Mood stabilizers

Carbamazepine (Tegretol) FDA indication, class. MOA, dosage

• Acute mania, mixed mania

• Anticonvulsant

• Inhibits release of glutamate, blocks and interacts with sodium channels

• 400-1200mg

Carbamazepine (Tegretol) Side effects

Sedation, dizziness, confusion, unsteadiness, headache, nausea, vomiting, diarrhea, benign leukopenia (up to 10%), rash, aplastic anemia, dermatologic reactions, SIADH, blurred vision, induction of mania or psychosis, cardiac problems, increased frequency of generalized convulsions

Carbamazepine (Tegretol) Special considerations

Slowly titrate, rapid discontinuation may increase the risk of relapse in bipolar, many drug/drug interactions, monitor closely for signs of unusual bleeding or bruising, mouth sores, infections, fever, or sore throat as the risk of aplastic anemia and agranulocytosis is 5-8 times greater than in general population. Use in pregnancy may increase neural tube defects or other congenital anomalies, prior to starting need (CBC, LFT, Kidney function, and Thyroid), blood counts every 2-4 weeks x2 months, then every 3-6 months for the duration of treatment. Individuals with the HLA-B 1502 allele (mostly in the Han Chinese) are at increased risk of developing Stevens Johnson syndrome and toxic epidermal necrolysis.

Lamotrigine (Lamictal) FDA indications, class, MOA, dosage

• Maintenance treatment of bipolar depression

• Anticonvulsant

• Inhibits release of glutamate and asparate, blocks and interacts with sodium channels

• 100-200mg - starting dose at 25mg and titrate up

Lamotrigine (Lamictal) side effects

Benign rash (10%), dose dependent blurred vision/double vision, dizziness, ataxia, sedation, headache, tremor, insomnia, poor coordination, fatigue, dose dependent nausea, vomiting, dyspepsia, rhinitis.

Lamotrigine (Lamictal) special considerations

Risk for Stevens Johnson’s Syndrome (must stop drug and possible hospitalization)

MUST titrate dose up slowly to limit risk of SJS,

When taking with depakote slower titration requried

Lithium (Eskalith) FDA indications, MOA, dosing

• Episodes of manic-depressive illness, maintenance treatment for manic depressive patients with a history of mania, acute mania/mixed mania (7 and up)

• Is a salt, mechanism unknown Start at 300mg 2-3 times daily, adjust dose with symptom management and plasma lithium levels

Lithium therapeutic level and lab schedule

• 0.6-1.2mEq/L

• lithium plasma levels Q1-2wks until desired concentration

• Then 2-3 months x6 months

• After stabilization Q6-12 months or after dose change

• Monitor Glucose, Cholesterol, Kidney, thyroid function, weight and BMI

NSAIDS and Lithium

NSAIDS can increase lithium concentrations

Lithium toxicity Mild

• 1.5-2.5 mEq/L

• nausea, vomiting, lethargy, fine tremors, fatigue

Lithium toxicity Moderate

• 2.5-3.5 mEq/L

• tachycardia, ataxia, agitation, confusion, delirium, hypertension

Lithium toxicity Severe

• >3.5 mEq/L

• Hyperthermia, hypotension, seizures, renal failure, coma, death

Lithium side effects

Generally mild - typically dose related

• Ataxia, dysarthria, delirium, tremor, memory problems, polyuria, polydipsia, diarrhea, nausea, weight gain, euthyroid or hypothyroid goiter, acne, rash, alopecia, leukocytosis *Propranolol may reduce tremor

Oxcarbazepine (Trileptal) FDA indication, class, MOA, Dosage

• Off label use for bipolar disorder mood stabilizer

• anticonvulsant

• inhibits release of glutamate, blocks and interacts with sodium channels

• 1200-2400mg

Oxcarbazepine (Trileptal) side effects and considerations

• not the most effective mood stabilizer

• Monitor sodium levels

• rapid discontinuation may increase or relapse bipolar symptoms

• Side effects: Sedation, dizziness, headache, ataxia, nystagmus, abnormal gait, confusion, nervousness, fatigue, nausea, vomiting, abdominal pain, dyspepsia, diplopia, vertigo, abnormal vision, rash, hyponatremia, rare activation of suicidal ideation and behavior

