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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. Longitudinal metabolic studies have
demonstrated cumulative lithium retention in some patients without
undue rise in plasma lithium values, indicating a possible intracellular
retention of lithium. There is some evidence that lithium may affect
the metabolism of potassium, magnesium and calcium.
INDICATIONS
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In
the treatment of acute manic episodes in patients with manic-depressive
disorders. Maintenance therapy has been found useful in preventing
or diminishing the frequency of subsequent relapses in bipolar manicdepressive
patients (with a strong history of mania).
CONTRAINDICATIONS
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Patients
with significant cardiovascular or renal disease. It is also contraindicated
in patients with evidence of severe debilitation or dehydration,
sodium depletion, brain damage and in conditions requiring low sodium
intake.
WARNINGS
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Lithium
therapy requires reaching plasma levels of lithium which are relatively
close to the toxic level. Since lithium is excreted primarily by
the kidney, adequate renal function and adequate salt and fluid
intake (2 500 to 3 000 mL) 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.
Means of obtaining accurate determination of serum lithium levels
should be available, since frequent serumdeterminations are required
specially during the initial period of treatment. Lithium toxicity
is closely related to serum lithium levels and during treatment
they should usually not exceed 1.5 mmol/L, if serious adverse reactions
and lithium intoxication are to be avoided. This lithium level refers
to a blood sample drawn before the patient has had his/her first
lithium dose of the day, therefore, 9 to 12 hours after his/her
last dose of drug. Serum lithium levels should usually be monitored
3 times weekly during the initial period of administration and periodically
as required thereafter. If lithium levels exceed 1.5 to 2 mmol/L,
the drug should be discontinued and, if appropriate, administration
resumed at a lower level after 24 hours. Prodromal toxic signs such
as fatigue, muscular weakness, incoordination, drowsiness, coarse
tremors, diarrhea and vomiting, provide a sensitive warning of lithium
intoxication.
In view of the limited dosage range of lithium compared to other
psychotropic agents, particular care is required for the patient
to receive exactly the prescribed number of lithium capsules.
Good kidney function and adequate salt and fluid intake are essential
to maintain lithium excretion.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.
Lithium should generally not be given to patients receiving diuretics,
since the risk of lithium toxicity is very high in such patients.
If diuretics are used during lithium therapy the serum lithium concentration
must be closely monitored.
Chronic lithium therapy may be associated with diminution of renal
concentrating ability, occasionally presenting as nephrogenic diabetes
insipidus, with polyuria and polydipsia. Such patients should be
carefully managed to avoid dehydration with resulting lithium retention
and toxicity. This condition is usually reversible when lithium
is discontinued.Morphologic changes with glomerular and interstitial
fibrosis and nephron atrophy have been reported in patients on chronic
lithium therapy. Morphological changes have also been seen in manic
depressive patients
never exposed to lithium. The relationship between renal functional
and morphologic changes and their association with lithium therapy
have not been established.
When kidney function is assessed for baseline data prior to starting
lithium therapy or thereafter, routine urinalysis and other tests
may be used to evaluate tubular function (e.g., urine specific gravity
or osmolality following a period of water deprivation, or 24-hour
urine volume) and glomerular function (e.g., serum creatinine or
creatinine clearance). During lithium therapy, progressive or sudden
changes in renal function, even within the normal range, indicate
the need for re-evaluation of treatment.
An encephalopathic syndrome (characterized by weakness, lethargy,
fever, tremulousness and confusion, extrapyramidal symptoms, eukocytosis,
elevated serum enzymes, BUN and FBS) followed by irreversible brain
damage has occurred in a few patients treated with lithium plus
haloperidol. A causal relationship between these events and the
concomitant administration of lithium and haloperidol has not been
established; however, patients receiving such combined therapy should
be monitored closely for early evidence of neurologic toxicity
and treatment discontinued promptly if such signs appear (see Precautions,
Drug Interactions). The possibility of similar adverse interactions
with other antipsychotic medication exists (see Precautions, Drug
Interactions).
Outpatients and their families should be warned that patients must
discontinue lithium therapy and contact their physician immediately
if such clinical signs of lithium toxicity as diarrhea, vomiting,
tremor, mild ataxia, drowsiness, fatigue or muscular weakness occur.
