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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 -
Medicina (Kaunas, Lithuania) Jun 2021Data regarding older age bipolar disorder (OABD) are sparse. Two major groups are classified as patients with first occurrence of mania in old age, the so called "late... (Review)
Review
Data regarding older age bipolar disorder (OABD) are sparse. Two major groups are classified as patients with first occurrence of mania in old age, the so called "late onset" patients (LOBD), and the elder patients with a long-standing clinical history, the so called "early onset" patients (EOBD). The aim of the present literature review is to provide more information on specific issues concerning OABD, such as epidemiology, aetiology and treatments outcomes. We conducted a Medline literature search from 1970-2021 using the MeSH terms "bipolar disorder" and "aged" or "geriatric" or "elderly". The additional literature was retrieved by examining cross references and by a hand search in textbooks. With sparse data on the treatment of OABD, current guidelines concluded that first-line treatment of OABD should be similar to that for working-age bipolar disorder, with specific attention to side effects, somatic comorbidities and specific risks of OABD. With constant monitoring and awareness of the possible toxic drug interactions, lithium is a safe drug for OABD patients, both in mania and maintenance. Lamotrigine and lurasidone could be considered in bipolar depression. Mood stabilizers, rather than second generation antipsychotics, are the treatment of choice for maintenance. If medication fails, electroconvulsive therapy is recommended for mania, mixed states and depression, and can also be offered for continuation and maintenance treatment. Preliminary results also support a role of psychotherapy and psychosocial interventions in old age BD. The recommended treatments for OABD include lithium and antiepileptics such as valproic acid and lamotrigine, and lurasidone for bipolar depression, although the evidence is still weak. Combined psychosocial and pharmacological treatments also appear to be a treatment of choice for OABD. More research is needed on the optimal pharmacological and psychosocial approaches to OABD, as well as their combination and ranking in an evidence-based therapy algorithm.
Topics: Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Valproic Acid
PubMed: 34201098
DOI: 10.3390/medicina57060587 -
International Journal of Molecular... Dec 2021Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best... (Review)
Review
Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.
Topics: Anticonvulsants; Antidepressive Agents; Antidepressive Agents, Second-Generation; Buspirone; Central Nervous System Stimulants; Depressive Disorder, Treatment-Resistant; Humans; Ketamine; Lithium
PubMed: 34884874
DOI: 10.3390/ijms222313070 -
Journal of Psychopharmacology (Oxford,... Oct 2023Postpartum psychosis (PPP) is a psychiatric emergency that generally warrants acute inpatient care. PPP is marked by the sudden onset of affective and psychotic symptoms... (Review)
Review
BACKGROUND
Postpartum psychosis (PPP) is a psychiatric emergency that generally warrants acute inpatient care. PPP is marked by the sudden onset of affective and psychotic symptoms with a rapid deterioration in mental state. Evidence suggests that PPP is a discrete disorder on the bipolar disorder spectrum with a distinct treatment profile and prognosis.
METHODS
We conducted a PubMed database search for various terms involving PPP and its treatment and included peer-reviewed articles published in English.
OBJECTIVE
To provide a treatment algorithm for the management of PPP based on available evidence.
RESULTS
Pharmacological therapy is the mainstay of PPP management in the acute phase. Evidence points to a combination of antipsychotics and lithium in the acute treatment of PPP. Electroconvulsive therapy can offer a rapid treatment response where required. Lithium appears to have the best evidence for relapse prevention and prophylaxis in PPP. Psychoeducation is essential and psychosocial interventions used in bipolar disorder may be effective in PPP.
CONCLUSION
Early detection and prompt treatment with antipsychotics and lithium, followed by maintenance treatment with lithium, is associated with a favourable prognosis in PPP.
