Bipolar Disorder Flashcards
Two main types of bipolar disorder?
- BDI
2. BDII
Define BDI:
Mood disorder with at least 1 wk of:
- elevated or irritable mood
- increased activity or E
Define BDII
Mood disorder w/ both of
- current/past HYPOMANIC episode, and
- current/past depressive episode
A person who has an episode of mania is automatically diagnosed as having…
BDI
T or F: Bipolar disorder is curable
F (it can only be managed and maintained, but not cured)
Which gender has more manic episodes, and which has more depressive episodes?
Males = manic
Women = depressive
In bipolar pts, what can antidepressants do to them?
It can cause them to suffer from mania
NE: excitatory or inhibitory NT?
excitatory
Serotonin: excitatory or inhibitory NT?
inhibitory
DA: excitatory or inhibitory NT?
excitatory
Besides serotonin, what other NT(s) are inhibitory?
GABA
glutamate: excitatory or inhibitory NT?
excitatory
T or F: Relapses in mood episodes make it easier to tx the pt.
F
It actually makes it harder since the brain becomes more and more sensitized and labile
One of the leading causes of death in BD
suicide
Main diff b/w mania and hypomania?
Hypomania symptoms last a shorter amt of time (~4 days), and are less severe
T or F: Patient is diagnosed w/ BDI if he/she has experienced only hypomanic episodes.
F
need a full manic episode for BDI dx
How long does a manic episode need to last to be dx’ed w/ BDI?
1 week at least
T or F: A manic episode is automatically dx’ed as BDII.
F
BDII is characterized by only hypomania and MDD
Differentiate b/w BDI and BDII
They BOTH have MDD, but only BDI has full manic episodes, whereas BDII has hypomania (and no mania)
As soon as mania is seen, it becomes BDI
What is unipolar illness?
MDD (just another term to distinguish it from bipolar disorder)
What is cyclothymia?
Mood disorder that cycles between manic and depressive states without ever fully meeting diagnostic criteria for hypomania, mania, or MDD
T or F: BDI dx can never be made without a full manic episode
T
What are the three main categories of mood stabilizers used for BD tx?
- Li
- anticonvulsants
- atypical antipsychotics
What’re the most commonly used drugs used as mood stabilizers?
- Li
2. valproic acid/divalproex
Li time to peak (liquid)
0.5-1h
Li time to peak (reg. release cap)
1-3 h
Li time to peak (XR)
4-12 h
Li t1/2 w/ normal renal fn:
12-27h
How does Li’s Vd in the elderly differ from that of normal adults?
It decreases due to less body water and lean body mass in elderly ppl
T or F: Li concs in elderly decrease due to reduced body water and lean body mass
F
[Li] INCREASES since it dissolves in less total body water (less dilution = higher conc)
Main elimination organ of Li?
Kidneys
Which plasma protein does Li bind to?
None
How is Li reabsorbed by the kidneys?
With Na
What kind of diet should pts taking Li avoid?
Na-free diets (will lead to the body holding on to/reabsorbing Na > the body will also hang on to/reabsorb Li)
How does dehydration affect Li levels and why?
It leads to reabsorption of Na > water AND Li follow > Li tox
How does pregnancy affect Li levels and why?
Preggos have more fluid > higher Vd > less plasma conc
How do sodium supplements affect Li levels and why?
Increased Na > increased excretion of Na by kidneys > increased Li excretion (bc Li follows Na)
Therapeutic Li range for acute mania tx:
1-1.2 mmol/L
Therapeutic Li range for maintenance bipolar disorder tx:
0.6-1 mmol/L
Therapeutic Li range for bipolar disorder tx in ELDERLY pop:
0.6-0.8 mmol/L
T or F: Li is very safe, hence monitoring is not req’d
F
It’s a narrow therapeutic range drug
When do we draw blood samples for TDM of Li?
12h post dose
Initial dosing of Li for acute mania?
600-900mg/day (in 1-2 divided doses)
After giving the initial 600-900mg/day Li dose for acute mania, what should we do?
Take 12h post dose levels (goal: 0.8-1.2mmol/L)
Common AEs of Li?
GI, esp. nausea
Normal starting Li doses for elderly pop for acute mania tx?
150mg-300mg
Normal Li maintenance doses for BD?