There is evidence of decreased tolerance to lithium once the acute
manic episode breaks. Therefore, when the acute attack subsides,
the dosage should be reduced rapidly in order to produce serum lithium
levels no higher than between 0.6 and 1.2 mmol/L.
PRECAUTIONS
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General:
Periodic review and monitoring of kidney and cardiovascular function
is advisable during therapy with lithium carbonate. Other laboratory
tests should be performed as indicated by the patient’s clinical
condition. The appearance of signs of toxicity or a rise in the
blood level of lithium after the dosage is stabilized should alert
the physician to determine the reasons for lithium accumulation.
Patients with Special Diseases and Conditions: Cardiovascular
Disease: Patients with underlying cardiovascular disease should
be observed carefully for signs of arrhythmias.
Thyroid Disorder: Since the formation of nontoxic goiters
has been reported during lithium therapy, the thyroid gland should
be examined before treatment and appropriate thyroid function tests
performed. Nontoxic goiters reported during prolonged lithium therapy
have disappeared following discontinuation of the medication. Treatment
with small doses of thyroxin or desiccated thyroid in patients who
develop a diffuse nontoxic goiter may stop further growth or lead
to shrinkage of the gland.
Concomitant Infection: In addition to sweating and diarrhea,
concomitant infection with elevated temperatures may also necessitate
a temporary reduction or cessation of medication.
Pregnancy: Pregnancy or Women of Childbearing Potential:
Lithium should not be used during pregnancy or in women of child-bearing
potential unless it cannot be substituted by other appropriate therapy
and in the opinion of the physician the expected benefits outweigh
the possible hazards to the fetus.
In various animal species lithium affects reproduction and has been
noted to have teratogenic effects. A group of spontaneous reports
concerning 37 mothers who received lithium during pregnancy included
2 who gave birth to infants with congenital malformations. Data
from lithium birth registries suggest that the drug may increase
the incidence of cardiac and other anomalies, especially Ebstein’s
anomaly.
When possible, lithium should be withdrawn for at least the first
trimester unless it is determined that this would seriously endanger
the mother.
If this drug is used during pregnancy, or if the patient becomes
pregnant while taking the drug, the patient should be apprised for
the potential hazards to the fetus.
When lithium is used during pregnancy, serum lithium concentrations
should be carefully monitored and dosage adjusted if necessary since
renal clearance of the drug and distribution of the drug into erythrocytes
may be increased during pregnancy. Pregnant women receiving lithium
may have subtherapeutic serum lithium concentrations if dosage of
the drug is not increased during pregnancy. Immediately postpartum,
renal clearance of lithium may decrease to pre-pregnancy levels;
therefore, to decrease the risk of postpartum lithium intoxication,
dosage of the drug should be reduced from 1 week before parturition.
Lactation: Lithium is excreted in human milk (concentrations
of 33 to 50% of those in the mother’s serum). Nursing should
not be undertaken during lithium therapy except in rare and unusual
circumstances where, in the opinion of the physician, the potential
benefits to the mother outweigh possible hazards to the child.
Geriatrics: Geriatric patients appear to be more susceptible
to adverse effects even when lithium levels are therapeutic.
Children: Since information regarding the safety and effectiveness
of lithium in children under 12 years of age is not available, its
use in such patients is not recommended. There has been a report
of a transient syndrome of acute dystonia and hyperreflexia occurring
in a 15 kg child who ingested 300 mg of lithium carbonate.
Discontinuation of Therapy: The majority of patients do not
experience withdrawal symptoms or rebound phenomenon upon cessation
of long-term lithium therapy. In view of the occasional reports
of sudden relapses occurring with abrupt discontinuation, gradual
discontinuation is recommended unless abrupt withdrawal is necessary
because of toxicity.
Drug Interactions: Diuretics or Angiotensin Converting Enzyme
(ACE) Inhibitors: Caution should be exercised when lithium and diuretics
or ACE inhibitors are used concomitantly because sodium loss may
reduce the renal clearance of lithiumand increase serum lithium
levels with risk of lithium toxicity.When such combinations are
used, the lithium dosage may need to be decreased and more frequent
monitoring of lithium plasma levels is recommended (see Warnings).
Haloperidol: It has been proposed that haloperidol and lithium
could have a combined inhibitory effect on striatal adenylate cyclase.
