Lithium serum levels

Parameters to monitor Perform the following laboratory tests prior to and periodically during lithium therapy Serum creatinine complete blood count urinalysis sodium and potassium fasting glucose electrocardiogram and thyroid function tests. Check lithium serum levels twice weekly until dosage is stabilized. Once steady state has been reached, monitor the level weekly. Once the patient is on maintenance therapy, the level may be checked every 2 to 3 months. 

Alert Side effects are dose related and seldom occur at lithium serum levels less than 1.5 mEq/L. 

Wilting I, Movig KL, Moolenaar M, Hekster YA, Brouwers JR, Heerdink ER, Nolen WA, Egberts AC. Drug-drug interactions as a determinant of elevated lithium serum levels in daily clinical practice. Bipolar Disord 2005 7 274-80. 

Adverse effects generally increase in incidence and severity as lithium serum levels Increase... 

Antacids and food can delay and decrease the absorption of tolmetin. NSAIDS are known to decrease renal clearance of lithium carbonate, thus increasing lithium serum levels and risks of adverse effects. Concomitant use of tolmetin and aspirin may decrease plasma levels of tolmetin. 

Most studies have found that sertraline does not decrease lithium serum levels (or does so only negligibly). Hence, the co-administration of these two agents is considered relatively safe (with regard to pharmacokinetic interactions). To date, the most serious reported adverse effect of the combined regimen was the enhancement of lithium-induced tremor. 

There are a few reports of rapid development of extrapyramidal side-effects (parkinsonism and tremor) or neurotoxicity (delirium and seizures) when iithium was co-ad ministered with fluphenthixoi, fiuphenazine, haloperidoi, thioridazine, or thiothixene. Some of these events were apparent while lithium serum levels were within the normal range. Chlorpromazine serum levels are reduced in the presence of lithium. 

Based on lithium serum levels average dose range is 900-1800 mg/d PO in divided doses 60-250 mg/d POin divided doses ... 

The true amount of variance explained between dose and lithium serum level is low enough to make these models clinically insignificant. 

In 9 out of 10 healthy subjects alcohol 0.5 g/kg raised the serum levels of a single 600-mg dose of lithium carbonate by 16%. Four subjects had at least a 25% increase in lithium levels. However these rises were not considered to be clinically important. In contrast a study in 20 healthy subjects given lithium carbonate (to achieve lithium serum levels of... 

In a study in 24 healthy subjects, lithium carbonate 500 mg twice daily was given for 7 days to obtain stable lithium serum levels, and then amisulpride 100 mg twice daily or placebo was added for a further 7 days. Amisulpride appeared to have no effect on lithium pharmacokinetics. In a pharmacokinetic analysis of amisulpride levels in patients with schizophrenia or schizoaffective disorder, dose-corrected amisulpride plasma levels were 1.8-fold higher in 3 patients taking lithium than in 13 patients taking amisulpride alone. Further study is needed to confirm this finding and establish its clinical significance. 

An 80-year-old man taking haloperidol, procyclidine, clonazepam, aspirin, digoxin and lithium (serum levels between 0.5 and 0.7 mmol/L) was additionally given indometacin 100 mg daily for arthritis, which was replaced, after 13 days, by ketorolac 30 mg daily. The next day his serum-lithium level was 0.9 mmol/L and 6 days later 1.1 mmol/L. Subsequently the patient developed severe nausea and vomiting, and both drugs were stopped. ... 

Wilting 1, Heerdink ER, Mersch PPA, Den Boer JA, Johannes A, Egberts ACG, Nolen WA. Association between lithium serum levels, mood state, and patient-reported adverse drug reactions during long-term hthium treatment a naturalistic follow-up study. Bipolar Disord 2009 11 (4) 434-40. 

Lewitzka U, Scheffczyk R, Ritter D, Doucette S, Bauer M, Bschor T. No correlation between lithium serum levels and psychopathological features during the euthymic interval of patients with recurrent affective disorder. Pharmacopsychiatry 2012 45(l) l-6. 

Lithium carbonate is rapidly absorbed after oral administration. The most common adverse reactions include tremors, nausea, vomiting, thirst, and polyuria Toxic reactions may be seen when serum lithium levels are greater than 1.5 mEq/L (Table 32-1). Because some of these toxic reactions are potentially serious, lithium blood levels are usually obtained during therapy, and the dosage of lithium is adjusted according to the results. 

LITHIUM The dosage of lithium is individualized according to serum levels and clinical response to the drug. The desirable serum lithium levels are 0.6 to 1.2 mEq/L Blood samples are drawn immediately before die next dose of lithium (8-12 hours after the last dose) when lithium levels are relatively stable During die acute phase die nurse monitors serum lithium levels twice weekly or until die patient s manic phase is under control. During maintenance therapy, the serum lidiium levels are monitored every 2 to 4 months. 

An initial examination of the extent to which lithium may prevent cannabis withdrawal in rats was conducted by Cui et al. (2001), who reported that, at clinically relevant serum levels, lithium prevented the appearance of the cannabis withdrawal syndrome. The authors also noted that these effects were accompanied by a release of oxytocin, which they conclude is responsible for suppression of the withdrawal signs. 

Lithium toxicity can occur with serum levels greater than 1.5 mEq/L, but the elderly may have toxic symptoms at therapeutic levels. Severe toxic symptoms may occur with serum concentrations above 2 mEq/L, including vomiting, diarrhea, incontinence, incoordination, impaired cognition, arrhythmias, and seizures. Permanent neurologic impairment and kidney damage may occur as a result of toxicity. 

Lithium clearance increases by 50% to 100% during pregnancy. Serum levels should be monitored monthly during pregnancy and weekly the week before delivery. At delivery, a dose reduction to prepregnancy doses and adequate hydration are recommended. 

