Bipolar

Question 0

Bipolar I vs II

Answer 0

Bipolar I one or more manic or mixed episode usually but not always with mdd episode

Bipolar II one or more episodes of major depression interspersed with hypomanic

Cyclothymic - two years of hypo manic and dysthymix episodes never meeting criteria for mdd or mania

Question 1

Manic vs mixed vs hypomanic

Answer 1

Manic at least 1 wk, same with mixed but hypo manic at least 4 days

Mixed: manic and major depression sx nearly every day for at least 1 week
- severe enough to markedly impair function

Hypomanic - Symptoms are not severe enough to cause marked impairment , no psychotic features

Question 2

Schizoaffective disorder - how does it differentiate from bipolar affective with psychotic features

Answer 2

SA - pt meets criteria for schizophrenia and has had delusions or hallucinations in absence of concomitant mood sx

Question 3

Rapid cycling

Answer 3

4 or more bipolar episodes in a year

Question 4

Antidepressants most likely to induce switch to mania (all can)

Answer 4

Tca and venlafaxine

• in any case, switch to mania may not be seen till 10 weeks into treatment

Question 5

Medications approved for maintenance tx of bipolar

Answer 5

Usually want to continue the drug used to achieve remission (adjust to lowest possible dose)

Lithium, lamotrigine, olanzapine, aripiprazole
Also valproic and carbamazepine esp with mania

Question 6

Bipolar depressed phase tx

Answer 6

Lithium or lamotrigine

Lithium - may take a month of more to tx depression, 6-10 days for mania (may be most effective as combo with antipsychotic for acute mania, more than either alone)

Question 7

Cautions for use of lithium

Answer 7

Pregnant pts (caution)
Cardiac disease, kidney disease, thyroid disorder
Monitor for urine specific gravity <1.005 (lithium decreases urine conc ability)

Diuretics including caffeine increase fluid and lithium excretion

Question 8

MOA of lithium

Answer 8

Precise not known
Normalizes or inhibits secondary messages systems - inhibits phosphoinositide signaling, inhibits adequate Cyclase signaling, normalizes guanine (G protein) signal

Decrease 5ht uptake and increases 5ht receptor sensitivity

Inhibits dopamine synthesis decreases beta receptors and inhibits DA-2 and beta receptor sensitivity

Enhances GABA activity, normalizes levels

Reduces glutamatergic activity

Modulates calcium metabolism

Increases choline and cholinergic activity

Inhibits WNT signaling

Question 9

Pharmacokinetics of lithium

Answer 9

IR tabs or caps F= 95-100%
ER tabs 60-90%
Solution 100% - 8meq/5 ml

Not metabolized really eliminate 95% excreted

Half life 20-27 hrs nl, 36-50 hrs elderly

Peak 
Ir 0.5-3 hr
ER 4-12 hr
Soln 15 min to 1 hr
Vol of distrib 0.3-0.4 L/kg

Question 10

Dosing of lithium

Answer 10

Acute mania 600 tid or 900 bid

Maintenance 900-2400 per day in 2-4 divided doses preferably w meals

Kids 6-12 yo 15-20 mg/kg/day in 3-4 div doses for mania, start at 10-20 for maint

Adolescents 12-18 : adult doses or as an alternative: start at 25 mg/kg/day in 2-3 divided doses with target dose of 30 in 2-3 days

If nephrogenic diabetes insipid us - some suggest diuretic - if thiazides used decrease lithium dose by 50%

Ace and arb increase lithium levels by 200-300%!
NSAIDs increase by -50% - silo sac Least likely

Question 11

Levels of lithium including when to draw

Answer 11

Drawn 4-5 days from start -
Drawn in morning 10-12 hrs after last dose

Rule of thumb: for every 300 mg increase expect to see 0.3 mg increase in pt wnl renal fxn

Therapeutic range
Acute mania: 0.8-1.5
Maintenance : 0.6-1.2 meq/L

1.5-2 mild tox: GI, nv, diarrhea
CNS lethargy, coarse tremor of hand, muscle weakness,

2-2.5 moderate tox GI severe as above, CNS confusion nystagmus ataxia twitching plus cardiac tox - flat or inverted t waves
>2.5 severe tox grisly impaired consciousness , sz, syncope coma, renal to curvy, cardiac death

