LITHIUM

brands

Class

• Neuroscience-based Nomenclature: lithium enzyme interactions (Li-Eint)
• Mood stabilizer

LITHIUM commonly prescribed for

(Bold for FDA approved)

How LITHIUM works

• Unknown and complex

• Alters sodium transport across cell membranes in nerve and muscle cells

• Alters metabolism of neurotransmitters including catecholamines and serotonin

• May alter intracellular signaling through actions on second messenger systems

• Specifically, inhibits inositol monophosphatase, possibly affecting neurotransmission via phosphatidyl inositol second messenger system

• Also reduces protein kinase C activity, possibly affecting genomic expression associated with neurotransmission

• Increases cytoprotective proteins, activates signaling cascade utilized by endogenous growth factors, and increases gray matter content, possibly by activating neurogenesis and enhancing trophic actions that maintain synapses

How long until LITHIUM works

• 1–3 weeks

Notable Side Effects

• Ataxia, dysarthria, delirium, tremor, memory problems

• Polyuria, polydipsia (nephrogenic diabetes insipidus)

• Diarrhea, nausea

• Weight gain

• Euthyroid goiter or hypothyroid goiter, possibly with increased TSH and reduced thyroxine levels

• Acne, rash, alopecia

• Leukocytosis

• Side effects are typically dose-related

Life Threatening Side Effects

• Lithium toxicity

• Renal impairment (interstitial nephritis)

• Nephrogenic diabetes insipidus

• Arrhythmia, cardiovascular changes, sick sinus syndrome, bradycardia, hypotension

• T-wave flattening and inversion

• Rare pseudotumor cerebri

• Rare seizures

weight gain

common

sedation

common

What to do about LITHIUM side effects

• Wait

• Wait

• Wait

• Lower the dose

• Take entire dose at night as long as efficacy persists all day long with this administration

• Change to a different lithium preparation (e.g., controlled-release)

• Reduce dosing from 3 times/day to 2 times/day

• If signs of lithium toxicity occur, discontinue immediately

• For stomach upset, take with food

• For tremor, avoid caffeine

• Switch to another agent

usual dosage range

• Mania: recommended 1.0–1.5 mEq/L

• Depression: recommended 0.6–1.0 mEq/L

• Maintenance: recommended 0.7–1.0 mEq/L

• Liquid: 10 mL 3 times/day (acute mania); 5 mL 3–4 times/day (long-term)

Dosage Forms

• Tablet 300 mg (slow-release), 450 mg (controlled-release)

• Capsule 150 mg, 300 mg, 600 mg

• Liquid 8 mEq/5 mL

long term use

• Indicated for long-term prevention of relapse

• May cause reduced kidney function

• Requires regular therapeutic monitoring of lithium levels as well as of kidney function and thyroid function

habit forming

• No

Renal Impairment

• Not recommended for use in patients with severe impairment

• Some experts recommend no dosing modification for estimated GFR >50 mL/ minute

Hepatic Impairment

• No special indications

Cardiac Impairment

• Not recommended for use in patients with severe impairment

• Lithium can cause reversible T-wave changes, sinus bradycardia, sick sinus syndrome, or heart block

Elderly

• Likely that elderly patients will require lower doses to achieve therapeutic serum levels

• Elderly patients may be more sensitive to adverse effects

• Neurotoxicity, including delirium and other mental status changes, may occur even at therapeutic doses in elderly and organically compromised patients

• Lower doses and lower plasma lithium levels (<0.6 mEg/L) are often adequate and advisable in the elderly

Children and Adolescents

• Safety and efficacy not established in children under age 7

• Use only with caution

• Younger children tend to have more frequent and severe side effects

• Children should be monitored more frequently

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Evidence of increased risk of major birth defects (perhaps 2–3 times the general population), but probably lower than with some other mood stabilizers (e.g., valproate)

• Evidence of increase in cardiac anomalies (especially Ebstein’s anomaly) in infants whose mothers took lithium during pregnancy

• No long-term neurobehavioral effects of late-term neonatal lithium exposure have been observed

• If lithium is continued, monitor serum lithium levels every 4 weeks, then every week beginning at 36 weeks

• Dehydration due to morning sickness may cause rapid increases in lithium levels

• Lithium administration during delivery may be associated with hypotonia in the infant; most recommend withholding lithium for 24–48 hours before delivery

• Monitoring during delivery should include fluid balance

• After delivery, monitor for 48 hours for “floppy baby syndrome”

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• Recurrent bipolar illness during pregnancy can be quite disruptive

• Taper drug if discontinuing

• Given the risk of bipolar relapse in the postpartum period, lithium should generally be restarted immediately after delivery

• This may mean no breast feeding, since lithium can be found in breast milk, possibly at full therapeutic levels

• Atypical antipsychotics may be preferable to lithium or anticonvulsants if treatment of bipolar disorder is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

• Some drug is found in mother’s breast milk, possibly at full therapeutic levels since lithium is soluble in breast milk

• Recommended either to discontinue drug or bottle feed

• Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

• Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be safer than lithium during the postpartum period when breast feeding