If haloperidol and lithium are used concomitantly, careful attention
should be given to the dose of both agents as well as to early detection
of neurotoxicity, particularly in the presence of one or more predisposing
factors which include large doses of one or both drugs, the presence
of acute mania, failure to discontinue drugs when adverse effects
occur, pre-existing brain damage, a history of extrapyramidal symptoms
with neuroleptic therapy alone, the concurrent use of anticholinergic
antiparkinsonian drugs, and the presence of other physiologic disturbances
such as infection, fever, or dehydration (see Warnings).
Phenothiazines: Both pharmacokinetic interactions and clinical
toxicity with the combined use of phenothiazines and lithium have
been described. Lithium-induced reductions in plasma chlorpromazine
levels, phenothiazine-induced increases in red cell uptake of lithium
and chlorpromazine-induced increases in renal lithium excretion
have been reported. Clinically, occasional cases of neurotoxicity
have been reported and may be more likely to occur with thioridazine
than other phenothiazines, when combined with lithium. Therefore,
the clinician should be alert for altered response to either drug
when used in combination and when either drug is withdrawn.
Non-steroidal Anti-inflammatory Drugs (NSAIDs): NSAIDs have
been reported to increase significantly, steady state plasma lithium
levels. In some cases lithium toxicity has resulted from such interactions.
In a patient stabilized on lithium and NSAIDs, discontinuation of
the NSAIDs may result in inadequate serum lithium concentrations.
When such combinations are used, increased plasma lithium level
monitoring is recommended.
Selective Serotonin Reuptake Inhibitors (SSRI) Drugs: Lithiummay
enhance the serotonergic effects of SSRI drugs.
Co-administration of lithium with SSRI drugs may lead to a higher
incidence of serotonin associated side effects and lithium toxicity.
Fluvoxamine: Several cases of adverse reactions including
convulsions have been reported in patients receiving concomitant
lithium and fluvoxamine.
Fluoxetine: There have been reports of both increased and
decreased lithium levels when lithium was used concomitantly with
fluoxetine. Cases of lithium toxicity have been reported.
Sertraline: In placebo-controlled study in normal volunteers
sertraline did not alter steady-state concentrations or renal clearance
of lithium. However, there was a high incidence of apparently treatment-related
side effects with the combination in this study, tremors being the
most frequently observed. There is no clinical experience with lithium
in sertraline treated patients.
Therefore, combined use of lithium and SSRI drugs should be carried
out with caution. Lithium levels should be monitored when these
drugs are administered concomitantly, so that appropriate adjustments
to the lithium dose may be made if necessary.
Carbamazepine: Several cases of neurotoxicity (in the absence
of toxic serum lithium concentrations) have been reported in patients
receiving lithium and carbamazepine, but the combination has also
been used to advantage in some manic patients. Patients should be
monitored for evidence of lithium toxicity when carbamazepine is
given concurrently. It is not yet established whether plasma lithium
concentrations are useful in monitoring this interaction since the
carbamazepine might increase the effect of lithium without increasing
plasma lithium concentrations.
Neuromuscular Blocking Agents: In patients receiving chronic
lithium therapy, the action of neuromuscular blocking agents (e.g.,
succinylcholine, pancuronium) may be prolonged.
Theophylline: Theophylline enhances the renal clearance of
lithium in most patients, thus tending to reduce serum lithium concentrations.
When initiating lithium therapy in a patient on chronic theophylline,
lithium dosage requirements may be higher than anticipated. When
initiating theophylline therapy in a patient on chronic lithium,
there may be reduced lithium response. Monitoring of serum lithium
concentration is recommended.
Calcium Channel Blockers (CCBs): The addition of verapamil
or diltiazem to patients stabilized on lithium therapy may result
in neurotoxicity. The CCB effects may be additive to that of lithium
on transmitter secretion in the nervous system. The use of CCBs
in the treatment of patients with bipolar disorders receiving lithium
should be commenced carefully with observation for neurotoxic effects.
The therapeutic range of lithium may need to be toward the lower
end when a CCB is coadministered.
Propranolol: Limited clinical data suggest that propranolol
may increase lithium serum concentrations, and its co-administration
with lithium may produce bradycardia. Pending further data, patients
maintained on lithium should be monitored for changed lithium serum
concentrations or exaggerated beta-blocker effects.
