Term Lithium Therapy Research Articles

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

An audit of lithium prescribing practices in an old age psychiatry service highlighting renal impairment in this cohort

AimsTo compare Lithium prescribing practices in a Psychiatry of Old Age (POA) Service in the North-West of Ireland among adults aged 65 years and over with best practice guidelines.MethodReview of the literature informed development of audit standards for Lithium prescribing. These included National Institute for Clinical Excellent (NICE) 2014 guidelines, The British National Formulary (2019) and Maudsley Prescribing Guidelines (2018). Data were collected retrospectively, using an audit-specific data collection tool, from clinical files of POA team caseload, aged 65 years or more and prescribed Lithium over the past one year.ResultAt the time of the audit in February 2020, 18 patients were prescribed lithium, 67% female, average age 74.6 years. Of those prescribed Lithium; 50% (n = 9) had a depression diagnosis, 44% (n = 8) had bipolar affective disorder (BPAD) and 6% (n = 1) had schizoaffective disorder.78% (n = 14) of patients were on track to meet, or had already met, the NICE standard of 3-monthly serum lithium level. Lithium levels were checked on average 4.5 times in past one year, average lithium level was 0.61mmol/L across the group and 39% (n = 7) had lithium level within recommended therapeutic range (0.6-0.8mmol/L).83% (n = 15) of patients met the NICE standards of 3 monthly renal tests, thyroid function test was performed in 89% (n = 16) and at least one serum calcium level was documented in 63% (n = 15). Taking into consideration most recent blood test results, 100% (n = 18) had abnormal renal function, 78% (n = 7) had abnormal thyroid function and 60% (n = 9) had abnormal serum calcium.Half (n = 9) were initiated on lithium by POA service and of these, 56% (n = 5) had documented renal impairment prior to initiation. Of patients on long term lithium therapy at time of referral (n = 9), almost half (n = 4) had a documented history of lithium toxicity.ConclusionThe results of this audit highlight room for improvement in lithium monitoring of older adults attending POA service. Furthermore, all patients prescribed lithium had impaired renal function, half had abnormal calcium and two fifths had abnormal thyroid function. This is an important finding given the associations between those admitted to hospital with COVID-19 and comorbid kidney disease and increased risk of inpatient death.Our findings highlight the need for three monthly renal function monitoring in older adults prescribed lithium given the additive adverse effects of increasing age and lithium on the kidney. Close working with specialised renal services to provide timely advice on renal management for those with renal impairment prescribed lithium is important to minimise adverse patient outcomes.

ADVERSE DRUG REACTION OF LITHIUM CARBONATE-A REVIEW

This study aims to review Lithium-associated ADRs during the treatment and its management. Databases of "Medline", "Google Scholar" and "PubMed" were searched with keywords for studies on ADRs of Lithium. All studies involving safety, monitoring and management of adverse drug reactions of Lithium were included. Most of the studies have reported that up to 50 to 80% of patients develop ADRs on Lithium. Common initial ADRs that develops within 1 w to 6 w are polydipsia and polyuria taken together (50 to 70%) followed by tremors (30 to 60%). GI symptoms (upset, abdominal pain and diarrhoea) up to 30% are other commoner ADRs of Lithium therapy and they mostly disappear later. Weight gain (20 to 50%), Hypothyroidism (14-34%) and Nephrotic diabetes insipidus develop during the long term Lithium therapy. Most of the ADRs are produced even at therapeutic range (0.6–1.2 mEq/l). As serum level increase, i.e. above 1.5 mEq/l, other serious ADRs like muscle fasciculation’s, worsening of tremor, dysarthria, ataxia, EPS, hallucination, and visual disturbances, seizures, coma, and death may be expected. Management of ADRs includes TDM, Dose reduction of Lithium, drugs like diuretics, beta blockers, SR preparations and sometimes withdrawal of the drug. We are concluded that Lithium can cause many ADRs depending upon dose and duration of therapy, hence, the Therapeutic Drug Monitoring of Lithium is necessary.

Effect of lithium on thyroid function in adolescents with mood disorder.

The purpose of the study was to determine thyroid gland volume and the frequency of thyroid dysfunction by using ultrasonography and laboratory parameters (TSH, T3, and T4) in long term lithium treated adolescent patients with mood disorder. In a cross-sectional study, we performed ultrasonography and thyroid function test in 30 adolescent patients on long-term lithium treatment for mood disorder. Patients with adequate serum lithium levels for one year or more were taken for the study. Ultrasonography examinations of thyroid gland and thyroid function test were performed in these patients. Patients who were on other mood stabilizers were taken up as controls. The thyroid stimulating hormone (TSH) levels and ultrasonographically measured thyroid volume were significantly higher in patients receiving lithium in comparison to patients with other mood stabilizers. A significant positive correlation was found between total thyroid volume and TSH levels. Adolescent mood disorder patients on long term lithium therapy have increased thyroid volume and isolated increases in serum TSH levels compared to those on other mood stabilizers.

