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Mood Stabilizers

Objectives
• At the end of the presentation, each student should be
able to:
• Explain the pharmacology of the treatment agents for bipolar
disorder
• Identify appropriate, guideline-based pharmacological
treatment options for bipolar disorder
• Explain the drug properties of the different pharmacological
treatment agents, including specific monitoring parameters for
certain agents and specific black box warnings
• Create a pharmacological treatment plan for a sample patient
case
What is Bipolar Disorder?
• Bipolar disorder (BPD) is a chronic, cyclic mental illness that is
characterized by recurrent fluctuations in mood, energy, and
behavior
• BPD is characterized as a mood disorder, similar to depression
• BPD is a lifelong illness with a variable course
• The symptoms, course, severity, and response to treatment differ
among individuals
• Overall prevalence of bipolar disorder is 4.5%
• There are various types of BPD
Symptoms of mania and hypomania
• DIGFAST
• Distractible
• Increased activity/psychomotor agitation
• Grandiosity/superhero mentality
• Flight of ideas or racing thoughts
• Activities that are dangerous or hypersexual
• Sleep decreased
• Talkative or pressured speech
Symptoms of Depression

• Let’s review!
• Acronym? What does each letter stand for?
• What are the essential features?
• How many symptoms to be considered a MDE (Major
Depressive Episode)?
• For how long?
Types of Bipolar Disorder Defined By Episodes

Disorder Type Episode


Bipolar I disorder Manic episode +/- major
depressive episode or mixed
episode
Bipolar II disorder Major depressive episode +
hypomanic episode

Cyclothymic disorder Chronic fluctuations between


subsyndromal depressive and
hypomanic episodes
Other Types of BPD
• Substance/Medication-Induced Bipolar and Related Disorder
• Bipolar and Related Disorder Due to Another Medical Condition
• Other Specified Bipolar and Related Disorder
• Symptoms characteristic of bipolar and related disorder that
cause clinically significant distress but do not meet full criteria for
any of the disorders
• Examples: short-duration hypomanic episodes, short-duration
cyclothymia
• Unspecified Bipolar and Related Disorder
• Same as ‘other specified bipolar and related disorder,’ but the
clinician chooses not to specify the reason why the criteria isn’t
met
“Mood Stabilizers”
• Lithium (Lithobid)
• Anticonvulsants
• Divalproex sodium/Valproic acid (VPA, Depakote)
• Lamotrigine (Lamictal)
• Carbamazepine (Tegretol)
• Oxcarbazepine (Trileptal)
• Antipsychotics (both typical and atypical)
Li Inhibition of Inositol Signaling
What Does Li do to Neurotransmitters?

• It has been discovered that Li:


• ↑Serotonin release (inhibitory)
• ↑ GABA activity (inhibitory)
• ↓ release of NE and DA (ecitatory)
• ↓ glutamate (excitatory)
• ↓ DA synthesis (excitatory)
Divalproex Sodium/Valproic Acid
(VPA; Depakote®)
• DOC mixed states of BPD
• MOA:
• indirectly ↓GSK-3 activity (like Li)
• ↓inositol
• ↑GABA effects
• Inhibits glutamate/NMDA receptors
Lamotrigine (Lamictal®)

• Prevention/treatment of bipolar depression not first line


• Maintenance treatment of bipolar I disorder
• MOA:
• Blocks voltage-gated Na+ channels →↓APs
• ↓glutamate release
Carbamazepine (Tegretol®)

• First line option for hypomanic episodes/states


• Bipolar depression
• MOA:
• Blocks voltage-gated Na+ channels
• Presynaptically ↓transmissions
Oxcarbazepine (Trileptal®)