Tricyclic Antidepressants: Both lithium and tricyclic antidepressants
lower the seizure threshold. An additive effect is possible.
Potassium Iodide: The hypothyroidic and goitrogenic effects
of lithium carbonate and potassium iodide (and possibly other iodides)
may be additive if the 2 drugs are used concurrently.
Diazepam: An isolated case has been reported of serious hypothermia
during concurrent treatment with lithium and diazepam. Since hypothermia
is potentially fatal if it occurs and its general incidence is not
known, it would be prudent to watch for this interaction during
concurrent treatment.
Sodium Bicarbonate: Patients on combined sodium bicarbonate
and lithium therapy should be monitored for decreased lithium effects.
Lithium blood levels may be helpful in assessing this interaction.
Sodium Chloride: Patients on salt-restricted diets who receive
lithium are prone to developing symptoms of lithium toxicity. In
contrast, increased sodium intake has been associated with reduced
therapeutic response to lithium.
Extremely large or small intakes of sodium chloride should be avoided
in patients receiving lithium (see Warnings).
Urea: Limited clinical experience indicates that urea may
enhance the renal excretion of lithium resulting in reduced lithium
serum concentrations.
Other: Isolated cases of lithium toxicity have been reported to
be induced by concomitant administration ofmazindol, methyldopa
and phenytoin.
ADVERSE
EFFECTS
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Mild
side effects may be encountered with lithium even when serum lithium
values remain below 1 mmol/L. The most frequent side effects are
the initial postabsorptive symptoms, believed to be associated with
a rapid rise in serum lithium levels. 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, and polyuria. These
do not necessarily require reduction of dosage.
Mild to moderate toxic reactions may occur at lithium levels from
1.5 to 2 mmol/L, and moderate to severe reactions at levels above
2 mmol/L.
A number of patients may experience lithium accumulation during
initial therapy, increasing to toxic levels 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 regular sequence
related to serum lithium levels. 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 and are usually
related to serum lithium levels:
Gastrointestinal: anorexia, nausea, vomiting, diarrhea, abdominal
pain and weight loss.
Neuromuscular: general muscle weakness, ataxia, tremor, muscle
hyperirritability, (fasciculation, twitchings, especially of facialmuscles
and clonicmovements of the limbs), choreoathetotic movement and
hyperactive deep tendon reflexes.
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.
Central and Peripheral Nervous System: urinary and fecal
incontinence, slurred speech, blackout spells, seizures, cranial
nerve involvement, psychomotor retardation, somnolence, toxic confusional
states, restlessness, stupor and coma.
Cardiovascular: arrhythmia, hypotension, peripheral circulatory
failure, cardiac collapse and peripheral edema.
ECG Changes: reversible flattening, isoelectricity or inversion
of T-waves.
EEG Changes: diffuse slowing, widening of frequency spectrum,
potentiation and disorganization of background rhythm. Sensitivity
to hyperventilation and paroxysmal bilateral synchronous delta activity
have also been described.
Autonomic Nervous System: blurred vision, dry mouth.
Thyroid Abnormalities: Euthyroid goiter and/or hypothyroidism
(including myxedema) accompanied by lower T3 and T4. Iodine uptake
may be elevated (see Precautions). Paradoxically, rare cases of
hyperthyroidism have been reported.
Genitourinary: albuminuria, oliguria, polyuria and glycosuria.
Dermatologic: drying and thinning of hair, anesthesia of
skin, chronic folliculitis, xerosis cutis, alopecia, exacerbation
of psoriasis, rash, and pruritus.
Allergic: allergic vasculitis.
Metabolic and Nutritional Disorders: thirst, hyperglycemia,
and dehydration.
Hematopoietic and Lymphatic: anemia, leukopenia, leukocytosis.
General: general fatigue, leg ulcers, metallic taste, and
slight elevation of plasma magnesium.
Miscellaneous Reactions Unrelated to Dosage Are: transient
electroencephalographic and electrographic changes, hyperthyroidism,
worsening of organic brain syndromes, excessive weight gain, edematous
swelling of ankles or wrists. 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.
Serious reactions to long-term therapy: In addition to other possible
adverse reactions, the main concern during chronic lithium therapy
centres on kidney function, the thyroid, parathyroid, the bones
and skin.