Unrecognised Free Water Loss in a Patient with Lithium-Induced Nephrogenic Diabetes Insipidus Can Cause Acute Kidney Injury and Near Fatal Hypernatremia...

Lithium is the commonest cause of drug induced nephrogenic diabetes insipidus (NDI) [1], a condition in which the patient passes large amounts of dilute urine due to the kidney’s loss of the ability to concentrate the urine in response to anti diuretic hormone (ADH). Affected patients may satisfy their polydipsia and avoid dehydration and hyper natremia if they have access to water, but severe hypernatremia can develop if they become acutely unwell or if oral intake of water is restricted. We report a patient on long -term lithium therapy for bipolar disorder who presented with severe confusion, dysarthria and disorientation, and subsequently developing severe hyper natremia and coma despite intravenous saline infusions. She was intubated and ventilated and successfully treated with initial volume expansion and subsequently with intravenous 5% dextrose in water.

MRI findings and renal function in patients on lithium therapy

Lithium is one of the most effective medications in the treatment of mood disorders. The long-term lithium therapy can alter kidney morphology and function. To evaluate the relation of Magnetic resonance imaging (MRI) of the kidneys and renal function in patients undergoing chronic lithium therapy. Thirty five consecutive patients with mood disorders who were undergoing lithium therapy for at least two years were evaluated with a 1.5 tesla MR imaging and renal function tests. The relationship between renal size, the presence, number and location of renal microcyst with renal function were evaluated. The partial correlation analysis was performed to assess correlation between variables. The mean size of kidney was 106.0 mm ± 6.0 and 106.0 mm ± 11.0 in right and left kidneys respectively. The mean number of microcysts in both kidneys was 6.2. There was a positive correlation between duration of lithium treatment and number of renal microcyst (P-value=0.03). Correlation between MRI findings and renal function tests was not statistically significant. The present study revealed that longer duration of lithium therapy can increase number of renal microcysts which is well shown with MR imaging. It seems that increasing renal microcysts may not be consistent with renal function impairment especially in earlier treatment phase. Thus the question arises is that MRI may not be as the first line method for clinicians who aim to assess renal function during long term lithium therapy.

Bipolar affective disorder preceding frontotemporal dementia in a patient with C9ORF72 mutation: is there a genetic link between these two disorders?

The FTD includes three main clinical syndromes: the behavioural variant (bvFTD), semantic dementia and progressive non-fluent aphasia [1]. For the BvFTD, which is characterized by a rich constellation of psychiatric and behavioural symptoms, the differential diagnosis with psychiatric disorders like schizophrenia and affective disorders, may be challenging [2, 3]. Recently a hexanucleotide repeat expansion in a noncoding region of the C9ORF72 gene has been identified as the cause of chromosome 9p21-linked ALS, FTD and ALS–FTD [4, 5]. We report the case of a man who developed from the age of 42 years an affective disorder characterized by repeated manic and hypomanic episodes. The manic phases were characterized by euphoria, racing thoughts, logorrhea, very high self-esteem, artistic hyperproductivity, little need for sleep. The patient fulfilled the DSM IV criteria for bipolar affective disorder (BPAD) type I [6] and was put on a long term lithium therapy with a good clinical response; during manic phases haloperidol was administered up to the acute episode resolution. The patient worked as a teacher until the age of 57 years. A patient’s maternal uncle developed a parkinsonism at the age of 60. The patient aged 64 presented to our neurological unit because he developed euphoria, impulsivity, logorrhea, sexual disinhibition with his wife, delusional fixed ideas with repetitive behaviours. He was obsessed by the idea of cleaning or putting petrol in his car and spent all day watching sport TV shows. As many of these symptoms were present in the past BPAD episodes, the patient underwent a new psychiatric examination; low doses of haloperidol were started without any improvement, so the therapy was stopped. Later a progressive cognitive impairment appeared. Neuropsychological assessment showed marked attention and executive functions troubles, working memory impairment, anomia and verbal fluency dysfunction. Neurologic examination revealed mild parkinsonism with postural tremor, camptocormia, diffuse bradykinesia and rigidity. Extrapyramidal symptoms arose when the patient was not under antipsychotic treatment. Mutations of TARDBP and PGRN genes were excluded. The patient has been found positive for a GGGGCC hexanucleotide repeat expansion in the first intron of C9ORF72 gene ([70 repeats). Brain MRI showed bilateral frontotemporal atrophy, prominent in frontal areas (Fig. 1). The orbitofrontal cortex was more involved than the dorsolateral prefrontal cortex; moreover there was a significant involvement of the fronto-insula and anterior cingulate gyrus. Perfusion SPECT demonstrated reduction of uptake in the left frontotemporal and right frontoparietal regions (Fig. 1). Structural and functional neuroimaging findings G. Floris G. Borghero A. Cannas F. D. Stefano F. Marrosu Department of Neurology, Azienda Universitaria-Ospedaliera of Cagliari and University of Cagliari, Cagliari, Italy

