Bipolar I: mix phases of manic-depressive, alternating with major depression

Bipolar II: depressive episodes are more frequent and intense than manic

 

Acute mania

• Mood stabilizer + BZD + antidepressants
• CCB (verapamil) occasionally used for mood stabilizing.

 

Valproate/valproic acid (Depakene, Stavzor), divalproex (Depakote)

• BBW: hepatic failure, teratogenicity (neural tube defects - spina bifida), pancreatitis
• SE: sedation, tremor, weight gain, thrombocytopenia, GI, alopecia (treat w/ selenium and zinc).
• Increase level of amitriptyline, CBZ, lamotrigine, paroxetine, phenobarbital, warfarin, zidovudine
• Avoid combination of valproate and lamotrigine (risk of serious rash), slow titration
• Salicylates may displace valproic acid from protein binding site, leading to toxicity, valproate may also displace phenytoin from albumin
• Do not break capsule, depakene capsule contains liquid irritating to mouth and throat

 

Carbamazepine (Tegretol, Carbatrol)

• Potent inducer and autoinducer, 3A4 substrate.
• Therapeutic range: 6-12 mcg/mL
• BBW: serious skin reaction (Asian ancestry must test HLA-B 1502, if positive, cannot use), aplastic anemia, agranulocytosis
• Rare SE: hepatotoxicity, lupus-like syndrome, SIADH/low Na level (think about the MOA of most epileptic drugs target Na+ channel)

 

Lamotrigine (Lamictal)

• BBW: serious skin reaction, increased risk with higher dose (slow titration to decrease risk of rash, in severe form can be Steven-Johnson syndrome)
• Increased risk aseptic meningitis
• Increased level by valproic acid
• Decreased level by strong inducer

 

Lithium (Lithobid, Eskalith)

• Avoid in renal impairment (Li is 100% renally cleared, kidney can't distinguish between Li and Na)
• GI upset, cognitive effects, cogwheel rigidity, hand tremor, weight gain, hypothyroidism
• Therapeutic range: 0.6 - 1.2 mEq/L
• Li toxicity: hand tremor, vomit, diarrhea, confusion, ataxia (CNS depression effects similar to alcohol), arrhythmia, SZ, brain damage.
• Increased level: decreased salt intake, NSAID (ibuprofen, worsened renal function), ACEI (hypo-Na), ARB, diuretics (thiazide), dehydration (loss of Na), metronidazole
• Decreased level: increase salt intake, caffeine, theophylline
• Increased 5HT syndrome with: SSRI/SNRI, TCA, triptans, linezolid, etc.
• Increased neurotoxicity risk (ataxia, tremor, nausea): verapamil, diltiazem, phenytoin, carbamazepine.

 

Antipsychotics approved for bipolar

• Aripiprazole, chlorpromazine, olanzapine (olanzapine/fluoxetine), risperidone, quetiapine, ziprasidone

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