Bipolar Disorder

Question 1

Types & Symptoms

Answer 1

Types:
- Bipolar 1 Disorder, Bipolar II Disorder, Cyclothymia Disorder, Unspecified bipolar and related disorder, substance-induced mood disorder
Symptoms:
- mania, hypomania, depression, mixed mania and depression

Question 2

Features of mania

Answer 2

• Mania: euphoria/elation, irritability, impulsive high risk behavior, decreased sleep and appetite
• hypomania: less severe mania
• depression

Question 3

Treatment of Bipolar

Answer 3

Hospitalization, psychotherapy, pharmacotherapy
- mood stabilizers: lithium, anticonvulsants
- atypical antipsychotics
- CCB (verapamil, nimodipine)
- combo therapy (+BZD)

Question 4

Lithium pharmacotherapy

Answer 4

• lithium leads to depletion of PIP2
• PIP2 activates Gq which activates phospholipase C. PLC cleaves PIP2 into IP3 and diacylglycerol. IP3 gets recycled back to membrane to PIP2 (lithium blocks this recycling, so membrane no longer has PIP2 and now when Gq pathway is activated, PLC has no substrate, so no signaling can occur.
• any receptor that couples to Gq - signaling will be impaired by lithium (serotonin, muscarinic, metabotropic, dopamine)

Question 5

Anticonvulsants for BPD

Answer 5

• valproic acid and sodium valproate
• carbamazepine
• lamotrigine
• topiramate

Question 6

Atypical antipsychotics for BPD

Answer 6

olanzapine
olanzapine + fluoxetine
quetiapine
risperidone
ziprasidone
lurasidone
aripiprazole

Question 7

Pharmacotherapy overview for BPD

Answer 7

1st line: usually lithium or valproic acid
- atypical antipsychotics can also be used 1st line as monotherapy or in combo with lithium or valproic acid
- many patients will take polytherapy with mood stabilizers

Question 8

Lithium use and dosing

Answer 8

• decreases number and severity of episodes in bipolar disorder
• associated with decrease in suicidality (narrow therapeutic index drug –evaluate if patient has suicidal plan)
• some difference in lithium content, but 1:1 conversion

Question 9

Lithium monitoring and adverse effects

Answer 9

• narrow therapeutic index (conc > 1.2-1.5mEq/L are toxic)
• toxicities: GI, ataxia, coarse hand tremor, altered mental status, seizure, lethargy, confusion, agitation
• SE: fine hand tremor, hypothyroidism, polyuria, polydipsia, acne, dry mouth, weight gain, ECG changes
• teratogenic – avoid in 1st trimester, caution in 2nd and 3rd trimester

Question 10

Valproate (valproic acid, divalproex)

Answer 10

• common 1st line agent for BPD
• available in several dosage forms (risk for med errors)
• ER is 10-15% less bioavailable than DR
• 1:1 conversion
• valproic acid syrup (IR) and capsule sprinkle form have higher risk of GI ulcerations
• serum levels 80-125 mcg/ml associated with most efficacy in mania

Question 11

valproic acid adverse effects

Answer 11

• CI in pregnancy !!! - teratogenic - neural tube defects, enduring negative effects on IQ on offspring
• polycystic ovarian syndroms occurs in up to 50% of women
• GI - anorexia, N/V/D, dyspepsia, ulceration
• thrombocytopenia, platelet dysfunction
• increased appetite - weight gain
• hyperammonemia

Question 12

Valproate - monitoring & drug interactions

Answer 12

• BIG concern with lamotrigine (increases risk of Stevens-johnson syndrome)
• pregnancy test, LFTs, CBC, serum ammonia if suspect hyperammonemia

Question 13

Carbamazepine

Answer 13

• 2nd or 3rd line for BPD
• known teratogen
• induce nearly all CYP450 enzymes
• ssociated with thrombocytopenia/hematologic effects

Question 14

Oxcarbazepine

Answer 14

• 2nd or 3rd line
• may be used as adjunctive therapy
• CYP450 3A4 inducer
• hyponatremia

Question 15

lamotrigine

Answer 15

• 1st line tx for DEPRESSIVE symptoms in BPD
• not useful for acute tx or manic episodes
• slow dose titration bc stevens johnson risk

Question 16

topiramate

Answer 16

• clinically used as adjunctive treatment
• may cause weight loss
• heat intolerance/hypohidrosis
• metabolic acidosis and kidney stones
• possible teratogen- cardiac structural defects