Adverse syndromes associated with lithium

Macritchie, Karine; Young, Allan

doi:10.1093/med/9780198527480.003.0006

Cited by 10 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed reduction in DA‐dependent striatal induction of c‐Fos and locomotor behavior in Tet/DN‐GSK‐3 mice fits well with the previously reported role of GSK‐3 as an important mediator of DA actions in the striatum (Beaulieu et al , 2004). This, together with the here reported importance of intact GSK‐3 activity for cortical and striatal neuron viability, may explain not only the motor deficit observed in Tet/DN‐GSK‐3 mice but also the tremor that appears as the most prominent motor side effect of the therapy of bipolar disorder with lithium, a well established GSK‐3 inhibitor (Klein and Melton, 1996; Macritchie and Young, 2004).…”

Section: Discussionmentioning

confidence: 62%

Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3 conditional transgenic mice

Gómez‐Sintes¹,

Hernández²,

Bortolozzi³

et al. 2007

EMBO J

View full text Add to dashboard Cite

Increased glycogen synthase kinase‐3 (GSK‐3) activity is believed to contribute to the etiology of chronic disorders like Alzheimer's disease and diabetes, thus supporting therapeutic potential of GSK‐3 inhibitors. However, sustained GSK‐3 inhibition might induce tumorigenesis through β‐catenin‐APC dysregulation. Besides, sustained in vivo inhibition by genetic means (constitutive knock‐out mice) revealed unexpected embryonic lethality due to massive hepatocyte apoptosis. Here, we have generated transgenic mice with conditional (tetracycline system) expression of dominant‐negative‐GSK‐3 as an alternative genetic approach to predict the outcome of chronic GSK‐3 inhibition, either per se, or in combination with mouse models of disease. By choosing a postnatal neuron‐specific promoter, here we specifically address the neurological consequences. Tet/DN‐GSK‐3 mice showed increased neuronal apoptosis and impaired motor coordination. Interestingly, DN‐GSK‐3 expression shut‐down restored normal GSK‐3 activity and re‐established normal incidence of apoptosis and motor coordination. These results reveal the importance of intact GSK‐3 activity for adult neuron viability and physiology and warn of potential neurological toxicity of GSK‐3 pharmacological inhibition beyond physiological levels. Interestingly, the reversibility data also suggest that unwanted side effects are likely to revert if excessive GSK‐3 inhibition is halted.

show abstract

Section: Discussionmentioning

confidence: 62%

Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3 conditional transgenic mice

Gómez‐Sintes¹,

Hernández²,

Bortolozzi³

et al. 2007

EMBO J

View full text Add to dashboard Cite

show abstract

“…Since its introduction into psychiatric pharmacotherapy 60 years ago, lithium remains the most effective agent in the treatment and prophylaxis of major mood disorders, particularly bipolar disorder (BD; Manji et al, 1999 ; Baldessarini et al, 2002 ; Grof and Muller-Oerlinghausen, 2009 ; Kovacsics and Gould, 2010 ). Despite the obvious advantages of chronic lithium therapy, its clinical use is often curtailed by its narrow therapeutic index and its devastating overdose-induced toxicity (Macritchie and Young, 2004 ). Accordingly, patients must be closely monitored not only at the beginning of treatment, but also during treatment maintenance, to keep serum lithium concentrations within a therapeutic window of 0.6–1.4 mM.…”

Section: Correlate With Pharmacological Inhibitionmentioning

confidence: 99%

GSK-3 mouse models to study neuronal apoptosis and neurodegeneration

Gómez‐Sintes

Hernández

Lucas

et al. 2011

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Increased GSK-3 activity is believed to contribute to the etiology of chronic disorders like Alzheimer’s disease (AD), schizophrenia, diabetes, and some types of cancer, thus supporting therapeutic potential of GSK-3 inhibitors. Numerous mouse models with modified GSK-3 have been generated in order to study the physiology of GSK-3, its implication in diverse pathologies and the potential effect of GSK-3 inhibitors. In this review we have focused on the relevance of these mouse models for the study of the role of GSK-3 in apoptosis. GSK-3 is involved in two apoptotic pathways, intrinsic and extrinsic pathways, and plays opposite roles depending on the apoptotic signaling process that is activated. It promotes cell death when acting through intrinsic pathway and plays an anti-apoptotic role if the extrinsic pathway is occurring. It is important to dissect this duality since, among the diseases in which GSK-3 is involved, excessive cell death is crucial in some illnesses like neurodegenerative diseases, while a deficient apoptosis is occurring in others such as cancer or autoimmune diseases. The clinical application of a classical GSK-3 inhibitor, lithium, is limited by its toxic consequences, including motor side effects. Recently, the mechanism leading to activation of apoptosis following chronic lithium administration has been described. Understanding this mechanism could help to minimize side effects and to improve application of GSK-3 inhibitors to the treatment of AD and to extend the application to other diseases.

show abstract

“…The main adverse effects of lithium are its narrow therapeutic index, the need for regular plasma monitoring, thyroid impairment and renal impairment with long-term use and withdrawal depression and mania on abrupt stoppage, which makes lithium unsuitable for poorly adherent patients [112]. Valproate has none of these problems.…”

Section: Expert Opinionmentioning

confidence: 99%

A review of valproate in psychiatric practice

Haddad

Das

Ashfaq

et al. 2009

Expert Opinion on Drug Metabolism & Toxicology

120

View full text Add to dashboard Cite

Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate and semisodium valproate. It has actions on dopamine, GABA and glutamate neurotransmission and intracellular signaling. Its main psychiatric use is to treat bipolar disorder. It has been used in other psychiatric disorders, including schizophrenia and borderline personality disorder, but data are insufficient to recommend this. In acute mania, valproate monotherapy has similar efficacy to antipsychotic drugs and lithium whereas the combination of valproate and an antipsychotic is more effective than either drug alone. In maintenance treatment of bipolar disorder, valproate monotherapy has comparable efficacy to olanzapine although placebo-controlled evidence is limited. Maintenance treatment with valproate and quetiapine or olanzapine is more efficacious than valproate alone when an acute episode responds to the combination. Common adverse effects of valproate include weight gain, gastrointestinal symptoms, sedation, tremor and mild elevation of hepatic enzymes. Serious hepatic toxicity is rare in adults. Many adverse effects are dose related and resolve with dose reduction. Valproate is teratogenic and specifically associated with neural tube defect. Preliminary evidence has linked in utero exposure to decreased verbal intelligence in the offspring. These effects, plus a probable increased risk of polycystic ovary syndrome, limit valproate's use in women of childbearing potential.

show abstract

Adverse syndromes associated with lithium

Cited by 10 publications

References 0 publications

Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3 conditional transgenic mice

Neuronal apoptosis and reversible motor deficit in dominant-negative GSK-3 conditional transgenic mice

GSK-3 mouse models to study neuronal apoptosis and neurodegeneration

A review of valproate in psychiatric practice

Contact Info

Product

Resources

About