte de l'histoire naturelle du TB et de l'hétérogénéité des sous-types. Ce ...

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Section: Natural History and Heterogeneity Of Bipolar Disordermentioning

confidence: 99%

Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

Duffy

2014

Can J Psychiatry

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“…In the 1970s, lithium was the first drug approved in the USA as well as many other countries for the maintenance treatment of bipolar disorder. Although, since then, several other drugs have become available for the maintenance treatment of bipolar disorder (such as valproate, olanzapine, quetiapine, aripiprazole, and lamotrigine) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), lithium has remained a first-line option (12)(13)(14). This position was supported by a systematic review and meta-analysis of five randomized controlled trials (n = 770) that compared lithium with placebo in the maintenance treatment of bipolar disorder, excluding trials that randomly assigned patients who had been stable on longterm lithium to continue or discontinue lithium.…”

Section: Willem a Nolen A And Richard H Weisler Bcmentioning

confidence: 99%

The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)

Nolen

Weisler

2012

Bipolar Disorders

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Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144).  Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd.Objectives: There is no robust proof that the efficacy of lithium in the prevention of manic and depressive episodes in bipolar disorder depends on its plasma level. This analysis aimed to compare the effect of lithium within the presumed therapeutic range of 0.6–1.2 mEq/L and below 0.6 mEq/L with that of placebo.Methods: We carried out a post hoc analysis of a double‐blind trial in which patients aged ≥18 years with bipolar I disorder (DSM‐IV) who had achieved stabilization from a manic, depressive, or mixed episode during open‐label treatment with quetiapine were randomized to continue quetiapine or to switch to lithium or placebo for up to 104 weeks. Of patients randomized to lithium, 201 obtained median lithium levels between 0.6 and 1.2 mEq/L, and 137 obtained median lithium levels <0.6 mEq/L. Their outcomes were compared with those of patients receiving placebo (n = 404). The primary outcome was time to recurrence of any mood event; additional outcomes included time to recurrence of a manic or depressive event.Results: Times to recurrence of any mood event as well as a manic or depressive event were significantly longer for the lithium 0.6–1.2 mEq/L group versus placebo and versus lithium <0.6 mEq/L, with no differences between lithium <0.6 mEq/L and placebo.Conclusions: The results support and expand previous findings that lithium should be dosed high enough to achieve plasma levels ≥0.6 mEq/L in order to achieve an effect in the prevention of both manic and depressive recurrences of bipolar I disorder. A major limitation is that the composition of the two lithium groups was not based on randomization.

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“…Unfortunately, it has a narrow therapeutic window limited by adverse effects, 3,4 and neither the mechanism of action nor its associated toxicity are well understood. Lithium modulates multiple key cellular signaling molecules, 3,5 including inositol monophosphatase (IMPase) and glycogen synthase kinase-3 (GSK-3), considered likely to be therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

et al. 2016

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Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T 2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tauand amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer's disease), and may explain lithium-associated motor symptoms in susceptible patients.

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A critical appraisal of lithium’s efficacy and effectiveness: the last 60 years

Cited by 84 publications

References 72 publications

Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

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