Bipolar Disorder Flashcards
What are the excitatory neurotransmitters?
- Norepinephrine
- Dopamine
- Glutamine
- Aspartate
What are the inhibitory neurotransmitters?
- Serotonin
- GABA
Kindling effect
Acceleration of episode frequency and treatment resistance with inadequate treatment
Manic episode (Bipolar I disorder)
Criteria have met for at least one manic episode
Major Depressive Episode (Bipolar II disorder)
- Criteria have been met for at least one hypomanic episode AND at least one major depressive episode
- NO manic episode
What is the diagnostic criteria of a manic episode?
- Abnormally and persistently elevated, expansive, or irritable mood with increased goal-directed activity/energy lasting at least 1 week and present most of the day, nearly every day
- Symptoms occur for at least one week
- Mood disturbances is severe enough to cause impairment in occupational or social functioning
- 3 or more of the symptoms must occur
What are the presentations of a manic episode?
- Grandiosity
- Decreased sleep
- Pressured sleep
- Racing thoughts
- Distracted
- Increased activity or pscyhomotor agitation
- Involvement in activities with serious consequences
What are the diagnostic criteria of a hypomanic episode?
- Abnormally and persistently elevated, expansive, or irritable mood with increased goal-directed activity/energy lasting at least 4 consecutive days and present most of the day, nearly every day
- Associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic
- The disturbance in mood and the change in functioning are observable by others
- The episode is NOT severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization
- 3 or more of the symptoms must be present
What are the diagnostic criteria of a depressive episode?
- Five or more of the symptoms during the same 2- week period and represent change from previous functioning
- At least one symptoms is depressed mood or loss of interest
- The symptoms cause clinically signified distress or impairment in social, occupational, or other important areas of functioning
- Major depressive episode is NOT required for a diagnosis of bipolar I disorder
Lithium
- Bipolar disorder, maintenance therapy, suicidality benefit
- Manic, depressive, mixed episodes
- First-line as monotherapy and combination therapy for maintenance therapy and acute manic, hypomanic, depressive, and mixed episodes
What are the mechanisms of Lithium?
Unknown but current hypothesis:
* Inhibits second messenger systems (inostol, adenylate cyclase, G protein) which dampens neurotransmission
* Enhanced GABA and serotonin transmission
* Increases neurogenesis and neuroprotection
What is the dosing of Lithium?
- Initial: 300-900 mg/day
- Maintenance: 900-1200 mg/day
What is the onset of effect of Lithium?
- Mania: 7-14 days
- Depression: 6-8 weeks
- 300 mg of oral formulations if lithium = 8.12 mEq
How is lithium eliminated?
Renally
What is the box warning of lithium?
Lithium toxicity
Symptoms of mild toxicity of lithium
Hand tremor, GI, fatigue
Symptoms of modertate lithium toxicity
Course hand tremor, confusion, slurred speech, unsteady gait
Symptoms of severe lithium toxicity
Seizures, stupor, coma, arrhythmia
What are some key points of lithium?
- After steady state (approx. 5 days)
- Obtain 12-hour levels for monitoring (trough)
- Linear dose to level response
What are the baseline labs for lithium?
- Renal panel (BUN, SCr, electrolytes)
- Thyroid function status
- Pregnancy test (as indicated)
- ECG for patients > 40 days old or underlying cardiac risk factors
What are some monitoring parameters of lithium?
- Li+ levels 5-7 days after dose adjustments
- Li+ levels for 1 month
- Li+ levels every 6 month
- BUN, SCr, electrolytes every 6-12 months
- Thyroid function status every 6-12 months
What are some side effects of lithium?
- GI
- Tremor/fatigue
- Polyuria/polydipsia
- Weight gain
- Dermatologic
- Leukocytosis
- Hypothyroidism
- Diabetes
What are some drugs that increase lithium levels?
- NSAIDs
- Thiazide diuretics
- ACEis/ARBs
What are drugs decrease Li levels?
- Theophylline
- Potassium-sparing diuretics
- Caffeine
Divalproex
- Bipolar mania, maintenance therapy
- First line therapy as monotherapy and combination therapy for manic, hypomanic, and mixed episode
- Preferred agent for mixed episodes
- May be beneficial in rapid cycling
What is the mechanism of Divalproex?
- Mechanism not understood
- Enhanced GABA
What is the dosing of Divalproex?
- Can be weight-based or fixed dose
- Start: 25 mg/kg/day
- Start: 500-1000 mg HS and increase by 250-500 mg every 1-3 days
- Target dose: 1500-2000 mg/day
How do you monitor Divalproex?
- Trough levels
- After steady state (approx. 3-5 days)
- Once daily ER formulations: 18-24 hours post-dose
- Twice daily DR formulation: ~12 hours post-dose
What is the therapeutic range of divalproex?
50-125 mg/L
What are the levels of divalproex and its effects?
- 75-100 mg/L: Ataxia, sedation, lethargy, fatigue
- 100-175 mg/L: Tremor
- > 175: Stupor or coma
What are the boxed warnings of divalproex?
- Hepatotoxicity (usually during the 6 months)
- Fetal risk
- Pancreatitis
What are some contraindications of divalproex?
- Hepatic disease or severe hepatic impairment
- Urea cycle disorders
What are some common side effects of divalproex?
- Nausea/vomiting
- Weight gain
- Alopecia
- Sedation
- Tremor
- Fatigue
What are some serious side effects of divalproex?
- Hepatic failure
- Thrombocytopenia (decrease Plt)
- Pancreatitis
- Hyperammonemai (increase NH3)–treat w/ levocarnitine
What are some baseline labs of divalproex?
