bipolar disorder - dr krysiak

2 hours = 10 questions

what is the average age of onset for bipolar disorder?

bipolar I: 18 yo

bipolar II: 22 yo

who does bipolar II occur more frequently in?

a. men

b. women

b.

T/F patients with bipolar disorder generally will have other mental health conditions

TRUE

what percent of patients with bipolar disorder have a family history of bipolar disorder?

50%

list factors associated with a diagostic change to bipolar disorder from MDD later in life

• rapid onset of depressive symptoms

• medication-precipitated hypomania

• family history

• substance abuse

• >4 episodes of depressive episodes

• earlier onset depression

the same general paradigm of ___________ can be applied to mania as well as depression

trimonoaminergic neurotransmitter system

treatments of MANIA _______ trimonoaminergic regulation of circuits associated with mania (SATA)

a. reduce

b. increase

c. stabilize

a. c.

what is the biogenic amine hypothesis?

excessive catecholamines (NE and DA) manifests as mania

deficits in central 5HT, NE, and DA contribute to depression

dysregulation of amino acid NTs

deficiency of _______ or excessive _________ activity causes dysregulation of neurotransmitters (increased DA and NE activity)

deficiency of GABA

excessive glutamate activity

cholinergic hypothesis

deficiency of _______ causes an imbalance in cholinergic adrenergic activity and can increase the risk of manic episodes

acetylcholine (ACh)

cholinergic hypothesis

increased central ________ can increase the risk of depressive episodes

acetylcholine (ACh)

_______ can precipitate manic like symptoms

a. hyperthyroidism

b. hypothyroidism

a.

_________ can precipitate a depression and be a risk factor for rapid cycling

a. hyperthyroidism

b. hypothyroidism

b.

clinical presentation

history of mania or hypomania that is __________

NOT caused by any other medical condition, substance, or psychiatric disorder

manic episode DSM-V criteria

elevated, expansive, or irritable mood, lasting at least 1 week

at least 3 of the following (4 if mood is irritable only):

• grandiosity

• decr. need for sleep

• pressured speech

• flight of ideas

• distractibility

• incr. in goal-directed activity

• excessive involvement in pleasurable activities

hospitalization to prevent harm to self or others or psychotic features

sx not due to a substance or medical condition

what is the less severe form of mania called?

what is the DSM-V criteria?

hypomania

4 days of abnormal or persistent elevated mood

hospitalization not required

no psychotic features

which are longer lasting and occur more often in bipolar II than bipolar I?

a. manic episodes

b. hypomanic episodes

c. depressive episodes

c.

which of the following is this:

episodes: manic or mixed ± major depression

diagnosis after 1 manic episode

a. bipolar I disorder

b. bipolar II disorder

c. cyclothymic disorder

a.

which of the following is this:

episodes: hypomanic ± major depression

no history of manic or mixed episode

a. bipolar I disorder

b. bipolar II disorder

c. cyclothymic disorder

b.

which of the following is this:

episodes: chronic fluctuations between hypomania and mild depression episodes that have never met full criteria for hypomania, manic, or depressive episodes

no asymptomatic time periods lasting > 2 months

a. bipolar I disorder

b. bipolar II disorder

c. cyclothymic disorder

c.

which of the following is this:

manic or hypomanic episode, with mixed features - full criteria met for manic or hypomanic episode with at least 3 sx of depression

a. with mixed features

b. rapid cycling

a.

which of the following is this:

at least 4 separate mood episodes (mania, hypomania, or depressive) occurred in the previous 12 months

a. with mixed features

b. rapid cycling

b.

why are many patients with bipolar disorder incorrectly diagnosed with unipolar major depression?

patients spend MORE TIME in the DEPRESSED state

if a patient with bipolar disorder is incorrectly diagnosed with unipolar depression, what can antidepressant monotherapy lead to?

incr. mood cycling, mixed states, and conversion to hypomania and mania

incr. suicidality

in the majority of patients when does mania occur?

just before or immediately after a depressive episode

T/F cycle frequency stays the same throughout the illness

FALSE — it accelerates — episodes can become longer in duration and more frequent with aging

what rating scales can be used for bipolar depression?

• young mania rating scale (YMRS)

• clinical global impressions scale - bipolar version (CGI-BP)

what are the goals of treatment during acute illness?

remission of active target symptoms

overall stabilization of mood

how long is therapy usually continued following acute response?