• Currently, there is less data supporting the use of oxcarbazepine in the


treatment of BPD
• Not as effective as other mood stabilizers
• MOA:
• Blocks voltage-sensitive Na+ channels
• Presynaptically, it acts to decrease synaptic transmission
Antipsychotics
• Two groups in this class: typical (1st generation) and atypical (2nd
generation) agents
• Classically, all antipsychotics are D2 receptor antagonists
• Typical antipsychotics (older drugs) have a greater affinity for D2
receptors
• Atypical antipsychotics (newer) bind to different receptors, in addition
to blocking D2 receptors:
• Block 5-HT2A receptors
• 3 are partial D2 agonists
• Some can also block 5-HT6 and 5-HT7 receptors
• Can also act as a 5-HT1A partial agonist
BPD Pharmacotherapy:
The Meds (Guidelines Second)!
Guidelines and Algorithms (Some of them)
• American Psychiatric Association (APA) guidelines
• Veterans Affairs/Department of Defense (VA/DoD) Clinical Practice
guidelines
• Canadian Network for Mood and Anxiety Treatments (CANMAT)
guidelines
• Updates to CANMAT guidelines by CANMAT and the International Society
for Bipolar Disorders (ISBD)
• World Federation of Societies of Biological Psychiatry (WFSBP) guidelines
• British Association for Psychopharmacology guidelines
• Texas Implementation of Medication Algorithms (TIMA) project
Goals of Treatment for ALL BPD
• Resolve acute manic, hypomanic, and depressive episodes
• Complete remission of symptoms
• Prevent further episodes
• Maintain good functioning
• Promote treatment adherence
• Minimize medication side effects
General recommendations for
manic/mixed/hypomanic episodes
• Assess for secondary causes of episode (alcohol or drug use, for
example)
• DC antidepressants (can induce a manic switch)
• Taper off stimulants and caffeine, if possible
• Treat substance abuse, if applicable
• Encourage good nutrition, exercise, adequate sleep, stress
reduction, and psychosocial therapy (nonpharmacological
treatments)
Hypomania
1ST - Initiate mood-stabilizing medication: lithium, valproate,
carbamazepine, or an atypical antipsychotic
Benzodiazepine?
Alternative option: OXC

2nd – If response is inadequate after 10-14 days of first-line


treatment(s) at optimized dose(s), consider a 2-medication combo:
a) Lithium + anticonvulsant or an atypical antipsychotic
b) Anticonvulsant + another anticonvulsant or an atypical
antipsychotic
Mania
1st – Initiate 2- or 3-medication combination:
(Lithium, valproate, or an atypical antipsychotic) plus a
benzodiazepine and/or a typical antipsychotic
Do not combine antipsychotics 3rd – If response is inadequate
Alternative option: CBZ; if no response, consider OXC after 10-14 days of second-line
treatments at optimized doses,
consider:
a) ECT or
b) Add clozapine to 2nd line
2nd – If response is inadequate after 10-14 days of first-line therapy
treatments at optimized doses, consider a 3-medication
combo:

a) Li + an anticonvulsant + an antipsychotic
b) Anticonvulsant + another anticonvulsant + an
antipsychotic
Acute Depressive Episode

• General recommendations
• Assess for secondary causes of depression (EtOH or drug use
• Taper off antipsychotics, benzodiazepines, sedative-hypnotics, if
possible
• Treat substance abuse, if applicable
• Encourage good nutrition, exercise, adequate sleep, stress reduction,
and psychosocial therapy (nonpharmacological treatments)
Mild/Moderate Depressive Episode

1ST - Initiate or optimize mood-stabilizing medication: lithium,


quetiapine, or lurasidone
Alternative options:
a) Lamotrigine
b) Valproate
c) Fluoxetine/olanzapine combination (Symbyax®)
Severe Depressive Episode
1st – Initiate or optimize mood-stabilizing medication: lithium
or quetiapine or lurasidone
Alternative options: Symbyax®, lamotrigine, valproate
If psychotic, add an antipsychotic (however, do not
combine antipsychotics) 4th – If response is
inadequate, consider
ECT