Topics: Female; Humans; Lithium; Psychotic Disorders; Bipolar Disorder; Antipsychotic Agents; Postpartum Period; Algorithms
PubMed: 37515460
DOI: 10.1177/02698811231181573 -
European Neuropsychopharmacology : the... Jan 2022The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder... (Review)
Review
The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder (BD). The PRISMA method was followed to search the MEDLINE for Randomized Controlled trials, Post-hoc analyses and Meta-analyses and review papers up to August 1st 2020, with the combination of the words 'bipolar', 'manic', 'mania', 'manic depression' and 'manic depressive' and 'randomized'. Trials and meta-analyses concerning the use of lithium either as monotherapy or in combination with other agents in adults were identified concerning acute mania (Ν=64), acute bipolar depression (Ν=78), the maintenance treatment (Ν=73) and the treatment of other issues (N = 93). Treatment guidelines were also identified. Lithium is efficacious for the treatment of acute mania including concomitant psychotic symptoms. In acute bipolar depression it is efficacious only in combination with specific agents. For the maintenance phase, it is efficacious as monotherapy mainly in the prevention of manic while its efficacy for the prevention of depressive episodes is unclear. Its combinations increase its therapeutic value. It is equaly efficacious in rapid and non-rapid cycling patients, in concomitant obsessive-compulsive symptoms, alcohol and substance abuse, the neurocognitive deficit, suicidal ideation and fatigue The current systematic review provided support for the usefulness of lithium against a broad spectrum of clinical issues in Bipolar disorder. Its efficacy is comparable to that of more recently developed agents.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds; Mania; Randomized Controlled Trials as Topic
PubMed: 34980362
DOI: 10.1016/j.euroneuro.2021.10.003 -
JAMA Psychiatry Jan 2022Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression.
OBJECTIVE
To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019.
INTERVENTIONS
Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo.
MAIN OUTCOMES AND MEASURES
Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide.
RESULTS
The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01928446.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Lithium; Male; Middle Aged; Outcome Assessment, Health Care; Suicidal Ideation; Suicide, Attempted; Veterans
PubMed: 34787653
DOI: 10.1001/jamapsychiatry.2021.3170 -
Medicina (Kaunas, Lithuania) Jun 2021Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of... (Review)
Review
Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of precursors and comorbidities that have been inadequately studied, so treatment remains obscure. The earlier the onset, the longer is the delay to first treatment, and both early onset and treatment delay are associated with more depressive episodes and a poor prognosis in adulthood. Ultra-rapid and ultradian cycling, consistent with a diagnosis of BP-NOS, are highly prevalent in the youngest children and take long periods of time and complex treatment regimens to achieve euthymia. Lithium and atypical antipsychotics are effective in mania, but treatment of depression remains obscure, with the exception of lurasidone, for children ages 10-17. Treatment of the common comorbid anxiety disorders, oppositional defiant disorders, pathological habits, and substance abuse are all poorly studied and are off-label. Cognitive dysfunction after a first manic hospitalization improves over the next year only on the condition that no further episodes occur. Yet comprehensive expert treatment after an initial manic hospitalization results in many fewer relapses than traditional treatment as usual, emphasizing the need for combined pharmacological, psychosocial, and psycho-educational approaches to this difficult and highly recurrent illness.
Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Child; Comorbidity; Humans; Lithium; Substance-Related Disorders
PubMed: 34207966
DOI: 10.3390/medicina57060601 -
Brain and Behavior Aug 2021Bipolar disorder (BD) poses a significant public health concern, with roughly one-quarter of sufferers attempting suicide. BD is characterized by manic and depressive... (Review)
Review
Bipolar disorder (BD) poses a significant public health concern, with roughly one-quarter of sufferers attempting suicide. BD is characterized by manic and depressive mood cycles, the recurrence of which can be effectively curtailed through lithium therapy. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li CO ), is associated with a host of adverse health outcomes following chronic use: these unwanted effects range from relatively minor inconveniences (e.g., polydipsia and polyuria) to potentially major complications (e.g., hypothyroidism and/or renal impairment). As these undesirable effects can limit patient compliance, an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes. Lithium orotate (LiC H N O ; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. LiOr is proposed to cross the blood-brain barrier and enter cells more readily than Li CO , which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns. This review addresses the controversial history of LiOr, complete with discussions of experimental and clinical efficacy, putative mechanisms of action, adverse effects, and its potential future in therapy.
