CNS Lecture 24-26: Pharmacotherapy of Bipolar Disorder

What is bipolar disorder?

chronic disorder characterized by shifts in mood that can range from severe depression to extreme mania

Bipolar disorder is more common in ____________.

women

Men typically have __________ onset of bipolar symptoms than women.

earlier

What is the median age of onset for bipolar disorder?

25 years

What are the risk factors of bipolar disorder?

**** 1st degree relative with BD ****

Genetics

Drug/alcohol use

Major life events for at risk individuals

Early adulthood

What is the BIGGEST risk factor for bipolar disorder?

having a 1st degree relative with BD

What are the adverse health behaviors associated with BD?

Substance use

Suicide

Risky behaviors

About how many patients with BD will attempt suicide at least once?

25-50%

What other diseases should be ruled OUT before diagnosing bipolar disorder?

***Substance-induced mood disorder*****

Schizophrenia

MDD

Hypothyroidism

Anemia

Neurologic illness

What is the #1 most important thing to rule out before diagnosing BD?

whether it was induced by a substance

If someone presents with mania (current or historical), what is their most likely diagnosis?

Bipolar 1

If someone presents with hypomania (current or historical), what is their most likely diagnosis?

Bipolar 2

If someone presents with depression and mania (assuming you ruled out MDD), what could they be diagnosed with?

Mixed features

If someone presents with depression and hypomania (assuming you ruled out MDD), what could they be diagnosed with?

Bipolar 2

Which type of bipolar disorder has the worst outcomes and highest suicide risk?

Mixed features

Bipolar 1

manic episode +/- depressive episode

What does a patient need to have in order to be diagnosed with bipolar 1?

Manic episode

Bipolar 2

hypomania and depression

Cyclothymic disorder

hypomanic + depression that are not severe enough to meed criteria for the DSM

What are the DSM criteria for a manic episode?

at least 1 week of sx almost daily

abnormally elevated, expansive, or irritable mood

Abnormally and persistently increased goal-directed activity

How long do manic symptoms have to last to be considered mania?

at least 1 week with symptoms almost daily

DIG FAST

Symptoms of Mania

Distractibility

Irresponsibility

Grandiosity

Flight of Ideas

Activity and Agitation

Sleep (decreased need)

Talkativeness

A manic episode is what to the brain?

TOXIC

How many DIG FAST symptoms does the DSM state a patient has to have for a manic episode?

3 or more

Hypomania is exclusive to what?

Bipolar 2

What are the DSM criteria for a hypomanic episode?

at least 4 days of sx

3+ DIG FAST symptoms (not as severe)

NOT SEVERE ENOUGH TO BE HOSPITALIZED

What is the main distinguisher between a hypomanic episode and a manic episode?

Mania is severe enough to require hospitalization whereas hypomania is NOT

Does Lithium work for BD with mixed features?

NO

What is the worst case scenario in BD?

Mixed features

When is BD considered to be rapid cycling?

4 or more mood episodes per year

Besides mixed features, which other type of BD has a poor prognosis?

Rapid cycling

Are antipsychotics mood stabilizers?

NO

What is a mood stabilizer?

anti-manic

What are the treatment options for bipolar disorder?

Lithium

Carbamazepine

Valproic acid

Lamotrigine

SGAs

When is Lithium used in BD?

Maintenance of BD

Acute mania

Lithium __________ the risk of suicide.

decreases

Lithium is considered to be the MOST effective medication at what?

Preventing re-hospitalization in BP1

Preventing mania relapse

What level of Lithium is considered to be subtherapeutic?

< 0.6 mmol/L

What level of Lithium is too high and can cause ADRs?

>0.8 mmol/L

What is the approximate Lithium level we want to achieve for acute mania?

0.8 - 1.5 mEq/L

What is the approximate Lithium level we want to achieve for maintenance?

0.6-1 mEq/L

At what level of Lithium would we see someone with GI upset and/or tremors?

1.5-2 mEq/L

At what level of Lithium would we see someone with confusion or somnolence?

2-2.5 mEq/L

At what level of Lithium would we see someone with seizures or even death?

>2.5 mEq/L

What are the different levels of Lithium toxicity?

GI upset/tremor = 1.5-2 mmol/L

Confusion/somnolece = 2-2.5 mmol/L

Seizures/death = >2.5 mmol/L

When should Lithium levels be drawn?

8-12 hours after last dose

How long until Li reaches steady state?

About 5 days

What drugs interact with Lithium?

