Side Effects of Lithobid (lithium)

Lithobid (lithium) is a positively charged element or particle that is similar to sodium and potassium used to treat manic episodes due to manic-depressive illness (bipolar disorder). It also is combined with antidepressants to treat depression. 

Lithobid interferes at several places inside cells and on the cell surface with other positively charged atoms such as sodium, potassium, calcium, and magnesium which are important in many cellular functions. It also interferes with the production and uptake of chemical messengers by which nerves communicate with each other (neurotransmitters).

Lithobid also affects the concentrations of tryptophan and serotonin in the brain. In addition, Lithobid increases the production of white blood cells in the bone marrow. Lithobid's effects usually begin within 1 week of starting treatment, and the full effect is seen by 2 to 3 weeks.

Common side effects of Lithobid include

• fine hand tremor,
• dry mouth,
• altered taste perception,
• headache,
• decreased memory,
• confusion,
• muscle weakness,
• weight gain,
• increased thirst,
• increased frequency of urination,
• mild nausea or vomiting,
• impotence,
• decreased sex drive,
• diarrhea, and
• kidney abnormalities.

Serious side effects of Lithobid include

• dehydration due to diarrhea or excessive urination, which can lead to lithium toxicity, and
• changes in the electrocardiogram (EKG, ECG), low blood pressure, and decreased heart rate.

Drug interactions of Lithobid include nonsteroidal anti-inflammatory drugs (NSAIDs) which can reduce the kidney's ability to eliminate Lithobid and lead to elevated levels of Lithobid in the blood and side effects from Lithobid. 

• Diuretics (water pills) should be used cautiously in patients receiving Lithobid. Diuretics that act at the distal renal tubule can increase blood concentrations of Lithobid. Diuretics that act at the proximal tubule are more likely to reduce blood concentrations of Lithobid. 
• ACE inhibitors may increase the risk of developing Lithobid toxicity by increasing the amount of Lithobid that is reabsorbed into the body in the tubules of the kidney and thereby reducing the excretion of Lithobid. 
• When carbamazepine and Lithobid are used together, some patients may experience side effects, including dizziness, lethargy, and tremor. 
• Central nervous system side effects also may occur when Lithobid is used with antidepressants. 
• Combining lithium with monoamine oxidase inhibitor (MAOI) class of antidepressants or other drugs that inhibit monoamine oxidase (for example, linezolid) may lead to serious reactions. 
• Medications which cause the urine to become alkaline such as potassium acetate, potassium citrate, sodium bicarbonate, and sodium citrate can increase the amount of Lithobid lost into the urine, resulting in lower blood concentrations of Lithobid and reducing the effects of Lithobid. 
• Caffeine appears to reduce serum Lithobid concentrations, and side effects of Lithobid have increased in frequency when caffeine is consumed. 
• Both diltiazem and verapamil have been reported to have variable effects on Lithobid levels in blood. 
• Methyldopa may increase the likelihood of Lithobid toxicity. 
• Various reactions have resulted when lithium is administered with phenothiazines, including delirium, seizures, encephalopathy, high fever or certain neurologic reactions that affect movement of muscles, called extrapyramidal symptoms. 
• Lithobid can cause goiter or hypothyroidism. The use of Lithobid with potassium iodide can increase the likelihood of this adverse reaction. 
• The use of the beta blocker, propranolol, with Lithobid can lead to a slow heart rate and dizziness. Other beta blockers also may interact with Lithobid and be associated with a slow heart rate. 

Lithobid crosses the placenta and has been associated with toxicity in the fetus. Children born to women taking Lithobid during pregnancy have an increased risk of goiter and cardiac anomalies. If possible, Lithobid should be withheld during the first trimester. Women of childbearing age who may require Lithobid should be counseled about becoming pregnant. 

Lithobid is secreted into breast milk. Symptoms of lithium toxicity, including changes in the electrocardiogram, have been seen in some breastfed infants, whose mothers were taking Lithobid. If possible, women taking Lithobid should not breastfeed their infants.

WARNING

Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy

Common side effects

The most common side effects that can occur in persons taking lithium are:

• Fine hand tremor
• Dry mouth
• Altered taste perception
• Headache
• Decreased memory
• Confusion
• Muscle weakness
• Weight gain
• Increased thirst
• Increased frequency of urination
• Mild nausea or vomiting
• Impotence
• Decreased libido
• Diarrhea
• Kidney abnormalities

Many of the gastrointestinal side effects (nausea, taste alterations, diarrhea) often disappear with continued therapy. Additionally, they may be less common if lithium is taken in divided doses with meals. If diarrhea or excessive urination lead to dehydration, lithium toxicity is possible. Lithium also can cause changes in the electrocardiogram (EKG, ECG), low blood pressure, and decreased heart rate.

