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LITHIUM
ABIMBOLA FARINDE, PhD., PharmD
Abimbola Farinde, PhD., PharmD is a healthcare professional and professor who has
gained experience in the field and practice of mental health, geriatrics, and
pharmacy. She has worked with active duty soldiers with dual diagnoses of a
traumatic brain injury and a psychiatric disorder providing medication therapy
management and disease state management. Dr. Farinde has also worked with
mentally impaired and developmentally disabled individuals at a state supported
living center. Her different practice experiences have allowed her to develop and
enhance her clinical and medical writing skills over the years. Dr. Farinde always
strives to maintain a commitment towards achieving professional growth as she
transitions from one phase of her career to the next.
DANA BARTLETT, RN, BSN, MSN, MA, CSPI
Dana Bartlett is a professional nurse and author. His clinical experience includes 16
years of ICU and ER experience and over 27 years as a poison control center
information specialist. Dana has published numerous CE and journal articles, written
NCLEX material, textbook chapters, and more than 100 online CE articles, and done
editing and reviewing for publishers such as Elsevier, Lippincott, and Thieme. He has
written widely on the subject of toxicology and was a contributing editor, toxicology
section, for Critical Care Nurse journal. He is currently employed at the Connecticut
Poison Control Center. He lives in Wappingers Falls, NY.
ABSTRACT
Lithium is an antimanic agent that causes mood stabilization in patients who
have bipolar disorder. Lithium is effective for the treatment of manic episodes,
and it is also a first-choice drug for maintenance treatment of bipolar disorder.
The safe and effective use of lithium requires close monitoring of the patient
symptoms and of the patient’s lithium levels, as well as a thorough
understanding of the potential complications and adverse effects of lithium
therapy.
1
NurseCe4Less.comPolicy Statement
This activity has been planned and implemented in accordance with the
policies of NurseCe4Less.com and the continuing nursing education
requirements of the American Nurses Credentialing Center's Commission on
Accreditation for registered nurses.
Continuing Education Credit Designation
This educational activity is credited for 2.5 hours at completion of the activity.
Pharmacology content is 2.5 hours.
Statement of Learning Need
Lithium is a well known antimanic agent in patients with bipolar disorder.
There are other uses of lithium that are off label and in combination with other
medication used to treat symptoms of bipolar disorder. Clinicians who treat
bipolar disorder infrequently may be unfamiliar with all of the helpful uses of
lithium, especially in special populations and for patients diagnosed with mixed
mood states.
Course Purpose
To inform health clinicians of the indications, uses, contraindications and
potential side effects of lithium.
Target Audience
Advanced Practice Registered Nurses, Registered Nurses, and other
Interdisciplinary Health Team Members.
Disclosures
Abimbola Farinde, PhD., PharmD, Dana Bartlett, RN, BSN, MSN, MA, CSPI,
William Cook, PhD, Douglas Lawrence, MA, Kellie Wilson, PharmD, Jennifer
McAnally, DNP, PMHNP-BC, Susan DePasquale, MSN, PMHNP-BC – all have no
disclosures. There is no commercial support.
2
NurseCe4Less.comSelf-Assessment of Knowledge Pre-Test:
1. Lithium is an antimanic agent that acts as ________________ in
patients who have bipolar disorder.
a. a hallucinogen
b. a mood stabilizer
c. an antipsychotic
d. an antidepressant
2. For _________________, lithium is often combined with an
antipsychotic.
a. hypomania
b. severe mania
c. mild mania
d. moderate mania
3. Bipolar disorder is a psychiatric disorder characterized by
episodes of
a. depression followed by periods of lethargy.
b. anxiety and concomitant depression.
c. mania, hypomania, and major depression.
d. anger and anxiety, followed by periods of calm.
4. A patient with mild renal impairment
a. may not take lithium.
b. must reduce the recommended dose.
c. may take lithium but with caution.
d. may take lithium but a low sodium diet is recommended.
5. The use of lithium during the first trimester of pregnancy may
cause a serious fetal cardiac malformation called
a. Epstein-Barr syndrome.
b. Ebstein’s anomaly.
c. Brugada syndrome.
d. Stevens-Johnson syndrome.
3
NurseCe4Less.comIntroduction
Lithium is a first-line choice for treating and preventing manic episodes
in patients who have bipolar disorder. Decades of experience and study trials
have proven that lithium can be a safe and effective drug. Lithium use requires
close monitoring of the patient’s physical symptoms and trends in lithium
levels given its narrow therapeutic window. The patient should be provided
with a thorough understanding of the potential complications and adverse
effects of lithium. The basic pharmacological profile, aspects of lithium
toxicity, and clinical pearls of lithium use are raised in the following sections.
Pharmacological Profile
Lithium has a labeled use as a treatment for patients with mood
disorders. There is evidence that lithium can also be useful, in combination
with other medications, for other off-label uses. Patients prescribed lithium
are routinely monitored for physical symptoms of toxicity and for elevated
serum levels that could lead to serious side effects, such as renal impairment
or thyroid dysfunction.
There are considerable drug-drug interactions with the combined use of
lithium and other drugs that require close monitoring to prevent a serious
outcome. This section addresses these specific considerations.