2-4 months

once there is mood stability for approximately __________ during continuation, maintenance treatment is considered

3 months

list nonpharm tx options for bipolar disorder

• adequate nutrition

  • diet: high in essential amino acids, fatty acids, and vitamins/minerals

• sleep, exercise, and stress reduction

• psycho-educational programs

  • interpersonal therapy

  • cognitive behavioral therapy

  • medication adherence education

• ECT — most data supporting its use

• TMS

when is lithium indicated?

manic episodes of bipolar disorder and maintenance

idk if we need to know

list the brand names and formulations of lithium carbonate and lithium citrate

lithium carbonate	brand	formulation
	eskalith	capsule
	eskalith CR	ER tablet
	lithobid	ER tablet
	generic	tablet capsule

lithium citrate

cibalith-s

solution

what is the target lithium serum concentration for ACUTE mania?

a. 0.6 - 1.2 mEq/L

b. 0.8 - 1.2 mEq/L

c. 0.6 - 1.0 mEq/L

d. 1.2 - 1.5 mEq/L

b.

what is the target lithium serum concentration for maintenance?

a. 0.6 - 1.2 mEq/L

b. 0.8 - 1.2 mEq/L

c. 0.6 - 1.0 mEq/L

d. 1.2 - 1.5 mEq/L

c.

in full mania, some patients may require what lithium levels?

a. 0.6 - 1.2 mEq/L

b. 0.8 - 1.2 mEq/L

c. 0.6 - 1.0 mEq/L

d. 1.2 - 1.5 mEq/L

d.

steady state concentrations of lithium are achieved after approximately _______ days of stable dosing

5 days

when should lithium levels be drawn?

morning

12-hour post dose level

lithium follows _______ kinetics

a. first order nonlinear

b. first order linear

c. michaelis-menten

b.

how is lithium metabolized and excreted?

NOT metabolized

95% excreted unchanged by glomerular filtration (kidney/renal)

how does the half-life of lithium compare between normal patients and elderly patients?

normal: 20-27 hours

elderly: 36-50 hours —> longer

when is lithium contraindicated? (SATA)

a. severe/unstable renal or cardiovascular disease

b. severe/unstable hepatic impairment

c. severe debilitation

d. dehydration or sodium depletion

a. c. d.

what is the BBW for lithium?

lithium toxicity

-levels should be routinely monitored

how long does it take for lithium to work for mania? depression?

mania: 6-10 days, full resolution up to 3 weeks

depression: >1 month

list the dermatologic adverse effects of lithium

• acne

• psoriasis

  • more common >50 y.o.

• alopecia/thinning hair

  • more common in women

  • thyroid levels need to be tested!!! (hypothyroidism)

what kind of cardiac adverse effects can lithium cause?

• atrioventricular block

• bradyarrhythmioas

• bradycardia

• lithium toxicity

  • ECG changes

  • arrhythmias

  • QTc prolongation

what kind of gastrointestinal adverse effects are seen with lithium?

• nausea

  • early in therapy

  • can change to ER formulation

• dry mouth/thirst

  • educate on adequate hydration

what kind of genitourinary adverse effects are seen with lithium?

• polyuria

  • can target lower serum levels and QD dosing

  • amiloride may be added

• acute kidney injury

  • most common in toxicity

• chronic kidney disease

T/F lithium causes hyperthyroidism and weight loss

FALSE — causes HYPOthyroidism and weight GAIN

T/F preexisting HYPOthyroidism is NOT a contraindication to starting lithium

TRUE

what kind of tremor is very commonly seen with lithium and usually resolves with continued treatment?

hand tremor

how do we treat lithium toxicity? (SATA)
a. activated charcoal

b. sodium polystyrene sulfonate

c. hemodialysis (HD)

b. c.

what drugs can INCREASE lithium levels? (SATA)

a. NSAIDs

b. ACEi/ARB

c. diuretics

d. methylxanthines

a. b. c.

with what drug class is the interaction with lithium delayed and not seen for a few weeks?

a. NSAIDs

b. ACEi/ARB

c. diuretics

d. methylxanthines

b.

which kind of diuretics have limited effects on lithium?

a. thiazides

b. loops

c. potassium sparing

c.

which leads to decreased lithium?

a. increased sodium

b. decreased sodium

a.

with lithium we want to monitor for _____ improvement of symptoms during acute episode

50%

what is the indication for divalproex?

acute manic or mixed episodes, w/w/o psychotic features associated with bipolar disorder

idk if we need to know

what is the initial dosing of divalproex?

