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NOTES

LITHIUM

CLINICAL RESPONSE
Patients presenting
with mania generally show
at least partial response to
lithium within the first 2
weeks of therapy
For patients presenting
with depression, the
timeframe is considerably
longer. It would be 4-6 weeks
to see the response.

INDICATION

Drug of choice for the


treatment and prevention of
bipolar disorder
Lithium carbonate and
citrate are the two clinically
relevant salt forms
Lithium carbonate
Lithium citrate is available
as liquid and helpful in
patients who are
noncompliant with tablets or
capsules
Indications:
As prophylaxis in
preventing both mania and
depression

ADMINISTRATION & DOSAGE


Daily dose: 600-3600mg
among different individuals
Majority requires: 15001800 mg/d
Almost always necessary to
give Lithium in divided doses
to avoid gastric distress when
initiating treatment
Medication is best taken
with or shortly after meals
Maintenance Therapy:
Patients who have one or
more episodes of illness per
year are candidates for
maintenance treatment

MOA
1. Effects on
neurotransmitters
Inhibit NE release and
accelerate its metabolism
May increase presynaptic
re-uptake of NE and 5-HT
2. Effect on second
messengers and G
proteins:
Inhibits conversion of IP to
inositol
leads to depletion of PIP2
PIP2 IP3 and DAG
For both a-adrenergic and
muscarinic transmission

Adjunct to TCAs & SSRIs


in patients who do not
respond fully to
antidepressants alone
Schizoaffective disorders
Schizophrenic symptoms
plus altered effects in the
form of depression and
excitement
should be in combination
with antipsychotics
Lithium alone is rarely
successful in treating
schizophrenia

Effect on G-proteins
involved in receptor
desensitization, in
modulating membrane
structure events, in
regulating transcription, in
mediating immune
responses, in regulating cell
growth, and in learning,
mood and memory

Bipolar Disorder:
Mild Mania:
Lithium alone is effective
Carbamazepine is useful
when manic episodes are not
controlled by lithium alone
Severe mania
Always add clonazepam /
lorazepam and often give one
of the anti-psychotic drugs
Depression
Requires concurrent use of
antidepressants

ADVERSE EFFECTS
Neurologic and Psychiatric
Tremor
Choreoathetosis, ataxia,
dysarthria, motor
hyperactivity, aphasia
Psychiatric disturbances
(confusion)
Thyroid function
Decreased thyroid activity
(hypothyroidism)

DRUG-DRUG INTERACTIONS
Decrease Lithium conc:
Methylxanthines
Osmotic Diuretics
Pregnancy (3rd trimester)
Urine alkalinizers
Increase Lithium conc:
ACE inhibitor
NSAIDs
Thiazides
Dehydration
Postpartum

Renal
Polyuria, polydipsia
reversible
Lithium-induced diabetes
insipidus
Treatment: amiloride
Long term renal dysfunction:
Chronic interstitial nephritis
Minimal change
glomerulopathy

Pregnancy
Lithium is transferred to
nursing infants through
breastmilk
Lithium toxicity in newborn:
lethargy, cyanosis, poor suck,
hepatomegaly
Increase in frequency of
cardiac anomalies (Ebsteins
anomaly)

Miscellaneous:
Acneiform eruptions
Folliculitis
Leukocytosis
OVERDOSE
Therapeutic overdose is
more common than
accidental ingestion due to
accumulation of lithium (eg.
use of diuretics , NSAIDs)
Any value over 2 mEq/L
must be considered as
indicating potential toxicity.
Normal Lithium serum
concentration:
0.6 1.4mEq/L

VALPROIC ACID
An anticonvulsant that is

Mechanism is unknown

DOSE-RELATED SIDE

Drugs known to increase VPA