Category
Lithium is categorized as an antimanic and mood stabilizing agent.1-3
Mechanism of Action
The mechanism of action by lithium causes mood stabilization in
patients who have bipolar disorder is not known. Lithium is rapidly absorbed
and there is no metabolism of lithium, so it is excreted unchanged.1-3
4
NurseCe4Less.comDrug Uses
Bipolar Disorder:
Lithium is used as a treatment of manic episodes and as maintenance
treatment in patients who have bipolar disorder.1-3
Bipolar Depression:
Lithium is used off-label for bipolar depression as an adjunct with an
antidepressant to treat symptoms of depression.1-3
Dosing: Adult
Immediate Release:
Begin at 300 mg, three times a day. Increase the dose by assessing the
patient’s response and how well the dose is tolerated. The maintenance dose
is usually 900 mg – 1800 mg a day in three-four divided doses.1
Extended Release:
Begin at 450 mg twice a day (or less). Increase the dose by assessing
the patient’s response and toleration of the dose. The usual maintenance dose
is 900 mg – 1800 mg a day, in two divided doses.1,2
Dosing: Geriatric
Geriatric dosing follows the same recommended guidelines that have
been published for adult dosing.1
Dosing Adjustment: Hepatic Impairment
There are no standard or recommended dosing adjustments for patients
who have hepatic impairment.1
5
NurseCe4Less.comDosing Adjustment: Renal Impairment
There are no standard or recommended dosing adjustments for patients
who have renal impairment.1 Lithium is excreted by the kidneys and in
patients who have renal impairment, lithium levels may become elevated and
lithium poisoning and renal damage can occur. If a patient’s renal function, as
reflected by the creatinine clearance (CrCL), is severely impaired, lithium
should only be used if absolutely needed and with close monitoring of the
patient and serum lithium levels.1
CrCl 30 to 89 mL/minute:
Start with a low dose and titrate up slowly and with frequent
monitoring.1
CrCl < 30 mL/minute:
Avoid use for patients with CrCL < 30 mL/minute. The use of lithium in
patients who have renal impairment should be done cautiously.1 If the renal
function, as reflected by the creatinine clearance (CrCL) is severely impaired,
lithium may be contraindicated.1
Creatinine Clearance (CrCL)
Creatinine clearance (CrCl) is a test that estimates glomerular filtration rate,
GFR. The GFR is a highly accurate reflection of kidney function but directly
measuring GFR is complex and invasive and using the CrCl is an acceptable and
widely used substitute method of estimating GFR. Creatinine clearance is
determined by measuring serum creatinine and measuring the amount of
creatinine in a 24-hour urine collection. The patient’s age and body weight and
the results of the tests are used with standard formulas like the Cockcroft-Gault
equation or the Modification of Diet in Renal Disease equation to establish a CrCl
value.
Normal CrCl for men is 107 – 139 mL/minute
Normal CrCl for women is 87 – 107 mL/min
6
NurseCe4Less.comAvailable Forms1,2
● Immediate release: Capsules, 150 mg, 300 mg, 600 mg.
● Immediate release: Tablets, 300 mg.
● Extended release: Generic, 400 mg, 450 mg. Brand name, Lithobid, 300
mg.
● Solution: 8 mEq/5 mL.
Contraindications
The use of lithium is contraindicated if the patient has hypersensitivity
to lithium or to any of the components of the product. Lithium should not be
used for patients who are debilitated or have severe cardiac or renal disease,
severe dehydration, or sodium depletion.1 For immediate release preparations
or solution, the concurrent use with a diuretic is contraindicated.1
US Boxed Warning
Lithium toxicity may be reflected by serum levels of the drug, and it can
occur at levels that are only slightly above the therapeutic level. The ability to
accurately and quickly measure serum lithium should be available.1,2
Warnings
Cardiovascular:
Lithium should be used very cautiously if the patient has significant
cardiovascular disease. The use of lithium can unmask the presence of
Brugada syndrome, a potentially life-threatening heart rhythm disorder.
Lithium should not be used if the patient has, is suspected to have, or is at
risk for having Brugada syndrome.1,2 Lithium may act as a direct myocardial
toxin, and it should be used cautiously in patients who have heart failure.1,2
7
NurseCe4Less.comEndocrine:
Lithium therapy may cause hypothyroidism. Use lithium cautiously if the
patient has hypothyroidism.1,2
Fluid and Electrolytes:
Dehydration, sodium depletion, and volume depletion can cause lithium
toxicity.1,2 Lithium should be avoided or used cautiously if the patient is
dehydrated, volume depleted and/or sodium depleted, if the patient has any
condition like diarrhea, or if the patient has an infection that may cause
volume depletion.1,2
The use of lithium may cause hypercalcemia. This can occur with or
without the presence of hyperparathyroidism (an overabundance of the
hormone parathyroid in the bloodstream). Older patients and women are at a
higher risk for this adverse effect. Hypercalcemia and hyperparathyroidism
are usually reversible once lithium therapy has been stopped but not always.1,2
Neurological:
Drowsiness is a common adverse effect of lithium. An association
between lithium and pseudotumor cerebri (idiopathic intracranial
hypertension), a neurological condition that can cause serious ocular adverse
effects, e.g., blindness, has been reported. If pseudotumor cerebri occurs,
discontinue use of lithium if possible.1,2
Psychiatric:
Use lithium cautiously if the patient is depressed or has suicidal behavior
or ideation.1,2
8
NurseCe4Less.comRenal:
Chronic use of lithium can cause nephrogenic diabetes insipidus,
decreasing the concentrating ability of the kidneys. Chronic use of lithium has
also caused structural changes in the kidneys like atrophy of nephrons and
glomerular fibrosis.1,2
Serotonin Syndrome:
Concurrent use of lithium and other serotonergic drugs can cause
serotonin syndrome. If a patient who is taking lithium develops
signs/symptoms of serotonin syndrome, the patient should stop taking lithium
immediately.1,2
Adverse Effects
The most common acute adverse effects of lithium are cognitive
impairment (e.g., changes in affect, concentration, and memory), loose
stools, nausea, polyuria, tremor, and weight gain.4
Pregnancy and Breastfeeding
Lithium crosses the placenta and using the drug during pregnancy has
been associated with fetal defects, birth complications, and neonatal medical
complications which may include arrhythmias, diabetes insipidus, floppy infant
syndrome, and lithium toxicity.1,2
The use of lithium during the first trimester has been associated with
fetal defects, primarily cardiac, including a potentially serious fetal cardiac
malformation called Ebstein’s anomaly. The risk of Ebstein’s anomaly
occurring is very small and lithium should not be withheld if its use is clearly
indicated.1,2 Clinicians should consider using fetal echocardiography and other
diagnostic tests if the mother has been taking lithium during the first
trimester.