900mg (600-1800mg/day)
T or F: Li doses do not have to be adjusted in renal impairment.
F
They are 95% eliminated in kidneys, so definitely need adjustments
How do loop diuretics affect Li levels?
Increases excretion of fluid > body holds on to Na > body holds on to Li > INCREASED Li levels
How do NSAIDs affect Li levels?
Nsaids reduce renal perfusion > increased Li levels
Li: Acute intoxication AEs
CNS, GI sys, kidneys
Li: Chronic toxicity AEs
CNS (slurred speech, blurred vision, confusion, lethargy) > drunk-like, essentially
What does Li having a linear PK profile mean for dosing?
Makes it easy > changes in doses are directly proportional to changes in plasma levels
What do we need to know before changing Li doses for a pt?
Kidney fn
What is divalproex sodium?
A valproic acid prodrug
What is valproic acid used for?
- seizures (broad spectrum anti-epileptic agent)
2. mood stabilizer for BD
Which plasma protein is valproic acid mostly bound to?
Albumin (85-90%)
Above what plasma levels of valproic acid does unbound fraction increase disproportionally to the dose?
above 500 micromol/L
Major route of valproic acid elimination
> 95% metabolized by liver
Valproic acid t1/2
12-18h
General valproic acid therapeutic range
350-700 micromol/L
T or F: It’s v. important that we get valproic acid within the target range.
F > it’s highly individualized
When do we take trough levels of valproic acid?
when it’s reached steady state (2-4 days after initial tx)
CI of valproic acid
Hepatic dz > reduced plasma proteins and clearance
DIs of valproic acid
- val. acid = enzyme inhibitor (CYP2C9, and others)
2. drugs that have stronger albumin binding > displace valproic acid
How do we adjust lamotrigine levels when on valproic acid?
Cut the dose in half since lamotrigine levels are increased by 50%
Main side effects of valproic acid
GI (N/V, anorexia), CNS (remor, sedation, ataxia), thrombocytopenia
MOA of lamotrigine:
- reduces release of glutamate (excitatory NT)
2. 5HT3 receptor inhibitor (weak)
What’s a very important aspect of lamotrigine dosing?
It must be titrated VERY SLOWLY to avoid rash
Titration of lamotrigine must be restarted if doses are missed for THIS long.
5 days of missed doses
When will we half a lamotrigine dose?
When pt is on valproic acid too
Carbamazepine MOA
- reduces repetitive APs in depolarized neurons via voltage-dependent sodium channels
- increases ADH release > increases reabsorption of H2O
Carbamazepine: main route of elimination
Hepatic via CYP
What’s special about carbamazepine?
It induces CYP3A4 and is metabolized by it too > it AUTOINDUCES its own metabolism
Half life of carbamazepine:
VARIABLE due to autoinduction
When does autoinduction reach its max?
after 3-4 wks of a stable dosing regimen
Common AEs of carbamazepine
GI (N/V, anorexia)
CNS (lethargy, dizziness, drowsiness, h/a, incoordination, ataxia, blurred vision, double vision, sedation)
Important idiosyncratic carbamazepine AE
SIADH > hyponatremia
How often should carbamazepine sampling take place during autoinduction phase?
q1-2 wks during auto-induction 1 h prior to her next dose
What are the three anticonvulsants used in BD?
valproic acid/divalproex, lamotrigine, and carbamazepine
Main type of antipsychotics used in BD?
Atypical (2nd gen)
General MOA of all antipsychotics?
DA blockade
T or F: Doses of antipsychotics are higher for bipolar disorder compared to doses for psychosis
F
Doses are LOWER compared to those used for psychosis
1st gen vs 2nd gen antipsychotics: which one has lower risk of extrapyramidal sx’s?
2nd gen (atypicals)
What’s the risk of using antidepressants in BD pts?
They can cause the pt to switch to mania, and can worsen manic episodes
When would antidepressants be appropriate in bipolar pts?
If pt is suffering from severe depression and has a hx of mild mania
Preferred antidepressants in bipolar pts:
- SSRIs (except paroxetine - it has neg evidence)
2. bupropion
Which antideps are assoc w/ higher risk of switching to mania?
SNRIs and TCAs
Main SSRIs used in BD pts
- citalopram
- escitalopram
- fluoxetine
- sertraline