2.

4-03
August 27, 2013
Angeline D. Alabastro, M.D. CNS Pharmacology III:
"One of things so bad about depression and bipolar disorder is that if you don't have Mood Stabilizers
prior awareness, you don't have any idea what hit you." – Kay Redfield Jamison

TRANSMASTER'S NOTE LITHIUM (ESKALITH, LITHOBID)

This is a lecture-based trans.  Classic mood stabilizer
 Narrow therapeutic range
OVERVIEW OF BIPOLAR DISORDER  Increased risk of adverse events and toxicity
 Increased risk of relapse
SYMPTOM DOMAINS  Onset of action is usually between 7-10 days
1. Mania  Significant long-term risk of hypothyroidism, which is
a. Euphoria treatable
b. Grandiosity  Many medications interact adversely
c. Pressured speech  Discontinuation should be achieved over 2-3 months, and
d. Impulsivity not before 4 weeks if possible
e. Excessive libido
f. Recklessness PHARMACOKINETICS
g. Diminished need for sleep
2. Depression
a. Depression
b. Anxiety
c. Irritability
d. Hostility
e. Violence or suicide
3. Psychosis
a. Delusions
b. Hallucinations
c. Sensory hyperactivity
4. Cognition
a. Racing thoughts
b. Distractibility
c. Poor insight
d. Disorganization
e. Inattentiveness
f. Confusion

ACTIONS OF LITHIUM ON ENZYMES

MOOD STABILIZERS
1. Lithium
2. Anticonvulsants
a. Carbamazepine
b. Valproic acid
c. Lamotrigine
3. Antipsychotics

GENERAL

PHARMACODYNAMICS
 Lithium
o Suppresses inositol
o Inhibits glycogen synthase kinase-3 (GSK-3)
 Carbamazepine
o Inositol inhibition
 Valproic acid
o Inositol and GSK-3 inhibition

PHARMACOKINETICS

DRUG DISTRIBUTION METABOLISM ELIMINATION

No PB kidneys, Renal
Lithium None
thyroid 18-20 hours
Hepatic,
CBZ Complete autoinducer, 15-28 hours
10, 11 epoxide CLINICAL USES
Hepatic  Bipolar affective disorder
VPA Rapid in CNS inhibitor or 8-17 hours o Especially manic phase
inducer o Success rate low among hospitalized
o Combination treatment used in severe cases

Martin, Cla Page 1 of 2

 CNS Pharmacology III: Mood Stablizers

o Depressive phase treated with anti-depressants  Blood dyscrasias not prominent

o No autonomic blocking effects
o Prophylactic use can prevent both mania and VALPROIC ACID
depression *Refer to 02.01-04 Antiepileptics
 Recurrent endogenous depression  Anti-manic effect
 Schizoaffective disorder  Efficacy equivalent to lithium in early stages of treatment
 Unipolar depression not responsive to antidepressants  Can rapidly increase dose over a few days
 Appropriate as first-step treatment
ADVERSE EFFECTS  Maintenance drug
 Used in conjunction with lithium
ORGAN SYSTEM CLINICAL COMMENTS
PRESENTATION
Cardiovascular ECG changes  T wave
suppression,
delayed or
irregular
rhythm,
increase in PVC
 Sick sinus node
syndrome
 Myocarditis
Dermatologic Acne  Worsens
Psoriasis  Treatment-
refractory
worsening
Rashes  Maculopapular
and follicular
Endocrine Hypothyroid state  5% goiter, 4%
clinically
significant
hypothyroidism
Hyperparathyroid  Clinically
state nonsignificant
Fetus Tricuspid valve  Ebstein anomaly
(teratogenic) malformation

Atrial septal defect

Gastrointestinal Anorexia  Usually early in
Nausea (10-30%) the treatmrnt
Vomiting and transient
Diarrhea (5-20%) may be the
early sign of
toxicity
 Slow release
preparations
may help
Hematological Granulocytosis  Maybe useful in
disorders such
as Felty’s
syndrome,
iatrogenic
neutropenia,
may counter
CBZ-induced
leukemia
Neurological Cognitive tremors
Renal Polyuria-  May be an
polydypsia indication of
(nephrogenic morphologic
diabetes insipidus) changes
 Requires
adequate
hydration

CARBAMAZEPINE
*Refer to 02.01-04 Antiepileptics
 Reasonable alternative to lithium
 Treatment and prophylaxis
 Given alone or in combination with lithium

Martin, Cla Page 2 of 2