1Lithium starting dose
IR: 300mg TID
ER: 450mg BID
2Lithium target blood levels
Acute mania: 0.8-1.2 mEq/L
Maintenance: 0.6-1.0 mEq/L
3Lithium CYP450 metabolism
None (renally excreted)
4Lithium onset of action
Mania: 6-10 days (full resolution may take up to 3 weeks)
Depression: ~ 1 month for maximal improvement
5Lithium warnings
Boxed warning: Lithium toxicity
Decreased renal ability to concentrate urine, nephrogenic diabetes insipidus (NDI)
Caution in patients with significant fluid loss
Avoid medications that significantly alter lithium concentration
Increased risk of fetal malformations, cardiac abnormalities (Ebstein’s anomaly)
6Nephrogenic Diabetes Insipidus treatment
Discontinue lithium if possible
If need to continue may consider amiloride
7Lithium toxcitity early presentation
Fine hand tremor, polyuria, mild thirst
8mild to moderate lithium toxicity
1.5-2.0 mEq/L
Diarrhea, vomiting, drowsiness, muscle weakness, decreased coordination
9moderate to severe lithium toxicity
2.0-2.5 mEq/L
Ataxia, blurred vision, tinnitus, EKG changes (t-wave flattening, heart block, arrhythmias)
10severe lithium toxicity
>3.0mEq/L
Neurological changes, coma
11Lithium toxicity treatment
Hemodialysis is effective in removing lithium
Significant decrease in concentration after one session however may have rebound effect
Recommended when:
• Level > 4.0 mEq/L
• Level > 2.5 mEq/L with serious cardiac/neurologic symptoms
12Drugs that increase lithium levels
NSAIDs
ACEIs/ARBs
Thiazide diuretics
Loop diuretics
Reduced sodium intake
13drugs that decrease lithium levels
Theophylline
Verapamil
Osmotic diuretics
caffeine
Sodium, sodium bicarbonate antacids
14Lithium in pregnancy?
Category D, fetal risk occurs, ebstein's anomaly
15VPA starting dose
Loading:
IR: 30 mg/kg x 2 days or, ER: 25mg/kg x 2 days THEN IR: 20mg/kg ER: 25 mg/kg
Titration: 500 or 750 mg qhs
16VPA target blood levels
50-125 mcg/mL (>70-90 mcg/mL preferred)
17VPA CYP450 metabolism
CYP2C19, Glucuronidation, oxidation
18VPA drug interactions
VPA increases the level of lamotrigine, warfarin
VPA levels are decreased by carbapenems, ritonavir
19VPA warnings
Boxed warnings:
Hepatic failure
Pancreatitis
Teratogenic effects, neural tube defects and decreased IQ
Dose-related thrombocytopenia
Hyperammonemia/encephalopathy
Hypothermia
DRESS
20VPA pregnancy
Pregnancy category D, neural tube defects
21Lamotrigine starting dose
25mg daily
22Lamotrigine onset of action
delayed due to slow titration
23lamotrigine warnings
Boxed warning: Life-threatening rash (SJS, TEN)
DRESS
Others: Blood dyscrasias, aseptic meningitis
24Lamotrigine CYP450 metabolism
None
25Lamotrigine drug-drug interactions
Estrogen containing products increase lamotrigine levels by up to 50%
VPA increases levels of lamotrigine
26Lamotrigine pregnancy?
Class C drug, can cause neural tube defects but at a lower rate than VPA
27CBZ starting dose
200mg BID
28CBZ CYP450 metabolism
Induces CYP3A4 and CYP1A2
29CBZ warnings
Boxed warnings:
Fatal hypersensitivity reactions: DRESS, SJS, TEN (25-30% risk of also having reaction to oxcarbazepine)
Anemia and agranulocytosis
Avoid in patients with history of hepatic
porphyria
Increased risk of suicidality
Teratogenicity
Potential for withdrawal seizures after abrupt discontinuation
Hyponatremia
Patients of asian decent must have testing done for the presence of HLA-B*1502, found almost exclusively in this population and has a 10x risk of developing SJS/TENS
30CBZ onset of action
~7 days in mania