Pharmacotherapy of Bipolar Disorder

These flashcards cover the pharmacotherapy of bipolar disorder, including diagnostic criteria, treatment guidelines, mechanism of action, dosing, monitoring, and side effects of mood stabilizers and antipsychotics.

According to the DSM-V, what is the core requirement for a diagnosis of Bipolar I disorder?

Criteria have been met for at least one manic episode.

How is Bipolar II disorder defined under DSM-5 criteria?

Criteria have been met for at least one hypomanic episode and at least one major depressive episode, and there has NEVER been a manic episode.

Is it possible for a patient's diagnosis to switch from Bipolar I to Bipolar II?

No, diagnosis can switch from Bipolar II to Bipolar I, but not the other way around.

What is the lifetime prevalence of comorbid anxiety in patients with Bipolar I (BP1) disorder?

$$61\%$$

Which medical comorbidities occur at a higher frequency and present earlier in patients with bipolar disorder?

Diabetes, dyslipidemia, obesity, and CVD (Cardiovascular Disease).

According to CANMAT 2018, which medications are listed as first-line monotherapy for acute mania?

Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone ($>6\,mg$), risperidone, and cariprazine.

What is the only first-line monotherapy recommended by CANMAT 2018 for treatment of acute Bipolar II depression?

Quetiapine

Why should antidepressants be used cautiously in bipolar disorder?

Due to increased risk of mood switching (mania/hypomania) and rapid cycling.

Which antidepressants have a lower potential for mood switching in bipolar patients?

SSRIs and bupropion

What is the reported onset of effect for Lithium in treating acute mania?

$7-14$ days

What is the therapeutic serum concentration range for Lithium?

$$0.6-1.2\,mEq/L$$

What are the specific Lithium therapeutic ranges for prophylaxis and acute mania?

Prophylaxis: $0.6-1\,mEq/L$; Acute Mania: $0.8-1.2\,mEq/L$

Describe the symptoms of severe Lithium toxicity ($>2.5\,mEq/L$).

Seizures, stupor, coma, and arrhythmia

At what serum level does Lithium toxicity require immediate dialysis regardless of symptoms?

$$>4\,mEq/L$$

Which drug classes are known to increase Lithium levels?

Thiazide diuretics, NSAIDs (except aspirin & sulindac), ACEi/ARB, metronidazole, carbamazepine, and phenytoin.

Which substances are known to decrease Lithium levels?

Caffeine, theophylline, and $K^+$ sparing diuretics.

What specific congenital heart defect is associated with Lithium use during pregnancy?

Ebstein’s Anomaly (malformation of tricuspid and right ventricle).

What is the therapeutic range for total divalproex levels?

$$50-120\,mcg/mL$$

When should a trough level be collected for Divalproex ER?

$18-24$ hours post-dose.

What are the baseline lab requirements before starting divalproex?

CBC with platelets, LFTs, and a pregnancy test.

What are the serious pregnancy risks associated with divalproex?

Neural tube defects, congenital malformations, and structural abnormalities.

What is the primary FDA-approved indication for Lamotrigine in bipolar disorder?

Maintenance

What is the expected time for a therapeutic effect to be seen with lamotrigine?

$6-8$ weeks

If a patient misses more than how many days of lamotrigine, must they restart the titration completely?

$>5$ days

How does Divalproex (VPA) affect lamotrigine levels and its titration schedule?

VPA increases lamotrigine levels; titration starts lower at $25\,mg$ every other day for weeks $1-2$, then $25\,mg$ daily for weeks $3-4$, and maxes at $100\,mg$ daily.

What is the most concerning adverse effect of lamotrigine that necessitates slow titration?

Steven-Johnson Syndrome (SJS)

What is the therapeutic drug monitoring level range for Carbamazepine?

$$5-12\,mcg/mL$$

What unique pharmacokinetic property does carbamazepine possess regarding its own metabolism?

Autoinduction: it lowers its own plasma levels over the first few weeks of treatment (decreases half-life from $25-65$ hours to $12-17$ hours).

Which genetic test is required for patients of Asian descent before starting carbamazepine?

HLA-B*1502

What are the teratogenic effects associated with carbamazepine?

Spina bifida, craniofacial defects, and cardiovascular malformations.