Psych Exam 4: Bipolar Disorder (Waters)

morbidity and mortality of bipolar vs MDD

both are higher in bipolar disprder

DSM-5 criteria for manic episode of bipolar disorder

A. at least 1 week (or any time if hospitalized) pf abnormal mood that is elevated, expansive, or irritable . significant increase in goal-directed activity or energy

B. at least 3 of the symptoms

C. significant social/occupational functioning, hospitalization required, or psychotic features present

D. not because of a substance/medical condition

DSM-5 symptoms for mania in bipolar disorder

must have 3 or more for mania (or 4 if irritable)

-inflated self esteem or grandiosity

-decreased need for sleep or feeling rested after only a few hours of sleep

-increased speech or speech that is pressured

-flight of ideas or subjective, racing thoughts

-easily distracted

-increased goal-directed activity or psychomotor agitation

-engaging in activities that result in detrimental outcomes (spending, sex, drugs)

DSM-5 criteria for a hypomanic episode in bipolar disorder

A. elevated, expansive, or irritable mood with increased activity or energy for 4 or more consecutive days

B. 3 or more symptoms the same as mania (4 if irritable)

C. change in functioning from baseline that is evident to others

D. impairment in social or occupational functioning that is not severe. hospitalization is not required and there are no psychotic symptoms

E. not due to a substance/treatment/condition

what doesn't affect diagnosis of type I vs II bipolar disorder

hospitalization for depressive episode

type I bipolar disorder

at least 1 manic episode

may have had previous hypomanic or depressive episodes

type II bipolar disorder

at least 1 hypoanic and depressive episode

no history of manic episode

mania 3 main characteristics of mania

->/= 1 week (unless hospitalized)

-may have psychotic features (hallucinations, paranoia, delusions)

-may need hospitalization

3 main characteristics of hypomania

->/= 4 days

- no psychotic features

- don't need hospitalization

type I vs II bipolar disorder

depends on the severity of mania/hypomania

depressive episodes can be equally severe in both I and II

how long do moods last in bipolar disorder

weeks- months

no day to day or less

mood lability

rapid changes in mood

more common in personality disorders and SUD than bipolar disorder

bipolar with mixed features

full criteria or one mood episode + 3+ symptoms of opposite

bipolar rapid cyclicing

- 4+ mood episodes have occurred wthin previous 12 months (mania, hypomania, depressive)

-separated by partial or full remission for 2+ months or switch to opposite polarity

bipolar psychotic features

delusions or hallucinations present at any time during an episode

-mood congruent or not

peripartum onset of bipolar disorder

mood symptoms occur during pregnancy or within 4 weeks of delivery

seasonal pattern of bipolar disorder

seasonal pattern of 1+ type of mood epipside with no non-seasonal episodes of that polarity for at least the previous 2 years

s/s of mania/hypomania

- begins abruptly with symptoms escalating over several days

-less need for sleep

-euphoric, elated, irritable

-may begin multiple new projects

- grandiosity (inflated self esteem)

-rapid, pressured, loud speech

-racing thoughts, flight of ideas

-excessive movement, distractability

DIG-FAST (mania symptoms)

Distractability

Indiscretions (excessive pleasure activities)

Grandiosity

Flight of Ideas

Activity increase

Sleep deficits

Talkativeness

psychotic features and suicide attempts in MDD vs bipolar depression

more common in bipolar depression than unipolar depression

diagnosis delay time for bipolar depression

6-8 years

which condition has the highest suicide rate of any psychiatric disorder

bipolar depression

common comorbidities with bipolar disorder

-anxiety

-SUD (type I)

-ADHD

-diabetes, dyslipidemia, obesity, CV disease

rating scales for depressive episodes of bipolar disorder

-MADRS, HAM-D

-bipolar depression rating scale (BDRS)

manic/ hypomanic rating scale

-young mania rating scale (YMRS)

-bech-rafaelsen mania scale (MAS)

-clinician administered rating scale for mania (CARS-M)

risk factors for bipolar disorder

-high for first-degree relative (very genetic)

-epigenetics (env factors)

