Mood Stabilizers as Medications lithium, Eskalith, Lithane, Lithonate, Lithobid, Camcolit, Priadel

Mood stabilizer: lithium, Eskalith, Lithane, Lithonate, Lithobid, Camcolit, Priadel

Generic Name: lithium carbonate
Brand Name(s): Eskalith, Lithane, Lithonate, Lithobid, Camcolit, Priadel
Common Use: Mood stabilizer
Potentiates antidepressants

Lithium is a monovalent cation which belongs to the group of alkali metals together with sodium, potassium and other elements with which it shares some of its properties.
The mechanism whereby lithium controls manic episodes and possibly influences affective disorders is not yet known.

Unlike other antimanic agents, it does not possess general sedative properties. There is evidence, however, that lithium alters sodium transport and may interfere with ion exchange mechanisms and nerve conduction. Fluid and electrolyte metabolism are believed to be altered in affective disorders and this may be related to the therapeutic action of lithium. Lithium enhances the uptake of norepinephrine and serotonin into the synaptosomes, thus reducing their action. It reduces release of norepinephrine from synaptic vesicles and inhibits production of cyclic AMP. Balance studies indicate that lithium may produce a transitory diuresis with increase in sodium and potassium excretion. A period of equilibrium or slight retention may follow but persistent polyuria may occur in some patients. There is evidence that therapeutic doses of lithium decrease the 24-hour exchangeable sodium. A low salt intake resulting in low tubular concentration of sodium will increase lithium reabsorption and might result in retention or intoxication.

Renal lithium clearance is, under ordinary circumstances, remarkably constant in the same individual but decreases with age and falls when sodium intake is lowered. The dose necessary to maintain a given concentration of serum lithium depends on the ability of the kidney to excrete lithium. However, renal lithium excretion may vary greatly between individuals and lithium dosage must, therefore, be adjusted individually. It has been suggested that manic patients retain larger amounts of lithium during the active manic phase, but recent studies have been unable to confirm a clear difference in excretion patterns. However, patients in a manic state seem to have an increased tolerance to lithium.

Acute manic episodes in patients with bipolar affective disorders. Maintenance therapy has been found useful in preventing or diminishing the frequency of subsequent relapses in bipolar manic-depressive patients (with a history of mania).

Contraindications
Patients with severe cardiovascular or renal disease and those with evidence of severe debilitation or dehydration, sodium depletion, brain damage. Conditions requiring low sodium intake.

Lithium therapy requires reaching plasma concentrations of lithium which are relatively close to the toxic concentration. Lithium is excreted primarily by the kidney; adequate renal function and adequate salt and fluid intake are essential in order to avoid lithium accumulation and intoxication. Thus, a decision to initiate lithium therapy should be preceded by a thorough clinical examination and evaluation of each patient, including laboratory determinations, ECG, and a very careful assessment of renal function. When sodium intake is lowered, lithium excretion is reduced. Diminished intake or excessive loss of salt and fluids, as a result of vomiting, diarrhea, perspiration or use of diuretics will also increase lithium retention. Thus, lithium should not be given to patients on a salt-free diet and sodium depletion must be carefully avoided. Therefore, it is essential for the patient to maintain a normal diet including adequate salt and fluid intake during lithium therapy. Salt supplements and additional fluids may be required if excessive losses occur. If diuretics are used during lithium therapy the serum lithium concentration must be closely monitored.

Adverse Side Effects

Mild adverse effects may be encountered even when serum lithium values remain below 1 mmol/L. The most frequent adverse effects are the initial postabsorptive symptoms, believed to be associated with a rapid rise in serum lithium concentrations. They include, gastrointestinal discomfort, nausea, vertigo, muscle weakness and a dazed feeling and frequently disappear after stabilization of therapy. The more common and persistent adverse reactions are: fine tremor of the hands, and, at times, fatigue, thirst, polyuria and nephrogenic diabetes insipidus. These do not necessarily require reduction of dosage.
Mild to moderate toxic reactions may occur at lithium concentrations from 1.5 to 2 mmol/L, and moderate to severe reactions at concentrations above 2 mmol/L.
A number of patients may experience lithium accumulation during initial therapy, increasing to toxic concentrations and requiring immediate discontinuation of the drug. Some elderly patients with lower renal clearances for lithium may also experience different degrees of lithium toxicity, requiring reduction or temporary withdrawal of medication. However, in patients with normal renal clearance the toxic manifestations appear to occur in a fairly predictable sequence related to serum lithium concentrations. The usually transient gastrointestinal symptoms are the earliest side effects to occur. A mild degree of fine tremor of the hands may persist throughout therapy. Thirst and polyuria may be followed by increased drowsiness, ataxia, tinnitus and blurred vision, indicating early intoxication. As intoxication progresses the following manifestations may be encountered: confusion, increasing disorientation, muscle twitchings, hyperreflexia, nystagmus, seizures, diarrhea, vomiting, and eventually coma and death.

The following adverse effects have been reported usually related to serum lithium concentrations:

Gastrointestinal:
Anorexia, nausea, vomiting, diarrhea, thirst, dryness of the mouth, metallic taste, abdominal pain, weight gain or loss.

Neurologic:
General muscle weakness, ataxia, tremor, muscle hyperirritability, (fasciculation, twitchings, especially of facial muscles and clonic movements of the limbs), choreoathetotic movement, hyperactive deep tendon reflexes.

CNS:
Anesthesia of the skin, slurred speech, blurring of vision, blackout spells, headache, seizures, cranial nerve involvement, psychomotor retardation, somnolence, toxic confusional states, restlessness, stupor, coma, acute dystonia. EEG changes recorded consisted of diffuse slowing, widening of the frequency spectrum, potentiation and disorganization of background rhythm. Sensitivity to hyperventilation and paroxysmal bilateral synchronous delta activity have also been described.

Cardiovascular:
Arrhythmia, hypotension, ECG changes consisting of flattening or inversion of T waves, peripheral circulatory failure, cardiac collapse.

Genitourinary:
Albuminuria, oliguria, polyuria, glycosuria.

Allergic:
Allergic vasculitis.

Dermatologic:
Dryness and thinning of the hair, leg ulcers, skin rash, pruritis.

Hematologic:
Anemia, leucopenia, leucocytosis.

Metabolic:
Transient hyperglycemia, slight elevation of plasma magnesium, goiter formation. Nontoxic, diffuse or nodular goiters have developed in some patients after initiation of therapy, apparently unrelated to other signs of lithium toxicity. A decrease of PBI and increased I(131) uptake also have been reported.
Hypercalcemia, associated with lithium induced hyper- parathyroidism, has also been reported.

Miscellaneous:
General fatigue, dehydration, peripheral edema.

Overdose

Lithium toxicity is closely related to the concentration of lithium in the blood and is usually associated with serum concentrations in excess of 2 mmol/L. Early signs of toxicity which may occur at lower serum concentrations were described under Adverse Effects and usually respond to reduction of dosage. Lithium intoxication has been preceded by the appearance or aggravation of the following symptoms: sluggishness, drowsiness, lethargy, coarse hand tremor or muscle twitchings, loss of appetite, vomiting, and diarrhea. Occurrence of these symptoms requires immediate cessation of medication and careful clinical reassessment and management. Signs and symptoms of lithium intoxication have already been described under Adverse Effects.

Discontinue lithium therapy. Support respiratory and cardiovascular functions. Depending on mental status, use ipecac syrup or gastric lavage. Follow with activated charcoal and saline cathartic if multiple ingestion is suspected (charcoal does not adsorb lithium effectively). Restore fluid and electrolyte balance.

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