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Current Neuropharmacology 2023Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorder. Due to its narrow therapeutic window (0.5-1.2 mM serum concentration),... (Review)
Review
Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorder. Due to its narrow therapeutic window (0.5-1.2 mM serum concentration), there is a stigma associated with lithium treatment and the adverse effects that can occur at therapeutic doses. However, several studies have indicated that doses of lithium under the predetermined therapeutic dose used in bipolar disorder treatment may have beneficial effects not only in the brain but across the body. Currently, literature shows that low-dose lithium (≤0.5 mM) may be beneficial for cardiovascular, musculoskeletal, metabolic, and cognitive function, as well as inflammatory and antioxidant processes of the aging body. There is also some evidence of low-dose lithium exerting a similar and sometimes synergistic effect on these systems. This review summarizes these findings with a focus on low-dose lithium's potential benefits on the aging process and age-related diseases of these systems, such as cardiovascular disease, osteoporosis, sarcopenia, obesity and type 2 diabetes, Alzheimer's disease, and the chronic low-grade inflammatory state known as inflammaging. Although lithium's actions have been widely studied in the brain, the study of the potential benefits of lithium, particularly at a low dose, is still relatively novel. Therefore, this review aims to provide possible mechanistic insights for future research in this field.
Topics: Humans; Lithium; Diabetes Mellitus, Type 2; Bipolar Disorder; Brain; Dietary Supplements
PubMed: 35236261
DOI: 10.2174/1570159X20666220302151224 -
British Journal of Hospital Medicine... Nov 2020Lithium is a mood stabiliser widely used in the treatment and prophylaxis of mania, bipolar disorders and recurrent depression. Treatment with lithium can give rise to... (Review)
Review
Lithium is a mood stabiliser widely used in the treatment and prophylaxis of mania, bipolar disorders and recurrent depression. Treatment with lithium can give rise to various endocrine and metabolic abnormalities, including thyroid dysfunction, nephrogenic diabetes insipidus and hypercalcaemia. Lithium may induce hypercalcaemia through both acute and chronic effects. The initial acute effects are potentially reversible and occur as a result of lithium's action on the calcium-sensing receptor pathway and glycogen synthase kinase 3, giving rise to a biochemical picture similar to that seen in familial hypocalciuric hypercalcaemia. In the long term, chronic lithium therapy leads to permanent changes within the parathyroid glands by either unmasking hyperparathyroidism in patients with a subclinical parathyroid adenoma or possibly by initiating multiglandular hyperparathyroidism. The latter biochemical picture is identical to that of primary hyperparathyroidism. Lithium-associated hyperparathyroidism, especially in patients on chronic lithium therapy, is associated with increased morbidity. Hence, regular monitoring of calcium levels in patients on lithium therapy is of paramount importance as early recognition of lithium-associated hyperparathyroidism can improve outcomes. This review focuses on the definition, pathophysiology, presentation, investigations and management of lithium-associated hyperparathyroidism.
Topics: Humans; Hypercalcemia; Hyperparathyroidism; Lithium; Parathyroid Glands; Parathyroid Neoplasms
PubMed: 33263481
DOI: 10.12968/hmed.2020.0457 -
Journal of Intensive Care Medicine May 2017Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of... (Review)
Review
Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination. This is most commonly due to impaired kidney function caused by volume depletion from lithium-induced nephrogenic diabetes insipidus or intercurrent illnesses and is also drug-induced. Lithium poisoning can affect multiple organs; however, the primary site of toxicity is the central nervous system and clinical manifestations vary from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures. Lithium poisoning has a low mortality rate; however, chronic lithium poisoning can require a prolonged hospital length of stay from impaired mobility and cognition and associated nosocomial complications. Persistent neurological deficits, in particular cerebellar, are described and the incidence and risk factors for its development are poorly understood, but it appears to be uncommon in uncomplicated acute poisoning. Lithium is readily dialyzable, and rationale support extracorporeal treatments to reduce the risk or the duration of toxicity in high-risk exposures. There is disagreement in the literature regarding factors that define patients most likely to benefit from treatments that enhance lithium elimination, including specific plasma lithium concentration thresholds. In the case of extracorporeal treatments, there are observational data in its favor, without evidence from randomized controlled trials (none have been performed), which may lead to conservative practices and potentially unnecessary interventions in some circumstances. More data are required to define the risk-benefit of extracorporeal treatments and their use (modality, duration) in the management of lithium poisoning.