OVERDOSAGE
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Symptoms:
Lithium toxicity is closely related to the concentration of lithium
in the blood and is usually associated with serum levels in excess
of 2 mmol/L. Early signs of toxicity which may occur at lower serum
levels 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 tremors 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.
In 8 cases of lithium poisoning described by Schou, the patients
frequently developed muscle rigidity with hyperactive deep reflexes,
generalized muscle tremors or fasciculations, attacks of hyperextension
of the limbs with gasping and wide opening of the eyes, and sometimes
epileptic seizures and various neurological dysfunction.
There was progressive impairment of consciousness and in some patients
coma. EEG changes in some patients consisted of decrease of alpha
activity and increase of theta and delta activity, the latter at
times paroxysmal with maximum activity frontally. Periods of beta
activity with sharp waves were also observed. The kidney function
was probably impaired in several patients. Three of these patients
died, all of pulmonary complications.
Treatment: No specific antidote for lithium poisoning is
known. The treatment of lithium poisoning is symptomatic. Early
symptoms of lithium toxicity can usually be treated by reduction
or cessation of dosage of the drug and resumption of treatment at
a lower dose after 24 to 48 hours. In severe cases of lithium poisoning,
the first and foremost goal of treatment consists of elimination
of this ion from the organism. Treatment of lithium poisoning is
1) lavage 2) correction of fluid and electrolyte imbalance, and
3) regulation of kidney function. Sodium depletion in particular
must be corrected. However, administration of large amounts of sodium
in the absence of depletion of this electrolyte has not been very
successful in many as a means of speeding lithium excretion. Lithium
excretion may be facilitated by the judicious use of the intravenous
urea, sodium bicarbonate, acetazolamide or aminophylline.
Hemodialysis is an effective and rapid means of removing the ion
from the severely toxic patient or in the presence of impaired renal
function. Infection prophylaxis, regular chest x-rays and preservation
of adequate respiration are essential.
DOSAGE
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Since lithium acts without the production
of “sedation”, some prefer it to neuroleptics or use these
to supplement lithium therapy and obtain rapid control of overt
manic behavior. Lithium also has a useful indication in those cases
that fail to respond to neuroleptics.
Selection of patients and approach to lithium therapy: The
results of lithium therapy depend largely on the nature and course
of the illness itself, rather than on the symptoms. The selection
of patients for long-term treatment requires a clearcut diagnosis
of primary affective disorder, the condition for which the stabilizing
effects of lithium have been found useful. The variables that have
been more consistently associated with response to lithium therapy
in patients with a primary affective disorder are: the good quality
of remissions with good function and no significant symptomatology
during the free intervals between previous episodes of illness;
low frequency of episodes, typically 1 or 2 (and not more than 3
or 4) per year, and symptomatology during the acute episodes that
meet strict criteria for a primary affective disorder (DSM-III:
Research Diagnostic Criteria).
Screening for lithium candidates should include at least a medical
history and physical examination with emphasis on the CNS, urinary,
cardiovascular, gastrointestinal and endocrine systems and the skin.
It should also include:
routine 24-hour urine volume, serum creatinine, record of weight,
an ECG, possibly electrolytes and TSH, and for long-term treatment,
creatinine clearance and a urine concentration test. Other examinations
and tests should be used when indicated. Monitoring lithium treatment
should include, for each visit, mental status, physical examination,
weight, 12-hour serum lithium and a check for lithium side effects
and compliance. It should also include serum creatinine every 2
months, plasma thyroid hormone and TSH every 6 to 12 months, particularly
in female patients,
and attention to renal and thyroid function should be maintained
throughout, with tests used for baseline screening repeated as required.
The first objective of treatment is to establish an effective and
safe daily dosage of lithium with the aid of standardized 12-hour
serum lithium levels maintained within the therapeutic range, as
high as necessary for efficacy, and with the patient as much as
possible free of significant side effects. Three daily doses should
be used initially, at least until the daily dosage is established.
The next aim is to move to an optimal dose, which should be as low
as possible, consistent with protection against relapse. During
follow-up, an adjustment to lower dosages may be
required to minimize adverse effects, and a change in the lithium
preparation used and/or the frequency of dosing, either towards
multiple doses or towards a single dose, may be necessary to handle
absorption-related adverse effects or concern over possible renal
toxicity. Intermittent lithium treatment in carefully selected patients
has been recommended by some lithium experts, but should not be
undertaken without careful planning and great caution.
