Carbamazepine
Tegretol
Package Insert

200 mg tablets; 100mg Chewable Tablets; Liquid (syrup) 100mg/5ml; Carbatrol XR Sprinkles 200, 300 mg capsules
D

Rapid dose increase: N/V, slurred speech, dizzy/drowsy, ataxia.  
Dose related:  ↑ LFT , sedation, ↓ WBC (agranulocytosis),ataxia, cognitive slowing.
Less dose related: tremor, cardiac conduction delay, SIADH ↓ Na+, ↓ T3/T4 Idiosyncratic: rash, hepatitis, aplastic anemia, decreased platelets    

WEIGHT GAIN = minimal

✓ CBC, BMP, LFT

✓ trough (prior to AM dose) level after 5d at steady dosage

ECG in pts >45yrs

No Ψ indications

Ø  Bipolar Mania, Impulse-Control D/O, PTSD, EtOH/benzo withdrawal

CI =hepatic disease 4-12 μg/ml

T1/2 = 25-65°; due to autoinduction it falls to 12-17° with repeated dosing, plateaus in 3-5 weeks. Peak levels in 4-5°
Hepatically metabolized CYP 3A4   PUBMED

CYP 450 3A4 inhibitors (↑ levels)  fluoxetine, fluvoxamine, nefazodone, trazodone, olanzapine, quetiapine, omeprazole, ibuprofen


CYP  3A4 inducers (↓  levels)   phenobarbital, phenytoin, theophylline

Tegretol increases Depakote levels

Initial  ( inpatient) 200 mg BID, ↑ by 200 mg/d; usual therapeutic range 400-1600mg/d (avg1000mg/d)

(outpt)↑ more slowly, 200mg q2-7d


Max   1800mg/d 		Blocks NE reuptake, ↓ NE release, ↓ DA and GABA turnover, blocks Ca influx, inhibits kindling

Divalproex Sodium
Depakote ER
Package Insert

250, 500 mg tabletsD
Common nausea, asymptomatic LAE ↑, prolonged menstrual cycles, amenorrhea, sedation, lethargy, tremor, hair loss, change in hair color or texture

Serious Hepatotoxicity (hepatic failure 1:10,000), pancreatitis, thrombocytopenia

WEIGHT GAIN = ++

✓ CBC, LFT, amylase/ lipase

✓  trough (prior to AM dose) level after 5d at steady dosage

Bipolar disorder, acute mania

Ø Schizoaffective D/O bipolar  type; adjunctive tx of schizophrenia, aggression, Cyclothymia at very low doses (125-500mg/day)

CI  =hepatic dz
85-125 ug/ml

T1/2 = 6-16°; Hepatically metabolized; nonspecifically inhibits P450 metabolism
• In children under 2 years, metabolites cause hepatic impairment.
• Salicylates increase valproic acid level
• Lamotrigine level is doubled by valproic acid
 • SSRIs and valproic acid mutually increase their levels
• Rifampin and anticonvulsants may increase valproate levels

Mood stabilization in 5-15 days

Initial  250-500 mg/d; ↑ to 750-1000 mg/d over 3-6 day. The usual dose is 1200-1500mg/d or can load with 25mg/kg/d for pts in acute mania

Max 60mg/kg/d		 ↑ GABA, inhibits GABA metabolism, ↑ GABAB receptor density

Lamotrigine
Lamictal
Package Insert

Tablets of 25, 100, 150, 200 mg; Chewable / dispersible tablets of 2, 5, 25 mgC

Common  diplopia, ataxia (at higher doses), blurred vision, dizziness, nausea, and vomiting.

Rare:  Stevens-Johnson syndrome (~0.1%), benign rash (discontinue immediately)

WEIGHT GAIN = neutral

✓ CBC, LFT

Bipolar I Maintenance

Ø  Bipolar II, schizoaffective disorder, borderline personality disorder, PTSD, and as adjunctive therapy for "treatment-resistant" unipolar depression

T1/2 = 15°; metabolized predominantly by glucuronic acid conjugation, 10% renally excreted unchanged
• Depakote roughly doubles the concentration of Lamictal
• Tegretol decreases Lamictal concentration by roughly 40%.

Initial   25mg/d wks 1&2, 50mg/d wks 3&4, 100mg/d wk 5, 200mg/d wk 6. Usual dose 200–400 mg/d.