-childhood: trauma, abuse, anxiety, subsyndromal conduct disorder

prevalence and gener prevalance of bipolar disorder

I is less common than 2

in type I the rate F=M

in type II the rate F>M

treatment with increasing episodes of bipolar disorder

episodes can become more frequent and harder to treat with each episode

age of bipolar onset

teens-mid 20s but diagnosis can be later

non-pharm treatment of bipolar disorder

-adequate sleep

-psychotherapy (adjunct)

-ECT

-bright light therapy (adjunct)

risk with bright light therapy

possible risk of switching to mania/hypomania

which 4 meds are NOT recommended in bipolar disorder

-topiramate

-zonisamide

-gabapentin

-levetiracetam

classic 4 mood stabilizers for bipolar

-lithium

-valproic acid (VPA)

-lamotrigine

-carbamazepine

what meds can be used to treat bipolar disorder

-classic mood stabilizers

-SGAs

acute treatment goal of bipolar

rapid control of behavioral symptoms, sleep restoration, mood stabilization

maintenance treatment goal

after mood stability has been achieved for 3 months

-continued improvement of functioning

-prophylaxis against future mood episodes

-may initially include meds used in an acute treatment--> goal of monotherapy

3 treatment goals of acute manic, hypomanic, and mixed episodes

-reduce agitation, aggression, impulsivity

-prevent harm to self/others

-atnidepressants should be tapered and discontinued when possible

antidepressants and bipolar disorder

may precipitate a switch from depressive episode into a mixed or mani/hypomanic episode

may occur 10 weeks later

IF used--> in combination with a mood stabilizer

no demonstrated benefit in depressive symptoms

manic/hypomanic first-line options

-lithium

-valproic acid

-SGAs

-lithium + SGA

-VPA + SGA

-haloperidol

manic/hypomanic 2nd line options

-alt 1st line

-CBZ

-ECT

mixed episode first-line treatment

-VPA

-CBZ

-SGAs (esp olanzapine)

mixed episode 2nd line treatment

alt first line

lithium response in mixed vs manic/hypomanic episodes

lithium is not effective for mixed bipolar episodes

when are psychotic features of bipolar most common

in manic episodes

treatment of psychotic features in bipolar

antipsychotics recommended first-line monotherapy for combo with mood stabilizer

is needed for psychotic features

first line treatment options for depressive episodes of bipolar disorder

-lithiium

-lamotrigine

-quetiapine

-lurasidone

-olanzapine + fluoxetine

bipolar I: consider lithium + VPA

second-line treatment options for depressive episodes of bipolar disorder

-alt first line

-combination of 2 first-line agents (but not 2 SGAs)

-cariprazine

-ECT

which SGAs should not be used in bipolar depression

aripiprazole and ziprasidone

how long should a med be continued after response to an acute episode

2-4 months

first-line maintenance treatment for bipolar

-continue med used in episode

-lithium

-lamotrigine (more depression)

-quetiapine, olanzapine, LAI risperidone

second-line maintenance treatment for bipolar disorder

- lithium + VPA or lamotrigine

-CBA

-alt SGA

duration of therapy for bipolar disorder

lifelong, can switch meds but should always be being treated

acute mania lithium target dose range

0.8-1.2 mEq/L

maintenance therapy target range for lithium

0.6-1.0 mEq/L

concentration of lithium in the body

- steady state occurs after 5 days of stable dosing

-measure trough levels

-follows first-order kinetics

why would we give lithium as a single dose?

reduce risk of renal toxicity, polyuria, and improve adherence

boxed warning of lihtium

lithium toxicity

-decreased renal ability to concentrate urine --> nephrogenic diabetes insipidus

-caution in pts with significant fluid loss

-avoid meds that alter conc

-increased risk of fetal malformations --> cardiac abnormalities

adverse effects of lithium

-acne

-psoriasis

-alopecia/thinning hair

-AV block or other conduction issues

-bradyarryhthmia

-nausea

-dry mouth/thirst

-polyuria

-AKI

-CKD

-hypothyroidism

-weight gain

-neurologic (tremor, seizures, coma, delirium, confusion)