2nd – If response is inadequate,


consider CBZ or adding an
3rd – If response is inadequate,
antidepressant
consider a 3-medication combo:

a) Lithium + lamotrigine + an
antidepressant
b) Lithium + quetiapine + an
antidepressant
Lithium (Li; Lithobid®)
• First line options for BPD
• DOC for manic state
• MOA - UNKNOWN
• monovalent cation (similar to Na+- body cannot tell the differences between
them
• Hypothesis 1
• Li directly inhibits 1p2 to Ip1 to inositol pathway→ ↓ free
inositol → ↓other enzymes
• Modulate energy metabolism
• Provide neuroprotection
• ↑ neuroplasticity
• Hypothesis 2
• Li inhibits glycogen synthase kinase-3 (GSK-3) s  same effect as
above
• Hypothesis 3
• LI ↓ generation of action potentials by gradually replacing Na+
• Hypothesis 4
• Li inhibits NE sensitive adenylyl cyclase  antidepressant and anti-
manic effects
• Properties
Lithium
• It is a monovalent cation
• rapidly absorbed
• not protein bound
• not metabolized
• excreted unchanged
• Indications
• 1st line agent for acute mania, acute bipolar depression, and maintenance treatment for
bipolar I and II disorders
• Efficacy
• 78% effective to stop acute manic/hypomanic episode
• More recently, slower onset of action has been discovered
• 6-8 weeks for treatment of depression
• More effective for maintenance tx in pt w/
• fewer prior episodes
• Hx of good functioning btwn episodes
• FHx of response to Li
• ↓suicide risk by 8-10 fold
• Efficacy:
Lithium Continued…
• Augment w/ the following to improve response to tx
• CBZ
• Lamotrigine
• VPA
• Dosing and administration:
• Initial dosing: 300 mg by mouth twice daily
• Dosing range: 900 – 2400 mg daily in divided doses
• Administer lower dose in renal impairment
• Dosing titration will depend on patient’s response to Li and
tolerance to side effects
• Immediate-release and extended-release preparations exist
• Usually would still administer > 1 time per day
• Why is it dosed > 1 time/day?
• Li is linked to a lot of GI ADR (Nausea) – helps ↓this
• When titrating ↑Bedtime dose first not AM dose
• Monitoring
• Everything except LFTs
Lithium: Monitoring

Baseline Q6-12 months


Physical Exam and General Chemistry X

Hematologic tests X X
(CBC w/ diff + platelets)

Metabolic tests X X
(FBG, Lipids, weight)

Liver function tests

Renal function tests X X

Thyroid function tests X X

Serum Electrolytes X X

Dermatological tests X X
Lithium Serum Drug Monitoring
• ***NEED TO OBTAIN DRUG BLOOD LEVELS WHEN ON LI***
• Levels at steady state by day 5
• Sample obtained 8-12 hours after the last dose on day 5 of tx
(before AM dose)
• Level is in therapeutic range + positive response
• Recheck 2 weeks later (week 7)
• Monitor Q3-6 months
• If level is not therapeutic, partial response, any dose change,
suspected medication interactions obtain another level in 5 days
of stable dose

• Target blood levels/concentrations:


• Maintenance: 0.6 – 1.2 mEq/L
• Acutely manic: up to 1.5 mEq/L
Lithium Toxicity
• Narrow therapeutic index – very toxic!
• Risk factors for Li toxicity:
• Na+ restriction (if Na is low H2O is low and [Li] ↑)
• Dehydration
• Vomiting, diarrhea (deplete vol status)
• Elderly
• DDI w/ drugs that ↓Li clearance
• 3 Levels of Li toxicity
• Mild (1.5-2.0 mEq/L)
• N/D
• Polyuria
• blurred vision
• fine resting tremor
• Confusion
• drowsiness
• Moderate (2.0-2.5 mEq/L)
• ↑confusion
• ↑ DTR
• myoclonic twitches
• ↑ restlessness
• Severe (> 2.5 mEq/L)
• Coma
• Convulsions
• cardiac dysrhythmias
• Renal failure
How to Treat Li Toxicity
• Transfer patient to emergency room depending on degree of toxicity
• Discontinue lithium (hold doses until levels ↓ to therapeutic range)
• If consciousness is impaired, oral airway needs to be protected
• Gastric lavage and IV (to remove unabsorbed lithium from GI tract )
• Indications for hemodialysis:
• Coma
• Convulsions
• respiratory failure
• deteriorating mental status
• renal failure
Li ADR

