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

From the Guidelines

Lithium carbonate therapy can cause several side effects, including tremor, polyuria-polydipsia, diarrhea, and subclinical hypothyroidism, as reported in a study published in 2021 1.

Common Side Effects

• Tremor
• Polyuria-polydipsia
• Diarrhea
• Subclinical hypothyroidism These side effects are commonly observed in patients undergoing lithium therapy, and it is essential to monitor them closely to prevent any severe complications.

Severe Side Effects

Lithium toxicity is a severe side effect that can occur at doses close to therapeutic concentrations, and it is closely related to serum lithium concentrations 1.

• Severe tremor
• Confusion
• Seizures
• Coma It is crucial to monitor serum lithium concentrations regularly, especially during the acute phase, to prevent lithium toxicity.

Monitoring and Precautions

Regular monitoring of the patient’s clinical state and serum lithium concentrations is necessary to minimize the risk of side effects 1.

• Serum concentrations should be determined twice per week during the acute phase and until the serum concentrations and clinical condition of the patient have been stabilized.
• Patients should be aware of the signs of lithium toxicity, such as severe diarrhea, vomiting, unsteady gait, muscle weakness, or significant tremor, and report them immediately to their healthcare provider.
• Patients should maintain consistent salt and fluid intake and avoid NSAIDs and diuretics, which can increase lithium levels.
• Dehydration, fever, or excessive sweating can raise lithium concentrations to toxic levels, and patients should be aware of these risks.

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 (lithium carbonate) therapy 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
• 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 Therapy

• Thirst and excessive urination, nausea and diarrhea, and tremor are common side effects of lithium therapy, which are typically no more than annoying but rather prevalent 3
• Weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage, and more likely to be associated with lithium nonadherence 3

Organ-Specific Side Effects

• Lithium has adverse effects on the kidneys, thyroid gland, and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests 3, 4, 5, 6
• Lithium-associated renal effects are relatively mild in most cases, but a small percentage of patients may show progressive renal impairment 3, 6
• Lithium-induced hypothyroidism is relatively common, but easily diagnosed and treated 3, 5
• Hyperparathyroidism from lithium is a relatively more recently recognized phenomenon 3, 6

Cardiovascular Side Effects

• Cardiac toxicity is observed in approximately 5% of patients, and severe bradycardia caused by a single dose of lithium is exceedingly rare 7

Management of Side Effects

• A simple set of management strategies, such as timing of the lithium dose, minimizing lithium levels within the therapeutic range, and prescription of side effect antidotes, can minimize the side effect burden for patients 3
• Regular controls of urine osmolarity, lithium, creatinine, thyroid-stimulating hormone, and calcium levels are essential to ensure the security of lithium treatment 6