Topics: Acute Disease; Antimanic Agents; Bipolar Disorder; Chronic Disease; Drug Overdose; Humans; Lithium; Neurotoxicity Syndromes; Practice Guidelines as Topic; Renal Dialysis; Renal Insufficiency
PubMed: 27516079
DOI: 10.1177/0885066616651582 -
International Journal of Molecular... Dec 2017Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines... (Review)
Review
Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines have recommended lithium to be the treatment of choice for acute manic, mixed and depressive episodes of BD, along with long-term prophylaxis. Lithium's specific mechanism of action in mood regulation is progressively being clarified, such as the direct inhibition on glycogen synthase kinase 3β, and its various effects on neurotrophic factors, neurotransmitters, oxidative metabolism, apoptosis, second messenger systems, and biological systems are also being revealed. Furthermore, lithium has been proposed to exert its treatment effects through mechanisms associated with neuronal plasticity. In this review, we have overviewed the clinical aspects of lithium use for BD, and have focused on the neuroprotective and neurotrophic effects of lithium.
Topics: Bipolar Disorder; Glycogen Synthase Kinase 3 beta; Humans; Lithium; Nerve Growth Factors; Neuronal Plasticity; Neuroprotection
PubMed: 29232923
DOI: 10.3390/ijms18122679 -
Journal of Psychiatric Practice Jan 2023The literature on lithium's role in suicide prevention is rife with competing interpretations and diverging opinions, in part stemming from the complexity of the... (Review)
Review
The literature on lithium's role in suicide prevention is rife with competing interpretations and diverging opinions, in part stemming from the complexity of the underlying literature base. Conclusions that lithium unequivocally offers suicide prevention benefits do not appear warranted based on the strength of existing studies. Given the evidence along with the indisputable risks associated with lithium (especially in overdose), and the need for sustained therapeutic dosing to achieve any theoretical antisuicide benefit, it seems evident that any potential role for lithium in suicide prevention is far narrower than originally hypothesized. As such, the goal of this article is to provide an evidence-informed, therapeutic risk management approach to clinical decision-making concerning the use of lithium for suicide prevention to ensure that such prescribing is done in a patient-centered fashion that mitigates, to the extent possible, the potential risks of lithium use. This includes a review of potential justifications for not employing lithium for suicide prevention, given the recommendations in the existing guidelines. Clinicians should approach this clinical decision in an individualized fashion with full consideration of the potential risks associated with lithium use and availability, as well as potential alternative treatment options. An individualized risk/benefit analysis must also take into consideration the presence of comorbid conditions; the acuity of suicide risk, and any history of self-directed violence, with special attention to suicide attempts via overdose; treatment adherence, past and present; the presence and/or strength of a therapeutic relationship; and other viable treatment options.
Topics: Humans; Lithium; Lithium Compounds; Bipolar Disorder; Suicide Prevention; Suicide, Attempted
PubMed: 36649553
DOI: 10.1097/PRA.0000000000000680 -
Journal of Affective Disorders Jul 2022To evaluate lithium in the treatment of acute bipolar depression. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate lithium in the treatment of acute bipolar depression.
METHODS
We conducted a systematic literature review for: 1) cross-over or parallel-group design studies comparing lithium response in bipolar versus unipolar depressed patients, and 2) parallel group studies of bipolar depressed patients comparing lithium versus placebo or other psychotropics. Meta-analyses using response rate as the primary outcome were conducted to evaluate lithium's efficacy.
RESULTS
The literature search yielded 947 records. Ultimately, 17 studies were included, totaling 1545 patients, including 676 who received lithium. The overall summary effects reveal that there were no statistically significant differences between lithium versus antidepressants or placebo, however, lithium performed numerically worse than antidepressants (RR = 0.61; 95%CI, 0.37-1.02; p = 0.06) but better than placebo (RR = 1.18; 95%CI, 0.99-1.41; p = 0.07). The specificity of lithium for bipolar versus unipolar depression was not supported in the primary analysis of all trials, though an analysis limited to double-blinded, monotherapy, cross-over studies revealed a statistically significant result supporting lithium's efficacy for those with bipolar depression.
LIMITATIONS
Limitations include study selection rules, the use of response rates rather than remission rates or continuous score outcomes, and the small number of studies included in each meta-analysis.
