Difference between revisions of "Lithium"

Revision as of 14:57, 15 October 2010

Medscape 2010 article

Introduction

Lithium, the lightest solid element on the periodic table, has a central role in managing pediatric bipolar disorder. This article describes the properties of lithium as a medication. For its role in the overall treatment guidelines, see the article on bipolar disorder.

Adult Psychiatry Review

• Lithium is effective in acute mania management and bipolar prophylaxis.
• Lithium has psychoactive properties only as a positively-charged ion, Li+; to this end, it is manufactured as a salt, i.e. lithium carbonate or lithium chloride. Lithium carbonate causes less GI irritation and, thus, preferred to LiCl. Lithium citrate is available in a syrup form.
• There is no "lithium receptor." It acts on many receptors, channels, and intracellular proteins. Among other effects it inhibits intracellular adenylyl cyclase, an enzyme in the second-messenger cascade of TSH, vasopressin (ADH), and many other cell processes. A serious side effect of lithium are hypothyroidism and failure to concentrate urine.
• Lithium has low therapeutic index (ratio of toxic level to therapeutic level, 1.5mM/1.0mM = 1.5) or a narrow therapeutic range (0.8 to 1.2mM). Levels are drawn 12hrs after last dose, 4-5 days after dose change (half-life ~ 24hrs).
• Li+ is excreted by the kidney; as a tiny cation, it is freely filtered at the glomerulus and reabsorbed at the proximal tubule. Therefore, its excretion is directly related to GFR; reduce lithium dose in the elderly
• Since reabsorption of Li+ and Na+ is competitive at the proximal tubule, hyponatremia (low Na+ diet, thiazides, dehydration) can lead to increase in Li+ rebasorption and toxicity, as it is returned to circulation. NSAIDs and tetracyclines can also precipitate lithium toxicity.
• Loop diuretics (furosemide), caffeine facilitate lithium excretion.

How to Start and Monitor

• Baseline assessment: H&P (including height and weight), calculate BMI,
• Labs: UA, Upreg, TSH, free T4, CBC, CMP (electrolytes, BUN, creatinine, calcium, albumin). Repeat q3-6mo and with dose adjsutment;
• Starting dose is 300mg BID (or qPM - maybe easier on the kidney, but causes higher peak level) and titrate weekly to 1500mg +/-300mg, to plasma levels of 1.0mM. Check levels 5 days after starting treatment.
• Check lithium levels q3-6mo and after each dose adjustment; lithium levels should be drawn 12 hr after last dose (e.g. in the AM before morning dose); therapeutic plasma level is between 0.8 and 1.2mEq/L.

Adverse Effects

Common: thirst, polyuria, fatigue, nausea, diarrhea, tremor, ataxia, acne, cognitive dulling, weight gain.
Other: benign leukocytosis, mild hypercalcemia, exacerbation of psoriasis, intermittent edema, EKG changes.
Rare: nephorgenic diabetes insipidus, EPS worsening.
Teratogenicity: small increase in risk in tricuspid valve disease and Ebstein's anomaly in the 1st trimester. Despite low risk, ECT and antipsychotics are preferred in pregnancy.
Toxicity may develop at therapuetic levels with symptoms of nausea, vomiting, diarrhea, muscle weakness, renal failure.

Managing lithium overdose

• Acutely, ensure ABCs, including intubation if necessary.
• Induction of vomiting/gastric lavage if overdose occurred < 4hrs ago,
• Continual gastric aspiration (NG tube) since lithium can be removed from gastric secretions
• Normal saline hydration if urine output is adequate. Hemodialysis is indicated in renal insufficiency and failure.

Additional Considerations in Children and Adolescents

• Lithium is not approved for children <12yo.
• Lithium had been studied and found effective for short-term maintenance treatment of bipolar disorder, for decreasing aggression, and for treatment of acute depression in teens (Lewis's 769). Thus, lithium may be a good option in depressed teens who need to regain functionality sooner than would be expected from an SSRI therapy.
• Children may need higher doses than adults, as they have higher GFR, leading to shorter lithium half-life in circulation, higher total body water to weight ratio (lithium is distributed through TBW), and lower ratio of brain-to-serum lithium concentrations.
• Dosing can start at 300mg BID and titrated up to 1000mg daily dose for children (10-30 mg/kg) and 1600mg/day for teens. Just like with adults, maintenance treatment usually requires lower dosages.
• Elevated TSH without decrease in T4 or symptoms of hypothyroidism can be tolerated with frequent monitoring and education.
• WBC count up to 15,000 cells/mm3 in asymptomatic children can be tolerated as well.
• Encourage contraception in female adolescents.
• Consider long-acting preparation to improve compliance and decrease polyuria.

High-Yield Facts

• While monitoring, check T4 in addition to TSH, since elevated TSH may be inconsequential.
• Acne and weight gain can be particularly distressing to teens on lithium.
• Benign tremor can be managed with prn propranolol.
• Disruption of sodium balance is the most common cause of toxicity, not overdose.
• Dialysis is indicated if levels are greater than 3mM with sx/s of toxicity, or greater than 4mM.

References

Based on the research findings, modest improvement can be anticipated in youths with acute-phase bipolar disorder. Adjunctive medications for symptom management of bipolar and comorbid diagnoses may be warranted. While lithium is an US FDA-approved medication for 12–18-year-olds with bipolar disorder, it requires diligent monitoring. Lithium's small therapeutic window (0.8 to 1.2 mEq/l) can precipitate significant adverse effects, particularly at toxic levels. To achieve an accurate lithium level, blood should be drawn 12 h after a dose. A physical examination should be completed before the start of lithium treatment, and the patient should not have any renal problems. Baseline blood work should include a lithium level, blood urea nitrogen, creatinine concentration, thyroid function tests, electrolytes and a complete blood count, and should be repeated every 6 months once steady state is achieved (usually reached after 1 week in children). Pregnancy tests should be obtained for adolescents of childbearing age and education on appropriate measures to prevent pregnancy should be discussed. The starting dose is usually 300 mg per day titrated up every 3–5 days until the level is within a therapeutic range. Patients should be educated regarding adequate fluid intake and the use of a reliable contraception method due to lithium's potential to cause birth defects. Lithium has demonstrated significant weight gain, and weight should be monitored. Adverse effects of lithium include nausea, vomiting, diarrhea, hypothyroidism, renal function abnormalities, polyuria, polydipsia, leukocytosis, tremors and acne. The dose should be either discontinued or lowered if lithium toxicity occurs. Lithium toxicity symptoms include loss of balance, increased diarrhea, vomiting, anorexia, weakness, ataxia, blurred vision, tinnitus, polyuria, coarse tremor, muscle twitching, irritability and agitation. Several drugs have been found to increase lithium levels including carbamazapine, nonsteriodal anti-inflammatory drugs, tetracyclines and thiazide diuretics.^[37]Theophylline and caffeine promote lithium excretion, resulting in lower serum levels of lithium at the same oral dose. Clinicians should discuss these potential interactions with patients and families.

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