The occurrence and severity of adverse reactions are generally directly related to serum lithium concentrations and to individual patient sensitivity to lithium. They generally occur more frequently and with greater severity at higher concentrations.

• Adverse reactions may be encountered at serum lithium concentrations below 1.5 mEq/L.
• Mild to moderate adverse reactions may occur at concentrations from 1.5 to 2.5 mEq/L, and moderate to severe reactions may be seen at concentrations from 2.0 mEq/L and above.
• 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 usually subside with continued treatment or with a temporary reduction or cessation of dosage.
• If persistent, a cessation of lithium therapy may be required.
• Diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination may be early signs of lithium intoxication, and can occur at lithium concentrations below 2.0 mEq/L.
• At higher concentrations, giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine may be seen.
• Serum lithium concentrations above 3.0 mEq/L may produce a complex clinical picture involving multiple organs and organ systems.
• Serum lithium concentrations should not be permitted to exceed 2.0 mEq/L during the acute treatment phase.

The following reactions have been reported and appear to be related to serum lithium concentrations, including concentrations within the therapeutic range:

• Central Nervous System: tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreoathetotic movements, hyperactive deep tendon reflex, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes.
• Cardiovascular: cardiac arrhythmia, hypotension, peripheral circulatory collapse, bradycardia, sinus node dysfunction with severe bradycardia (which may result in syncope), Unmasking of Brugada Syndrome.
• Gastrointestinal: anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion.
• Genitourinary: glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst and polydipsia.
• Dermatologic: drying and thinning of hair, alopecia, anesthesia of skin, acne, chronic folliculitis, xerosis cutis, psoriasis or its exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS).
• Autonomic Nervous System: blurred vision, dry mouth, impotence/sexual dysfunction.
• Thyroid Abnormalities: euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4. ¹³¹Iodine uptake may be elevated. 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, exophthalmos, dehydration, weight loss, leucocytosis, headache, transient hyperglycemia, hypercalcemia, hyperparathyroidism, albuminuria, excessive weight gain, edematous swelling of ankles or wrists, metallic taste, dysgeusia/taste distortion, salty taste, thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, and dental caries.

Some reports of nephrogenic diabetes insipidus, hyperparathyroidism, and hypothyroidism which persist after lithium discontinuation have been received.

A few reports have been received of the development of painful discoloration of fingers and toes and coldness of the extremities within one day of starting lithium treatment. The mechanism through which these symptoms (resembling Raynaud's Syndrome) developed is not known. Recovery followed discontinuance.

Diuretic-, ACE-, and ARB-induced sodium loss may increase serum lithium concentrations. Start with lower doses of lithium or reduce dosage, while frequently monitoring serum lithium concentrations and signs of lithium toxicity.

Concomitant administration of lithium with serotonergic drugs can precipitate serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs.

Examples of serotonergic drugs include

• selective serotonin reuptake inhibitors (SSRI),
• serotonin and norepinephrine reuptake inhibitors (SNRI), and
• monoamine oxidase inhibitors (MAOI).

Concomitant administration of methyldopa, phenytoin, or carbamazepine with lithium may increase the risk of adverse reactions with these drugs.

The following drugs can lower serum lithium concentrations by increasing urinary lithium excretion:

• acetazolamide,
• urea,
• xanthine preparations, and
• alkalinizing agents such as sodium bicarbonate.

Concomitant extended use of iodide preparations, especially potassium iodide, with lithium may produce hypothyroidism.

Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of

• ataxia,
• tremors,
• nausea,
• vomiting,
• diarrhea, and/or
• tinnitus.

Concurrent use of metronidazole with lithium may provoke lithium toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely.

Concurrent use of fluoxetine with lithium has resulted in both increased and decreased serum lithium concentrations. Patients receiving such combined therapy should be monitored closely.

Nonsteroidal anti-inflammatory drugs (NSAIDs): Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between a NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations.

There is also evidence that other nonsteroidal anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with celecoxib 200 mg BID as compared to subjects receiving lithium alone.

Lithium may impair mental and/or physical abilities. Patients should be cautioned about activities requiring alertness (e.g., operating vehicles or machinery).