Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation

Hamstra, Sophie I.; Roy, Brian D.; Tiidus, Peter M.; MacNeil, Adam J.; Klentrou, Panagiota; MacPherson, Rebecca E. K.; Fajardo, Val A.

doi:10.2174/1570159x20666220302151224

Cited by 20 publications

(21 citation statements)

References 186 publications

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“…Furthermore, we found that mdx -VWRLi mice had greater novel object recognition compared with mdx -VWR mice, suggesting that Li supplementation had an additive effect, which is impressive given that the mdx -VWRLi mice ran significantly less. Thus, we attribute the improvements in spatial memory in the mdx -VWRLi mice largely to Li supplementation, which is consistent with the neuroprotective effects of Li 35,60–62 .…”

Section: Discussionsupporting

confidence: 82%

“…Furthermore and similar to our tideglusib experiments, the mdx -VWRLi mice had the lowest RER compared with the mdx -SED mice, which is indicative of enhanced oxidative fiber expression (Figure S2). Given the fact that oxidative fibers are more insulin sensitive than their glycolytic counterparts 36 and that Li is a well-known insulin mimetic 35 , we next examined the effects of VWR and Li on insulin sensitivity. Insulin tolerance tests show that mdx -SED mice were insulin resistant compared with WT, mdx -VWR, and mdx -VWRLi mice (Figure 2E-F).…”

Section: Resultsmentioning

confidence: 99%

“…Li is an already FDA-approved drug used in the treatment of bipolar disorder. Though Li toxicity has been observed in the clinical setting, these adverse events have been associated with long term therapy with relatively higher doses (above serum Li of 1.0 mM) 35 . In the present study, we used a dose below the clinically used window of 0.5 mM – 1.0 mM serum Li concentration, which was still able to produce significant benefits on skeletal muscle specific force production, cardiac muscle diastolic and systolic function, and metabolic and cognitive health in mdx mice.…”

Section: Discussionmentioning

confidence: 99%

“…In line with minimizing stress on the animal during exercise training, GSK3 inhibition was afforded with Li supplementation that was provided through drinking water rather than tideglusib via oral gavage. Li is a natural inhibitor of GSK3 and is most commonly used for the treatment of bipolar disorder; however, within a narrow therapeutic range of 0.5-1.0 mM serum Li concentration 35 . Here, we treated mdx mice with a low dose of lithium chloride (50 mg/kg/day via drinking water), which resulted in a serum Li concentration of 0.15 ± 0.05 mM (n = 9).…”

Section: Lithium Treatment Improves Muscle Function In MDX Mice Subje...mentioning

confidence: 99%

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GSK3 inhibition improves skeletal muscle function and whole-body metabolism in the severe DBA/2Jmdxmouse model

Hamstra

Whitley

Braun

et al. 2022

Preprint

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Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder that leads to early mortality. We examined the pathogenic contribution of glycogen synthase kinase 3 (GSK3) to DMD using the mdx model. GSK3 is a serine/threonine kinase that has been implicated in other muscular dystrophies and our initial results showed that overactivation of GSK3 may contribute to increased disease severity found in DBA/2J (D2) mdx mice vs C57BL/10 mdx mice. In support of this, treating D2 mdx mice with the GSK3 inhibitor, tideglusib (10 mg/kg/day), increased muscle mass, strength, and fatigue resistance. We also found elevated proportions of oxidative fibers and increased utrophin mRNA, while muscle necrosis and oxidative stress were reduced. Finally, young D2 mdx mice displayed early diastolic dysfunction, and this was blunted with tideglusib treatment, an effect attributed to lowered oxidative stress and fibrosis. This study highlights the therapeutic potential of tideglusib and GSK3 inhibition for DMD.

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Lithium Treatment Improves Muscle Function In MDX Mice Subje...mentioning

confidence: 99%

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GSK3 inhibition improves skeletal muscle function and whole-body metabolism in the severe DBA/2Jmdxmouse model

Hamstra

Whitley

Braun

et al. 2022

Preprint

Self Cite

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“…Taken together, lithium may reduce neuroinflammationrelated suicidal behavior by inhibiting inflammatory pathways. Second, lithium may also prevent some of the physical comorbidities that lead to premature death [47].…”

Section: Discussionmentioning

confidence: 99%

Mortality and Lithium-Protective Effects after First-Episode Mania Diagnosis in Bipolar Disorder: A Nationwide Retrospective Cohort Study in Taiwan

