Bipolar Flashcards
Bipolar I vs II
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
Manic vs mixed vs hypomanic
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
Schizoaffective disorder - how does it differentiate from bipolar affective with psychotic features
SA - pt meets criteria for schizophrenia and has had delusions or hallucinations in absence of concomitant mood sx
Rapid cycling
4 or more bipolar episodes in a year
Antidepressants most likely to induce switch to mania (all can)
Tca and venlafaxine
- in any case, switch to mania may not be seen till 10 weeks into treatment
Medications approved for maintenance tx of bipolar
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
Bipolar depressed phase tx
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)
Cautions for use of lithium
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
MOA of lithium
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
Pharmacokinetics of lithium
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
Dosing of lithium
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
Levels of lithium including when to draw
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
Tx lithium tox
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
Take lithium with or without food?
Prob with - could be with or without
Food lowers diarrhea rate and could increase absorption v slightly
If SE occur take w food
Fastest onset of action in mania
Prob antipsychotic but with loading dose valproate may be as fast , but LD is less well tolerate
Valproate for bipolar
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
Valproate dosing
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
Carbamazepine contraindications
History of bone marrow suppression, porphyria, cbz or tca toxicity,
Contraindicated with mAO-I, clozapine, other meds that cause bone marrow suppression
mOA of CBZ:
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
Carbamazepine notes
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
Lamotrigine notes
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
Dosing of lamotrigine
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
Only atypicals approved for bipolar mania acute tx in children and adolescents age 10-17 years
Risperidone , aripiprazole