Diuretics (Loops, Thiazides)

NSAIDs

ACE/ARBs

Caffeine/Theophylline

Lithium is considered a salt, so it relies heaily on what two things?

Fluid balance

Renal Function

What labs MUST be monitored for a patient on Lithium?

**SCr and BUN

**Thyroid fxn

CBC and Electrolytes

EKG

Pregnancy

ADRs of Lithium

Hand tremor (intention)

Acne

Non-toxic goiter

Weight gain

GI upset

Cardiac

What is the BBW of Lithium?

lithium toxicity - monitor therapy

What are important counseling points with Lithium?

Dietary consistency

Drug interactions

S/sx of Toxicity

Can patients take Lithium while pregnant?

No - Ebstein Anomaly

Can patients take Lithium while breastfeeding?

NOOOO

Carbamazepine is ALWAYS ___________ ________.

second line

What is Carbamazepine used for?

2nd line for Acute manic or mixed episodes

Carbamazepine therapy is __________ effective than Lithium.

less

Carbamazepine has ________ effect on release to depression.

little

Carbamazepine is considered to be a metabolism ___________.

inducer

What drugs interact with Carbamazepine?

Birth control (less effective)

Inducers

Clozapine

Can you combine Clozapine with Carbamazepine?

NO - both affect WBC counts

What parameters need to be monitored with Carbamazepine (triple C)?

CBC (platelets, WBC)

CMP (Na, LFTs)

ADRs of Carbamazepine

Rash

Leukopenia

Thrombocytopenia

Hyponatremia

BBW of Carbamazepine

Anemia or agranulocytosis

SJS/TENs

What gene puts people at higher risk of SJS with Carbamazepine?

HLA-B*1502 (asain people)

If a female patient of childbearing age needs to be on Carbamazepine, they should also be on what medication?

Birth control

What are the counseling points to hit with Carbamazepine?

~2 months for effect

Lab monitoring

Drug interactions

Rash education

Avoid sudden d/c

What is the indication for Valproic Acid?

Acute mania

Mixed episodes

Maintenance

What is the max dose of VPA?

60 mg/kg/day

What dose do we normally target with Valproic acid?

~20 mg/kg

Which BD treatment is weight based dosing?

Valproic acid

Valproate should be used very __________ in people who ovulate/menstruate.

CAUTIOUSLY

What drugs increase levels of VPA?

Inhibitors

Guanfacine

Salicylates

Topiramate

What drugs decrease levels of VPA?

Inducers

Carbamazepine

Carbapenems

Phenytoin

Rifampin

VPA is a metabolism _____________.

Inhibitor

What lab parameters must be monitored with VPA?

Pregnancy

CBC

CMP

Which BD treatment is hepatically burdensome?

VPA

ADRs of VPA

GI upset

Sedation

Tremor

Thrombocytopenia

BBW of VPA

Hepatic failure

Pancreatitis

Which medication is category C for migraines but category D for BD?

VPA

What are the counseling points to hit wtih VPA?

Pregnancy and Lactation

Avoid sudden d/c

Follow-up

Drug interactions

Lamotrigine is used for what?

bipolar depression

Does Lamotrigine treat mania?

NO

Can Lamotrigine be used as maintenance monotherapy for BD 1?

NO

What is critical with Lamotrigine?

Titration

How is Lamotrigine titrated?

Start at 25 mg/day then increase by 25mg every 2 weeks to a target dose of 200mg

If a drug regimen includes Carbamazepine, what should be done with the Lamotrigine dose?

Double dose

If a drug regimen includes VPA/Divalproex, what should be done with the Lamotrigine dose?

half the dose

What is the drug interaction between birth control and Lamotrigine?

BC decreases the levels of Lamotrigine

What should be monitored with Lamotrigine?

Renal fxn

LFTs

ADRs of Lamotrigine

Rash (titrating too quickly)

BBW of Lamotrigine

SJS/TEN

What are important counseling points for Lamotrigine?

Medication adherence

Pregnancy and lactation

Skin Self Examinations

How long can a patient miss their dose of Lamotrigine before having to restart titration?

5 days or more

What drug(s) are considered to be the mainstay of bipolar disorder treatment?

SGAs

Which treatments can be used for mania?

Olanzapine

Quetiapine

Risperidone

Ziprasidone

Abilify

Asenapine (?)

Which treatments can be used for bipolar depression?

Olanzapine

Quetiapine

Lamotrigine

Which treatments can be used for mixed features?

Olanzapine

Quetiapine

Risperidone

Ziprasidone

Abilify

Asenapine (?)

Olanzapine

Zyprexa