Difference between revisions of "Lithium"

Revision as of 15:30, 15 October 2010

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, carbamazepine, 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

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.

Clinical Considerations in Children and Adolescents

• Lithium is not approved (but frequently used) 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.
• Lithium is generally well tolerated in pediatric population, and more effective than other mood stabilizers in preventing relapse.
• 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.
• While there is no definitive link between lithium and seizure threshold, risperidone is preferred in children with seizures.

High-Yield Facts

• Lithium orotate is a lithium salt marketed as a supplement and available without prescription. While its efficacy had not been adequately studied, it can cause toxicity just like lithium carbonate.
• 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 (dehydration, NSAIDs, etc) 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.
• Lithium and clozapine are two drugs that have shown do decrease suicidality.

References

Lewis's Child and Adolescent Psychiatry 2007 Handbook of Psychiatric Drug Therapy 2010

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