Lecture 20: Drugs for Bipolar Disorder Flashcards
diagnostic criteria for bipolar I (vs. II)
- at least one episode of mania
6 symptoms of mania
- irritability
- high risk activities
- inflated self esteem
- flight of ideas
- distractibility
- decreased need for sleep
5 differences between BD and MDD
- briefer duration
- more rapid onset
- anergia
- psychomotor retardation
- reversed vegetative symptoms (overeating and oversleeping)
BD prevalence
1%
age of onset
15-19
are males and females equally affected?
yes for BD1
no for BD2 (women > men)
mortality rate for BD
25-50% attempted suicide, 20% completed
compared to depression, BP has
higher heritability
BD may be ___% comorbid with another axis I disorder
100%
BD has significant reductions in volume of ___ (2)
PFC
hippocampus
BD has decrease in number of __ (2) in ___
neurons and glial cells
PFC
BD has reduced amount of ___
N-acetyl-aspartate
mood stabilizers may reverse impairments in ___
BDNF, brain structure
BDNF is part of the ___ family of growth factors
neurotrophin
neurotrophin
proteins induce survival, development, function, repair, and plasticity of neurns
rita levi-montalcini
1986 nobel prize for discovering nerve growth factor (causes developing cells to grow by stimulating surrounding nerve tissue)
lithium increases levels of (2)
- N-acetyl-aspartate
2. gray matter volume
lithium, valproate, and carbamazepine interact with __-
various enzymes involved in 2nd and 3rd messenger pathways
four classes of drugs
- lithium
- anticonvulsant mood stabilizers
- atypical antipsychotics (olanzapine)
- omega 3 fatty acids
6 anticonvulsant mood stabilizers
- carbamazepine
- valproic acid
- gabapentin
- lamotrigine
- topiramate
- oxcarbazepine
lithium efficacy
60-80% of acute episodes; 1/3 relapse
2 reasons lithium is used less often
- difficult to use safely
2. no patent -> low profits
metabolism of lithium
excreted unchanged by kidneys
3 (+1) clinical effects against mania for lithium
- decreases number, frequency, intensity of episodes
2. decreases subtle, transient mood swings between episodes
days for response of Li
5-10 days
what percent of people show good to excellent response to Li?
2/3
what percent of people show partial response to Li?
80%
what percent of Li treated patients have adverse reactions?
35-95%
how is Li overdose treated?
dialysis
Li has a ___ therapeutic range
narrow
variations in __ intake affect Li retention
Na
4 most common Li side effects
- hand tremor
- incoordination
- nystagmus
- muscle weakness
choreoathetosis
big body movements that aren’t controllable (e.g. flinging your arms up)
2 CNS complaints for Li
- complaints about creativityproductivity
2. lack/loss of excitement
8 other side effects of Li
- antithyroid
- polyuria
- inhib vasopressin
- dipsogenic
- weight gain
- acne
- toxic arrhythmias in overdose
pregnancy risk percent
4-12%
what antiepileptic is no longer used?
carbamazepine (tegretol)
teratogen
causes malformation in embryos
comorbid substance abuse for BD I; BD II?
60%
50%
guideline for manic/mixed episodes
lithium with antipsychotic, valproate with antipsychotic
less ill patients are referred to
lithium, valproate, or antipsychotics like olanzapine
patients with depressive episodes are commonly prescribed __
lithium, lamotrigine
oxcarbazepine difference from carbamazepine
additional oxygen molecule
2 benefits of oxcarbazepine over carbamazepine
- does not induce hepatic enzymes
2. fewer drug-drug interactions
valproic acid MoA
binds to and inhibits GABA transaminase, increasing available GABA. may inhibit GABA reuptake; Na+ action potentials; gene transcription
% valproic acid response rate in Li resistant patients
70%
valproic acid is best in combination with ___
lithium, olanzapine
MoA of carbamazepine
inactivates voltage-sensitive sodium channels (probably 2nd messengers)
hyponatremia
electrolyte disturbance in which Na levels are too low
leukopenia
decrease in number of WBCs
6 side effects of carbamazepine
- sedation
- dry mouth
- blurred vision
- constipation
- blood disorders
- hyponatremia
3 major problems with carbamazepine
- autoinduction of CYP450
- hepatic toxicity
- blood problems
4 side effects of oxcarbazepine
- tiredness
- headache
- dizziness
- ataxia
oxcarbazepine has been shown to be superior to placebo in the treatment of ___
acute mania
carbamazepine should be replaced with ___
oxcarbazepine
teratogenic effects of valproic acid
neural tube defects (spina bifida) in first trimester
side effects of valproic acid (7)
- GI distress
- weight gain
- liver signs
- tremors
- sedation
- hair loss
- increased risk of PCOS; menstrual irregularities; hormonal problems
lamotrigine half life
26 hours
MoA lamictal
inhibits glutamate release
about ___ of refractory patients respond to lamictal, vs __ for gabapentin or placebo
50%
25%
about ___% of BD patients improve with topiramate
50%
unique advantage of topiramate
weight loss
topiramate has greater ___ than gabapentin or lamotrigine
cognitive dysfunction
4 side effects of topamax
- tingling
- irritability
- anxiety
- depression
use of topamax as an adjunct
improve efficacy and reduce weight gain of other agents
clozapine has more effect on mania or depression?
depression
risperidone is more antidepressant or antimanic?
antidepressant
hypothesis of antimanic action
dopamine blockade
omega 3 MoA
dampen signal transduction mechanisms