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NurseCe4Less.comIf lithium must be used during the first trimester the lowest effective
dose should be used. Serum levels should be closely followed and it may be
beneficial to start therapy after the time of organogenesis. Lithium therapy
should be discontinued 24 to 48 hours before delivery.1 Physiological changes
of pregnancy may affect maternal serum lithium levels.1
Lithium is excreted in breast milk. The serum concentrations in nursing
infants can be considerable, 10%-50% of the maternal dose.1 Significant
adverse effects like cyanosis, hypotonia, hypothermia, and ECG changes have
been reported to occur in nursing infants exposed to lithium, and the use of
lithium while breastfeeding is not recommended unless the benefits outweigh
the risks.1,2
If lithium is used during nursing, the infant should be closely monitored
for signs of lithium toxicity and for normal growth, and it is important to be
sure the infant is well hydrated. The mother’s serum lithium concentration
should be measured periodically, as well.1,2
Dietary Concerns
Lithium can be taken with or without food. Patients taking lithium should
be sure to maintain an adequate fluid and sodium intake.1,2 This is important
in avoiding lithium toxicity as discussed above in the section discussing “Fluid
and Electrolytes.”1,2
Laboratory Tests and Lithium Levels
Before starting therapy with lithium, baseline measurements of BUN,
creatinine, complete blood count (CBC), calcium, electrolytes, estimated
glomerular filtration rate (eGFR), and thyroid function studies should be
done;1,2 recommendations for scheduling periodic measurements of these
tests will be discussed later in the module. If the patient is > 40 years old, a
baseline 12-lead electrocardiogram (ECG) should be done. A beta-HCG
pregnancy test should be done in women of child-bearing age.1
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NurseCe4Less.comLithium levels should be measured immediately before the next dose is
scheduled to be given; this ensures that a steady state level is obtained.2 The
normal serum lithium level is 0.6 – 1.2 mEq/L. A serum lithium level provides
valuable information, but an assessment of the patient’s condition cannot be
based on only the level.2
Clinical Pearls: Lithium
This section provides detailed information on issues that are of practical
interest to clinicians. Many of the topics from the basic pharmacology section
will be covered here, along with a discussion of the Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for diagnosing a
manic episode.
Drug Uses
Bipolar disorder is a psychiatric disorder characterized by episodes of
mania, hypomania, and major depression.5 Bipolar disorder is a chronic
condition that can be managed but not cured. The mania, hypomania, and
depression can be quite severe and for many people, there are significant
functional consequences attendant to these episodes.6
There are two types of bipolar disorder, type I and type II. Manic
episodes are a feature of type I, and lithium is a first-line choice for treating
manic episodes.7,8 For severe mania, lithium is often combined with an
antipsychotic. Lithium is also effective for treating mild to moderate manic
episodes.7 It is one of the primary drugs used for maintenance treatment of
bipolar disorder;3,9-10 it as been estimated to reduce the relapse rate by 30
percent.10
Manic Episode: DSM-5 Criteria
Criteria A through D constitute a manic episode. At least one lifetime
manic episode is required for the diagnosis of bipolar I disorder.12
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NurseCe4Less.comDSM-5 Criteria A:
During a manic episode there is a distinct period of abnormally and
persistently elevated, expansive, or irritable mood and abnormally and
persistently increased activity or energy, lasting at least one week and present
most of the day, nearly every day (or any duration if hospitalization is
necessary).12
DSM Criteria B:
During the period of mood disturbance and increased energy or activity,
three (or more) of the following symptoms (four if the mood is only irritable)
are present to a significant degree and represent a noticeable change from
usual behavior:12
1. Inflated self-esteem or grandiosity.
2. Decreased need for sleep (feels rested after only three hours of sleep).
3. More talkative than usual or pressure to keep talking.
4. Flight of ideas or subjective experience that thoughts are racing.
5. Distractibility (attention too easily drawn to unimportant or irrelevant
external stimuli), as reported or observed.
6. Increase in goal-directed activity (either socially, at work or school, or
sexually) or psychomotor agitation (purposeless activity).
7. Excessive involvement in activities that have a high potential for painful
consequences (engaging in unrestrained buying sprees, sexual
indiscretions, or foolish business investments).
DSM-5 Criteria C:
The mood disturbance is sufficiently severe to cause marked impairment
in social or occupational functioning or to necessitate hospitalization to
prevent harm to self or others, or there are psychotic features.12
12
NurseCe4Less.comDSM-5 Criteria D:
The episode is not attributable to the physiological effects of a substance
(a drug with addictive potential, a medication, other treatment) or to another
medical condition.12
Dosing Adjustment: Geriatric Patients
The prescribing information for lithium does not have specific dosing
recommendations for geriatric patients, and there is limited data on lithium
administration in the elderly.13-16 The standard advice is to use the lower end
of the dosing range.1,2,13
There are cogent and persuasive reasons for dosing at lower ranges in
elderly. Lithium is excreted by the kidney, and glomerular filtration rate (GFR)
decreases as people age.13 Older patients often have a lower lean body mass
and total body water, and these changes affect the volume of distribution of
lithium.13
Lithium can cause injury to the kidneys, and the risk of lithium-induced
renal damage is apparently higher in geriatric patients.13,17 In addition, elderly
patients are more likely to have comorbidities that increase the risk for renal
impairment, like coronary artery disease, diabetes mellitus, and
hypertension.18
The duration of lithium therapy has been associated with an increased
risk for renal damage.19 Common adverse effects of lithium like drowsiness
may be particularly harmful to older patients. Older patients have a higher
risk for lithium toxicity than do younger patients due to age related changes
in pharmacokinetics and pharmaodynamics.4,13
Dosing Adjustment: Hepatic Impairment
Lithium is not metabolized by the liver, and there are no standard or
recommended dosing adjustments for patients who have hepatic impairment.
13
NurseCe4Less.comLong-term use of lithium may cause mild, transient, and self-limiting
elevations of serum transaminases, but discontinuation of use or changing the
dose is not necessary.20 There are no reported cases of acute liver failure or
chronic liver damage caused by lithium.20
Dosing Adjustment: Renal Impairment
Lithium is excreted unchanged by the kidneys, and the prescribing
information states that lithium should not be used if the patient has severe
renal impairment. The prescribing information recommends: CrCl 30 to 89
mL/minute: Start with a low dose and titrate up slowly and with frequent
monitoring; and for CrCl < 30 mL/minute, use should be avoided.21
The Kidney Disease Improving Global Outcomes (KDIGO) guidelines
classify chronic kidney disease (CKD) by assessment of urinary albumin
excretion or by estimated glomerular filtration rate (eGFR). Based on eGFR,
the KDIGO recognizes five grades of CKD.21
● G1: Normal, eGFR ≥ 90 mL/min/1.73 m2
● G2: Mildly decreased, eGFR 60-89 mL/min/1.73 m2
● G3a: Mildly to moderately decreased, eGFR 45-59 mL/min/1.73 m2
● G3b: Moderately to severely decreased, eGFR 30-44 mL/min/1.73 m2
● G4: Severely decreased, eGFR 15-29 mL/min/1.73 m2
● G5: Kidney failure, eGFR 60
mL/min/1.73 m2 would need downward dosing adjustments of lithium.22,23
However it should be noted that there are no standardized, accepted
guidelines for prescribing lithium for patients who have renal impairment,
lithium excretion depends on renal function, and lithium itself is nephrotoxic.