The cooperation of patients and relatives is required throughout.
Before deciding on the institution of long-term treatment, it is
essential to establish that the patient has clearly responded to
a course of stabilizing lithium therapy and that the risk of such
therapy is acceptable. Maintaining a patient with a lithium non-responsive
condition on long-term therapy poses an unacceptable risk. A decision
with regards to long-term therapy can be made during a time-limited
trial of lithiumtherapy with frequent reassessment of outcome. The
following are among the factors to be reassessed before a decision
is made: careful reconfirmation
of the diagnosis of primary affective disorder, the health status
of the patient, the side effects of lithium therapy experienced
by the patient, and the response to treatment. Assessment of response
to treatment is based strictly on firm evidence of relapse prevention
during a reasonable trial period, but can be assisted by consideration
of the predictors of response outlined above. Great pains should
be taken to exclude false responders and false non-responders. It
should also be borne in mind that non-responders are more susceptible
to the adverse effects
of lithium.
Acute mania: The therapeutic dose of lithium for the treatment
of acute mania should be based primarily on the patient’s clinical
condition. It must be individualized for each patient according
to blood levels and clinical response. Manic patients usually require
serum lithium levels in excess of 1 mmol/L, and the dosage should
be adjusted to obtain serum levels between 1 and 1.5 mmol/L (in
blood samples drawn before the patient has had his/her first lithium
dose of the day).
In properly screened adult patients, the suggested initial daily
dosage for acute mania is 1 800 mg (approximately 50 mmol), divided
into 3 doses. In view of the large variability of renal lithium
excretion between individuals, it is suggested that lithium treatment
be started at a dose between 600 and 900 mg/day, reaching a level
of 1 200 to 1 800 mg in divided doses on the second day. Depending
on the patient’s clinical condition, the initial dosage should
be adjusted to produce the desired serum lithium level. The weight
of the patient should also influence the choice of the initial dose.
Lithium should be used cautiously and in reduced doses in the elderly
patient, usually in the range of 600 to 1 200 mg/day. Serum lithium
levels should be monitored frequently and kept below 1.5 mmol/L.
Long-term Control: After the acute manic episode subsides,
usually within a week, the dosage of lithium should be rapidly reduced
to achieve serum levels between 0.6 and 1.2 mmol/L (with the level
kept below 1.5 mmol/L), since there is evidence at this time of
a decreased tolerance to lithium. The average suggested dosage at
this stage is 900 mg/day (approximately 25 mmol), divided into 3
doses, with a range usually between 600 and 1 200 mg/day. If a satisfactory
response is not obtained in 14 days, lithium therapy should be discontinued.
When the manic attack is controlled, lithium administration should
be maintained during the expected duration of the manic phase, since
early withdrawal might lead to relapse. It is essential to maintain
clinical supervision of the patient and monitor lithium levels as
required during treatment (see Warnings and Precautions).
Lithium may be used concomitantly with neuroleptic drugs, (see Warnings
and Precautions, Drug Interactions).
Serum lithium levels in uncomplicated cases receiving maintenance
therapy during remission should be monitored at least every 2 months.
Patients abnormally sensitive to lithium may exhibit toxic signs
at serum levels of 1 to 1.4 mmol/L. Elderly patients often respond
to reduced dosage and may exhibit signs of toxicity at serum levels
ordinarily tolerated by other patients.
Note: Blood samples for serum lithium determinations should
be drawn immediately prior to the next dose when lithium concentrations
are relatively stable (i.e., 8 to 12 hours after the previous dose).
Total reliance must not be placed on serum levels alone. Accurate
patient evaluation requires both clinical and laboratory analysis.
SUPPLIED
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150 mg: Each ivory #3, hard
gelatin capsule contains: lithium carbonate 150 mg; capsule shell:
imprinted with "erfa". Tartrazine-free. Opaque plastic
bottles of 100.
300 mg: Each green and ivory #1, hard gelatin capsule contains:
lithium carbonate 300 mg; capsule shell: imprinted with "erfa".
Tartrazine-free. Opaque plastic bottles of 1 000.
Store at 15 to 30°C.
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