lithium therapeutic window range

narrow therapeutic window

0.6-1.2 mEq/L ideal

mild to moderate lithium toxicity levels and symptoms

1-5-2 mEq/L

D/V, drowsy, muscle weakness, decreased coordination

moderate to severe lithium toxicity level range and symptoms

2.0-2.5mEq/L

ataxia, blurred vision, tinnitus, EKG chages

severe lithium toxicity levels and symptoms

> 3.0 mEq/L

neurological changes, coma

what is not effective on lithium toxicity

activated charcoal, forced diuresis

hemodialysis in lithium toxicity

is effective in removing lithium

when to recommend hemodialysis in lithium toxicity

> 4.0 mEq/L

>2.5mEg/L with serious cardiac/neurological symptoms

which drugs increase lithium levels

-NSAIDs

-ACE inh's/ ARBs

-thiazide diuretic

-loop diuretics

- reduced sodium intake

which drugs decrease lithium levels

- theophylline

-verapamil

-osmotic diuretics

-caffeine

-sodium bicarbonate antacids

safety monitoring acronym for lithium

LITH

Levels

Insipidus (Diabetes insipidus)

TSH/Tremor (Hypothyroidism)

Hydration status (hyponatremia, increased Li levels)

kindling

overtime the brain becomes sensitized -> pathways within the CNS are reinforced if episodes are not treated

more likely to have future episodes that occur independently of an outside stimulus

VPA effect

not much on depressive, more controlling manic

loading strategy of VPA

-less common

-20mg/kg (25mg/kg if ER)

-may consider 30mg/kgx2 days THEN 20mg/kg (25mg/kg if ER)

TDD of 20mg/kg --> 50-125 mcg/mL (steady state)

titration strategy of VPA

initiate 500 or 750mg QMs with rapid titration to 20mg/kg dose

may titrate by 500mg/day

therapeutic steady state range of VPA

50-125mcg/mL as the trough level

which VPA forms are tablets

divalproex sodium ER and DR

DR is enteric coated

IV and solution VPA form

divalproex sodium IR

which form of VPA is in capsule form

valproic acid IR

which VPA comes in sprinkle capsules

divalproex sodium DR

which VPA formulations are dose BID?

divalproex DR, vilproate sodium IR, valproic acid IR

which VPA formulation is dosed once per day

divalproex sodium ER

when to draw trough levels for VPA in bipolar

4-5 days after initiation or change in dose

when changing to ER VPA

level may decrease so may need to increase the dose

contrainditations of VPA

-hepatic disease

-urea cycle disorders

-pregnancy (for migraines)

BBWs for VPA

-hepatic failure

-pancreatits

-teratogenic effects (neural tube defects and decreased IQ)

other warnings for VPA

-dose-related thrombocytopenia

-hyperammonemia/encephalopathy

-hypothermia

-DRESS

adverse effects of VPA

-rash

-alopecia

-N/V/D

-constipation

-transaminitis, hepatotoxicity

-pancreatitis

-weight gain

-hyperammonemia

-thrombocytopenia

-ataxia

-diplopia

-dizziness

-sedation

-tremor

general presenting symptoms of VPA toxcity

mainly neurological manifestations

-ataxia

-tremor

-CNS depression

-may progress to seizures, coma, and death

also hyperammonemia

which drugs have anti-kindling properties

VPA and lamotrigine

protein binding in VPA toxicity

degree of protein binding decreases with higher concentrations in the blood

effect of carbapenem antibiotics + VPA

reduced VPA levels

-increased risk of withdrawal seizures

-very fast!

lamotrigine + VPA

causes increased lamotrigine levels (x2)

must decrease lamotrigine dose by 50%

phenytoin + VPA

may decrease phenytoin level

ritonavir + VPA

increased clearance of VPA

lamotrigine dosing, why is it so slow

to reduce risk of SJS/TEN

lamotrigine titrating up schedule

weeks 1-2: 25mg/day

weeks 3-4: 50mg/day

weeks >/=5; 100mg/day

max lamotrigine dose

400mg/day when alone

lamotrigiene dosing schedule when added to VPA

weeks 1-2: 25mg every other day or 12.5mg/day

weeks 3-4: 25mg/day

weeks >/=5: 50mg/day

max lamotrigine dose when added to VPA

100mg

warnings with lamotrigine

BBW: SJS, TEN

DRESS

blood dyscrasias, aseptic meningitis

delayed hypersensitivity reaction with lamotrigine SJS/TEN

doesn't occur until several weeks until after initiation

prodromal period with SJS/TEN

most pts with this reaction

flu-like symptoms, fever, lesions on face and upper torso