Bipolar Disorder Flashcards
What is bipolar disorder?
a serious brain disorder characterized by extreme alterations in mood, energy level, and thought processes, with a reduced capacity to function “normally” in daily life; associated with HIGH RATES OF MEDICATION NON-ADHERENCE
What medications may produce manic-like symptoms?
-antidepressants= TCAs, MAOIs, SSRIs
-anxiolytics= buspirone, benzodiazepines
-stimulants= cocaine, MPH, AMP, ephedrine, pseudoephedrine
-endocrine= corticosteroids, thyroid supplements, androgens
-others: levodopa, EtOH, bronchodilators
Describe Bipolar I Disorder
at least 1 manic episode- if a patient has a manic episode (even if the have hypomanic/depression episodes) it is considered B1D
Describe Bipolar II Disorder
at least 1 hypomanic/depressive episode, but if pt has a manic episode then they would be categorized as B1D
What are the goals of treatment of Bipolar Disorder?
-eliminate mood episode/remission of symptoms
-mood stabilization; recurrence/relapse prevention
-return to baseline psychosocial functioning
-maximize adherence
-educate patient, family, caregivers
-treat comorbid substance use and use disorders
-avoid stressors or substances that precipitate an acute episode
What are the potential pharmacological treatment options for Bipolar Disorder?
-lithium
-valproic acid
-carbamazepine
-lamotrigine
-antipsychotics
MOA: Lithium (Li)
increases 5HT (serotonin) function, reduces dopamine function, and enhances GABA and normalizes levels
What are the benefits of using Lithium in Bipolar Disorder?
BAP GUIDELINES: the most effective treatment preventing relapse and hospital admissions in Bipolar I Disorder
alleviates mania and provides prophylaxis against both manic and depressive episodes. anti-suicidal effects also seen and benefits for impulsivity
What is the Black Box Warning of Lithium?
lithium toxicity is closely related to serum lithium concentrations and can occur at doses close to therapeutic concentrations
What is the dosing of Lithium?
600-1800mg/day in 1-3 divided doses
AVOID IN SEVERE RENAL IMPAIRMENT
What are the baseline monitoring parameters before treatment with Lithium?
-ECG (especially if age >50 or if history of CV disease)
-blood pressure
-thyroid function
-parathyroid hormone/calcium
-CBC
-BMP
-pregnancy status
What is the reasoning for monitoring ECG while on lithium?
sick sinus syndrome, BRADYCARDIA, unmask Brugada syndrome, AV block
What is the reasoning of monitoring thyroid function while on lithium?
lithium can precipitate hypothyroidism
What is the reasoning for monitoring CBC while on lithium?
risk of leukocytosis (75-100% may have it to some degree)
What is the reasoning for monitoring BMP while on lithium?
Na+ (hyponatremia) and kidney function (risk of nephrogenic diabetes insipidus)
When would serum lithium levels be monitored in bipolar patients?
4-5 days after initiation at ~12 hours post dose
What is the treatment of lithium toxicity?
*a medical emergency; rapid, aggressive treatment is needed to reduce risk of suffering permanent neurologic damage *
if mild= hold dose, if severe (any Li level >6 or chronic use Li level >4)= hemodialysis
What are the risk factors for lithium toxicity?
-sodium restriction
-dehydration
-vomiting
-diarrhea
-fever
-heavy exercise
-large quantities of caffeine or alcohol
-pregnancy & delivery
What are the adverse effects of lithium?
-tremor (high incidence): can be reduced with slow titration
-cognitive problems: agitation/confusion/mental dullness
-nausea/vomiting/diarrhea
-dermatologic: rashes
-weight gain
-polyuria/excessive thirst
What are the drug interactions of lithium?
-diuretics
-NSAIDs
-renin angiotensin system antagonists (ACEI or ARBs)
What is the reasoning for discouraging the use of lithium during pregnancy?
lithium can cause epsteins anomaly when used in the first trimester and causes neonatal toxicity
What is the indication of Valproic Acid in Bipolar Disorder?
acute mania & maintenance
With what condition may valproic acid be specifically useful with?
comorbid substance use disorder
What are the black box warnings of Valproic Acid?
-hepatoxicity, hepatic failure
-pancreatitis
-contraindicated in mitochondrial disorders/urea cycle disorders
-fetal risk
What are the monitoring parameters for Valproic Acid?
-CBC
-LFTs
-pregnancy test
-drug levels (50-125 mccg/mL) which are obtained at steady state
What are the adverse effects of Valproic Acid?
-sedation, N/V/D, dizziness
-tremor
-PCOS (10% risk)
-increased AST/ALT
-hyperammonemia and/or hyperammonemic encephalopathy
What are the drug interactions of Valproic Acid?
topiramate due to increased risk of hyperammonemic encephalopathy
Why is Valproic Acid contraindicated in women in child-bearing age?
teratogenic (BBW)= malformations, developmental delays, autism
What is the indication of Carbamazepine?
acute mania and mixed episodes NOT A FIRST LINE OPTION- COMBO THERAPY
Which drug induce auto-induction metabolism?
carbamazepine
What are the black box warnings of Carbamazepine?
-SJS/TEN: genetic testing for HLA-B*15:02
-aplastic anemia and agraulocytosis
What are the special dosing recommendations for Carbamazepine?
-slow titration to minimize neurological adverse effects
-close monitoring around dosing adjustments or dosage conversions
What is the target drug plasma level of Carbamazepine?
4-12 mcg/mL
What are the adverse effects of Carbamazepine?
-dizziness, diplopia, ataxia, drowsiness, confusion
-cardiac conduction abnormalities= tachycardia, bradyarrhythmia, AV block
-SIADH/hyponatremia
What are the drug interactions of Carbamazapine?
-hormonal contraceptives= decreased efficacy
-lamotrigine= enhances the adverse/toxic effects of LTG
What are the recommendations for pregnant patients while on Carbamazepine?
folic acid supplementation
What is the indication of Lamotrigine?
maintenance therapy of BPD or bipolar depression (off label)
NOT EFFECTIVE FOR MANIA
What are the black box warnings of Lamotrigine?
SJS/TEN do not exceed recommended dose titrations
What drugs titration must be restarted if >5 half lives of dosing have been missed?
Lamotrigine
What are the adverse effects of lamotrigine?
-headache
-diplopia
-ataxia, somnolence
-blurred vision
-N/V/D
-considered a class 1B antiarrhythmic at therapeutically relevant drug concentrations
-benign rash
What are the drug interactions of Lamotrigine?
-valproic acid (decreases clearance of LTG)
-carbamazepine, phenytoin, primidone, phenobarbital (increase clearance of LTG)
-oral contraceptives (increased clearance of LTG)
What drug is cautioned to be used in children <16 yo due to serious rash?
Lamotrigine
What is the place of second generation antipsychotics in the treatment of bipolar disorder?
first line as monotherapy or in combination in acute mania
What is the first line treatment for mania?
mood stabilizers or atypical antipsychotics
What drugs may be used for depressive episodes in BPD?
-mood stabilizers: lithium, lamotrigine
-atypical antipsychotics: quetiapine, lurasidone (recommended in children), olanzapine, cariprazine
What is the recommendation of antidepressant use in BPD?
avoid use due to precipitation of mania, especially avoid TCA due to high risk of switch rates
What drugs are recommended maintenance treatment?
lithium, valproic acid, lamotrigine, quetiapine
