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PubMed1994

Lithium increases susceptibility of muscle glucose transport to stimulation by various agents.

Lithium is thought to have an insulin-like effect on glucose transport and metabolism in skeletal muscle and adipocytes. However, we found that lithium had only a minimal effect on basal glucose transport activity in rat epitrochlearis muscles. Instead, lithium markedly increased the sensitivity of glucose transport to insulin, so that the increase in glucose transport activity induced by 300 pM insulin was approximately 2.5-fold greater in the presence of lithium than in its absence. Lithium also caused a modest increase in insulin responsiveness. This enhancement of the susceptibility of the glucose transport process to stimulation was not limited to insulin, because lithium induced increases in the susceptibility of glucose transport to stimulation by contractile activity, hypoxia, a phorbol ester, and phospholipase C. Lithium also blunted the activation of glycogen phosphorylase by epinephrine. These effects were not mediated by inhibition of adenylate cyclase, because neither basal- nor epinephrine-stimulated muscle cAMP concentration was affected by lithium treatment. The effects of lithium on glucose transport and metabolism in skeletal muscle are strikingly similar to the persistent effects of exercise. These results support the possibility that lithium might be useful in the treatment of insulin resistance in patients with non-insulin-dependent diabetes mellitus.

3-O-Methylglucose↗
PubMed1996

Lithium stimulation of rat pancreatic beta-cell replication is mediated through pertussis toxin-sensitive GTP-binding proteins and occurs independently of Ca2+ influx, cAMP, or protein kinase C activation.

We recently demonstrated the mitogenic and secretagogic actions of lithium in the insulin-producing pancreatic beta-cell (Sjöholm A, Welsh N, Hellerström C: Lithium increases DNA replication, polyamine content and insulin secretion by rat pancreatic beta-cells in vitro. Am J Physiol 262:C391-C395, 1992). In this study, the influence of lithium on beta-cell signal transduction pathways was monitored and their importance for the stimulated cell replication and hormone secretion was elucidated by selective pharmacological probes. To this end, fetal rat pancreatic islets enriched in beta-cells were isolated and cultured for 3 days with or without 10 mmol/l LiCl. This resulted in a marked mitogenic response by the beta-cells, of similar magnitude to that obtained by pharmacological activation of cAMP-dependent protein kinases by forskolin or the Sp-diastereomer of cAMP or protein kinase C stimulation by phorbol ester. However, neither did lithium affect the islet content of cAMP (whereas forskolin did), nor was the mitogenic response to the ion impeded when islets were pretreated with the Rp-diastereomer of cAMP, a specific antagonist of cAMP-dependent protein kinases, or by the Ca2+ channel blocker D-600. The protein kinase C inhibitor 1-(5'-isoquinolinesulfonyl)-2-methylpiperazine prevented the mitogenicity of phorbol ester, but not that of lithium. Conversely, addition of increasing concentrations of inositol along with lithium also did not affect the mitogenicity of the ion, providing indirect evidence against the involvement of protein kinase C in mediating the growth-promoting effect of lithium in this system. It was found that pretreatment of islets with pertussis toxin, which inactivates GTP-binding proteins by ADP-ribosylation, prevented the mitogenicity and part of the secretagogic action of lithium. It is concluded that although specific activation of the cAMP and protein kinase C signaling systems appears sufficient to trigger a mitogenic response of the beta-cell, lithium seemingly does not work through any of these systems nor via Ca2+ influx in promoting beta-cell mitogenesis. Our results, moreover, suggest that the actions of lithium are conveyed by pertussis toxin-sensitive GTP-binding proteins.

Animals↗
PubMed1982

Potential pitfalls in the evaluation of the usefulness of hemodialysis for the removal of lithium.

A 50-year old female who was comatose from an overdose of lithium was treated with hemodialysis. Serum lithium concentrations declined 47% during a 3-h hemodialysis but increased afterwards, peaking 8 h after hemodialysis was stopped. Hemodialysis clearances were estimated by equations using extraction ratios of lithium from whole blood, serum, and red cells, and flows of whole blood, serum or red cells. The amount of lithium removed was calculated from these clearances as well as measured directly in the dialysate. Errors were introduced into the calculation of the amount of lithium removed by hemodialysis unless whole blood concentrations of lithium and whole blood flows were used. These arose because extraction of lithium from serum (0.7 +/- 0.3, mean +/- SD) was greater than that from whole blood (0.49 +/- 0.06) or from red blood cells (0.18 +/- 0.12). Despite the rapid decrease in serum concentrations of lithium during hemodialysis and rebound afterwards, the patient's neurologic status did not change concurrently. The patient did not regain consciousness until lithium concentrations fell to less than 0.4 meq/L in serum and 0.1 meq/L in cerebrospinal fluid. The lack of parallel change in serum concentrations and coma probably reflects the lag time in equilibration between lithium concentrations in serum and brain.