Question 12

Tx lithium tox

Answer 12

Mild: Tx lithium tox: hold for 1 day and re eval:

Collect f and e imbalance - give IV nacl 0.9% - body will take in sodium and excrete lithium

Severe tox- intermittent HD 12 hrs on 12 hrs off- goal: decrease level below 1 on 6-8 hr post dialysis

Other se - acne- dose dependent
Thyroid - interferes w synthesis - add thyroid don’t necessarily decrease lithium dose

Question 13

Take lithium with or without food?

Answer 13

Prob with - could be with or without

Food lowers diarrhea rate and could increase absorption v slightly

If SE occur take w food

Question 14

Fastest onset of action in mania

Answer 14

Prob antipsychotic but with loading dose valproate may be as fast , but LD is less well tolerate

Question 15

Valproate for bipolar

Answer 15

Contraindicated in liver dz
Relative contraindications of hematologic dz, pregnancy, hypersensitive to VPA

MOA: increase GABA levels and effect at receptor
Anti kindling properties may help rapid cycling

Question 16

Valproate dosing

Answer 16

Loading dose 20 mg/kg
Maint 20-60 mg/kg/day
Quick calc: add zero to pt weight and adjust to nearest dose form

Level for mania 50-125 mcg/ml, tox above 150

ER dose is approximately 1.15x EC

Question 17

Carbamazepine contraindications

Answer 17

History of bone marrow suppression, porphyria, cbz or tca toxicity,
Contraindicated with mAO-I, clozapine, other meds that cause bone marrow suppression

Question 18

mOA of CBZ:

Answer 18

Blocks sodium channels
Stimulates release of anti diuretic hormone
Blocks ca influx through NMDA receptor and decrease ca serum concn
Modulates aspartate and glutamate release
Anti kindling properties may decrease rapid cycling

Question 19

Carbamazepine notes

Answer 19

3a4 inducer
Onset is in 3 days
Max effect about 30 days 
Induces own metab so...
Half life is 25-65 hrs at first and 12-17 hrs after repeated dosing 

Test for Hla B 1502 in popn such as Han Chinese due to 10 fold increased risk of Stevens Johnson or toxic epidermal necrosis

Dose: 200 mg bid and increase q 3-4 days
Usual range 600-1600mg/day in divided doses goal range cbz; 8-12 mcg/ml
Kids 8-18: 15 mcg/kg/day in divided doses goal range : 7-10 mcg/ml

Take IR tab or suspension with food
Void grapefruit

Question 20

Lamotrigine notes

Answer 20

Restart initial titration if withheld more than 3-5 half lives (approximately 3-5 days if no intxn)- then, retire are from start

FDA approved for long term bipolar maint
Onset of action is slow because of dose titration schedule
Appears to be most useful for bipolar pts with depressed phase - both acute and prophylactic therapy

MOA: blocks voltage sensitive na channels
Anti kindling properties for rapid cycling and mixed

Metabolized by UGT
Inducible and inhibitable!!!!! For this reason half life is -24 hr
But can range from 14 hr with inducers to 59 hr with inhibitors!

Take with or without food - with food if gi upset

Oral contraceptives may decrease lamotrigine levels - talk to hcp if starting or stopping oc’s

Not usually sedating - can take am or pm

Question 21

Dosing of lamotrigine

Answer 21

Monotherapy diff than combo with CBZ inducer or VPA inhibitor
Mono:
Weeks 1-2 25 mg daily
Weeks 3-4 50 mg daily
Wk 5 100 mg daily
Week 6 and hereafter : 200mg qday

Combo:
Cbz inducer - higher dose - double with additional 300mg wk
1-2 50mg
3-4 100mg
5: 200 mg
6: 300mg
7: 400mg

With inhibitor VPA- almost half 
1-2: 25 mg every OTHER day or 12.5mg qday
3-4 25 mg qday
5: 50mg qday
6: 100mg qday

Question 22

Only atypicals approved for bipolar mania acute tx in children and adolescents age 10-17 years

Answer 22

Risperidone , aripiprazole