For patients taking lithium, baseline measurements of BUN, creatinine,
eGFR, and urinalysis should be done prior to initiating lithium therapy, they
should be re-measured every two to three months during the first six months
14
NurseCe4Less.comof lithium therapy, and then measured every six to 12 months.4 For patients
who have renal impairment, closer monitoring and more frequent assessment
may be prudent.
US Boxed Warning
Lithium toxicity may be closely related to serum levels, and it can occur
at levels that are only slightly above the therapeutic level. The ability to
accurately and quickly measure serum lithium should be available.1,2
Acute, acute-on-chronic, or chronic lithium toxicity can cause significant
morbidity and long-term, chronic neurological damage.24-26 Timely
measurement of serum lithium levels is essential for assessment and
treatment of a patient who has lithium intoxication.
Serum lithium levels must be carefully interpreted. Therapeutic serum
lithium is 0.6 – 1.2 mEq/L, and a level of > 1.5 mEq/L has been defined as
toxic, but the serum lithium level is not an accurate predictor of lithium toxicity
nor does the level correlate well with the severity of lithium toxicity.24-27
Patients who have levels > 4.0 mEq/L may be relatively asymptomatic.24
A lithium level as low as 0.57 mEq/L has been reported to cause serious
lithium poisoning.28
The lithium level - along with the patient’s clinical presentation and other
laboratory test results – can be used to help determine the appropriate
treatment. For example, hemodialysis is an effective treatment for lithium
toxicity, and hemodialysis is recommended if 1) the serum lithium level is >
5.0 mEq/l, 2) if the level is > 4.0 mEq/L and the patient’s serum creatinine is
> 2.0 mg/dL, 3) if the serum lithium level is > 2.5 mEq/L and there is evidence
of serious toxicity like coma or seizures, 4) if the patient has renal
insufficiency, or 5) if there is intolerance of aggressive fluid resuscitation.24
15
NurseCe4Less.comWarnings
Cardiovascular:
Prescribing information and authoritative sources advise that lithium
should be used cautiously in patients who have cardiovascular disease.
Lithium use has been associated with both benign and life-threatening
cardiovascular adverse effects.29-36 Some of these are relatively common and
they occur during otherwise uneventful use of the drug: sinus bradycardia and
T wave inversion are well known adverse effects of lithium, the latter being
noted in 16%-33% of all patients taking the drug.32 Other cardiovascular
adverse effects happen only if the lithium level is elevated, or they have been
documented in just a few case reports, e.g., Brugada syndrome and
myocardial infarction.32
Because information about these adverse effects is relatively scarce, it
can be difficult to determine their clinical significance or to identify which
patients are susceptible and the reason. For example, ECG changes like T
wave inversion and bundle branch block may persist for years and cause no
harm,33 but the unmasking of the Brugada syndrome may cause cardiac
arrest. The prudent clinician would carefully assess the patient’s
cardiovascular health, perform a baseline 12-lead ECG before prescribing
lithium, schedule follow-up exams and ECGs as needed, and determine the
benefits and risks of lithium use for that patient.
The cardiovascular adverse effects associated with lithium use may
include asystole, atrioventricular block, bradycardia, cardiomyopathy, heart
failure, interstitial myocarditis, junctional rhythms, myocardial infarction,
premature ventricular beats, QT prolongation SA node blocks, SA node
dysfunction, ST segment and T wave changes, and ventricular fibrillation.27,29-
36
Some are common, e.g., bradycardia and T wave inversion,33 and others
are rare, typically being documented by one or two case reports.31,32,34
Brugada syndrome is an uncommon genetic cardiac condition that is
characterized by ECG changes, ventricular tachy-arrhythmias, and sudden
16
NurseCe4Less.comdeath.37 Patients who have Brugada syndrome may simply have ECG changes
or the disease may present with syncope, palpitations, or a dangerous
ventricular arrhythmia,29 and the Brugada syndrome may be unmasked by the
use of lithium.1,33 This appears to be a very uncommon occurrence and there
are very few documented cases.33 Prior to starting therapy with lithium,
patients should be examined for the presence of Brugada syndrome and for
factors for that increase the risk of the disease, e.g., family history of Brugada
syndrome, palpitations, syncope, and a family history of sudden death before
age 45.1 Lithium should not be prescribed for patients who have Brugada
syndrome unless its use is absolutely necessary and if it is prescribed,
consultation with a cardiologist and close monitoring of the patient are
mandatory.1
Lithium may act as a myocardial toxin. The American Heart Association
(AHA) published a review of drugs that may cause or exacerbate heart failure,
and lithium was identified a direct myocardial toxin.34 The mechanism of action
is not clear - possibly a direct effect of the drug on the myocardium, adrenergic
stimulation, or interference with calcium ion efflux - and the AHA’s conclusions
were that 1) The effect was considered to be major, 2) The level of supporting
evidence was categorized as level C, meaning that very limited populations
were evaluated, and the information is from case studies, consensus opinion
of experts, and standards of care, and 3) The onset is intermediate or delayed,
and the effect is reversible when the patient stops taking the drug.34
Thyroid Disorders:
Lithium can cause thyroid disorders. Goiter and hypothyroidism are the
most common.38 Goiter is the enlargement of the thyroid gland, and it is a
common adverse effect of lithium therapy, with a reported incidence of 30-
59%.38,39 It is not completely understood how lithium causes goiter, but it is
likely that lithium decreases thyroid hormone secretion and release, resulting
in compensatory thyroid gland enlargement.38,39
The onset of lithium-induced goiter can be weeks after after initiation of
treatment or it may be delayed for years.38,40 It typically presents as a diffuse,
17
NurseCe4Less.comnon-tender neck swelling, the TSH level is increased, the T3 and T4 levels are
decreased.38 A large, visible goiter that causes signs and symptoms of
compression is unusual.38 Treatment of lithium-induced goiter is the same as
treatment of goiter from other etiologies.38 Discontinuing the use of lithium if
a goiter develops is not recommended;38 the patient should be treated with
standard care.38
Hypothyroidism has been reported in 6%-52% of all patients taking
lithium.38,39 Most cases are subclinical: the patient is asymptomatic, but the
TSH level is elevated. The patient may or may not have a goiter.38 Lithium-
induced hypothyroidism is more likely to happen to women over age 45, and
the risk factors for developing this adverse effect may include increased age,
a family history of hypothyroidism, or the presence of thyroid
autoantibodies.38,39 The clinical presentation is identical to hypothyroidism
from other causes, with depressed mood, fatigue, lethargy, dry skin, weight
gain, and increased sensitivity to cold.38,41 Lithium-induced hypothyroidism
should be treated using standard guidelines.38
Thyroid function studies should be measured before the patient begins
taking lithium, measured once or twice during the first six months of
treatment, and these tests should be repeated every six to 12 months for
several years;4,38 perhaps more frequently if the patient is considered high-
risk.4 The presence of goiter or hypothyroidism does not mean that lithium