Max 400mg/d
Discontinuation ↓ dose over at least 2 wks

Decreases Na+ channel activity Prolongs Na+ channel inactivation
Inhibits N- and P-type Ca2+ channels

Lithium
Lithobid
Package Insert

Eskalith capsule - 300 mg
Eskalith CR tablets - 450 mg
Lithobid SR tablets - 300 mg
Lithium Carbonate capsules 150,D 300, 600 mg, tablets - 300 mg

Common  polyuria, polydipsia, weight gain, cognitive problems, tremor, sedation, impaired coordination, GI distress, hair loss, benign leukocytosis, acne, and edema.
Level 1.5-2mmol/l: drowsy, ataxia, slurred speech, hypertonicity, tremor dose related, Tx=Inderal
Level >2mmol/l: arrhythmias, ↓ HR, myocarditis, seizures, coma, death

WEIGHT GAIN = + (25-60% average weight gain 16.5lbs)

✓ Li level (12° after last dose) after 5d at steady dosage  (initially & after each dose ∆, Q WK x 3-4 wks, then Q 1-6mos)

✓ BUN/Cr, CBC & TSH initially & Q6-12mos

✓ ß-HCG(♀)

✓ ECG if >40 or cardiac hx (flattened or inverted T-waves common)

Bipolar disorder  maintenance, acute mania
Ø  Cyclothymia, mania in schizoaffective D/O, MDD augmentation, ↓ violent behavior, ↓ suicide

Acute Mania
1.0-1.5 mEq/L

Maintenance
0.6-1.2 mEq/L

T1/2 = 24°, steady state in 5 days, peak level in 1-2° with regular formulation; 4°in slow release forms

 Renally excreted

Thiazides ↑ Li levels by 30 –50%.
NSAIDs, ACE inhibitors can also ↑ Li level
↓ Na+ can ↑ Li level (kidneys confuse Li for Na and hold onto Li) Coffee and theophylline ↓ Li level

Lithobid SR

Initial 300mg BID-TID

Acute Mania   optimal level  1-1.5 mEq/L, usually achieved 1800 mg/day

Maintenance  0.6-1.2 mEq/L, usually achieved with  900-1200 mg/day.

Discontinuation  ↓ dose over at least 2 wks

Modifies second messenger system:
Inhibits IMP → ↑ inositol phosphate → ↓ PIP2 → membrane-stabilization → ↓ neuron response to synaptic input

Topiramate
Topamax
Package insert

Tablets of 25, 100, and 200 mg; Sprinkle capsules of 15 and 25 mg.C

Common cognitive dulling, confusion and memory problems, somnolence, dizziness, ataxia, nystagmus, paresthesias, anorexia
Less Common  renal calculi (1.5%), non-gap metabolic acidosis, Acute Myopia and Secondary Angle Closure Glaucoma

WEIGHT GAIN = neutral / loss (dose-related)		 ✓  serum bicarb, BUN/Cr

No Ψ indications

Ø    Bipolar D/O, MDD, eating D/O, sleeping D/O, PTSD, cluster HA

T1/2= 21°, 70-80% renal elimination (give ½ dose if renal impaired)

Carbamazepine & phenytoin ↓ levels ~40% , valproate ↓ levels ~15%

↓ effectiveness of oral contraceptives

Initial   50 mg/d; ↑ to 400 mg/day in divided doses over 8 weeks (to minimize SE)

Max   200mg BID

Discontinuation gradually		 Potentiates inhibitory effects of GABA (acting at a site different from BDZs and BARBs), blocks Na+ channels

Gabapentin
Neurontin
Package Insert

Capsules of 100, 300, 400 mg; Tablets of 600, 800 mg; and Solution 250 mg/5mlC

Common somnolence, dizziness, ataxia, fatigue, blurred vision, tremor, rash
Uncommon ↓ WBC

 WEIGHT GAIN = +

(dose-related, gain 16 lbs)

None

✓ BUN/Cr if suspect renal impairment (renal dosing)

No Ψ indications

Ø    Bipolar D/O, anxiolytic, neuropathic pain

T1/2 = 5-7°, peaks in 2-3°, reaches steady state in 1-2 days, high lipid solubility, is not metabolized by the liver (100% renal elimination), has no protein binding

Initial 300 mg a day, then 300 mg BID on 2nd day, then 300mg TID on 3rd day.
Usual dose 900-1500 mg/d for mood disorders.

Max ≥ 3600mg/d

Analog of GABA that does not act on GABA receptors, ↑ GABA activity