Lithium Salts

Pronunciation

Class: Antimanic Agents
VA Class: CN750
CAS Number: 554-13-2
Brands: Eskalith, Lithobid

Warning(s)

  • Lithium toxicity is closely related to serum lithium concentrations and can occur at dosages close to therapeutic levels.404 428

  • Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy.404 428 (See Renal Effects under Cautions.)

Introduction

Antimanic agent.404 428

Uses for Lithium Salts

Bipolar Disorder

Management of bipolar disorder, 410 422 particularly acute manic or mixed episodes in patients with bipolar 1 or bipolar 2 disorder.401 403 404 405 406 407 409 410 411 412 421 422

A first-line agent in the initial treatment of depressive, manic, or mixed episodes in patients with bipolar disorder.401 421 a

Combination therapy with an atypical antipsychotic, another mood stabilizing agent, and/or antidepressant may be required to adequately treat rapid cycling and more severe depressive, manic, or mixed episodes.401 403 411 412 420 421 422 423

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Maintenance therapy has been shown to prevent or diminish the intensity of subsequent manic episodes in patients with bipolar disorder with a history of mania.403 404 405 407 410 412 421 422 424

Major Depression

Should be used only in patients who fail to respond to other antidepressants.a

Schizoaffective and Schizophrenic Disorders

Limited effectiveness when used alone; should be used only after antipsychotic agents have failed.439 a

May be added to existing antipsychotic therapy, but efficacy of such combined therapy has varied in different clinical studies.439 Careful monitoring (e.g., serum lithium concentrations, adverse effects, possible adverse drug interactions) recommended.439 a

Disorders of Impulse Control

Has reduced temper outbursts, impulsive antisocial behavior, and the number of assaultive acts in a small number of adults with disorders of impulse control.a

Psychiatric Disorders in Children

Treatment of children with apparent mixed bipolar disorder symptomatology, hyperactivity with psychotic or neurotic components, or aggressive behavior or aggressive outbursts associated with attention-deficit hyperactivity disorder (ADHD); should be used only after more conservative therapies have failed.a

Neutropenia and Anemia

Treatment of neutropenia or anemia secondary to antineoplastic drugs.a

Routine use not recommended for congenital, idiopathic, or cyclic neutropenias; Felty’s syndrome; or aplastic anemia.a

Hyperthyroidism

Treatment of hyperthyroidism; other treatments (e.g., radioactive iodine, surgery, propylthiouracil, methimazole) currently are preferred.a

SIADH

No longer considered one of the therapies of choice; generally has been replaced with other more effective and/or less toxic therapies (e.g., demeclocycline).a

Lithium Salts Dosage and Administration

General

  • Careful monitoring of serum lithium concentrations and clinical status of the patient is mandatory and patients should be carefully instructed in the safe use of the drug.404 428

  • Carefully review the precautions and contraindications associated with lithium use before initiating therapy.404 428

  • Monitor serum lithium concentrations twice weekly during initiation of the acute phase of therapy and until serum concentration and clinical condition have stabilized;404 405 428 patient’s ability to tolerate high serum lithium concentrations usually decreases as initial manic symptoms begin to subside.a

  • After the patient has been stabilized, monitor serum concentrations at least every 2 months in most patients.404 405 428

  • Onset of acute antimanic effect of lithium usually occurs within 5–7 days; full therapeutic effect often requires 10–21 days.a

  • The manufacturers suggest that steady-state serum lithium concentrations be determined immediately before the next dose (i.e., 8–12 hours after the previous lithium dose).404 405 428 Total reliance must not be placed on serum lithium concentrations alone; accurate patient evaluation requires both careful clinical and laboratory evaluation.404 405 428

  • Serum lithium concentrations of 1–1.2 mEq/L usually are required during acute affective episodes.401 427 Serum concentration should not exceed 1.5 mEq/L during the acute treatment phase.401 427

  • If manifestations of lithium toxicity occur (see Lithium Toxicity under Cautions), temporarily discontinue for 24–48 hours, then resume at a lower dosage.404 405 428

Administration

Oral Administration

Administer orally, preferably with meals in divided doses.404 428

Administer conventional tablets, capsules, or oral solution 3 or 4 times daily;404 428 twice daily administration may be associated with adverse GI or nervous system effects.a Administer extended-release tablets 2 or 3 times daily.404 405 a