cannot be used and if adverse effects occur, the thyroid dysfunction should be
treated.38
Hypercalcemia and Parathyroid Hormone:
Lithium may cause hypercalcemia, an increased parathyroid hormone
level, and hyperparathyroidism.1,4,42,43 The exact incidence of these adverse
effects is not known. A retrospective case review done in 2018 found a 26%
prevalence of hypercalcemia, and the risk of developing hyperparathyroidism
from chronic lithium use has been estimated at 10%.42
18
NurseCe4Less.comMany patients do not develop clinical signs and symptoms from these
laboratory abnormalities.4 There are documented cases of symptomatic
lithium-induced hypercalcemia, and hypercalcemia may or may not resolve
after lithium use is discontinued.42,43 In addition, hypercalcemia may
complicate other adverse effects of lithium like cardiovascular disorders,
nephrogenic diabetes, and renal disease.44
There are four options for treating lithium-associated hypercalcemia: 1)
Discontinue lithium therapy, 2) Careful monitoring of the patient, 3) Lowering
serum calcium by treatment with a calcimimetic drug, e.g., cinacalcet, and 4)
Surgery.42
Psychiatric:
People who have bipolar disorder have a high risk for suicide. There is
strong and consistent evidence that lithium has a protective effect and it
reduces the risk for suicide.45-49 This may be the case because of litium’s effect
as a mood stabilizer, which reduces aggressiveness and impulsivity.49 It may
also be that a patient’s greater contact with professional health care also helps
reduce the risk for suicide.49 Nevertheless, it is recommended that lithium
should be used cautiously if a patient is depressed or has suicidal behavior or
ideation.1
Serotonin Syndrome:
Lithium used in combination with serotonergic drugs, e.g., selective
serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake
inhibitors, can cause serotonin syndrome.50 Serotonin syndrome is a
potentially fatal condition that is caused by excessive serotonergic activity.
Excessive serotonergic activity occurs with the use, misuse, or abuse of drugs
that 1) inhibit serotonin reuptake, 2) act as direct serotonin agonists, 3)
decrease the breakdown of serotonin, 4) increase the release of serotonin, or
5) increase serotonin formation.51 Serotonin syndrome can occur with use of
a single serotonergic drug but concurrent use of two serotonergic drugs, e.g.,
fluoxetine and lithium is a more common cause.51
19
NurseCe4Less.comThe onset of serotonin syndrome is usually within six hours of the last
time a medication was taken and most patients have mild to moderate signs
and symptoms like agitation, clonus, diaphoresis, fever, hyperreflexia, and
tremor, but serious morbidities and fatalities caused by serotonin syndrome
are possible.51 Serotonin syndrome is a clinical diagnosis; there are no tests
that can confirm its presence. Treatment is symptomatic and supportive.
Renal Function:
Lithium can have significant negative effects on renal function, which
may include nephrogenic diabetes insipidus, nephrotic syndrome, and chronic
kidney disease and end-stage renal disease.52 Nephrogenic diabetes insipidus
is defined as a decreased ability to concentrate urine that is caused by
decreased activity of and resistance to antidiuretic hormone (ADH).
Antidiuretic hormone is a hormone that is secreted by the posterior
pituitary gland, and its primary function is maintaining normal body fluid
osmolarity. In the kidneys, ADH increases the water permeability of the
collecting tubules, causing water to be reabsorbed rather than excreted as
urine. Lithium causes resistance to ADH and inhibits ADH activity.52,53
Lithium is the most common cause of nephrogenic diabetes insipidus.53
In long-term users of the drug, the prevalence of nephrogenic diabetes
insipidus has been reported to be 50-73%.53 The primary characteristics of
nephrogenic diabetes insipidus are nocturia, polydipsia, and polyuria (often
defined as a urine output > 3000 mL/24).52,54 Hypernatremia can occur, as
well.55 The primary risk factor for nephrogenic diabetes insipidus is the
duration of the lithium therapy; the longer the duration, the greater the risk.53
Non-responsiveness to lithium and the use of slow-release preparations may
also increase the risk.56 Although polyuria is one of the primary signs of
nephrogenic diabetes insipidus, many patients who are prescribed lithium will
develop polyuria but only 15∼20% will develop nephrogenic diabetes
insipidus.57
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NurseCe4Less.comLithium-induced nephrogenic diabetes insipidus can be reversible, partly
reversible, or it can become permanent. It may be reversible if the duration
of lithium therapy is relatively brief, e.g., two to six years.53 However, it is not
known at what point nephrogenic diabetes insipidus becomes irreversible.56 If
discontinuing treatment with lithium is not possible, a low-sodium diet should
be prescribed, and the potassium-sparing diuretic amiloride, a thiazide
diuretic, an NSAID, or desmopressin can be used.54
Nephrotic syndrome is a rare complication of lithium therapy.57 It is
caused by glomerular injury, and it is characterized by urinary excretion of >
3 g of protein a day, hypoalbuminemia (< 3 g/dL), and peripheral edema.52,54
The mechanism of action by which lithium causes nephrotic syndrome is not
known.57 If nephrotic syndrome occurs, fluid restriction should be started and
if possible, lithium therapy should be discontinued.52,58 In some cases,
corticosteroids were successfully used to treat nephrotic syndrome.52,58
A mild decline in renal functioning of approximately 15-30% is common
in patients on long-term lithium therapy.52,59 Lithium can damage the kidneys,
and long-term lithium therapy has been associated with chronic kidney
disease (CKD) and end-stage renal disease (ESRD).52,56,59-61
The major risk factors for CKD and ESRD include duration of treatment,
the cumulative dose, and repeated episodes of high serum lithium level.52,56,59
Acute lithium intoxication, comorbidities (e.g., diabetes mellitus,
hypertension), and advanced age have also been identified as risk factors.52
The onset of a decline in renal function appears to occur after 10-15 years of
use.60 The latent period between the beginning of lithium therapy and the
onset of ESRD has been reported to be 20-27 years.52,56,60
Fortunately, CKD and ESRD are uncommon complications of lithium
therapy: the prevalence of ESRD in chronic lithium users has typically been
found to be < 1.0%.56,61 ESRD has occasionally been reported to be higher.52
Also, some researchers have questioned the relationship between the drug
and CKD and ESRD. Chang, et al. (2020) wrote that “... older lithium users
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NurseCe4Less.comcommonly have chronic kidney disease (CKD), although rates are not different
compared to community-dwelling non-lithium older patients.”59
Davis, et al. (2018) noted that “... there continues to be evidence which
suggests that lithium may not increase the risk of CKD ... Our analysis
suggests there is no effect of stable lithium maintenance therapy (lithium
levels in therapeutic range) on the rate of change in eGFR over time.”56
Post (2018) questioned whether lithium therapy caused reduction in
eGFR, the author noted that recent literature reviews suggest that decreased
renal function is related to episodes of lithium toxicity.60 Chang, et al. (2020)
wrote that some research had shown no increase in prevalence of ESRD in
patients taking lithium.59
Pregnancy and Breastfeeding
Treating a pregnant patient who has bipolar disorder and takes lithium
is pregnant is a complex clinical challenge, and there are five primary issues
to consider.