Female↗
PubMedDate not supplied

Lithium-induced nephrogenic diabetes insipidus.

BACKGROUND: Lithium can cause nephrogenic diabetes insipidus in up to 20 to 40 percent of patients currently taking the medication, and a subset of these patients will have a persistent concentrating defect long after lithium is discontinued. They are at risk for serious hypernatremia when fluid intake is restricted for any reason. METHODS: MEDLINE as used to search the key words "nephrogenic diabetes insipidus" and "lithium" from 1990 to the present. A case report describes a patient who had been off lithium for 8 years and who developed hypernatremia after she was transferred to a new long-term facility and the staff attempted to control the patient's polydipsia. The diagnosis and treatment of nephrogenic diabetes insipidus are also discussed. RESULTS: This case of persistent nephrogenic diabetes insipidus 8 years after discontinuing lithium is the longest ever reported. Certainly, a number of patients have varying degrees of persistent lithium-related nephrogenic diabetes insipidus. Although pathologic changes are associated with persistent nephrogenic diabetes insipidus, the exact mechanism of the persistent defect is unknown. The mechanism of acute lithium-induced nephrogenic diabetes insipidus while the patient is on lithium is related to changes in intracellular cyclic adenosine monophosphate. CONCLUSIONS: Patients currently taking lithium and patients with a remote history of lithium treatment need to be monitored for signs and symptoms of nephrogenic diabetes insipidus. Physicians need to be aware of the potential for nephrogenic diabetes insipidus in these patients and care for them appropriately.

Chlorthalidone↗
PubMed1998

Lithium treatment and risk of suicidal behavior in bipolar disorder patients.

BACKGROUND: Lithium may exert an antisuicidal effect in bipolar disorder patients, but this hypothesis requires further testing by direct comparison of patients with and without lithium treatment. METHOD: Risk of life-threatening suicidal acts over time and associated factors were analyzed in 310 patients with DSM-IV bipolar I (N = 186) or II (N = 124) disorder evaluated for a mean of 8.3 years before, and prospectively during, a mean of 6.4 years of lithium maintenance in a mood disorder clinic; 185 were also followed for a mean of 3.7 years after clinically discontinuing lithium. RESULTS: In 5233 patient-years of observation, 58 patients made 90 suicide attempts (8 were fatal). Survival analyses with Weibull modeling with adjustments for covariates indicated a highly significant 6.4-fold adjusted hazard ratio during versus before and 7.5-fold ratio after versus during lithium maintenance. Suicidal acts were more common early in the course of illness before lithium and were associated with prior suicide attempts, greater proportion of time depressed, and younger age. After the discontinuation of lithium, suicidal acts were more frequent in the first year than at later times or before start of lithium treatment. Fatalities were 9 times more frequent after versus during treatment. CONCLUSION: Lithium maintenance was associated with marked reduction of life-threatening suicidal acts, the number of which sharply increased after discontinuing lithium. Suicidal behavior was strongly associated with prior suicide attempts, more time depressed, and younger age or recent onset. Greater attention to suicidal risk in patients with bipolar depression and assessment of all proposed mood-stabilizing agents for antisuicidal effects are strongly encouraged.

Adolescent↗
PubMed2004

A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder.