20 mg/kg/day in divided doses over 12 hours

T/F exact serum levels of divalproex indicative of response in bipolar disorder have NOT been established

TRUE

can patients with bipolar disorder switch dosage forms of divalproex without significantly altering the dose?

what if it’s for a seizure disorder?

bipolar disorder: switch w/o alteration

seizure disorder: must alter

idk if we need to know

list the brand names and formulations of divalproex sodium and valproic acid

divalproex sodium	brand	formulation
	depakote	EC tablet DR tablet
	depakote ER	ER tablet
	depakene	syrup
	depakote sprinkles	capsule

valproic acid

stavzor

delayed release capsule

the rate of absorption differs among preparations of divalproex but it is mostly _______

rapid

divalproex is extensively bound to _______

unbound serum concentrations may be more helpful than total serum concentrations

albumin

list CIs of divalproex

• hepatic disease or significant hepatic dysfunction

• hypersensitivity

• urea cycle disorders

• mitochondrial disorders

• pregnancy

what is the BBW for divalproex?

• hepatic failure

• pancreatitis

• teratogenic effects

list warnings/precautions for divalproex

• dose related thrombocytopenia

• hyperammonemia/encephalopathy

• hypothermia

• DRESS

• incr. risk of suicidality

• teratogenicity

  • neural tube defects and decr. IQ scores

the effects of divalproex can be seen as early as _______ with loading dose

3 days

list ADRs of divalproex

• dermatologic

  • rash, SJS, TEN, DRESS

  • alopecia

• gastrointestinal

  • n/v/d/c

  • transaminitis and hepatotoxicity

    • fulminant liver failure: w/in first 6 months

    • MONITOR LFTs

  • pancreatitis

    • d/c if occurs

• endocrine/metabolic

  • significant WEIGHT GAIN

  • hyperammonemia

    • mild: reduce dose or hold

    • moderate-severe: tx with L-carnitine or lactulose

    • don’t need to monitor unless they have sx

• thrombocytopenia

• neurologic

  • ataxia, diplopia, dizziness, sedation

  • tremor (high doses)

• toxicity

what medications interact with divalproex?

what is the effect?

• lamotrigine

  • lamotrigine levels increase

  • give reduced dose (blue pack)

• phenytoin

• warfarin

  • increased effects of warfarin —> incr. bleeding risk

list monitoring parameters for the efficacy of divalproex

• monitor for response

• 50% improvement of symptoms during acute episode

• early response is predictive of remission

when is lamotrigine indicated?

maintenance tx of bipolar I disorder

who is clearance of lamotrigine higher in?

lower?

when do we need to decrease the dose?

clearance higher: children

clearance lower: elderly

decrease dose: hepatic disease

why does lamotrigine have a slow titration schedule?

reduce risk of SJS/TEN

with lamotrigine, any break in patient therapy for > _____ warrants retitration

> 5 days

what is the BBW for lamotrigine?

other warnings/precautions?

BBW: SJS/TEN

DRESS

risk of blood dyscriasis

incr. risk of suicidality

aseptic meningitis

if a patient is developing SJS/TEN, what will we see several weeks prior to the rash?

after someone gets it with lamotrigine should we rechallenge?

flu-like symptoms

do NOT rechallenge

what is the indication for carbamazepine?

what dosage form?

acute manic or mixed episodes of bipolar I disorder, monotherapy or adjunctive treatment

ER CAPSULE ONLY

recall

what is special about carbamazepine and it’s half life?

AUTOINDUCTION

begins after 3-5 days of therapy, completed 3-5 weeks after stable dose maintained

recall

what kind of testing is required before initiating carbamazepine?

HLA-B*1502 allele testing in Asian patients

positive —> incr. risk of SJS/TEN

list CIs of carbamazepine

• bone marrow suppression

• use with MAOIs, nefazodone, or lurasidone

• use with delavirdine or other NNRTIs

what is the BBW with carbamazepine?

other warnings?

BBW: fatal hypersensitivity reactions —> DRESS, SJS/TEN; anemia and agranulocytosis

incr. risk of suicidality

teratogenicity

HYPOnatremia

withdrawal seizures

what is the onset of action of carbamazepine in acute mania?

