What are the side effects of lithium (lithium carbonate)?

From the Guidelines

Lithium can cause several side effects, including nephrotoxicity, renal tubular dysfunction, and increased risk of lithium toxicity, especially with prolonged use or concomitant NSAIDs, as noted in the 2021 study 1.

Common Side Effects

• Nausea
• Diarrhea
• Dry mouth
• Increased thirst
• Increased urination
• Weight gain
• Fine hand tremors

Serious Side Effects

• Severe tremors
• Confusion
• Slurred speech
• Seizures
• Signs of lithium toxicity (vomiting, diarrhea, unsteady walking, and drowsiness)

Long-term Effects

• Thyroid problems (hypothyroidism)
• Kidney damage
• Hyperparathyroidism

Monitoring and Precautions

• Regular blood monitoring is essential due to lithium's narrow therapeutic window, as recommended in the 2014 study 1
• Typical therapeutic blood levels range from 0.6-1.2 mEq/L, with toxicity more likely above 1.5 mEq/L
• Factors that can increase lithium levels and risk of toxicity include dehydration, reduced salt intake, certain medications (especially NSAIDs, ACE inhibitors, and some diuretics), and kidney problems, as noted in the 2014 study 1
• Patients should maintain consistent salt and fluid intake and report any new medications to their doctor to avoid dangerous interactions with lithium.

From the FDA Drug Label

ADVERSE REACTIONS Lithium toxicity: The likelihood of toxicity increases with increasing serum lithium levels. Serum lithium levels greater than 1.5 mEq/l carry a greater risk than lower levels. However, patients sensitive to lithium may exhibit toxic signs at serum levels below 1. 5 mEq/l. Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium levels below 2 mEq/l. At higher levels, giddiness, ataxia, blurred vision, tinnitus and a large output of dilute urine may be seen. Serum lithium levels above 3 mEq/l may produce a complex clinical picture involving multiple organs and organ systems Serum lithium levels should not be permitted to exceed 2 mEq/l during the acute treatment phase. Fine hand tremor, polyuria and mild thirst may occur during initial therapy for the acute manic phase, and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of lithium administration These side effects are an inconvenience rather than a disabling condition, and usually subside with continued treatment or a temporary reduction or cessation of dosage. If persistent, a cessation of dosage is indicated. The following adverse reactions have been reported and do not appear to be directly related to serum lithium levels Neuromuscular: Tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), ataxia, choreo-athetotic movements, hyperactive deep tendon reflexes Central Nervous System: Blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, acute dystonia, downbeat nystagmus Cardiovascular: Cardiac arrhythmia, hypotension, peripheral circulatory collapse, sinus node dysfunction with severe bradycardia (which may result in syncope). Neurological: Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been reported with lithium use If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields and eventual blindness due to optic atrophy. Lithium should be discontinued, if clinically possible, if this syndrome occurs. Gastrointestinal: Anorexia, nausea, vomiting, diarrhea. Genitourinary: Albuminuria, oliguria, polyuria, glycosuria Dermatologic: Drying and thinning of hair, anesthesia of skin, chronic folliculitis, xerosis cutis, alopecia and exacerbation of psoriasis. Autonomic Nervous System: Blurred vision, dry mouth. Thyroid Abnormalities: Euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4. Iodine 131 uptake may be elevated. (See PRECAUTIONS) Paradoxically, rare cases of hyperthyroidism have been reported. EEG Changes: Diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm. EKG Changes: Reversible flattening, isoelectricity or inversion of T-waves. Miscellaneous: Fatigue, lethargy, transient scotomata, dehydration, weight loss, tendency to sleep Miscellaneous reactions unrelated to dosage are: Transient electroencephalographic and electrocardiographic changes, leucocytosis, headache, diffuse non-toxic goiter with or without hypothyroidism, transient hyperglycemia, generalized pruritis with or without rash, cutaneous ulcers, albuminuria, worsening of organic brain syndromes, excessive weight gain, edematous swelling of ankles or wrists, and thirst or polyuria, sometimes resembling diabetes insipidus, and metallic taste. A single report has been received of the development of painful discoloration of fingers and toes and coldness of the extremities within one day of the starting of treatment of lithium. The mechanism through which these symptoms (resembling Raynaud’s Syndrome) developed is not known. Recovery followed discontinuance.

The side effects of lithium include:

• Neuromuscular: tremor, muscle hyperirritability, ataxia, choreo-athetotic movements, hyperactive deep tendon reflexes
• Central Nervous System: blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, acute dystonia, downbeat nystagmus
• Cardiovascular: cardiac arrhythmia, hypotension, peripheral circulatory collapse, sinus node dysfunction with severe bradycardia
• Neurological: pseudotumor cerebri (increased intracranial pressure and papilledema)
• Gastrointestinal: anorexia, nausea, vomiting, diarrhea
• Genitourinary: albuminuria, oliguria, polyuria, glycosuria
• Dermatologic: drying and thinning of hair, anesthesia of skin, chronic folliculitis, xerosis cutis, alopecia and exacerbation of psoriasis
• Autonomic Nervous System: blurred vision, dry mouth
• Thyroid Abnormalities: euthyroid goiter and/or hypothyroidism (including myxedema)
• Miscellaneous: fatigue, lethargy, transient scotomata, dehydration, weight loss, tendency to sleep 2

From the Research

Common Side Effects of Lithium

• Thirst and excessive urination 3
• Nausea and diarrhea 3
• Tremor 3
• Weight gain 4, 3
• Cognitive impairment 3
• Renal effects, including renal insufficiency and nephrogenic diabetes insipidus 4, 5, 3
• Thyroid effects, including hypothyroidism 4, 3
• Hyperparathyroidism 3
• Increased serum calcium levels 4
• Hair loss, although not statistically significant 4
• Skin disorders, although not statistically significant 4
• Major congenital abnormalities, although not statistically significant 4

Less Common but Serious Side Effects

• Renal failure, which can be rare but serious 4, 5, 6
• Interstitial nephropathy, which can occur after 10-20 years of lithium administration 6
• Neurological symptoms, including cerebellar dysfunction, which can occur at high serum lithium levels (>2 mM) 7
• Permanent brain damage, which can occur with prolonged lithium intoxication (>2 mM) 7

Management of Side Effects

• Regular monitoring of serum lithium levels, kidney function, and thyroid function 4, 5, 3
• Minimizing lithium levels within the therapeutic range 3
• Prescribing side effect antidotes, such as amiloride for nephrogenic diabetes insipidus 5
• Considering alternative treatments, such as switching to another mood stabilizer, in cases of severe side effects 5, 3