Bipolar Disorder

Question 1

Drugs used to treat bipolar disorder

Answer 1

Atypical antipsychotic agents
Oxcarbazepine
Lamotrigine
Lithium 
Valproic Acid

Question 2

Adverse effects: Oxcarbazepine

Answer 2

o	Anti-seizure agent
o	Na+ channel blocker
o	Adverse effects: similar to carbazepine (diplopia, cognitive dysfunction, drowsiness, ataxia; rare sever blood dyscrasias and Stevens-Johnson syndrome; teratogenic) 
o	Hyponatremia more common 
o	Does not induce drug metabolism

Question 3

Adverse effects: Lamotrigine

Answer 3

o Anti-seizure agent
o Delays time to occurrence of mood disorders in stabilized patients
o Clinical findings are more robust for depression
o Adverse effects: dizziness, ataxia, nausea, rash, rare Stevens-Johnson syndrome

Question 4

Adverse effects: Valproic acid

Answer 4

o Anti-seizure agent
o Increases GABA function
o Adverse effects: drowsiness, nausea, tremor, hair loss, weight gain, hepatoxocity in infants, inhibition of hepatic drug metabolism

Question 5

Describe the adverse effects associated with lithium therapy

Answer 5

Adverse reactions (frequent [75%] and can occur at therapeutic concentrations)
o CNS: fine tremor, ↓ libido, anorexia, drowsiness, confusion
o CV: ECG abnormalities, bradycardia
o GI: xerostomia, altered sense of taste, NVD; reduced if taken with food
o UG: polyuria (with polydipsia; disappears after a few weeks)
o ↓ Thyroid function → goiter (4%)
o Edema, weight gain (30%)
o Leukocytosis

Precautions
o Narrow therapeutic window; monitoring of serum levels is essential
o Renal insufficiency or diuretic drugs
o Pregnancy Risk Category D

Question 6

List important drug-drug interactions involving lithium.

Answer 6

Drug interactions that increase lithium concentration:
o	Dehydration
o	Thiazides
o	NSAIDs
o	ACE-Is
o	Loop diuretics 

Note: caffeine and theophylline increase renal Lithium clearance

Question 7

Lithium: MOA

Answer 7

MOA = complex
o Affects 6 different enzymes involved in:
• Phosphatase enzymes → IP3 substrate depletion → 2nd messenger disruption
• AMP production
• GNG
• Glycogenolysis
• GSK3 = inhibits axonal growth and synaptic remodeling