- CBC with platelets
- LFTs (hepatic function)
- Pregnancy test
What are some ongoing labs for divalproex?
- Valproate level 3-5 days after dose adjustments
- Valproate level every 6-12 months
- CBC every 6-12 months
- LFTs every 6-12 months
- NH3 if symptomatic or suspicion
What are some drugs that increase valproate levels?
- Aspirin
- Warfarin
- Risperidone
- Fluoxetine
What are some drugs that decrease valproate levels?
- Carbamazepine
- Carbapenems
- Rifampin
Lamotrigine
- Bipolar depression, maintenance therapy
- First line as monotherapy and combination therapy for depressive episodes
What is the mechanism of Lamotrigine?
- Exact mechanism not well understood
- Sodium channel blockade, decrease glutamate
What happens if patients misses more than 5 days of lamotrigine?
Restart titration
What are some common side effects of lamotrigine?
- Nausea/vomiting
- Rash
- Somnolence/fatigue
What are some serious side effects of lamotrigine?
- Stevens-Johnson Syndrome and toxic epidermal necrolysis (TEN)
- Angioedema
- Multi-organ failure
What is the boxed warning of lamotrigine?
Life-threatening rashes (SJS and TEN)
What are the baseline labs of lamotrigine?
- BUN, SCr
- LFTs
What are the ongoing labs of lamotrigine?
- BUN, SCr every 6-12 months
- LFTs every 6-12 months
Carbamazepine
- Bipolar disorder, mania, or mixed episodes
- Second-line as monotherapy and combination therapy for manic, hypomanic, and mixed episodes
What is the dosing of carbamazepine?
- Initial: 400 mg/day (divided BID)
Increase by 200 mg/day q5-7 days - Usual dose: 600-1200 mg/day
What are the therapeutic levels of carbamazepine?
4-12 mg/L
What are the carbamazepine’s levels and its effect?
- > 8 mg/L: Nausea, vomiting, headache, dizziness, blurred, vision
- > 40 mg/dL: Apnea, dystonia, coma
What is the boxed warning of carbamazepine?
- Serious dermatologic reactions and HLA-B 1501 allele
- Aplastic anemia & agranulocytosis
What are some contraindications of carbamazepine?
- Bone marrow depression
- Concurrent MAOI use
- Concurrent NNRTI
- Hepatic failure
What are the warnings of carbamazepine?
- Avoid if history of hepatic porphyria
- Increased suicidality
- Teratogenicity
- Potential for withdrawal seizure if discontinued abruptly
- Hyponatremia
What are the common side effects of carbamazepine?
- Nauea/vomiting
- Blurred vision
- Dizziness
- Somnelence
What are some serious side effects of carbamazepine?
- Stevens-Johnsons Syndrome
- Toxic Epidermal Necrolysis
- Anemia
- Agranulocytosis
- Hepatic failure
What is the baseline monitoring of carbamazepine?
- HLA-B 1502 allele patients of Asian descent (risk of fatal rash)
- CBC
- LFTs
- BUN, SCr, electrolyte
- Pregnancy test
What are the ongoing monitoring labs of carbamazepine?
- Carbamazepine level 5 days after dose adjustments
- Carbamazepine level every 6-12 months
- CBC every 6-12 months
- BUN, SCr, electrolytes every 6-12 months
What are drugs that increase of carbamazepine level?
Phenobarbital
What are the CYP metabolism of carbamazepine?
Induces CYP1A2, 2C19, 2C8, 2C9, 3A4, P-gp
-decrease oral hormonal contraceptives, theophylline, warfarin, and itself (auto-inducers)
What are some patient counseling of carbamazepine?
- Stopping medication abruptly may lead to adverse effect
- Adequate trial duration: 2-3 weeks
What is the 1st line monotherapy of acute mania?
- Lithium
- Divalproex
- Risperidone
- Quetiapine
- Aripiprazole
- Ziprasidone
- Asenapine
- Paliperidone
What is the 2nd line adjunctive therapy for acute mania?
With lithium or divalproex:
* Risperidone
* Quetiapine
* Olanzapine
* Aripiprazole
* Asenapine
What is the 2nd line monotherapy of acute mania?
- Carbamazepine
- ECT
- Haloperidol
What is the 2nd line adjunctive therapy of acute mania?
Lithium and divalproex
What is the 3rd line monotherapy of acute mania?
- Chlorpromazine
- Clozapine
- Oxcarbazepine
- Tamoxifen
- Cariprazine
What is the 3rd line combination therapy of acute mania?
- Lithium or divalproex and haloperidol
- Lithium and carbamazepine
- Adjunctive tamoxifen
What monotherapy is not recommended for acute mania?
- Gabapentin
- Topiramate
- Lamotrigine
- Verapamil
- Tiagabine
What are the combination therapy that is not recommended for acute mania?
- Risperidone and carbamazepine
- Olanzepine and carbamazepine
What is the 1st line monotherapy for acute depression?
- Lithium
- Lamotrigine
- Quetiapine
What is the 1st line combination therapy of acute depression?
- Lithium or divalproex and SSRI
- Olanzapine and SSRI
- Lithium and divalproex
- Lithium or divalproex and bupropion
What is the 2nd line monotherapy of acute depression?
- Divalproex
- Lurasidone
What is the 2nd line combination therapy of acute depression?
- Quetiapine and SSRI
- Adjunctive modafinil
- Lithium or divalproex and lamotrigine
- Lithium or divalproex and lurasidone
What is the third line monotherapy of acute depression?
- Carbamazepine
- Olanzepine
- ECT
