Chronic lithium toxicity: Considerations and systems analysis

Article Figures & Data

Table 1.

Clinical and laboratory manifestations of chronic lithium toxicity

VARIABLE	MANIFESTATION
Laboratory value
Serum lithium concentration	Mild toxicity: 1.5 to 2.5 mmol/L Moderate toxicity: > 2.5 to 3.5 mmol/L Severe toxicity: > 3.5 mmol/L
Clinical findings
Central nervous system	Early onset of symptoms
• Mild toxicity	Weakness, light-headedness, fine tremor, nystagmus
• Moderate toxicity	Muscle twitching, fasciculation, tinnitus, drowsiness, hyperreflexia, slurred speech, apathy
• Severe toxicity	Parkinsonism, psychosis, memory deficits, pseudotumour cerebri
Renal	Nephrogenic diabetes insipidus, interstitial nephritis, renal failure
Cardiovascular	Nonspecific electrocardiography changes, Ebstein anomaly^*
Gastrointestinal	Nonspecific
Dermatologic	Dermatitis, ulcers, localized edema
Endocrine	Hypothyroidism or hyperthyroidism, hyperparathyroidism
Hematologic	Aplastic anemia

Table 2.

Drug interactions

INTERACTION	DRUG OR DRUG CLASS
Pharmacokinetic
Increase in SLC^*	Angiotensin-converting enzyme inhibitors
	Angiotensin receptor blockers
	β-blockers
	Cisplatin
	Cyclooxygenase-2 inhibitors
	Cyclosporine A
	Methyldopa
	Metronidazole
	Nonsteroidal anti-inflammatory drugs^†
	Phenytoin
	Tetracycline
	Thiazide diuretics
	Verapamil
Decrease in SLC	Acetazolamide
	Aminophylline
	Theophylline
	Topiramate
	Caffeine
	Nifedipine
	Osmotic diuretics
	Sodium bicarbonate
	Bulk-forming laxatives
Pharmacodynamic
Might worsen neurotoxicity	Antidepressants
	Antipsychotics
	Carbamazepine
	Diltiazem
	Verapamil
	Serotonin receptor agonists
	Piroxicam
	Phenytoin^‡
Might worsen thyroid changes	Iodide salts or iodine
	Phenytoin
	Carbamazepine
Might increase polyuria	Antidepressants
Might increase polyuria	Phenytoin
Might contribute to sinus node dysfunction	Carbamazepine

SLC—serum lithium concentration.
↵* An increase in SLC can also be caused by reduced sodium intake.
↵† Other than acetylsalicylic acid.
↵‡ Can cause tremor.
Data from Juurlink et al,³ Grandjean and Aubry,¹⁰ Uldall et al,¹¹ Langlois and Paquette,¹² and the American Geriatrics Society 2012 Beers Criteria Update Expert Panel.¹³