BACKGROUND: Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association.
METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models.
RESULTS: Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer\'s disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15).
CONCLUSIONS: The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.

OBJECTIVE: Lithium is an effective psychoactive drug. It has a narrow therapeutic margin, with subtherapeutic levels or intoxication commonly occurring. Therapeutic drug monitoring (TDM) of lithium has several barriers. This scoping review aims to describe and analyze existing and emerging technologies for lithium TDM and to describe the lithium quantification parameters (precision, accuracy, detection limit) attributed to each technology.
METHODS: PubMed, Scopus, Web of Science, and Google Scholar were searched. Studies that described lithium quantification and complied with PRISMA-ScR guidelines were included. Articles selection was conducted by 2 researchers. Good precision was defined if its relative standard deviation <3%; acceptable, from 3% to 5%; and low, >5%. Accuracy was considered good if the error <5%; acceptable, 5%1 to 0%; and low if it was >10%.
RESULTS: Of the 2008 articles found, 22 met the inclusion criteria. Of these, 14 studies concerned laboratory devices, in which precision was found to be low in one third of cases, and half had good precision. Accuracy of one third was good, another third was low, and the remaining third did not report accuracy. The other 8 studies concerned portable devices, in which precision was low in more than 60% of the cases and good in 25% of the studies. Accuracy was low in 50% of the cases, and good in just over a third. Limits of detection included the therapeutic range of lithium in all studies.
CONCLUSIONS: Among emerging technologies for lithium TDM, precision and accuracy remain a challenge, particularly for portable devices.

The role of lithium as a possible therapeutic strategy for neurodegenerative diseases has generated scientific interest. We systematically reviewed and meta-analyzed pre-clinical and clinical studies that evidenced the neuroprotective effects of lithium in Alzheimer\'s (AD) and Parkinson\'s disease (PD). We followed the PRISMA guidelines and performed the systematic literature search using PubMed, EMBASE, Web of Science, and Cochrane Library. A total of 32 articles were identified. Twenty-nine studies were performed in animal models and 3 studies were performed on human samples of AD. A total of 17 preclinical studies were included in the meta-analysis. Our analysis showed that lithium treatment has neuroprotective effects in diseases. Lithium treatment reduced amyloid-β and tau levels and significantly improved cognitive behavior in animal models of AD. Lithium increased the tyrosine hydroxylase levels and improved motor behavior in the PD model. Despite fewer clinical studies on these aspects, we evidenced the positive effects of lithium in AD patients. This study lends further support to the idea of lithium\'s therapeutic potential in neurodegenerative diseases.

Lithium is widely used as treatment of acute mania and as prophylactic therapy for bipolar disorder. International and national guidelines also consider lithium as a possible treatment of acute bipolar depression. Research on the use of lithium in bipolar depression, however, seems to be limited compared to the data available for its efficacy in the other phases of bipolar disorder.
To provide a systematic review of the evidence for lithium in the treatment of acute bipolar depression and provide directions for further research.
A systematic review of clinical studies investigating the use of lithium in bipolar depression was performed using preferred reporting items for systematic reviews and meta-analyses guidelines in Pubmed, Embase and Psychinfo using the medical subjects headings and free text terms \"lithium,\" \"bipolar depression,\" \"dosage,\" \"serum concentration\" and \"bipolar disorders.\"
This review included 15 studies with a total of 1222 patients, between the age of 18 and 65, suffering from bipolar depression of which 464 were treated with lithium. There are currently only limited and low-quality data on the efficacy of lithium as a treatment of bipolar depression. It appears that there have been no placebo controlled randomized controlled trials with lithium concentrations that are considered to be therapeutic. The older studies suffered from limitations such as small sample sizes, insufficient treatment lengths, and insufficient monitoring of serum concentrations.
In contrast to data for the treatment of mania and prophylaxis, robust data on the efficacy of lithium in bipolar depression is currently lacking, making it impossible to make conclusions regarding efficacy or inefficacy, for which further research is needed.

OBJECTIVE: To identify the risks and benefits of clozapine‑lithium co-prescription.
METHODS: Articles published in English or French were identified with a MEDLINE, Web of Sciences and PsycINFO search, from inception through January 2023, using the term \'clozapine\' in combination with \'lithium\'. Data were synthesized narratively.
RESULTS: Of the 67 articles included in the review, more than half (n = 38, 56.7 %) were focused on clozapine-related blood dyscrasia. A body of evidence drawn from case reports and retrospective chart studies highlights the potential benefits of lithium prescription for clozapine-related neutropenia, since this strategy may avoid clozapine discontinuation or allow its rechallenge. The most documented adverse drug reactions (ADRs) associated with clozapine‑lithium co-prescription are neurotoxic events, which may be prevented or detected early by clinical, electroencephalographic and therapeutic drug monitoring. Causality assessment cannot be established for other reported ADRs occurring during clozapine‑lithium co-prescription. The benefits of the combined prescription on psychotic and/or mood symptoms are poorly documented.
CONCLUSIONS: The risks and benefits of clozapine‑lithium co-prescription require further exploration as the combination might significantly contribute to reducing underprescription or premature discontinuation of clozapine.