Topiramate (Topamax) FDA indications, class, MOA, dosing

• Off label-bipolar disorder, off label psychotropic drug-induced weight gain, off label binge eating disorder

• Anticonvulsant

• Inhibits glutamate, potentiates GABA, blocks sodium channels, carbonic anhydrase inhibitor

• 25-400mg

Topiramate (Topamax) side effects and special considerations

• Sedation, asthenia, dizziness, ataxia, paresthesia, nervousness, nystagmus, tremor, nausea, appetite loss, weight, blurred or double vision, mood problems, problems concentrating, confusion, memory problems, psychomotor retardation, language problems, speech problems, fatigue, taste perversion, metabolic acidosis, kidney stones, secondary angle-closure glaucoma, oligohidrosis and hyperthermia, sudden unexplained deaths in epilepsy, and rare activation of suicidal ideation and behavior

• Monitor baseline and periodic serum bicarbonate levels to monitor hyperchloremic, non-anion gap metabolic acidosis, may reduce effectiveness of oral contraceptives, rapid discontinuation may increase risk of relapse in bipolar patients

Valproate (Depakote) FDA indications, Class, MOA, Dosing

• Acute mania and mixed episodes

• anticonvulsant

• increases GABA in the brain, blocks sodium channels

• 500-1500mg

• Available in sprinkles, ER, or DR

• ER can be given daily but drug levels are 10-20% lower

Valproate (Depakote) Side effects

Sedation, dose dependent tremor, dizziness, ataxia, asthenia, headache, abdominal pain, nausea, vomiting, diarrhea, reduced appetite, constipation, dyspepsia, weight gain, alopecia

Propranolol may reduce tremor

MVI fortified with zinc and selenium may help reduce alopecia

Valproate (Depakote) therapeutic level and lab monitoring and drug interactions and considerations

• Prior to treatment labs (CBC, coags, LFT), need to monitor BMI, weight, LFT, and platelet counts

• Therapeutic plasma levels range from 50-125, toxic level is greater than 150

• caution with Lamictal - can double levels of depakote

• teratogenic effects

• plasma levels are lowered with carbamazepine, phenytoin, ethosuximide, phenobarbital, and rifampin, ASA may inhibit metabolism of valproate and increase levels

• Plasma levels may be increased by felbamate, chlorpromazine, fluoxetine, fluvoxamine, topiramate, cimetidine, erythromycin, and ibuprofen

• Rapid discontinuation increases risk of relapse with bipolar disorder

Valproate Toxicity

• Elevated liver enzymes

• nausea/vomiting

• abdominal pain/heartburn

• tremor

• hair loss

• Overdose effects

  • Restlessness

  • hallucinations

  • sedation

  • coma or death

FDA approved mood stabilizers in children/adolescents

• Lithium - acute mania/mixed mania (7 and up)

• Antipsychotics

  • Lurasidone (Latuda) and Olanzapine/fluoxetine (Symbyax) - Bipolar depression 10+

  • Risperidone (Risperidal), Asenapine (Saphris), and Aripiprazole (Abilify) - acute mania/mixed mania 10+

  • Quetiapine (Seroquel) monortherapy or adjunct to lithium or valproate for acute mania 10+

  • Olanzapine (Zyprexa) acute mania/mixed mania 13+

Mood stabilizers special considerations in the elderly

• may require lower doses with aging to decrease side effects

• be aware of polypharmacy

• may require more frequent monitoring

Pearls in treating Bipolar disorder

• use antidepressants with caution, meds can destabilize mood and induce rapid cycling or suicidal ideation

• always assess ALL other medications that client is taking for interactions

• Can augment with other classes of medications

• use of stimulants can induce mania