Extended-release preparations should be swallowed intact and should not be chewed, crushed, or halved.405

Lithium citrate oral solutions may be useful in patients unable to swallow capsules or tablets; 5 mL of a commercially available solution contains about 8 mEq of lithium and is approximately equivalent to 300 mg of lithium carbonate.404 428

Dosage

Available as lithium carbonate and lithium citrate; dosages expressed in terms of the salts.404 428

Pediatric Patients

Bipolar Disorder
Acute Episodes
Oral

Children ≤11 years of age: Usual dosages not established; lithium carbonate dosages of 15–20 mg/kg (about 0.4–0.5 mEq/kg) daily or equivalent lithium citrate dosages have been given in 2 or 3 divided doses.427 (Do not exceed usual adult dosages.a )

Children ≥12 years of age: Dosages usually are the same as those of adults.427

Maintenance Dosages
Oral

Usual maintenance dosages have not been established; dosage should be adjusted according to serum lithium concentrations, patient tolerance, and clinical response.a

Adults

Bipolar Disorder
Acute Episodes
Oral

Initially, 1.8 g daily as conventional lithium carbonate capsules or tablets, given in 3 or 4 divided doses, or 30 mL (about 48 mEq of lithium) of lithium citrate oral solution daily, given in 3 divided doses.404 428

Alternatively, 900 mg twice daily (morning and evening) or 600 mg 3 times daily as extended-release lithium carbonate tablets.404 405

Maintenance Dosages
Oral

900 mg to 1.2 g daily as conventional lithium carbonate capsules or tablets, given in 3 or 4 divided doses, or 15–20 mL (about 24–32 mEq of lithium) of lithium citrate oral solution daily, given in 3 or 4 divided doses. This dosage generally provides serum lithium concentrations of 0.6–1.2 mEq/L.404 405 427 428

Alternatively, 900 mg to 1.2 g daily as extended-release lithium carbonate tablets, given in 2 or 3 divided doses.404 405

Prescribing Limits

Pediatric Patients

Bipolar Disorder
Oral

When calculating dosage based on weight, do not exceed usual adult dosage.a 428

Adults

Bipolar Disorder
Oral

Maintenance dosage usually should not exceed 2.4 g of lithium carbonate (65 mEq) daily.427

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.405 Lower initial dosages (e.g., ≤900 mg of lithium carbonate daily) and more gradual dosage titration recommended.401 405

May have decreased renal function; monitor renal function and adjust dosage accordingly.405

Dosages that produce serum lithium concentrations at the lower end of therapeutic range may be sufficient for maintenance.401 (See Geriatric Use under Cautions.)

Pregnant Women

Dosages generally need to be increased during pregnancy but should be reduced 1 week before parturition or when labor begins.a (See Fetal/Neonatal Morbidity and Mortality and also see Pregnancy under Cautions.)

Cautions for Lithium Salts

Contraindications

  • Significant renal or cardiovascular disease, severe debilitation, dehydration, sodium depletion, or concomitant therapy with diuretics; very high risk of lithium toxicity under such conditions.404 428

  • Only begin lithium in such patients if psychiatric indication is life-threatening, and other treatments have failed; however, must use with extreme caution, including daily serum lithium determinations and adjustment to usually low doses ordinarily tolerated by these individuals.404 428 In such instances, hospitalization is a necessity.404 428

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal toxicity (e.g., increase in cardiac and other anomalies, especially Ebstein’s anomaly) when administered to pregnant women, but potential benefits may be acceptable in certain conditions despite the possible risks to the fetus.a 428

If used in women of childbearing potential, during pregnancy, or if a patient becomes pregnant during treatment, the patient should be be informed of the potential hazard to the fetus.428

Whenever possible, lithium should be withdrawn for at least the first trimester unless it is determined that this would seriously endanger the mother.428 (See Pregnant Women under Dosage and Administration and see Pregnancy under Cautions.)

Lithium Toxicity

Risk of toxicity increases with increasing serum lithium concentrations.428 Serum concentration should not exceed 1.5 mEq/L during the acute treatment phase.401 427

Serum lithium concentrations >1.5 mEq/L usually carry a greater risk than lower levels. (See General under Dosage and Administration.)428

Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium concentrations <2 mEq/L.428 At higher levels, giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine may be seen.428

Serum lithium levels above 3 mEq/L may produce a complex clinical picture involving multiple organs and organ systems.428 (See General under Dosage and Administration.)