BACKGROUND: Two clinical trials, prospectively designed for combined analysis, compared placebo, lithium, and lamotrigine for treatment of bipolar I disorder in recently depressed or manic patients. METHOD: 1315 bipolar I patients (DSM-IV) enrolled in the initial open-label phase, and 638 were stabilized and randomly assigned to 18 months of double-blind monotherapy with lamotrigine (N = 280; 50-400 mg/day fixed dose or 100-400 mg/day flexible dose), lithium (N = 167; serum level of 0.8-1.1 mEq/L), or placebo (N = 191). The primary endpoint was time from randomization to intervention for a mood episode. Data were gathered from August 1997 to August 2001. RESULTS: Lamotrigine and lithium were superior to placebo for time to intervention for any mood episode (median survival: placebo, 86 days [95% CI = 58 to 121]; lithium, 184 days [95% CI = 119 to not calculable]; lamotrigine, 197 days [95% CI = 144 to 388]). Lamotrigine was superior to placebo for time to intervention for depression (median survival: placebo, 270 days [95% CI = 138 to not calculable]; lithium, median not calculable; lamotrigine, median not calculable). Lithium and lamotrigine were superior to placebo for time to intervention for mania (median survival not calculable for any group). Results of additional analyses adjusted for index mood were similar; however, only lithium was superior to placebo for intervention for mania. There was no evidence that either active treatment caused affective switch. Adverse event analysis indicated more diarrhea (19% vs. 7%, p <.05) and tremor (15% vs. 4%, p <.05) in lithium-treated patients compared with lamotrigine-treated patients. CONCLUSIONS: Lamotrigine and lithium stabilized mood by delaying the time to treatment for a mood episode. Lamotrigine was effective against depression and mania, with more robust activity against depression. Lithium was effective against mania.

Adult↗
PubMed2005

Incidence of delirium in older adults newly prescribed lithium or valproate: a population-based cohort study.

BACKGROUND: The use of lithium carbonate for the treatment of mood disorders in old age has decreased at a dramatic rate in favor of valproate. Because of lithium's narrow therapeutic range, neurotoxicity can be an important complication in lithium therapy and potentially influence prescription patterns. Therefore, we compared the incidence of delirium in older adults with mood disorders who were newly dispensed either lithium or valproate. METHOD: Using 4 population-based administrative databases from the province of Ontario, Canada (the Ontario Drug Benefit program, the Canadian Institute for Health Information, the Ontario Health Insurance Plan, and the Registered Persons Data Base), we were able to identify a cohort of mood disorder patients 66 years and older who were newly dispensed lithium or valproate over an 8-year period (1993-2001). Measures were taken to ensure that the sample was composed of mood disorder patients. As a comparator, we included a known deliriogenic drug, benztropine. The main outcome measure was a new diagnosis of delirium on a hospitalization record during 1 year of follow-up. RESULTS: Our study cohort consisted of 2422 new users of lithium and 2918 new users of valproate over an 8-year period. There was no statistically significant difference in the incidence of delirium between lithium (2.8 per 100 person-years) and valproate (4.1 per 100 person-years). Compared with patients who received lithium, patients who received benztropine had a significantly higher risk of delirium (p < .001). CONCLUSION: The incidence of hospitalizations with delirium was similar in patients treated with lithium and valproate. These findings add to the evidence suggesting that the shift away from the use of lithium carbonate to manage mood disorders in older adults is not justified on the basis of concerns of neurotoxicity.

Adult↗
PubMed1999

Effect of lithium maintenance therapy on thyroid and parathyroid function.

OBJECTIVES: To assess changes induced by lithium maintenance therapy on the incidence of thyroid, parathyroid and ion alterations. These were evaluated with respect to the duration of lithium therapy, age, sex, and family history (whether or not the patient had a first-degree relative with thyroid disease). DESIGN: Prospective study. SETTING: Affective Disorders Clinic at St. Mary's Hospital, Montreal. PATIENTS: One hundred and one patients (28 men and 73 women) with bipolar disorder receiving lithium maintenance therapy ranging from 1 year's to 32 years' duration. The control group consisted of 82 patients with no psychiatric or endocrinological diagnoses from the hospital's out-patient clinics. OUTCOME MEASURES: Laboratory analyses of calcium, magnesium and thyroid-stimulating hormone levels performed before beginning lithium therapy and at biannual follow-up. RESULTS: Hypothyroidism developed in 40 patients, excluding 8 patients who were hypothyroid at baseline. All patients having first-degree relatives affected by thyroid illness had accelerated onset of hypothyroidism (3.7 years after onset of lithium therapy) compared with patients without a family history (8.6 years after onset of lithium therapy). Women over 60 years of age were more often affected by hypothyroidism than women under 60 years of age (34.6% versus 31.9%). Magnesium levels in patients on lithium treatment were unchanged from baseline levels. After lithium treatment, calcium levels were higher than either baseline levels or control levels. Thus, lithium treatment counteracted the decrease in plasma calcium levels associated with aging. CONCLUSIONS: Familial thyroid illness is a risk factor for hypothyroidism and hypercalcemia during lithium therapy.