• 93% of patients experience side effects • Non dose-related (more common w/ LT Tx)
• 2 categories: • Structural changes in the kidneys (glomerular
• Initial, dose-related sclerosis, tubular atrophy)
• GI distress (nausea, vomiting, diarrhea, dyspepsia) • Impaired H2O resorption and ↑SCr
• Give with food
• Give bigger dose at bed time
• Thyroid changes (hypothyroidism usually
• Give entire dose at badtime occurs after 6-18 months of therapy)
• Muscle weakness and lethargy (develops in about • Li sits in thyroid gland →interferes with
30% of patients)
• Give dose at bedtime
TSH production and ↑formation of
• Polydipsia and polyuria thyroid antibodies
• Fine hand tremor • ↑TSH↓T3 & 4
• ↓dose
• Add propanolol
• Benign and reversible cardiac changes
• Cardiac dysrhythmias and heart block if
OD
• Reversible leukocytosis
• Dermatologic changes (acne, exacerbation of
psoriasis)
• Weight gain
• Neurologic disturbances (EPS, slurred speech,
myasthenia gravis)
• Alopecia (MV with zinc and selenium can help)
Li DDI’s
• ↓Li Elimination →↑Li Levels
• TZD
• Removes H20 and Na+ from body → ↑[Li]
• Reabsorbs Li → ↑ [Li]
• NSAIDs (naproxen, ibuprofen) & COX-2 inhibitors (Celecoxib)
• ↓PG synthesis → ↓renal blood flow → ↓Li elimination
• ↑Na retention → ↑[Li]
• ACEi’s (Lisinopril)
• Inhibit Angiotensin I to II → ↑vasodilation → ↓aldosterone → Na retention →
↑[Li]

• Neurotoxicity
• CCB’s
• Carbamazepine (Tegretol)
Divalproex Sodium/ Valproic acid (Depakote)
• FDA-approved for the treatment of acute mania and mixed episodes
• More effective Tx than Li for mixed states!
• Many different formulations
• Efficacy:
• Has been shown to be as effective as lithium and olanzapine in
patients with pure mania
• More effective than lithium in mixed states and rapid cycling (4
episodes in a 12mo time period)
• Lithium + valproate = added positive effect for treatment-refractory
rapid cycling and mixed states; combo is also efficacious in
maintenance therapy for BPD I
• Combining valproate with other BPD agents (carbamazepine,
lamotrigine, atypical antipsychotics) can be effective
• MONITORING IS KEY!
VPA/Depakote Dosing
• Weight based dosing
• Pt with acute mania need higher doses than those with
Hypomania
• Acute mania – 20 mg/kg/day in divided doses (approximately,
250 – 500 mg by mouth twice daily)
• Hypomania, elderly patients – 5-10 mg/kg/day in divided doses
• Maximum recommended dosage – 60 mg/kg/day
• Immediate release and extended-release products exist

• Monitoring
• Everything except renal, thyroid and electrolytes
VPA Continued…
• Monitoring parameters for VPA
Baseline Q6-12 months