Renal Effects

Diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia, possible following chronic lithium therapy.428 Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy also possible.428

Measurement of 24-hour Clcr, renal-concentrating ability, and a urinalysis recommended prior to initiating therapy.a Renal function should then be evaluated every 2–3 months for the first 6 months, then every 6–12 months during therapy or whenever clinically indicated.401 420

If progressive or sudden changes in renal function, even within the normal range, occur during lithium therapy, reevaluate need for therapy with the drug.a

Interactions

Encephalopathic syndrome reported with concomitant use with antipsychotic agents.404 405 428 May be similar to or same as neuroleptic malignant syndrome (NMS).404 405 (See Specific Drugs under Interactions.)

May prolong effects of neuromuscular blocking agents.404 405 428 (See Specific Drugs under Interactions.)

General Precautions

Concomitant Illnesses

Decreased tolerance to lithium has been reported to ensue from protracted sweating, diarrhea, or concomitant infection with elevated temperatures and may necessitate a temporary reduction or cessation of medication.404 428 a Patients should maintain their usual fluid (2.5–3 L/day) and sodium intake, and supplement these in the event of fever (e.g., during infections), vomiting, or diarrhea.404 428 a

Sodium-restricted Diet

Use with caution in patients whose sodium intake is restricted;a stabilize sodium intake and carefully titrate lithium dosage to avoid increased serum lithium concentrations that may occur with sodium depletion.a

Endocrine Effects

Hypothyroidism, with manifestations ranging from mild to severe myxedema, may occur within weeks to years after initiating lithium therapy; rarely, hypothyroidism may persist after discontinuance of the drug.a Geriatric patients and patients with antithyroglobulin antibody, a prior history of Graves’ disease or Hashimoto’s thyroiditis, or those receiving iodine appear most at risk.a Paradoxically, a few cases of hyperthyroidism also have been reported.

Preexisting thyroid disorders are not contraindications to lithium therapy.404 428 Patients with underlying hypothyroidism should have thyroid function (T3, T4, and TSH concentrations) evaluated yearly and be given supplemental thyroid therapy when needed.a

Specific Populations

Pregnancy

Category D.428 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Women of childbearing age receiving lithium should be counseled about methods of birth control.a If used during pregnancy, carefully monitor serum lithium concentrations and adjust dosage accordingly.a (See Pregnant Women under Dosage and Administration.)

Lactation

Lithium is distributed into milk;428 discontinue nursing or the drug, taking into account the importance of the drug to the woman.428

Pediatric Use

Safety and efficacy have not been established in children <12 years of age;404 405 428 a however, the drug has been used in this age group when benefits were thought to outweigh risks.a

Transient acute dystonia and hyperreflexia occurred in a 15-kg child who ingested 300 mg of lithium carbonate.404 405 428

Geriatric Use

Insufficient experience with extended-release tablets in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.405

Age-related differences in response to lithium generally not observed.405

Use with caution; geriatric patients appear more susceptible to adverse effects (e.g., adverse nervous system and neuromuscular effects), even at therapeutic serum concentrations, and more prone to developing lithium-induced goiter and clinical hypothyroidism.404 a Some clinicians recommend that thyroid function tests be performed every 6–12 months in these patients.a

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy; geriatric patients should receive initial lithium dosages in the lower end of the usual range (see Geriatric Patients under Dosage and Administration).405

Lithium is substantially excreted by the kidneys; consider monitoring renal function and adjust dosage if necessary since geriatric patients are more likely to have decreased renal function.405

Common Adverse Effects

Fine hand tremor, polyuria, mild thirst, transient and mild nausea, and general discomfort may appear during the first few days of lithium administration; usually subside with continued treatment, a temporary reduction of dosage, or temporary cessation.405 428 If persistent, a cessation of therapy is indicated.405 428

Interactions for Lithium Salts

Lithium is not metabolized.a

Electroconvulsive Therapy

Acute neurotoxicity with prominent delirium has occurred in patients receiving lithium and electroconvulsive therapy (ECT) concurrently.a Some clinicians recommend decreasing lithium dosage or withdrawing the drug 2 days prior to ECT.a

