If It Doesn’t Work (for bipolar disorder)

✽ Many patients have only a partial response where some symptoms are improved but others persist or continue to wax and wane without stabilization of mood

• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory

• Consider increasing dose, switching to another agent or adding an appropriate augmenting agent

• Consider adding psychotherapy

• Consider biofeedback or hypnosis for pain

• For bipolar disorder, consider the presence of noncompliance and counsel patient

• Switch to another mood stabilizer with fewer side effects or to extended-release carbamazepine

• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)

Best Augmenting Combos for Partial Response or Treatment Resistance

• Lithium

• Atypical antipsychotics (especially risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole)

• Valproate (carbamazepine can decrease valproate levels)

• Lamotrigine (carbamazepine can decrease lamotrigine levels)

✽ Antidepressants (with caution because antidepressants can destabilize mood in some patients, including induction of rapid cycling or suicidal ideation; in particular consider bupropion; also SSRIs, SNRIs, others; generally avoid TCAs, MAOIs)

Tests

✽ Before starting: blood count, liver, kidney, and thyroid function tests

• During treatment: blood count every 2–4 weeks for 2 months, then every 3–6 months throughout treatment

• During treatment: liver, kidney, and thyroid function tests every 6–12 months

• Consider monitoring sodium levels because of possibility of hyponatremia

✽ Before starting: individuals with ancestry across broad areas of Asia should consider screening for the presence of the HLA-B*1502 allele; those with HLA-B*1502 should not be treated with carbamazepine

CARBAMAZEPINE: SIDE EFFECTS

How Drug Causes Side Effects

• CNS side effects theoretically due to excessive actions at voltage-sensitive sodium channels

• Major metabolite (carbamazepine-10, 11 epoxide) may be the cause of many side effects

• Mild anticholinergic effects may contribute to sedation, blurred vision

Notable Side Effects

✽ Sedation, dizziness, confusion, unsteadiness, headache

✽ Nausea, vomiting, diarrhea

• Blurred vision

✽ Benign leukopenia (transient; in up to 10%)

✽ Rash

Life-Threatening or Dangerous Side Effects

✽ Rare aplastic anemia, agranulocytosis (unusual bleeding or bruising, mouth sores, infections, fever, sore throat)

✽ Rare severe dermatologic reactions (Stevens-Johnson syndrome)

• Rare cardiac problems

• Rare induction of psychosis or mania

✽ SIADH (syndrome of inappropriate antidiuretic hormone secretion) with hyponatremia

• Increased frequency of generalized convulsions (in patients with atypical absence seizures)

• Rare activation of suicidal ideation and behavior (suicidality)

Weight Gain

• Occurs in significant minority

Sedation

• Frequent and can be significant in amount

• Some patients may not tolerate it

• Dose-related

• Can wear off with time, but commonly does not wear off at high doses

• CNS side effects significantly lower with controlled-release formulation (e.g., Equetro, Carbatrol)

What to Do About Side Effects

• Wait

• Wait

• Wait

• Take with food or split dose to avoid gastrointestinal effects

• Extended-release carbamazepine can be sprinkled on soft food

• Take at night to reduce daytime sedation

• Switch to another agent or to extended release carbamazepine

Best Augmenting Agents for Side Effects

• Many side effects cannot be improved with an augmenting agent

CARBAMAZEPINE: DOSING AND USE

Usual Dosage Range

• 400–1,200 mg/day

• Under age 6: 10–20 mg/kg per day

Dosage Forms

• Tablet 100 mg chewable, 200 mg chewable, 200 mg

• Extended-release tablet 100 mg, 200 mg, 400 mg

• Extended-release capsule 100 mg, 200 mg, 300 mg

• Oral suspension 100 mg/5mL (450 mL)

How to Dose

• For bipolar disorder and seizures (ages 13 and older): initial 200 mg twice daily (tablet) or 1 teaspoon (100 mg) 4 times a day (suspension); each week increase by up to 200 mg/day in divided doses (2 doses for extended release formulation, 3–4 doses for other tablets); maximum dose generally 1,200 mg/day for adults and 1,000 mg/day for children under age 15; maintenance dose generally 800–1,200 mg/day for adults; some patients may require up to 1,600 mg/day

• Seizures (under age 13): see Children and Adolescents

• Trigeminal neuralgia: initial 100 mg twice daily (tablet) or 0.5 teaspoon (50 mg) 4 times a day; each week increase by up to 200 mg/day in divided doses (100 mg every 12 hours for tablet formulations, 50 mg 4 times a day for suspension formulation); maximum dose generally 1,200 mg/day

• Lower initial dose and slower titration should be used for carbamazepine suspension