CONCLUSIONS
These meta-analyses do not support lithium as a first-line treatment for acute bipolar depression. However, the bipolar vs. unipolar sensitivity analysis and the modest, though non-significant advantage over placebo suggest lithium may still be a viable treatment option. Larger and more rigorously-designed studies are needed to determine lithium's full range of efficacy relative to placebo and other psychotropics.
Topics: Antidepressive Agents; Bipolar Disorder; Depression; Humans; Lithium; Lithium Compounds
PubMed: 35429528
DOI: 10.1016/j.jad.2022.04.058 -
Psychopharmacology Bulletin 1991Lithium, in various forms, has been used in the treatment and prophylaxis of bipolar affective disorder since the mid-1960s. In the past 30-plus years, much has been... (Review)
Review
Lithium, in various forms, has been used in the treatment and prophylaxis of bipolar affective disorder since the mid-1960s. In the past 30-plus years, much has been learned regarding lithium's effects on the renal function, improved ways and forms of administering and monitoring serum lithium levels, the effect of mood state on lithium kinetics, and the influence of age and disease factors. Furthermore, the interaction of lithium with other psychotropics as well as with non-psychotropics, in particular, the diuretics and nonsteroidal anti-inflammatory agents, has frequently become a source of concern. This review highlights current knowledge on these topics with a view toward future developments.
Topics: Humans; Lithium
PubMed: 1813895
DOI: No ID Found -
Neuroscience and Biobehavioral Reviews May 2023Here an overview is provided on therapeutic/neuroprotective effects of Lithifum (Li) in neurodegenerative and psychiatric disorders focusing on the conspicuous action of... (Review)
Review
Here an overview is provided on therapeutic/neuroprotective effects of Lithifum (Li) in neurodegenerative and psychiatric disorders focusing on the conspicuous action of Li through autophagy. The effects on the autophagy machinery remain the key molecular mechanisms to explain the protective effects of Li for neurodegenerative diseases, offering potential therapeutic strategies for the treatment of neuropsychiatric disorders and emphasizes a crossroad linking autophagy, neurodegenerative disorders, and mood stabilization. Sensitization by psychostimulants points to several mechanisms involved in psychopathology, most also crucial in neurodegenerative disorders. Evidence shows the involvement of autophagy and metabotropic Glutamate receptors-5 (mGluR5) in neurodegeneration due to methamphetamine neurotoxicity as well as in neuroprotection, both in vitro and in vivo models. More recently, Li was shown to modulate autophagy through its action on mGluR5, thus pointing to an additional way of autophagy engagement by Li and to a substantial role of mGluR5 in neuroprotection related to neural e neuropsychiatry diseases. We propose Li engagement of autophagy through the canonical mechanisms of autophagy machinery and through the intermediary of mGluR5.
Topics: Humans; Neuroprotection; Lithium; Neurodegenerative Diseases; Autophagy; Neuronal Plasticity
PubMed: 36996994
DOI: 10.1016/j.neubiorev.2023.105148 -
Connecticut Medicine Mar 1990Lithium utility and toxicity are reviewed. Lithium continues to be the most useful agent available for the prophylaxis and treatment of bipolar illness. Lithium... (Review)
Review
Lithium utility and toxicity are reviewed. Lithium continues to be the most useful agent available for the prophylaxis and treatment of bipolar illness. Lithium augmentation of antidepressants is useful in treatment-resistant unipolar depression. Utility in other psychiatric disorders, such as schizoaffective, alcoholism, or aggressive behavior, is documented only when a significant affective component coexists. In internal medicine, lithium has proven useful in the prophylaxis of cluster headaches and in ameliorating chemotherapy-induced neutropenia. Other miscellaneous uses in both psychiatry and medicine have been anecdotally reported and are reviewed. However, the use of lithium may be limited by acute and chronic toxic side effects. Acute toxicity almost always manifests as central nervous system (CNS) dysfunction, and the degree of toxicity usually parallels the extent of CNS dysfunction. Chronic toxic manifestations effect cardiac, renal, and endocrine systems. In fetu exposure may be teratogenic.
Topics: Humans; Lithium; Mental Disorders
PubMed: 2182284
DOI: No ID Found -
Clinical Pharmacology and Therapeutics 1970
Clinical Trial Comparative Study Review
Topics: Adjustment Disorders; Bipolar Disorder; Calcium; Chronic Disease; Clinical Trials as Topic; Depression; Electroencephalography; Humans; Lithium; Natriuresis; Potassium; Sodium
PubMed: 4906726
DOI: 10.1002/cpt1970112168