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Increased plasma lithium concentrations resulting in several cases of lithium intoxicationa

If used concomitantly, adjust lithium dosages and carefully monitor serum lithium concentrationsa

Some clinicians advise against concomitant ACE inhibitor use in geriatric patients or those patients with CHF, renal insufficiency, or volume depletiona

Alkalinizing agents (e.g., sodium bicarbonate)

May increase renal excretion of lithiuma

Higher lithium dosage may be requireda

Anticonvulsants (e.g., carbamazepine, phenytoin)

Adverse neurologic effects following concomitant therapy with carbamazepine or phenytoina

Concurrent use of lithium and phenytoin may increase serum lithium concentrationsa

Clinical importance not determineda

Antidepressants, SSRIs (e.g., fluoxetine, paroxetine)

Possibly associated with increased serum lithium concentrations, lithium toxicity, and/or serotonin syndrome (e.g., absence seizures, agitation, ataxia, confusion, diarrhea, dizziness, dysarthria, stiffness of the extremities, tremor);404 405 a decreased serum lithium concentrations also reported405

Use with caution and monitor closely404 405

Antipsychotic agents (e.g., haloperidol, phenothiazines)

Acute encephalopathic syndromes or extrapyramidal reactions (e.g., NMS or NMS-type reactions), possibly resulting in irreversible brain damage, parkinsonian movements, and dyskinesiasa 404 405 428

Nausea and vomiting, which are occasionally signs of lithium intoxication, may be masked by the antiemetic effect of some phenothiazines when used concurrentlya

Monitor patients for adverse neurologic effects, especially when large dosages of lithium and an antipsychotic agent are used; combined therapy should be promptly discontinued if such signs or symptoms appear404 405 428 a

β-Adrenergic blocking agents

Absence of tremor may make lithium intoxication more difficult to diagnosea

Monitor for other signs and symptoms of lithium intoxicationa

Baclofen

May cause hyperkinetic movementsa

Calcium-channel blocking agents (e.g., verapamil)

May potentiate the toxic effects of lithium; neurotoxicity (e.g., ataxia, choreoathetosis, tremors, tinnitus), adverse GI effects (e.g., nausea, vomiting, diarrhea), and bradycardia reporteda

Decreased serum lithium concentrations following initiation of verapamil in patients stabilized on lithium therapya

Use with cautiona

Monitor serum lithium concentrations and patient; adjust lithium dosage accordingly when verapamil is initiated or discontinued in patients receiving lithium therapya

Diazepam

Profound hypothermia has been reported in at least one patienta

Widespread use usually without unusual adverse effects indicates that it is safe in most patientsa

Diuretics (e.g., amiloride, aminophylline, furosemide, spironolactone, thiazides, urea)

Decreased lithium clearance resulting in increased serum lithium concentrations and several cases of lithium intoxication have occurred with concomitant thiazide usea

Other diuretics (e.g., aminophylline, furosemide, spironolactone, urea) also may reduce renal clearance of lithiuma

Amiloride does not appear to substantially affect lithium pharmacokinetics in most patientsa

Concomitant use usually is contraindicateda 428

If used in combination with thiazide diuretics, usual initial dosage of lithium should be reduced by about 50% and the patient and serum lithium concentrations should be monitored carefully;a subsequent lithium dosage should be adjusted as necessarya

Iodides

Additive or synergistic hypothyroid effect; may result in hypothyroidisma

Concomitant use is not recommended; if used concomitantly, monitor closely for signs and symptoms of hypothyroidisma

Metronidazole

May increase serum lithium concentrations, resulting in signs of lithium toxicitya

Use with caution; monitor serum lithium concentrations frequentlya

Neuromuscular blocking agents (e.g., pancuronium, succinylcholine)

May prolong the latency of neuromuscular blockadea

Use with caution and carefully monitor patients during concomitant use;a consider temporary discontinuance of lithiuma

NSAIAs (e.g., celecoxib, indomethacin, piroxicam)

Decreased renal clearance of lithium, which may lead to increased serum or plasma lithium concentrations and lithium toxicity404 405 428 a

Monitor serum lithium concentrations and observe patient for signs and symptoms of lithium intoxication404 405 428 a