Analysis of Variance↗
PubMedDate not supplied

[50 years lithium treatment].

Answers have been sought to the following questions of current interest: Does lithium have a prophylactic action? The claim that such an action has never been demonstrated was based on wrong assumptions, biased selection of references, and unjustified generalizations. What effect does long-term lithium treatment have on the patients' suicidal behavior? There is a close association between long-term lithium treatment, on the one hand, and lowered mortality and reduced suicidal behavior, on the other; no such association has been demonstrated for other mood stabilizers. What are the effects of lithium when given during pregnancy and lactation? The risk/benefit ratio of lithium is lower than that of the anticonvulsant drugs. Are new drugs about to oust lithium? Among contending drugs the anticonvulsants carbamazepine and valproate have attracted particular interest, but the evidence for a prophylactic action in typical bipolar disorder is weak or missing. What are the requirements of the designs of future comparative trials? In order to prove new drugs prophylactically superior to lithium, trial designs must be such that they provide valid information; some proposals are outlined here. Which drug or drugs should be used for prophylactic treatment? In addition to prophylactic superiority over lithium the new drugs must be as good as or better than lithium as regards a number of other properties, including risk/benefit ratio during pregnancy and lactation, and a close association between long-term treatment and lowered suicidal behavior. The most urgent problem at the present time is to compare in a just and balanced manner the prophylactic efficacy and other relevant properties of new drugs with those of lithium. Many manic-depressive patients' health and sometimes life depend on whether at any time they are given the best prophylactic drug available.

Adult↗
PubMedDate not supplied

Influence of lithium on the cellular environment.

In order to study the influence of lithium on the cellular environment, we conducted research in multiple experimental models: groups of rats with normal cerebral excitability and groups susceptible to audiogenic convulsion, rat neuroglia cultures and perfusion of dog isolated head. We assumed blood composition to be a good indicator of cell environment composition. Blood serotonin level differs in the two groups of animals. Lithium induces a decrease of blood serotonin and an increase of amine concentration in some of the cerebral regions of rats susceptible to audiogenic convulsions. Inverse effects occur in rats with normal cerebral excitability. In the perfused, isolated head of a dog, lithium immediately decreases blood serotonin level. Na and water have a diminished metabolization during the first 24 hrs. in both animal groups. Decrease in metabolization is somewhat greater in hyperexcitable animals. Within 48 hrs. after lithium injection, there is an increase of Na metabolization, probably determined by its storage in the interstice. Renal elimination of K decreases under the influence of lithium 48 hrs. after administering one dose of lithium. Lithium induces, immediately after injection, a decrease of blood Na concentration in the efferent flow of the jugular vein of a perfused dog head. When used in cell cultures, lithium (2 mM concentration) stimulates glial cells division (astrocytes, oligodendrocytes), increases their growth and aging rates. The effects of lithium may be due to its toxicity. Therefore, lithium alters the composition of the cellular environment depending on dose and on the state of the body.

Amines↗
PubMed2000

Is the EEG helpful in diagnosing and monitoring lithium intoxication? A case report and review of the literature.

Lithium is potentially toxic to the central nervous system. Clinical lithium neurotoxicity may appear at any time during therapy and may go unrecognized. Failure to appreciate this fact leads to delays in diagnosis and treatment, placing the patient at risk of permanent neurological damage or death. In spite of a largely clinical diagnosis of lithium intoxication, the EEG provides an objective criterion of intoxication. We report a case of lithium intoxication with neurotoxic symptoms associated with marked EEG changes despite moderate lithium serum levels. In contrast to the interindividually varying EEG changes under uncomplicated lithium therapy, pathological EEG findings are the rule in the case of intoxication. Several reports evince a closer relationship between neurotoxic symptoms with EEG changes than with serum levels of lithium. This is of clinical interest with respect to intoxication under therapeutic lithium serum levels, since the EEG is the only examination indicating an intoxication. In patients with intoxication, the phenomenon of long-lasting EEG changes after discontinuation of lithium is discussed with respect to neuronal storing of lithium and persisting neurological disturbances.

Aged↗
PubMed2003

Lithium treatment and suicide risk in major affective disorders: update and new findings.