Effect of Pregnancy on Bipolar Disorder:
It is not clear if pregnancy decreases or increases increase the risk of
mood disorders or if the disease has no effect on the course of the illness.62,63
A literature review done by Salim, et al. (2018) concluded: “The extant
literature cannot answer the question of how pregnancy affects the course of
bipolar disorder …”63
Continuing Lithium Therapy During Pregnancy:
The decision to continue lithium therapy during pregnancy should be
made on a case-by-case basis. The benefits and risks of doing so must be
carefully considered by the patient and the clinician, and the patient should
be advised of how the disorder will be managed, e.g., frequent monitoring of
serum levels, dosing adjustments.
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NurseCe4Less.comUsing lithium during pregnancy can cause harm to a fetus and/or a
neonate; however, discontinuing lithium therapy or not using lithium may
increase the risk for mood episodes.64,65 Lithium can be safely used during
pregnancy.64 Hendrick (2019) recommended that patients who have moderate
to severe bipolar disorder should be treated with lithium or continue lithium
therapy during pregnancy.65
Risks of Lithium Therapy During Pregnancy:
Lithium therapy during the first trimester has been associated with an
increased risk of spontaneous abortion.66 However, this risk may be disease-
specific and may not be caused by the drug.66 A recently published literature
review by Sharma, et al. (2020) concluded that lithium use during the first
trimester has not been associated with an increased risk for spontaneous
abortion.64
Lithium moves easily and efficiently across the placenta.64 The use of
lithium during the first-trimester pregnancy has been associated with cardiac
abnormalities - Ebstein’s anomaly is the one most often mentioned - and
increased birth weight.64,66,67 Exposure during the second and third trimester
has been associated with lithium toxicity in the infant, premature labor,
polyhydramnios, and neonatal complications of cardiomegaly, gastrointestinal
bleeding, goiter and hypothyroidism, hepatomegaly and jaundice,
hypoglycemia, nephrogenic diabetes insipidus, premature labor, and shock.66-
68
Maternal lithium toxicity has been associated with neonatal cyanosis
hypotonicity, hypothyroidism, neuromuscular abnormalities, lower Apgar
scores, and longer hospital stays and nephrogenic diabetes insipidus.67-69
Lithium does not appear to negatively influence a child’s neurologic
development.67,69 The use of lithium during the first trimester has consistently
been associated with an increased, significant risk for fetal cardiac
malformations.64,66,69,70 The incidence of this complication is not known, but
recently published studies and literature reviews have found that the risk is
not high, lower than the traditionally reported estimates and that the
association is dose-dependent; the higher the dose, the greater the risk.69,70
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NurseCe4Less.comDosing Lithium During Pregnancy:
Because of physiologic changes like increased hepatic and renal activity,
increased glomerular filtration of the drug, and an increased plasma volume
that occur during pregnancy, lithium levels decrease during pregnancy.64,67,69
The decrease can be significant, up to 34%, it is the highest in the third
trimester, and a decrease in serum lithium level has been reported to occur in
up to 62.1% of patients.67 During the second and third trimester, the dose of
lithium may need to be as much as twice the dose used before pregnancy.62
Lithium therapy should be stopped twenty-four to 48 hours before
delivery.66-68 Doing so can help prevent neonatal complications.66-68 After
delivery the dose should be returned to the pre-pregnancy dose.62
Preconception Care and Monitoring During Pregnancy:
With close monitoring, lithium can be safely used for pregnant women.64
Preconception counseling about the risks and benefits of using lithium during
pregnancy should be done several months before becoming pregnant or done
immediately if the patient becomes pregnant and is taking lithium.64 The
lowest effective dose should be used.64 The patient should be monitored for
episodes of depression, hypomania, and mania.62,64
There should be counselling of the patient to stay well hydrated.62 All
pregnant women should abstain from using alcohol, tobacco, and illicit
drugs.64 Counseling about alcohol, tobacco, and illicit drugs is especially
important because many people who have bipolar disorder have a substance
use disorder.3
Screening for fetal cardiac abnormalities should be done at 16-18 weeks
gestation using fetal echocardiography and high-level ultrasonography.62,68
Newborns should be monitored for the presence of lithium toxicity for 10 days
after birth.62
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NurseCe4Less.comBreastfeeding
There are several ways of determining — or in this case, making an
informed decision — if lithium can be safely used during breastfeeding.
Excretion into Breast Milk:
Lithium is excreted into breast milk.1,71,72,73 However, the amount is
highly variable.71 A literature review by Imaz, et al. (2019) found that the
mean concentration of lithium in breast milk was 0.34 mEq/L, the milk to
maternal serum level ratio averaged 0.49,73 and the authors concluded:
1) the amount of lithium excreted into breast milk is low, 2) the mean
concentration of lithium in breast milk and the milk to maternal serum level
ratio cannot be used to determine if a nursing infant will or will not be
adversely affected by lithium in breast milk, and 3) multiple factors determine
the concentration of lithium in breast milk.73
Nursing Infant’s Lithium Level:
The serum lithium level of a nursing infant can be measured directly,
and it can be compared to the mother’ serum level. A literature review by
Newmark, et al. (2019) found that the serum lithium levels of nursing infants
ranged from 0.04 to 0.97 mEq/l and in most cases, the serum level was < 0.6
mEq/L, the lower limit of therapeutic normal for adults.72 Imaz, et al. (2019)
found that the mean serum lithium level in nursing infants was 0.26 mEq/L,
the range was 0.02 to 1.40 mEq/L and in most cases, the level was < 0.3
mEq/L.73
The serum lithium level in nursing infants has been found to be 10-67%
of the maternal serum lithium level with and the average is 32%.71,72 The
infant plasma (I/P) ratio is the infant’s plasma level of a drug divided by the
mother’s plasma level.73 An I/P ratio of 25% unacceptable73 and in their review, Imaz et al. (2019)
found a mean I/P ratio of 0.28% with a range of 0.04 to 2.00.