Spectrum of lithium induced thyroid abnormalities: a current perspective

BackgroundLithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. Thyroid abnormalities associated with treatment with lithium have been widely reported in medical literature to date. These include goitre, hypothyroidism, hyperthyroidism and autoimmune thyroiditis. This current review explores the varied thyroid abnormalities frequently encountered among patients on lithium therapy and their management, since lithium is still a fundamental and widely drug used in psychiatry and Internal Medicine.MethodsPubMed database and Google scholar were used to search for relevant English language articles relating to lithium therapy and thyroid abnormalities up to December 2012. The search terms used were lithium treatment, thyroid abnormalities, thyroid dysfunction, goitre, hypothyroidism, hyperthyroidism, thyrotoxicosis, autoimmune thyroiditis, lithium toxicity, treatment of affective disorders and depression and side effects of antipsychotic drugs. Reference lists of the identified articles were further used to identify other studies.ResultsLithium affects normal thyroid functioning through multiple mechanisms. At the cellular level, it decreases thyroid hormone synthesis and release. It also decreases peripheral deiodination of tetraiodothyronine (T4) or thyroxine by decreasing the activity of type I 5’ de-iodinase enzyme. Hypothyroidism and goitre (clinically and/ultrasonographically detected) are the most prevalent thyroid abnormalities among patients on long term lithium therapy. Lithium induced hyperthyroidism is very infrequent. Lithium increases the propensity to thyroid autoimmunity in susceptible individuals due to its effect of augmenting the activity of B lymphocytes and reducing the ratio of circulating suppressor to cytotoxic T cells.ConclusionsThyroid function tests (serum thyroid stimulating hormone, free thyroid hormones-T4 and triiodothyronine [T3] concentrations and thyroid auto-antibodies) and assessment of thyroid size clinically and by thyroid ultrasonography ought to be performed among patients initiating lithium therapy at baseline and later annually. More frequent assessment of thyroid function status and size during the course of therapy is recommended among middle aged females (≥50 years), patients with a family history of thyroid disease and those positive for thyroid auto-antibodies (anti-thyroid peroxidase and TSH receptor antibodies).

MRI Findings in Chronic Lithium Nephropathy: A Case Report

Patients on long term lithium therapy for affective disorders may develop renal toxicity. It may manifest as nephrogenic diabetes insipidus with renal biopsy showing interstitial fibrosis, sclerotic glomeruli and cyst formation. Magnetic resonance imaging demonstrates the presence of microcysts in patients on long-term lithium therapy, suggesting a possible cause for their nephrotoxicity. We describe the typical magnetic resonance imaging appearance of renal microcysts in a 53 year old woman on chronic lithium therapy.

Long term lithium therapy: a neuroprotective or neurotoxic factor? A systematic review of existing data

Materials and methods The MEDLINE was searched with the combination of the word: 'Lithium' with key words that referred to every possible effect on the central nervous system. The papers were classified into those supporting a neuroprotective effect, those in favor of a neurotoxic effect and those neutral. The papers were classified in research in humans, animal and in vitro research, case reports, and review/opinion articles.

Modulation of the canonical wnt signalling by lithium therapy may be the mechanism of goitre formation in thyroid

Lithium, a monovalent cation, is widely used in the management of bipolar psychiatric disorders. It has been shown experimentally that despite the euthyroid state maintained by thyroxine, lithium causes nodular swelling and goiter in some patients. Currently the mechanism of lithium effects on thyroid growth is not clear. Previous experimental studies indicate an increased proliferation with low dose lithium in FRTL-5 cells. Lithium is known to inhibit GSK3ß, a phosphorylating enzyme operative in the degradation of free ß-catenin. Stabilized, free ß-Catenin upon nuclear translocation induces cell proliferation in many cell types including the thyroid. Thus, lithium is expected to lead to a functional activation of canonical wnt signalling pathway by increasing the free ß-catenin levels. Recent data of our group suggest an increased proliferation potency of thyroid tumor cells due to an increase in free ß-catenin levels. Here we investigated the potential role of wnt-ß-catenin signalling under lithium treatment to understand the interaction of lithium with the ß-catenin:TCF/LEF signaling pathway. We observed that in thyroid cancer cell lines (ARO, FTC133, NPA), lithium at various concentrations differentially inactivated the proteosome (20mM) and GSK3ß activity (20mM) by more than 50%. Phospho-peptide mapping using pan ß-catenin and phospho-ß-catenin (Ser37 specific) monoclonal antibodies showed that lithium stabilized total and phosphorylated ß-catenin in a dose (20mM, 20mM) and time (0, 12hrs, 24hrs, 48hrs) dependant manner increasing the free ß-catenin levels. Hence, it is shown that lithium has an important regulatory function in the canonical wnt signaling in thyroid. The mechanism of goitre formation in long term lithium therapy may thus be due to modulation of the ß-catenin:TCF/LEF signalling pathway which may drive the thyrocytes into excessive growth and proliferation.