BACKGROUND: Evidence that therapeutic benefits of psychiatric treatments include reduction of suicide risk is remarkably limited and poorly studied. An exception is growing evidence for such suicidal risk reduction with long-term lithium maintenance. This report updates and extends analyses of lithium treatment and suicides and attempts. METHOD: We pooled data from studies providing data on suicidal acts, patients at risk, and average exposure times with or without lithium maintenance therapy, and considered effects of lithium on selected subgroups. RESULTS: Data from 34 reported studies involved 42 groups with lithium maintenance averaging 3.36 years, and 25 groups without lithium followed for 5.88 years, representing 16,221 patients in a total experience of 64,233 person-years. Risks for all suicidal acts/100 person-years averaged 3.10 without lithium versus 0.210 during treatment (93% difference) versus approximately 0.315 for the general population. For attempts, corresponding rates were 4.65 versus 0.312 (93% difference), and for completed suicides, 0.942 versus 0.174 (82% difference). Subjects with bipolar versus various recurrent major affective disorders showed similar benefits (95% vs. 91% sparing of all suicidal acts). Risk reductions for unipolar depressive, bipolar II, and bipolar I cases ranked 100%, 82%, and 67%. Suicide risk without lithium tended to increase from 1970 to 2002, with no loss of effectiveness of lithium treatment. CONCLUSION: The findings indicate major reductions of suicidal risks (attempts > suicides) with lithium maintenance therapy in unipolar >/= bipolar II >/= bipolar I disorder, to overall levels close to general population rates. These major benefits in syndromes mainly involving depression encourage evaluation of other treatments aimed at reducing mortality in the depressive and mixed phases of bipolar disorder and in unipolar major depression.

Bipolar Disorder↗
PubMed2004

[Adverse effects of lithium treatment and safety routines].

Successful lithium treatment of manic disorders was reported in 1949 by John Cade. This marked the beginning of the pharmacological era in psychiatry. In spite of the emergence of alternative drugs with antimanic and moodstabilising properties, lithium remains the primary long-term treatment for preventing relapse of bipolar disorders. Among the adverse effects of lithium treatment are unintentional lithium intoxication, nephropathy, hypothyroidism, hypercalcemia, hyperparathyroidism, diarrhoea, tremor, weight gain, and effects on the fetus and the newborn child. Early detection or prevention of adverse effects, particularly lithium intoxication, is vital for safety. Therefore, P-lithium and P-creatinine are assessed every 4 months (and pre-lithium) while thyroid and parathyroid function, weight, 24 h consumption of liquids (or 24 h urinary output), B-glucose, and blood pressure are assessed annually (and pre-lithium). Urinary concentrating capacity and glomerular filtration rate are always measured after 5 years of lithium treatment, and always when clinically indicated. Patient education and annual reinforcement of his/her knowledge of pertinent aspects of the treatment and of risk factors for lithium intoxication are important aspects for ensuring safety.

Bipolar Disorder↗
PubMed1988

Lithium intoxication: clinical course and therapeutic considerations.

Lithium therapy has various neurologic cardiovascular, and renal side effects. Lithium intoxication with a serum lithium level of greater than or equal to 3.5 mEq/l is considered potentially lethal and hemodialysis therapy is recommended. We reviewed the clinical course and therapy of 55 patients with lithium toxicity seen during a 6-year period. Forty-two patients had acute lithium intoxication following the ingestion of an overdose. In 13 patients, toxicity developed during maintenance therapy with the drug. The patients with acute intoxication had significantly milder symptoms than those with chronic intoxication. Ten patients with acute intoxication had a serum lithium concentration of 3.5 mEq/l or higher. None of these 10 patients had severe neurologic or cardiovascular symptoms. Five patients were treated with hemodialysis and 5 patients were not. Serum lithium concentration did not differ between the two groups (4.7 +/- 0.7 and 5.7 +/- 1.0 mEq/l, respectively). No patient in either group died or suffered permanent sequelae of lithium toxicity. In conclusion, patients with acute lithium toxicity frequently have mild symptoms, despite potentially lethal levels and may not require hemodialysis therapy. On the other hand, patients who develop toxicity while receiving chronic maintenance therapy are more likely to have severe symptoms. Patients with severe symptoms and serum lithium levels above the therapeutic range should be treated with hemodialysis.

Adult↗
PubMed1979

[Lithium balance in mania].