Adjust lithium dosages as neededa

Opiate agonists

Interferes with opiate-induced euphoria and diminishes the analgesic effect of opiates (narcotic analgesics)a

Sodium

Changes in sodium intake in patients receiving lithium may alter the renal elimination of lithiuma

Patients should be advised to avoid substantial changes in their sodium intakea

When drugs with a high sodium content (e.g., antacids) are used concomitantly with lithium, serum lithium concentrations should be monitoreda

Tetracycline

Increased serum lithium concentrationsa

The clinical importance of this effect has not been determineda

Lithium Salts Pharmacokinetics

Absorption

Bioavailability

Conventional lithium carbonate capsules and tablets are 95–100% absorbed.a

Extended-release lithium carbonate tablets are 60–90% absorbed.a

Lithium citrate oral solutions are essentially 100% absorbed.a

Onset

Acute antimanic effect usually occurs within 5–7 days; full therapeutic effect often requires 10–21 days.a

Food

Food does not appear to affect the bioavailability of lithium.a

Plasma Concentrations

Therapeutic serum lithium concentrations usually range from 1–1.2 mEq/L during acute affective episodes.401 427 428

A 12-hour steady-state serum lithium concentration is used by most clinicians for monitoring serum concentrations; this concentration shows a high intraindividual (but not interindividual) reproducibility.a (See General under Dosage and Administration.)

Distribution

Extent

Widely distributed into most body tissues and fluids, including bone, brain tissue, erythrocytes, saliva, and thyroid.a

Lithium freely crosses the placenta; maternal and fetal serum concentrations are approximately equal.a The milk of nursing women contains lithium concentrations that are approximately 33–50% of those in serum.a

Plasma Protein Binding

Lithium is not bound to plasma proteins.a

Elimination

Metabolism

Lithium is not metabolized.a

Elimination Route

Principally renal.428

Half-life

Approximately 24 hours.428

Special Populations

In geriatric patients and patients with impaired renal function, serum half-lives of 36 and 40–50 hours, respectively, have been reported.a

Clearance and distribution into erythrocytes may be increased during pregnancy.a Immediately postpartum, renal clearance of lithium may decrease to pre-pregnancy levels.a

Lithium is readily removed by hemodialysis but not as readily removed by peritoneal dialysis.a Rebound increases in serum lithium concentration frequently occur 5–8 hours after dialysis.a

Stability

Storage

Oral

Capsules, Tablets, and Extended-release Tablets

Well-closed containers at 15–30°C.404 405 a Protect from moisture.405

Solution

Tight containers at 15–30°C.404 a

Actions

  • Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown.404 405 428

  • Decreases renal-concentrating ability and water reabsorption and initially increases sodium and potassium excretion.a Some of these effects are overcome by counteracting physiologic mechanisms, while others may persist.a GFR may be slightly decreased in patients receiving prolonged lithium therapy.a

  • Various effects on the thyroid gland; principal effect is to block the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin.a This results in a decrease in circulating T4 and T3 concentrations and a feedback increase in serum thyrotropin concentration.a Lithium also inhibits thyrotropin-stimulated adenylate cyclase activity and thyrotropin-induced release of thyroidal iodine 131, decreases intrathyroidal iodothyronine-iodotyrosine ratios, and inhibits colloid droplet formation.a

Advice to Patients

  • Importance of avoiding dehydration and maintaining usual sodium and fluid intake; importance of reporting polyuria and any prolonged vomiting, diarrhea, or fever to clinician.404 428

  • Importance of immediately discontinuing lithium therapy and consulting a clinician if signs of lithium intoxication (e.g., muscle twitching, tremor, mild ataxia, drowsiness, muscle weakness, diarrhea, vomiting) occur.404 428

  • Importance of advising patients that lithium may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).404 428

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.404 428

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.404 428

  • Importance of informing patients of other important precautionary information.404 405 428 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Lithium Carbonate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

150 mg (4.06 mEq of lithium)

Lithium Carbonate Capsules

Roxane

300 mg (8.12 mEq of lithium)*

Eskalith (with benzyl alcohol and povidone)

GlaxoSmithKline

600 mg (16.24 mEq of lithium)

Lithium Carbonate Capsules

Roxane

Tablets

300 mg (8.12 mEq of lithium)

Lithium Carbonate Tablets (with povidone; scored)