Lithium. Current status in psychiatric disorders.

Lithium is the recommended treatment for the prophylaxis of bipolar affective disorder. The drug is also effective in the prophylactic treatment of recurrent unipolar depression, although many psychiatrists prefer to use antidepressant drugs for this indication. The efficacy of lithium is well established in the short term treatment of mania, although neuroleptic drugs are required at the start of treatment for more severely disturbed patients. Lithium augmentation of antidepressant drugs is increasingly popular for the treatment of resistant depression. It is now common practice to maintain serum lithium concentrations in the range 0.5 to 0.8 mmol/L, which is generally as effective as higher concentrations while reducing the incidence of adverse effects and intoxication. Some individuals may nevertheless require higher serum concentrations. Most adverse effects such as tremor and gastrointestinal upset are usually minor and often transient. There is no good evidence of nephrotoxicity with long term treatment, but persistent polyuria can occur. Hypothyroidism, with or without goitre, can occur uncommonly during long term lithium therapy. Prescribers should be alert to, and patients should be educated about, the predisposing factors and early symptoms relating to lithium intoxication. Specialist mood disorder clinics can facilitate safer and more effective lithium treatment.

Long term lithium therapy reduces mortality amongst patients with bipolar and recurrent depressive disorders

Long term lithium therapy reduces mortality amongst patients with bipolar and recurrent depressive disorders

Effect of chronic lithium on sensitivity to light in male and female bipolar patients

1. Sensitivity to white light was quantified in euthymic bipolar male and female patients maintained on long term lithium therapy and age and sex matched unmedicated controls. 2. The Dark Adaptation Threshold procedure was used to assess sensitivity of both the cone and rod photoreceptors to short pulses of light. 3. Male and female controls did not differ in sensitivity to light. 4. Male patients in comparison to both controls and female patients evidenced reduced sensitivity to light during the cone and rod portion of the dark adaptation procedure. 5. Female patients did not differ from controls on sensitivity to light. 6. Using these and other published data the results were interpreted as suggesting that lithium reduces sensitivity to light during adaptation to dark.

The effect of short term lithium administration on suppressibility of parathyroid hormone secretion by calcium in vivo.

We performed graded calcium infusions twice in six normal young men, once without medication and a second time after they had received therapeutic doses of lithium carbonate for 5 days. The serum lithium level was 0.73 +/- 0.08 meq/liter (mean +/- SE) at the beginning of the calcium infusion and reached 0.97 +/- 0.13 150 min after receiving a lithium dose (210 min after beginning the test). There was no significant difference in mean basal serum calcium, plasma PTH, or nephrogenous cAMP for the untreated and treated periods. There was also no significant difference in calcium suppressibility of PTH secretion, as reflected by changes in nephrogenous cAMP. Changes in plasma PTH in response to calcium infusion likewise did not differ for the two periods, with the exception of a slightly greater degree of suppression in the unmedicated state (77% vs. 57% on lithium: P less than 0.02, by paired t test) at the last time point of the calcium infusion. The data show that short term administration of therapeutic doses of lithium does not alter the set-point for calcium suppression of PTH secretion in man. Further studies of calcium suppressibility of PTH secretion in subjects receiving long term lithium therapy will be needed to evaluate the pathophysiology of lithium-induced hypercalcemia.

Renal function related changes in lithium kinetics.

The renal clearance of lithium will decrease, and hence the risk of acute lithium toxicity will increase, in any situation leading to dehydration and sodium depletion. Patients on long term lithium therapy with progressively declining urinary concentrating ability may be at special risk in this regard. Chronic histological changes in the kidney attributed to lithium therapy correlate with age rather than with the duration of lithium therapy. Age-related renal histological changes are associated with decreased glomerular filtration rate and therefore reduced renal lithium clearance. Thus, the dose of lithium should be reduced with advancing age.