Carvalho,

Hsu,

Vieta

et al. 2024

Psychother Psychosom

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Introduction: This study aimed to estimate all-cause mortality in patients after a first-episode mania (FEM) and examine whether six guideline-recommended medications can reduce mortality. Methods: The cohort included population-based FEM samples and matched controls from Taiwan, spanning 2007 to 2018. The primary outcomes assessed were all-cause/suicide-related mortality, while the secondary outcome focused on mortality associated with pharmacological treatments. We compared mortality in post-FEM patients and age-/sex-matched controls without any diagnosed bipolar disorders and patients with and without psychopharmacological treatment using Cox regression analysis, respectively. Statistics were presented with time-to-event adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs). Results: The study included 54,092 post-FEM patients and 270,460 controls, totaling 2,467,417 person-years of follow-up. Post-FEM patients had higher risks of all-cause mortality (AHR 2.38, 95% CI: 2.31–2.45) and suicide death (10.80, 5.88–19.84) than controls. Lithium (0.62, 0.55–0.70), divalproex (0.89, 0.83–0.95), and aripiprazole (0.81, 0.66–1.00) were associated with reduced all-cause mortality compared to non-users. There were no significant all-cause mortality differences for quetiapine (0.95, 0.89–1.01), risperidone (0.92, 0.82–1.02), and paliperidone (1.24, 0.88–1.76) users. When accounting for drug action onset times in sensitivity analyses, only lithium significantly reduced all-cause mortality (AHR range 0.65–0.72). There were 35 and 16 suicide deaths in post-FEM patients and controls, respectively. No drug had a significant effect on suicide deaths (lithium: 6; divalproex: 7; aripiprazole: 0; quetiapine: 10; risperidone: 4; paliperidone: 1). Conclusion: Post-FEM patients had a higher risk of all-cause/suicide-related mortality, and lithium treatment might reduce all-cause mortality.

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Lithium, the gold standard drug for bipolar disorder: analysis of current clinical studies

Airainer,

Seifert

2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Lithium is the gold standard drug in the treatment of bipolar disorder. Despite increasing scientific interest, relatively few patients with bipolar disorder receive lithium therapy. Lithium is the only drug that is effective in the prophylaxis of manic, depressive, and suicidal symptoms. Lithium therapy is also associated with a variety of adverse drug reactions and the need for therapeutic drug monitoring. Numerous studies have focussed on the efficacy and safety of both lithium-monotherapy and lithium-add-on therapy. The aim of this study is to provide a systematic overview of clinical studies on lithium therapy for bipolar disorder from the last 7 years and to present a critical analysis of these studies. The results provide an up-to-date overview of the efficacy, tolerability, and safety of lithium therapy for bipolar disorder and thus improve the pharmacotherapy of bipolar disorder. A total of 59 studies were analysed using various analysis parameters. The studies were also categorised into different subgroups. These are lithium-monotherapy, lithium vs. placebo/drug, and lithium + adjunctive therapy. The majority of the studies (N = 20) had a duration of only 3–8 weeks. Only 13 studies lasted for > 40 weeks. Lithium was superior to aripiprazole, valproic acid, and quetiapine in terms of improving manic symptoms. Lithium therapy resulted in a lower relapse rate compared to valproic acid therapy. Lithium was more neuroprotectively effective than quetiapine. Fourteen of the 22 add-on therapies to lithium showed a predominantly positive effect on the treatment outcome compared to lithium-monotherapy. Only the add-on therapy with sertraline led to a higher rate of study discontinuations than lithium-monotherapy. Lithium is a safe and effective treatment option for children. However, risperidone and quetiapine were superior to lithium in some aspects, which is why these drugs should be considered as an alternative treatment option for children. Collectively, current clinical studies highlight the relevance of lithium in the treatment of bipolar disorder.

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Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation

Cited by 20 publications

References 186 publications

GSK3 inhibition improves skeletal muscle function and whole-body metabolism in the severe DBA/2Jmdxmouse model

GSK3 inhibition improves skeletal muscle function and whole-body metabolism in the severe DBA/2Jmdxmouse model

Mortality and Lithium-Protective Effects after First-Episode Mania Diagnosis in Bipolar Disorder: A Nationwide Retrospective Cohort Study in Taiwan

Lithium, the gold standard drug for bipolar disorder: analysis of current clinical studies

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