Roxane, Rugby

Tablets, extended-release

450 mg (12.18 mEq of lithium)

Eskalith CR (scored)

GlaxoSmithKline

Tablets, extended-release, film-coated

300 mg (8.12 mEq of lithium)

Lithobid Slow-release (with povidone and propylene glycol)

JDS Pharma

Lithium Citrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

8 mEq (of lithium) per 5 mL

Lithium Citrate Syrup (with alcohol 0.3%)

Major, Morton Grove, Roxane

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lithium Carbonate 150MG Capsules (ROXANE): 90/$18.99 or 270/$56.97

Lithium Carbonate 300MG Capsules (ROXANE): 90/$25.99 or 180/$42.97

Lithium Carbonate 300MG Controlled-release Tablets (ROXANE): 30/$17.99 or 90/$35.97

Lithium Carbonate 450MG Controlled-release Tablets (GLENMARK PHARMACEUTICALS): 60/$35.99 or 180/$87.97

Lithium Citrate 8MEQ/5ML Syrup (ROXANE): 500/$59.99 or 1500/$150.96

Lithobid 300MG Controlled-release Tablets (NOVEN THERAPEUTICS): 90/$222.00 or 270/$625.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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402. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed (text revision). Washington, DC: American Psychiatric Association; 2000:362, 382-401, 427-8.

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404. GlaxoSmithKline. Eskalith (lithium carbonate) Controlled-Release Tablets prescribing information. Research Triangle Park, NC. 2003 Sep.

405. Solvay Pharmaceuticals Inc. Lithobid (lithium carbonate, USP) Slow-Release Tablets prescribing information. Marietta, GA; 2002 Dec.

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422. Sachs GS et al. The expert consensus guideline series: medication treatment of bipolar disorder 2000. Postgrad Med. 2000 Apr.

423. Gonzalez-Pinto A, Tohen M, Lalaguna B et al. Treatment of bipolar I rapid cycling patients during dysphoric mania with olanzapine. J Clin Psychopharmacol. 2002; 22:450-4. [IDIS 487633] [PubMed 12352266]

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426. Tohen M, Chengappa KNR, Suppes T et al. Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatr. 2002; 59:62-9. [IDIS 474664] [PubMed 11779284]

427. USP DI: drug information for the health care provider. Johnson KW, ed. 22th ed. Englewood, CO: Micromedex, Inc; 2002:1907-12.

428. Roxane Laboratories. Lithium carbonate capsules and tablets and lithium citrate syrup USP prescribing information. Columbus, OH; 2002 May.

429. Garbutt JC, West SL, Carey TS et al. Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA. 1999; 281:1318-25. [IDIS 422893] [PubMed 10208148]

430. Dorus W, Ostrow DG, Anton R et al. Lithium treatment of depressed and nondepressed alcoholics. JAMA. 1989; 262:1646-52. [IDIS 259343] [PubMed 2504944]

431. Henry GC. Lithium. In Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank’s Toxicologic emergencies. 7th ed. New York: McGraw Hill; 2002:894-9.

432. Yassa R. Lithium-methyldopa interaction. CMAJ. 1986; 134:141-2. [IDIS 210399] [PubMed 3080214]

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434. O’Regan JB. Adverse interaction of lithium carbonate and methyldopa. CMAJ. 1976; 115:385-6.

435. Byrd GJ. Lithium carbonate and methyldopa: apparent interaction in man. Clin Toxicol. 1977; 11:1-4. [PubMed 872534]

436. Beckmann U, Oakley PW, Dawson AH et al. Efficacy of continuous venovenous hemodialysis in the treatment of severe lithium toxicity. J Toxicol Clin Toxicol. 2001; 39:393-7. [IDIS 468308] [PubMed 11527234]

437. van Bommel EF, Kalmeijer MD, Ponssen HH. Treatment of life-threatening lithium toxicity with high-volume continuous venovenous hemofiltration. Am J Nephrol. 2000; 20:408-11. [PubMed 11093000]

438. Menghini VV, Albright RC Jr. Am J Kidney Dis. 2000; 36:E21.

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a. AHFS drug information 2003. McEvoy GK, ed. Lithium Salts. Bethesda, MD: American Society of Health-System Pharmacists; 2003: 2405-2414.

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