Physical Exam and General Chemistry X

Hematologic tests X X

Metabolic tests X X

Liver function tests X X

Renal function tests

Thyroid function tests

Serum Electrolytes

Dermatological tests X X
Serum drug levels VPA/Depakote
• ***NEED TO OBTAIN DRUG BLOOD LEVELS WHEN ON VPA
(like Li but larger therapeutic range) ***
• Therapeutic level: 50 – 125 mcg/mL (for bipolar)
• Take blood level ~ 12 hours after last dose on the 5th day of
treatment
• Obtain a blood level after each change in dose
VPA/Depakote Toxicity
• Unlike Li Toxicity - Usually benign, but may serious, very rare
• SSx of toxicity:
• Hyperthermia/hypothermia
• Tachycardia
• Hypotension
• Confusion and somnolence
• Dizziness
• Nausea and vomiting
• Renal failure
• Tremors
• Treatment
• Support the airway
• May need to administer activated charcoal to decontaminate
• Hemodialysis may be warranted
VPA/Depakote ADR
• Most common are dose-related GI complaints (nausea, vomiting,
indigestion, anorexia, diarrhea, and flatulence)*
• Give with food
• Lower dose
• Give at bedtime
• Switch to XR
• Mild tremor & Weight gain (like Li)
• Lethargy
• Prolonged bleeding (dt inhibition of platelet aggregation and
thrombocytopenia)
• Monitor bleeding and bruising
• Transient ↑in Liver enzymes (monitor liver enzymes)
• ****BBW for HEPATOTOXICITY AND PANCREATITIS!!!****
VPA/Depakote DDI’s
• Highly protein bound → can be displaced by other protein bound
drugs when combined (i.e. phenytoin, carbamazapine) → ↑ [free
VPA ]
• CYP450 enzyme inhibitor
• VPA + Phenobarbital  ↓ phenobarbital clearance → ↑
[phenobarbital]
• Oral contraceptives → ↑VPA clearance → ↓ [VPA]
• Same effect in Lamotrigine (Lamictal)
• Lamotrigine (lamictal) + VPA → SJS/TENs
• Use ½ dose of Lamotrigine when combined with VPA to ↓ SJS/TENs risk
• VPA ↓ UDP enzymes (glucoronidation) → ↓Lamotrigine metabolism →
↑ [Lamotrigine]
Lamotrigine (Lamictal)
• FDA-approved for the maintenance treatment of BPD;
• not FDA approved for but very effective alternative to 1st line therapy to
prevent/treat bipolar depression
• Not 1st line bc requires slow dose increases therefore not good for acute issues
• Efficacy:
• Possesses both antidepressant and mood-stabilizing effects
• Low rate of manic switch
• Dosing and administration:
• Initial : 25 mg daily
• Range: 50-400 mg PO (divided doses)
• Slowly increase dose!!!!!! Slow titration!!!!! To ↓risk of SJS/TENS
• Example: 25 mg QD x 2 weeks →50mg QD x2 weeks → ↑50mg
increments weekly
• Doses of 400 mg daily have shown no advantages
• Need to adjust dose in hepatic and renal impairment

• Monitoring
• Only Derm for SJS/TENs
Lamotrigine (Lamictal) Monitoring

Baseline Q6-12 months

Physical Exam and General Chemistry X

Hematologic tests

Metabolic tests

Liver function tests

Renal function tests

Thyroid function tests

Serum Electrolytes

Dermatological tests X X
(dt risk of SJS/TENS)
Lamotrigine (Lamictal) ADR
• Common
• HA
• Nausea
• Dizziness and drowsiness
• Ataxia
• Tremor
• Rash (self-limiting and resolves eventually)  may progress to
life-threatening conditions!
• ***BBW for SJS/TENS***
• Serious rash + fever/sore throat
• May require hospitalization
• DC Tx
• Titrate doses SLOWLY and use ½ dose when combined with VPA to
↓risk
Stevens-Johnson Syndrome (SJS)
• Prodrome of Flu-like symptoms → painful red/purple rash that
spreads/blisters
• Symptoms:
• Fever, sore throat, fatigue, cough, and burning eyes (flu-like
symptoms prior to rash)
• Facial and tongue swelling
• Hives
• Skin pain
Lamotrigine (Lamictal) DDI’s
• Lamotrigine + VPA → SJS/TENs (1/2 the lamotrigine dose)
• VPA inhibits UDP (glucoronidation) enzymes → ↓ metabolism of
Lamotrigine → ↑ [Lamotrigine]
• Lamotrigine + oral contraceptives → ↑Lamotrigine clearance
→ ↓[Lamotrigine]
• Same as VPA/Depakote
• Lamotrigine + Carbamazepine (Tegretol) = ↑CNS ADR
• Low CYP PK interactions – mostly metabolized by
glucoronidation
Carbamazepine (Tegretol)
• FDA-approved for the treatment of acute mania (2nd line) and mixed episodes
associated with BPD I
• Many formulations: immediate release and extended release
• Acute anti-manic effects are comparable to lithium
• Carbamazepine + Li, VPA, or antipsychotics used for treatment-resistant
patients experiencing a manic episode
• Also reserved for patients who are unable to tolerate or who have an
inadequate response from Li or VPA
• Dosing and administration:
• Initial: 200mg PO BID
• Range: 200-1800mg/day BID-QID (↑by 200 mg/day every 2-4 days)

