Mood Stabilizers

• Lithium
  • Reduces suicide risk, takes 2-3 weeks to work
    • Spas have a high content of lithium
    • Works better in Euphoric Bipolar Disorder
    • 9x higher risk for suicide when coming off of
  • CI: CKD, HD, Hyponatremia, diuretics
  • Baseline: BUN, Cr, Calcium, Urinalysis, TSH, EKG if coronary risk
  • Therapeutic level: Lithium (0.6-1.2)
  • SE:
    • Hypothyroidism (add levothyroxine rather than stopping)
    • Benign Leukocytosis
    • Acute (GI)
      • Tremor, ataxia, weakness, polyuria, vomiting, diarrhea
      • AMS, Seizures, fasciculations, tremor
    • Chronic (Neuro)
      • Nephrogenic DI (MCC of), CKD, Thyroid dysfunction, Hyperparathyroidism: Polyuria in 50-70%
      • Hypercalcemia (QT shortening)
      • Treat with hemodialysis
  • Lithium Toxicity
    • ≥1.5 mEq/L: coarse tremor, tremulousness, confusion, arrhythmia, ataxia, nausea, diarrhea, nystagmus, hyperreflexia, dysarthria, dystonia
      • Fine Tremor – treat with propranolol
      • Hypothyroid – treat with levothyroxine
      • Nephrogenic Diabetes Insipidus (hypernatremia)
        • Amiloride < stopping
    • ≥2.5 mEq/L: Seizures, coma
      • With signs of toxicity
        • Direct nephrotoxicity – renal tubular acidosis
      • Treat with hemodialysis
    • ≥3 mEq/L: Death
    • ≥4 and creatinine ≥2: AMS, Life-threatening
      • Dialysis regardless
  • Overdose
    • Decreased renal perfusion with concurrent use of Thiazides, NSAIDS, ACEI, dehydration, tetracyclines, metronidazole
    • Volume depletion (renal failure)
• Valproic Acid (VPA)
  • Dose:
    • Valproic Acid (Depakene): Tablet, liquid (TID/BID)
      • Trough after 3 days
      • Therapeutic level: Valproate (50-200 for seizures, ≥100 = SE)
    • Divalproex Sodium (Depakote): Tablet, sprinkle, ER, IV
      • = 2 VPA + Na+

  • MOA: increases sodium channel inactivation, increases GABA concentration by inhibiting GABA transaminase

    • Adding w/alcohol, antipsychotics increase sedation
    • Increases aspirin, carbamazepine, diazepam, amitriptyline, and phenobarbital
      • Increases lamotrigine by double and increases SJS risk
    • Decreases phenytoin and desipramine
    • May augment anticoagulants
    • Fluoxetine may increase VPA
    • 10–16-hour half life
  • Use: Acute mania, TBI, migraines, epilepsy
    • Worse than lithium at depression/SI
    • Better in bipolar symptoms from cognitive disorders and migraine prophylaxis
    • Better in substance abuse, rapid cycling
  • SE: GI distress and liver problems, alopecia, neural tube defects
    • Liver Dysfunction (monitor LFTs and platelets)
      • Elevated LFTs/Hepatic failure MC during 1st 6 months
    • Sedation, teratogenesis, weight gain, hair loss, PCOS
  • CI: Pregnancy
  • Valproic Acid Toxicity
    • Somnolence, hepatotoxicity, weight and appetite changes, alopecia, insomnia, thrombocytopenia, lethargy, comatose, hypotension, tremor
• Carbamazepine (Tegretol)
  • Dose: 200mg BID to target of 1200mg total per day
  • Therapeutic level: Carbamazepine/CBZ (60-120)
  • MOA: voltage gated sodium channel blocker
    • Reduces antipsychotics, TCAs, benzos, seizure meds/mood stabilizers, warfarin, Tylenol, methadone, doxycycline, oral contraceptives
      • Reduces lamotrigine
    • Increased by fluoxetine, cimetidine, CCBs, gemfibrozil, grapefruit
    • Decreased by ETOH and phenytoin
    • Increased toxicity by VPA
  • Use: Bipolar disorder, Anticonvulsant, anticholinergic, antineuralgic, antidiuretic
    • Antiseizure, trigeminal neuralgia, bipolar
    • 2nd line mood stabilizer
      • Good for rapid cycling bipolar disorder (≥4 mood episodes/year)
  • SE: Risk of aplastic anemia and agranulocytosis, SJS, neural tube, hyponatremia, cytochrome P450 induction, diplopia, vertigo, hepatotoxic
    • Decreases T3/T4 (increased deiodination mainly), Decreases OCP efficacy, ataxia, blood dyscrasias
    • CMP and B-HCG required
    • 15% benign maculopapular rash within 3 weeks, may stop and retry
    • Neutropenia often caused by drug-induced agranulocytosis, aplastic anemia (2%)
    • CBCs monthly for 3-6m then at that interval
      • If ANC <2000, monitor with more frequent FBCs
      • If ANC <100, discontinue
  • Overdose: hepatotoxicity and sedation
    • 2-6 weeks after starting causative drug
      • Phenytoin or carbamazepine
    • SIADH (hyponatremia), cytochrome p450 induction
    • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
    • Rash, facial edema, lymphadenopathy, and fever
• Oxcarbazepine (Trileptal)
• Lamotrigine (Lamictal)
• Levetiracetam (Keppra)
• Topiramate (Topamax)
• Lacosamide (Vimpat)
• Gabapentin (Neurontin)