Lithium

Q: Bipolar

Lithium use based on FDA approval in bipolar disorder, where it treats and prevents all mood episodes and lowers the risk of suicide. Lithium's risks, including renal, thyroid, and toxicity, reviewed with patient.

Q: Depression

Lithium use based on controlled trials in recurrent depression, where it treats and prevents future episodes and reduces suicide risk (Undurraga J et al, J Psychopharmacol 2019;33(2):167-176). Lithium's risks, including renal, thyroid, and toxicity, reviewed with patient.

Q: Psychotic Depression

Lithium use based on clinical trials in psychotic depression (Birkenhäger TK et al, J Clin Psychopharmacol 2009, 29(5):513-515). Lithium's risks, including renal, thyroid, and toxicity, reviewed with patient.

Q: Disruptive behavior in children (ODD, DMDD, Conduct Disorder)

Lithium use based on FDA approval in children and trials where it improved externalizing problems in children (such as from conduct disorder, oppositional defiant disorder, conduct disorder, disruptive mood dysregulation disorder, and ADHD) (Janiri D et al, Curr Neuropharmacol. 2023;21(6):1329-1342). Lithium's risks, including renal, thyroid, and toxicity, reviewed with patient.

Q: Amphetamine, methamphetamine, stimulant use disorders

Lithium use based on its neuroprotective properties and preclinical data where it reduced the neurotoxic effects of high-dose stimulant use (Kitanaka N et al, Curr Drug Res Rev 2019;11(2):85–91). Lithium's risks, including renal, thyroid, and toxicity, reviewed with patient.

Q: Dementia prevention

Low-dose lithium use based on its ability to prevent dementia in epidemiologic and small randomized trials (Lu Q et al, Eur Neurol. 2024;87(2):93-104). Lithium's risks, including renal, thyroid, and toxicity, reviewed with patient.

Q: Suicide prevention

Lithium use based on its ability to prevent suicide independent of its effects on mood (Smith KA, Cipriani A. Bipolar Disord. 2017;19(7):575-586). Lithium's risks, including renal, thyroid, and toxicity, reviewed with patient.

Mood stabilizer (neuroprotective; restores circadian biology; inhibition of Inositol monophosphatase, adenylyl-cyclase, GMP, glycogen synthase kinase 3; serotonin increase)

Bipolar Depression¹
Mania/Mixed¹(7+)
Treatment Resistant Depression¹
Psychotic depression²
Prevention after ECT (with nortriptyline in MDD)

Anti-Suicide in mood d/o¹
Dementia Prevention²
Schizophrenia negative symptoms³
Reduces neurotoxicity of stimulant use disorders.

Features

Generic, Non-sedating, Medication, Child-Approved, Non-controlled, Child-Studied, Weight-Free

Handout

Dosing

By serum level. Target: Bipolar or unipolar depression (0.6-0.8), Mania (0.8-1.1), Maintenance in bipolar I (0.8). Lower target by 30% in elderly, but same targets in children. ER better tolerated.

Start 300 mg qhs and raise by 300 mg every 2-5 days (start lower 150 mg, and raise every 7 days toward 450 mg, if drug interactions, elderly, or phobic of lithium). Check levels 5 days after target dose.

Dementia prevention: Use low dose lithium, 15-150 mg (for < 150 mg use liquid lithium citrate each 8meq/5ml = 300 mg).

INTERACTIONS are unpredictable; their potency varies widely by patient. Warn of OTC interaction with NSAIDs (ibuprofen, naproxen), but aspirin/Tylenol are OK, and the prescription NSAID clinoril is usually OK. Fear the thiazide and loop diuretics (the “-ides”, eg hydrochlorothiazide), ACE inhibitors (the “-prils”, eg lisinopril), and angiotensin II antagonists (the “-sartans”, eg losartan), and some antibiotics (metronidazole, tetracycline).

Management

Lithium is best for ‘classic bipolar’ with clean separation of (hypo)mania/depression, low rates of comorbidity (except panic), low rapid cycling/mixity. Classic can be bipolar I or II. Lithium is the only drug besides clozapine that reduces suicide risk. Good for childhood bipolar (approved to age 7).

Warn of tremor, thirst, but weight gain is rare (not detectable in controlled trials), as is fatigue (1 in 28 risk). Advise them that, with increased thirst, avoid caloric beverages and diet sodas (which cause weight gain indirectly).

Nearly all side effects treatable with antidotes or by lowering dose, see:

Side Effect Management

Hypothyroidism: Treatable. Lithium works best when thyroid is optimized (tsh around 2.5). OK to give lithium to patients with thyroid disorder.

Renal: Explain as “the kidneys slow with age, and lithium can rarely make that worse so we check labs and stop if needed.” This problem is not detectable if level kept below 0.8. To prevent renal damage give NAC 2,000 daily.

Hyperparathyroidism: Check with calcium level. Can cause fatigue, flu-like symptoms and, if untreated, bone thinning.

Cardiac: t-wave flattening/inversion, S-A node dysfunction, bradycardia, and rare ventricular premature contractions. Seek cardiology clearance if patient has heart disease.

Rare acne, psoriasis.

Medical Benefits: lower risk of dementia, cancer, osteopenia, heart disease, stroke, anti-aging properties (prevents damage to DNA), longer life-span.

Toxicity: Impairs kidneys and cerebellum (balance). Drink lots of gatorade (or water) if toxic. Can restart after toxicity. Avoid drug interactions, dehydration.

EMR Text

Bipolar

Lithium use based on FDA approval in bipolar disorder, where it treats and prevents all mood episodes and lowers the risk of suicide.