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NurseCe4Less.comThe Infant’s Dose:
The infant’s dose can be calculated using the relative infant dosage
(RID) formula.74 Infant dose (mg/kg/day) x 100 ÷ maternal dose
(mg/kg/day). The infant dose is calculated, in this case from the concentration
of the drug in breast milk. A RID of 25%
use of the drug is contraindicated.74 Only one study was found that estimated
the RID is ring infants exposed to lithium. Moretti, et al. (2003) reported that
the mean RID was 12.2%, 11 of the 23 infants had a RID of between 10-25%,
and one had a RID > 25%.75
Adverse Effects:
There are many published reports of nursing infants who were exposed
to lithium and who did not develop adverse effects.71 The review by Newmark,
et al. (2019) located 32 cases of neonatal lithium exposure and adverse effects
occurred in three (9.4%).72 Two infants had feeding problems which were
temporary and one had cyanosis, hypotonia, lethargy, and poor feeding.76,77
There was one child who had an increased TSH (temporary) and two cases of
increased BUN and or serum creatinine.72
The use of lithium during breastfeeding has been discouraged in past.1
Some clinicians believe that with the proper precautions, it can be used safely
during nursing.71 Research is limited on this topic.72,73,78 The published
information is from small, short-term studies, case reports, and case series
and the quality of the research has been characterized as low to moderate.73
Most of the adverse effects have been minor and temporary, but the number
of reported cases of infant lithium exposure during nursing is so small that it
is not possible to know what adverse effects may occur and to whom.78 Also,
the adverse effects that have been reported may have been caused by the
infant’s health, other medications that mother was taking, or due to lithium
exposure during gestation.72
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NurseCe4Less.comAside from the I/P ratio, the RID, the maternal dose, the excretion of
lithium into breast milk, how much lithium a nursing infant is exposed to, and
how the infant will be affected depends on many factors, may include: 1) an
infant’s ability to metabolize and eliminate lithium, 2) how much milk was
removed from the breast during a previous feeding, 3) when the dose of
lithium was last taken in relation to feeding, 4) how much milk the child
consumes during a feeding, 5) oral bioavailability, and 6) infant’s age.73,79
The decision to continue or stop lithium therapy during breastfeeding
should be done after considering the risks and benefits of either approach. It
must be presumed that someone taking lithium is deriving a benefit, and there
are risks to the pregnant woman if she stops taking it. The benefits to an
infant of breastfeeding are considerable and well-established.73 It appears that
the risks from lithium in breast milk are small but it is not possible to know
what the risks are or to whom and how often they may occur.
When continuing or stopping the use of lithium during breastfeeding,
the only reasonable approach is a case-by-case assessment.73 If lithium
therapy is to be continued, careful monitoring of the mother and the infant
needs to be done.
Lithium overdose is usefully divided into two categories: 1) acute and
2) acute-on-chronic.80 An acute poisoning occurs when a lithium-naïve patient
takes an overdose of lithium; acute-on-chronic occurs when a patient who has
been taking lithium ingests an excessive amount. An acute-on-chronic
overdose is potentially more serious because the acute ingestion adds to the
pre-existing CNS tissue drug level.80
Lithium Overdose
Lithium overdose is characterized by gastrointestinal and neurologic
signs and symptoms.24,27 Nausea, vomiting and diarrhea are common after an
acute overdose.24 Neurologic signs in acute and acute-on-chronic overdose
are common and may include ataxia (a lack of muscle control), CNS
depression (mild to severe), lethargy, myoclonic jerks, slurred speech, and
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NurseCe4Less.comtremor.24,27 In severe overdose, coma convulsions, and encephalopathy can
occur.24,27 Significant neurologic complications, e.g., serious cerebellar and
cognitive dysfunction, may have a delayed onset, they can persist for weeks,
months, and years and occasionally, they are irreversible and
permanent.24,27,80 The latter is a condition referred to as syndrome of
irreversible lithium effectuated neurotoxicity, otherwise known as SILENT.24,27
Initial treatment of a lithium overdose should include assessment and
stabilization of the patient’s airway, breathing, and circulation. Serum BUN
and creatinine, electrolytes, thyroid function studies, and acetaminophen,
salicylate, and lithium level should be measured, and a 12-lead ECG should
be done.24,27
The inside surface of some phlebotomy tubes is coated with lithiated
heparin. Using these tubes in patients with lithium overdose, or suspected
lithium overdose, can result in a falsely elevated serum lithium level.24
Clinicians must make sure the tubes are not coated with lithiated heparin.24
A pregnancy test should be done if the patient is a female of child-
bearing age.24 The clinician should find out how much the patient took and
when, consider the possibility of a co-ingestant, and review the patient’s past
medical history. it is also important to know what prescription medications the
patient takes and if renal impairment exists.
