5.2 Pharmacotherapy of bipolar disorder Flashcards
What are comorbidities of bipolar disorder?
- Alcohol and substance use common
- Anxiety disorders are common comorbidities and can significantly impact remission of mood episodes if left untreated or inadequately treated
What other disease is experienced most often in bipolar disorder?
Depression
- Can lead to misdiagnosis
How does the DSM5 define bipolar 1 disorder?
- > = 1 manic episodes
- Depressive or hypomanic episode may have occurred
- Manic episodes generally last >= 1 week
How does the DSM5 define bipolar 2 disorder?
- Major depressive and hypomanic episodes
- Hypomanic episodes generally last >= 4 days
What is 1st line for bipolar disorder?
Mood stabilizers are foundation of acute and maintenance tx:
- Usually lithium or valproic acid
- (Atypicals can also be 1st line, as monotherapy or in combo w lithium or valproic acid)
What is the therapeutic index of lithium?
Narrow
What is lithium associated with?
Associated with decrease in suicidality
What are the levels of lithium for it to be a mild to severe toxicity? What must be thought about if it reaches these levels?
1.5 - >3.0 mEq/L:
- Think about renal fxn, possible hemodialysis
What are toxicities of lithium?
- GI
- Ataxia
- Coarse hand tremor
- Altered mental status
- Seizure
- Lethargy
- Confusion, agitation
What are the SEs of lithium?
- Fine hand tremor
- Hypothyroidism
- Polyuria, polydipsia
- Acne
- Dry mouth
- Weight gain
- ECG changes
What teratogenic effects does lithium have?
Cardiac structural abnormality (Ebstein’s anomaly)
When should lithium be avoided and used w caution during pregnancy?
- AVOID during 1st trimester
- Use w caution in 2nd and 3rd trimester
What are laboratory monitoring parameters of lithium?
- SCr, BUN (lithium is almost entirely renally excreted)
- Na (important), K, Ca
- ECG (esp if >40 yo or CV risk factors)
- TSH, T4
- Parathyroid hormones
- CBC w differential
- Weight
- Pregnancy test
What are the drug interactions associated w lithium?
- Decrease Li renal clearance w ACEi, ARBs, thiazide diuretics, NSAIDs, dehydration
- Increased Li renal clearance w caffeine, osmotic diuretics, +/- w loops, Na bicarb, high Na intake
- Toxicity related to Na depletion through thiazides
What is an issue w valproate associated w its dosage forms?
Available in several dosage forms –> risk for med errors
What is the difference between the valproate ER and DR dosage forms?
ER dosage form is 10-15% less bioavailable than DR dosage form
What is the conversion between the valproate ER and DR dosage forms?
1:1 conversion, expect lower serum conc w ER (not clinically significant)
What can valproic acid syrup (IR) and capsule sprinkle form have a risk of?
Higher risk for GI ulcerations (usually esophageal)
What are the optimal serum levels of valproate for most efficacy?
Serum levels 80-125 mcg/ml has most efficacy for mania
When should the optimal serum levels of valproate be achieved?
Obtain level at least 96 hours (4 days) after 1st dose or dose increase
Is valproic acid teratogenic? What are the teratogenic effects?
Yes
- Unsafe in any trimester of pregnancy; obtain baseline pregnancy test
- Neural tube defects, lower IQ in offspring
What can valproic acid commonly cause in women?
Polycystic ovarian syndrome occurs in up to 50% of women
What are the AEs of valproic acid?
- GI: anorexia, N/V/D, dyspepsia, ulceration
- Thrombocytopenia, platelet dysfxn
- Increased appetite: weight gain of 6-8 kg
- Hyperammonemia
What are the laboratory monitoring parameters of valproic acid?
- Baseline: pregnancy test, LFTs, CBC w differential
- Valproate serum conc
- Serum ammonia if suspect hyperammonemia; otherwise routine monitoring not necessary