7 days

list ADRs of carbamazepine

• dermatologic

  • rash

  • SJS/TEN

• GI

  • n/v/c/dry mouth

  • hyponatremia

    • risk: advanced age, other meds, female

• hematologic

  • agranulocytosis/aplastic anemia

• neurologic

  • ataxia

  • dizziness

  • somnolence

  • tremor

• toxicity

  • > 12 mcg/mL: ataxia and nystagmus

  • > 40 mcg/mL: coma and seizures

list drug interactions with carbamazepine and their effects

• CYP3A4 and 1A2 substrates

• antidepressants

• antiretrovirals

• antipsychotics

• clozapine

• apixaban/dabigatran/rivaroxaban/warfarin

• hormonal contraception

all of them have decr. serum concentrations

T/F SGAs can improve mania within several days

TRUE

antipsychotics can be given as _____ in bipolar disorder targeting psychotic symptoms (SATA)

a. adjunctive therapy acutely (waiting for mood stabilizer to take effect)

b. monotherapy for acute episode

a. b.

what antipsychotics are first line?

second line?

first line:

• quetiapine

• lurasidone + lithium/divalproex acid

second line:

• fluoxetine/olanzapine (symbyax)

• cariprazine

what antipsychotics are used for acute mania? (SATA)

a. aripiprazole

b. olanzapine

c. olanzapine/fluoxetine

d. quetiapine

e. risperidone

f. ziprasidone

g. asenapine

h. cariprazine

i. lurasidone

a. b. d. e. f. g.

what antipsychotics are used for acute depression? (SATA)

a. aripiprazole

b. olanzapine

c. olanzapine/fluoxetine

d. quetiapine

e. risperidone

f. ziprasidone

g. asenapine

h. cariprazine

i. lurasidone

c. d. i.

what antipsychotics are used for maintenance? (SATA)

a. aripiprazole

b. olanzapine

c. olanzapine/fluoxetine

d. quetiapine

e. risperidone

f. ziprasidone

g. asenapine

h. cariprazine

i. lurasidone

ALL

remember risperidone has a LAI

when are benzodiazepines used?

combo with other medications for ACUTE tx of mania or mixed episodes

used as short term adjunctive sedative hypnotic agent

effective in acutely agitated patients

what are the general guidelines for acute manic or mixed episodes?

• assess for secondary causes

• d/c antidepressants

• taper off stimulants and caffeine

• treat substance use

• encourage good nutrition

what are the guidelines for treating HYPOMANIA?

first

• optimize current mood stabilizer of not adherent or initiate mood-stabilizing medication

  • lithium, valproate, carbamazepine, SGAs

• add benzo for short-term adjunctive tx of agitation or insomnia if needed

• oxcarbazepine is alternative med

second (inadequate response)

• 2 drug combo

  • lithium + antiseizure med or SGA

  • antiseizure med + antiseizure med or SGA

what are the guidelines for treating MANIA?

first

• optimize mood stabilizer or med regimen if non-adherent or initiate new mood-stabilizing 2 or 3 drug combos

  • lithium, valproate, SGA

• PLUS A BENZO and/or antipsychotic for short-term adjunctive tx of agitation or insomnia

  • lorazepam is recommended for catatonia

• alternative: carbamazepine (oxcarbazepine if not responding)

second (if response is inadequate)

• 3 drug combo

  • lithium + antiseizure med + antipsychotic

  • antiseizure med + antiseizure med + antipsychotic

third (if response is inadequate)

• consider ECT for mania with psychosis or catatonia

• add clozapine for tx-refractory illness

should we combine antispychotics for manic episodes?

NO

what are the guidelines for acute depressive episode?

• assess for secondary causes (alcohol or drug use)

• taper off antipsychotics, benzos, or sedative-hypnotic agents if possible

• treat substance use/misuse

• encourage good nutrition

T/F antidepressants can be used as monotherapy

FALSE — use with a mood stabilizer

when do we consider maintenance treatment?

what is the goal of maintenance treatment?

mood stability for ~3 months during continuation treatment

goal: prophylaxis against future mood episodes

list meds that are FDA approved for the prevention of recurrence of bipolar disorder

lithium

lamotrigine

risperidone LAI

olanzapine

ziprasidone

quetiapine

aripiprazole