Lithium ions. Lithium salts (e.g., acetate, carbonate) are effective in controlling the manic phase. The effect becomes evident approx. 10 d after the start of therapy. The small therapeutic index necessitates frequent monitoring of Li+ serum levels. Therapeutic levels should be kept between 0.8-1.0 mM in fasting morning blood samples. At higher values there is a risk of adverse effects. 

Sedvall, G., Petersson, U., and Fyro, B., Individual differences in serum levels of lithium in human subjects receiving fixed doses of lithium carbonate. Relation to renal lithium clearance and body weight. Pharmacol. Clin. 2, 231-235 (1970). 

Serum lithium levels Draw blood samples immediately prior to the next dose (8 to 12 hours after the previous dose) when lithium concentrations are relatively stable. Do not rely on serum levels alone. 

Absorption/Disthbution - Lithium is readily absorbed from the Gl tract. Peak serum levels occur in 0.5 to 3 hours and absorption is complete within 8 hours. Onset of action is slow (5 to 14 days). Until the desired therapeutic effect is attained, maintain a steady-state serum level of 0.8 to 1.4 mEq/L, then slowly decrease the lithium dose to a maintenance level. The therapeutic serum level range is from 0.4 to 1 mEq/L. 

III.a.4.3. Changes in renal blood flow. Blood flow through the kidney is partially controlled by the production of renal vasodilatory prostaglandins. If the synthesis of these prostaglandins is inhibited (e.g. by indomethacin), the renal excretion of lithium is reduced with a subsequent rise in serum levels. The mechanism underlying this interaction is not entirely clear, as serum lithium levels are unaffected by some potent prostaglandin synthetase inhibitors (e.g. aspirin). If an NSAID is prescribed for a patient taking lithium the serum levels should be closely monitored. 

In this example, simulation of the lithium serum concentration profile based on population PK data reveals that this patient has a higher than normal clearance. Furthermore, the first level was not a trough level. The model-based profile and subsequent Bayesian individualization process are shown in Figure 4.4B. 

Lithium has numerous pharmacologic effects. It is able to cross through sodium channels, competing with monovalent and divalent cations in cell membranes (AHFS, 2000). Animal studies have shown that lithium at a serum level of 0.66 + — 0.08 mEq/L can increase the amphetamine-induced release of serotonin (5-hydroxytryptamine [5-HT]) and the concentrations of a serotonin metabolite (e.g., 5-hydroxyindoleacetic acid [5-HIAA]) in the perifornical hypothalamus (PFH) of rats before and after chronic lithium chloride administration (Baptista et ah, 1990), a mechanism possibly involved in lithium s antidepressant effect. The precise neurobiological mechanisms through which lithium reduces acute mania and protects against recurrence of illness remain uncertain (Lenox and Hahn,... 

J.E, Cole, K., and Lavelle, J. (1998) Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med 321 1489-1493. 

Perils RH, Sachs GS, Lafer B, et al Effect of abrupt change from standard to low serum levels of lithium a reanalysis of double-blind lithium maintenance data. Am J Psychiatry 159 1155-1159, 2002... 

Several controlled trials have shown that lithium is efficacious in the maintenance treatment of bipolar disorder, with higher serum levels (0.8 1 mol/1) being more indicative of successful prophylaxis (Keck and McElroy. 2002). Valproic acid also appears to have efficacy in maintenance therapy, specifically in bipolar patients with mixed mania and rapid cycling (Bowden et al., 1995). The results concerning carbamazepine s efficacy as a maintenance medication are controversial (Stuppaeck et al., 1994). Other potential agents with some evidence of good maintenance value include clozapine and olanzapine. A combination of lithium and carbamazepine or other anticonvulsants is recommended under certain conditions if an adequate preventive effect cannot be obtained with the substances individually (Bauer et al., 2002). 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

CNS adverse effects can be the result of toxic serum levels, which may result from accidental or intentional patient ingestion of lithium doses exceeding clinical needs (334). Patients with organic brain impairment are also at increased risk of neurotoxicity. Toxicity may also be caused by reduced clearance of lithium from the body. 

Because no antidote is available, treatment is supportive. A patient s condition should be monitored closely, including fluid intake and output, mental status, and serum levels of lithium, creatinine, and electrolytes. Patients with normal renal function should be able to clear lithium unassisted. If necessary, attempts should be made to remove excess lithium from the body by gastric lavage and emesis. 

CBZ s molecular structure is similar to imipramine. It is primarily metabolized by the liver and, like lithium, has a narrow therapeutic index, predisposing to toxicity with elevated serum levels. 

Simhandl C, Denk E, Thau. The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders. J Affect Disord... 

Lithium is rapidly absorbed, reaching peak serum concentrations in 2-3 hours. It is not protein-bound and is excreted unchanged by the kidney at a rate proportional to the glomerular filtration rate. It is best given as a single daily dose around 22.00 hours and steady state serum levels are reached after 5-7 days of dosing, with the elimination half-life being around 10-24 hours for most people. Most proprietary formulations of lithium in current use are in the form of a slow-release preparation. There can be variations in kinetics between different proprietary brands and it is therefore best for individual patients to remain on the same brand. 

The decision to use lithium as prophylactic treatment depends on many factors the frequency and severity of previous episodes, a crescendo pattern of appearance, and the degree to which the patient is willing to follow a program of indefinite maintenance therapy. If the present attack was the patient s first or if the patient is unreliable, one might prefer to terminate treatment after the episode has subsided. Patients who have one or more episodes of illness per year are candidates for maintenance treatment. Although some patients can be maintained with serum levels as low as 0.6 mEq/L, the best results have been obtained with higher levels, such as 0.9 mEq/L. 

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