Lithium is not adsorbed by activated charcoal. If the patient is awake,
has a normal gag reflex and a functioning gastrointestinal tract, whole bowel
irrigation (WBI) with a polyethylene glycol solution can be used to
mechanically flush any remaining lithium out of the gut.24,27 There is no
antidote for lithium poisoning.80 Patients should be treated with symptomatic,
supportive care, IV hydration and if needed, hemodialysis.24,27 After an
overdose, the peak serum lithium level can be delayed for up to 12 hours or
longer. After the initial measurement, lithium levels should be done every two
to four hours; this is done to determine the trend and to determine if hydration
therapy is being effective.24
28
NurseCe4Less.comIf the patient is symptomatic or has a measurable lithium level,
intravenous (IV) hydration with 0.9% normal saline solution at twice the
calculated maintenance fluid rate should be started.24 Isotonic saline increases
renal excretion of lithium and hydration itself will help prevent retention of
lithium. An acute lithium ingestion does not cause renal damage, but chronic
lithium therapy can and chronic lithium therapy can also cause nephrogenic
diabetes insipidus. Patients who have taken an acute-on-chronic overdose are
being given isotonic saline hydration are at risk for hypernatremia so in these
patients, serum sodium should be closely monitored.24,27
Hemodialysis is effective at removing lithium.24 The primary indications
for hemodialysis are for patients with serious neurologic complications
(regardless of the serum level), e.g., coma, seizures; and for patients with
impaired renal function, e.g., a patient who is anuric and cannot eliminate
lithium in the urine.24,27 Hemodialysis may also be recommended for any
patient if the serum level is > 5.0 mEq/L; in patients whose lithium level is >
4.0 mEq/L and who have a serum creatinine > 2.0 mg/dL; and in patients who
have a high serum level and cannot tolerate vigorous IV hydration.24
A measurable serum lithium level confirms the ingestion of the drug,
but the level is just one of the factors used to decide if a patient should be
dialyzed and interpreting the significance of the level must be done with the
following points in mind.
● When was the level done? Lithium levels rise and then fall as the drug
moves into the CNS tissue and this can be a lengthy process.24
● Acute ingestion versus acute-on-chronic ingestion is important to ascertain
because of (probable) lithium saturation of the CNS tissues in an acute-
on-chronic ingestion; any abnormally high lithium level in these patients
likely indicates a greater risk for harm.24
● There is a poor correlation between lithium levels and clinical
presentation.24 A patient with a high level may not be seriously ill, but
severe toxicity has occurred in patients whose lithium level is in the
therapeutic range.81
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NurseCe4Less.com● The lithium level cannot predict which patients will develop serious
complications.24
There are no universally accepted guidelines for using hemodialysis as
a treatment for lithium overdose. The published recommendations indicate
that the decision on whether to use hemodialysis is based on clinical
experience and expert opinions:27 the decision to use hemodialysis should be
made based on the type of ingestion, the patient’s renal function, the clinical
presentation, and the lithium level.27 The importance of each factor and its
usefulness as a guide for prescribing hemodialysis must be determined by the
bedside clinician.27
The movement of lithium between the intracellular and extracellular
spaces is slow and after hemodialysis, the level may decrease and then
increase.80 A lithium level should be measured approximately six hours after
hemodialysis has been finished and clinicians should be prepared to re-dialyze
the patient if needed.80
Lithium and Sleep
Bipolar disorder is known to be associated with altered circadian rhythm
and insomnia. Yin and colleagues (2006) noted that lithium was a “potent
inhibitor of glycogen synthase kinase 3 (GSK3), which regulates circadian
rhythm in several organisms.”81 The authors discussed how lithium works at
the cellular level to target the biological clock.
Coyle (2007) discussed the effect of lithium in the animal model to
lengthen the circadian cycle and explained that the “effective treatment of
bipolar disorder must address two issues: the management of the presenting
mood disturbance and the prevention of the recurrence of subsequent
episodes… GSK3β may serve as the bridge between the mood-normalizing
effects of the mood stabilizers and their ability to attenuate subsequent mood
cycling in bipolar disorder… In the mouse, GSK3β is expressed in the
suprachiasmatic nucleus and liver where its phosphorylation exhibits robust
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NurseCe4Less.comcircadian oscillations.”81 Coyle suggested a novel off-label approach to the use
of lithium to inhibit GSK3 phosphorylation and to prolong the circadian cycle.81
Lithium and Aggression
Four studies were discussed in a Canadian review of lithium efficacy in
aggressive youth with comorbid drug use and attention deficit hyperactivity
disorder (ADHD) where lithium with placebo to treat aggression in hospitalized
youth was conducted. There were 184 children enrolled as participants in the
research and the majority were male.82
Study trials were conducted between 2 to 6 weeks. One study reported
no difference in behaviors in youth with chemical dependency that were taking
lithium and placebo whereas a significant difference was found between
lithium and placebo on all behavioural measures studied.82 Other studies
reported a mix of significant and nonsignificant results on multiple behavioural
outcomes. Three studies with data that could be incorporated into a meta-
analysis showed that treatment with lithium was associated with a higher odds
of response or remission than placebo.82
While the evidence for lithium is inconsistent in the research, the general
consensus in psychiatry is that it can show benefit in combination with other
medication targeting symptoms of anxiety, mood disorder, mixed states, and
hostility, aggression or violence in mood dysregulated patients in general.82
Case Studies: Lithium
The following two case studies are examples of the use of lithium in
varied age groups, the benefit of combining lithium with other medication to
control mood dysregulation, and the potential risks of lithium use, such as in
elderly patients.83,84
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NurseCe4Less.comCase Study 1: Aggression and Self-harming
A 22-year-old male was admitted to a neurosurgery unit after an anger
outburst during which he exhibited an automatic masticatory-like movement.
The patient reportedly had no prior history of neurologic or psychiatric
illness.83
The patient transferred to the neurology unit for further examination
and was diagnosed with seronegative limbic encephalitis, based on laboratory
findings and brain imaging. He had primary symptoms of serious aggression
and anger outbursts.83 For medical and psychiatric safety, the patient was
kept in a secluded, quiet room and administered valproate 800 mg/d,
levopromazine [promethazine] 75 mg/d, and risperidone 4 mg/d.83
The patient continued to show aggressive behaviors despite increases
of valproate to 1,200 mg/d (96.5 µg/mL) and levomepromazine to 250 mg/d,
and the patient’s serious aggression and anger outbursts persisted to the point
of aggressing against medical staff and self-harming behaviors of beating on
himself. Eventually, carbamazepine 500 mg/d (7.8 µg/mL) was combined,
however, the patient’s symptoms were partially remitted. After lithium 1,000
mg/d (0.98 mEq/L) was added the patient’s serious aggression and anger
outbursts reportedly showed a significant decrease, and he was moved out of
seclusion. He was reported to communicate with medical staff in a polite
manner.83
Once a level of stability was achieved, valproate, risperidone, and
levomepromazine were able to be tapered to discontinue without exacerbation
of the aggressive behavior. The patient was reportedly able to joke with
medical staff while smiling. Collateral information from family and friends
indicated the patient had returned to his premorbid state. The patient
eventually discharged on combination lithium 800 mg/d (0.71 mEq/L) and
carbamazepine 600 mg/d of (7.4 µg/mL) and was followed up 3 months after
hospital discharge as stable and employed, as well as showing good family
and social relationships.83
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