Lithium balance studies were performed in 19 patients suffering from mania and 6 patients suffering from depression. The following results were obtained: (1) The mean daily requirement for lithium in the manic patients was 52 mM, in those with depression 30 mM (additional requirement in manic patients 73%). (2) Renal elimination of lithium, after optimal blood lithium levels had been reached, was 76% in mania and 97% in depression (retention in manic patients 21%). (3) In mania there was an unchanged lithium half-life time (12-13.5 h). (4) In mania and depression no significant differences in lithium and creatinine clearance were noted. (5) Standard diet or unrestricted sodium chloride administration did not significantly influence the lithium requirement or lithium retention. After exclusion of a renal or dietetic cause for increased lithium requirement or retention during mania, the existence of a 'lithium pool' dependent on the presence of a manic psychosis seems probable. As a result of this, somatic influences on endogenous psychosis have to be taken into account.

Adolescent↗
PubMed1983

Free energy changes in ribonuclease A denaturation. Effect of urea, guanidine hydrochloride, and lithium salts.

The unfolding of ribonuclease A by urea, guanidine hydrochloride, lithium perchlorate, lithium chloride, and lithium bromide has been followed by circular dichroic and difference spectral measurements. All three abnormal tyrosyl residues are normalized in urea and guanidine hydrochloride (delta epsilon 287 = -2700), only two are normalized in lithium bromide and lithium perchlorate (delta epsilon 287 = -1700), and only one is exposed in lithium chloride solutions (delta epsilon 287 = -700). The Gibbs energies are 4.7 +/- 0.1 kcal mol-1 for urea- and guanidine hydrochloride-denaturation, 3.8 +/- 0.2 kcal mol-1 for lithium perchlorate-denaturation, and 12.7 +/- 0.2 kcal mol-1 for lithium chloride- and lithium bromide-denaturation of ribonuclease A. The latter results suggest that the mechanism of the unfolding process in urea and guanidine hydrochloride is quite different from that in lithium salts.

Animals↗
PubMedDate not supplied

[Pharmacokinetics of low-dose lithium in healthy volunteers].

The pharmacokinetics of lithium in healthy volunteers receiving low doses of lithium as Lithium Oligosol by sublingual route were investigated in two randomized crossover studies (lithium vs placebo) with a two week wash-out period. In the first study, 8 volunteers received a single dose (1.68 mg) of lithium and in the second 8 another volunteers received repetitive doses of lithium (0.56 mg twice a day) during 11 days. The plasma concentration of lithium was determined by an electrothermal atomic absorption spectrometry. The plasma concentrations of lithium measured during the placebo period were about 1 microgram/L, the peak concentration was 99.4 +/- 22.2 micrograms/L in the single dose study and 49.6 +/- 5.4 micrograms/L in the multiple doses study. In this last one, the residual plasma levels of lithium were between 20 and 25 micrograms/L. The pharmacokinetics parameters measured were: T1/2 = 22.6 +/- 3.1 h; Vd/F = 0.70 +/- 0.09 L/kg and Cl/F = 1.53 +/- 0.12 L/h. The plasma concentrations of lithium are strictly dependent on intake from food or drugs.

Administration, Sublingual↗
PubMedDate not supplied

Measurement of human brain lithium in vivo by MR spectroscopy.

PURPOSE: To quantify lithium in the human brain. METHODS: A 7Li MR spectroscopy method was developed with special features for high precision including: a) sampling a large cerebral volume to maximize the signal-to-noise ratio; b) adiabatic excitation pulses to ensure uniform spin mutation; c) morphometric analysis of the MR images of the sampled cerebrum; d) a mathematical model derived from empirical data to correct for receiver inhomogeneity effects; and e) a long interpulse delay, to eliminate errors arising from uncertain T1 values. RESULTS: A theoretical precision of 5.2% and an accuracy of better than 7.2% in someone with a brain lithium level of 1.0 mEq per liter of cerebral volume and precision and accuracy of 6.8 and 8.6%, respectively, in someone with 0.5 mEq/L brain lithium was calculated. This level of precision was surpassed in phantoms and patients. Brain lithium in 10 patients treated with lithium carbonate varied from 0.52 to 0.87 mEq/L (mean = 0.58 mEq/L; SD = 0.17 mEq/L). Brain-to-serum lithium ratios varied from 0.50 to 0.97 mEq/L (mean = 0.77 mEq/L; SD = 0.14 mEq/L). Substantial variation in brain lithium was observed in patients with similar serum lithium. CONCLUSIONS: A highly reliable method to quantify human brain lithium by 7Li MR spectroscopy has been implemented. Unexpected variability in brain versus serum levels of lithium was detected in patients with bipolar disease.

Brain Chemistry↗