BACKGROUND: Bipolar disorder is a complex psychiatric disorder where long-term treatment is crucial to maintain stabilization. Although largely well tolerated, lithium has a wide spectrum of adverse effects in different organs and seems to also cause taste and smell disorders, which remain rare and not largely described. We aim to present a rare case of hyposmia and dysgeusia secondary to lithium treatment in a bipolar patient and also conduct a review on these rare lithium adverse effects.
METHODS: The case is a 43-year-old woman with type I bipolar disorder who became stabilized and fully functional with lithium therapy. After 4 months of treatment, she began to notice progressive hyposmia and dysgeusia. After multiple diagnostic and screening tests, lithium was implicated as the cause of the symptoms, which led to a switch to valproic acid. After 3 months, she was not compensated with valproic acid treatment, returned to lithium therapy despite its adverse effects, and became stabilized again.
CONCLUSIONS: There are few data on lithium therapy taste and smell adverse effects. Most studies on this topic are likely to be case reports. Lithium therapy may cause dysgeusia and hyposmia, although mechanisms are not fully understood. These adverse effects can interfere negatively in patient\'s treatment adherence. Therefore, physicians who prescribe lithium should be aware of them. Further structured studies are needed to better understand these lithium rare adverse effects and the appropriate way to assess and monitoring them.

UNASSIGNED: Ductal carcinoma in situ (DCIS) is the earliest and most curable form of breast cancer. Patients who harbour this disease for quite some time usually have micro invasion by virtue of high-grade disease or big size. Herein, we report a case of 56-year-old postmenopausal woman presenting with a one-year history of blood-stained nipple discharge from right breast. She was a known case of depression receiving oral anti-depressants containing lithium for 20 years. Her mammogram was performed followed by ultrasound breast. Mammogram identified suspicious clusters of micro calcifications hence subjected to stereotactic core biopsy which revealed two separate foci of high-grade DCIS. Therefore, based on her clinical, radiological, and pathological findings she was subjected to mastectomy and sentinel node biopsy. Final histopathology showed big DCIS (10×8×3 cm in size) with immunohistochemical stains confirmed no invasive focus on extensive sampling. Therefore, we postulated that it might be correlated to the use of Lithium which has anti-cancer properties.

The prevalence of posttraumatic stress disorder (PTSD) co-occurring in people with bipolar disorder (BD) is high. People with BD and PTSD may experience different outcomes and quality of life after pharmacologic treatment than those with BD alone. This review systematically explores the impact of PTSD on pharmacologic treatment outcomes for adults with BD.
We conducted a systematic search up to November 25, 2021, using MEDLINE Complete, Embase, American Psychological Association PsycInfo, and the Cochrane Central Register of Controlled Trials to identify randomized and nonrandomized studies of pharmacologic interventions for adults with BD that assessed for comorbid PTSD. We used the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool to assess the risk of bias.
The search identified 5093 articles, and we reviewed 62 full-text articles. Two articles met inclusion criteria (N = 438). One article was an observational study, and the other was a randomized comparative effectiveness trial. The observational study examined lithium response rates and found higher response rates in BD alone compared with BD plus PTSD over 4 years. The randomized trial reported more severe symptoms in the BD plus PTSD group than in those with BD alone following 6 months of quetiapine treatment. There was no significant difference in the lithium treatment group at follow-up.
Comorbid PTSD may affect quetiapine and lithium treatment response in those with BD. Because of the high risk of bias and low quality of evidence, however, these results are preliminary. Specific studies exploring comorbid BD and PTSD are required to inform pharmacotherapy selection and guidelines appropriately. (International Prospective Register of Systematic Reviews ID: CRD42020182540).

To evaluate lithium in the treatment of acute bipolar depression.
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.
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 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.
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.

This mini-review aims to show a discrepancy between favorable data of lithium\'s therapeutic activity and the decreased use of the drug worldwide. The data point to lithium as the best mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most encouraging psychiatric use of lithium is the augmentation of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium is the most efficacious antisuicidal drug among all mood stabilizers. The drug also exerts antiviral, immunomodulatory, and neuroprotective effects which may be of major clinical value. On the other hand, the data of lithium use show that its therapeutic application in many countries has declined. A reason for this can be the introduction and heavy promotion of other mood-stabilizers, while lithium is an \"orphan\" drug with the minimal interest of any drug company. Probably, very important is also a perception of lithium as a \"toxic drug\", pointing to its side effects, mainly thyroid, renal and cognitive ones. In recent years, several proposals to turn back this anomalous association appeared, challenging a negative perception of lithium and optimizing its long-term administration. They show the data on lithium superiority over other mood stabilizers and point to the proper management of the lithium-induced side effects. This endeavor aims to allow a larger number of mood disorder patients to become beneficiaries of lithium use.