Topics: Antimanic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds; Organometallic Compounds
PubMed: 34196467
DOI: 10.1002/brb3.2262 -
Journal of Child and Adolescent... Sep 2021To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or mixed episodes in youths with early course bipolar I disorder.... (Randomized Controlled Trial)
Randomized Controlled Trial
To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or mixed episodes in youths with early course bipolar I disorder. Six-week, randomized, double-blind clinical trial of lithium versus quetiapine for the treatment of adolescents with acute manic/mixed episode. Target dose of quetiapine dose was adjusted to a target dose of 400-600 mg and target serum level for lithium was 1.0-1.2 mEq/L. Primary outcome measure was baseline-to-endpoint change in the Young Mania Rating Scale (YMRS). Secondary outcomes were treatment response (50% or more decrease from baseline in YMRS score) and remission (YMRS score ≤12, Children's Depression Rating Scale-Revised [CDRS-R] total score ≤28 and Clinical Global Impression Bipolar Severity Scale [CGI-BP-S] overall score of ≤3, respectively). A total of 109 patients were randomized (quetiapine = 58 and lithium = 51). Participants in the quetiapine treatment group showed a significantly greater reduction in YMRS score than those in the lithium group (-11.0 vs. -13.2; < 0.001; effect size 0.39). Response rate was 72% in the quetiapine group and 49% in the lithium group ( = 0.012); no differences in remission rates between groups were observed. Most frequent side effects for lithium were headaches (60.8%), nausea (39.2%), somnolence (27.5%), and tremor (27.5%); for quetiapine somnolence (63.8%), headaches (55.2%), tremor (36.2%), and dizziness (36.2%) were evidenced. Participants receiving quetiapine experienced more somnolence ( < 0.001), dizziness ( < 0.05), and weight gain ( < 0.05). Treatment with both lithium and quetiapine led to clinical improvement. Most study participants in this study experienced a clinical response; however, less than half of the participants in this study achieved symptomatic remission. The head-to-head comparison of both treatment groups showed quetiapine was associated with a statistically significant greater rate of response and overall symptom reduction compared with lithium. Trial registration: clinicaltrials.gov NCT00893581.
Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Female; Humans; Lithium; Male; Mania; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome
PubMed: 34520250
DOI: 10.1089/cap.2021.0039 -
Brazilian Dental Journal 2022The aim of this study was conducted to assess the fracture resistance of zirconia reinforced lithium silicate all ceramic material "Celtra Press" compared to lithium...
The aim of this study was conducted to assess the fracture resistance of zirconia reinforced lithium silicate all ceramic material "Celtra Press" compared to lithium disilicate one "IPS e-max Press" under simulated oral conditions. Fourteen ceramic crowns were fabricated on epoxy dies which were duplicated from stainless steel master die and divided into two equal groups (n=7) according to the material of construction; Group A: Crowns fabricated with IPS e-max Press material and Group B: Crowns fabricated with Celtra Press material. The crowns were then cemented onto their corresponding dies with a self-adhesive resin cement and subjected to thermocycling and cyclic loading. Then they were loaded to fractur in a universal testing machine. The results were tabulated and statistically analyzed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Student t-test used to compare mean values. The significance level was set at P ≤ 0.05 and 95% Confidence interval. Statistical analysis was performed using Graph Pad Instat (Graph Pad, Inc.) software for windows. The mean ± SD values of fracture resistance were recorded for lithium Disilicate group (1706.01 ±154.32 N) meanwhile the mean ± SD value recorded with celtra group were (1550.67±196.71 N). Zirconia reinforced lithium silicate ceramic crowns produced comparable fracture resistance values to lithium disilicate ceramic crowns and both tested materials are within the clinically acceptable values in the posterior area.
Topics: Humans; Lithium
PubMed: 36477957
DOI: 10.1590/0103-6440202204993