• Dose adjustment necessary in hepatic disease, but not in renal


impairment

• Monitoring
• Everything except thyroid and metabolic test
Carbamazepine (Tegretol) Monitoring
Baseline Q6-12 months

Physical Exam and General Chemistry X

Hematologic tests X X
(CBC and platelets at baseline -
subsequent monitoring is
individualized )
Metabolic tests

Liver function tests X X

Renal function tests X

Thyroid function tests

Serum Electrolytes X X

Dermatological tests X X
Carbamazepine (Tegretol) Serum Monitoring
• Only obtained to guide toxicity!
• )Not the same as monitoring with Li or VPA where you are looking for
efficacy and therapeutic range ∴ not drawn as often)
• Draw levels 12 hours after the last dose
• Initial therapy - Q1-2 weeks during the first 2 months
• Maintenance therapy - Q3-6 months after first two months
• Auto-induces it’s own metabolism (both substrate and inducer of
3A4)→ ↓t1/2 of medication over time (medication reaches steady state
faster when dose is adjusted in pt when it is not initial tx)
• One week after changing dose (during first two months)
• 2-3 days after changing dose (after first two months)
• Goal level: 6-10 mcg/mL
• Can use 4 mcg/mL if pt is responsive
• Max 14 mcg/mL if tx resistant
Carbamazepine (Tegretol) ADR
• Neurosensory side effects are common (HA, fibromyalgia)
• Nausea
• Hyponatremia
• Risk↑with age
• Monitor serum electrolytes at baseline and Q6-12mo
• risk of causing seizures
• Transient leukopenia
• Bone marrow suppression
• Carbamazepine + Clozapine (Clozaril) → ↑ risk
• Clozapine (Clozaril) 2nd gen antipsychotic
• SSx of acute overdose:
• Ataxia
• Diplopia and nystagmus
• Cardiac conduction changes
• In Severe cases – Seizures & Coma

• **BBW**
• SJS/TENs
• HLA-B*1502 allele (MC in Asian pt – 10x ↑ risk) → SJS/TENs
• Need to test Asian pt for this allele and Carbamazepine is CI if present
• Aplastic anemia/agranulocytosis
Carbamazepine (Tegretol) DDI’s
• Auto-induces its own metabolism – both substrate and inducer of 3A4
• Induces CYP3A4 and other CYP enzymes to a lesser degree (1A2,
2C9/2C10, and 2D6)
• ↑metabolism → ↓ [of many medications] including oral contraceptives
• Carbamazepine + VPA/Depakote → displacement from proteins → ↑ [free
Carbamazapine]
• Carbamazapine and VPA are both highly protein bound
• ↓Carbamazapine dose when combined with VPA to ↓risk of toxicity
• Carbamazepine + Clozapine (Clozaril) →↑risk bone marrow suppression
from both agents
• CYP Inhibitors → ↓ metabolism→ carbamazepine toxicity
• Non DHP CCBs - diltiazem, verapamil
• SSRIs - Fluoxetine (Prozac), Fluvoxamine (Luvox)
Oxcarbazepine (Trileptal)
• Not FDA-approved for BPD
• Currently, there is less data supporting use of oxcarbazepine over
carbamazepine in the treatment of BPD
• Administer oxcarbazepine if patients have failed other treatments or
have experienced intolerable side effects
• Advantages over CBZ:
• milder ADR
• no autoinduction of CYP enzymes (3A4)
• fewer DDIs
• Dosing and administration:
• Initial : 150-300mg PO BID
• ↑ dosing 300-600 mg Q3-6 days
• Range: 300-1200mg/day BID dosing
• Adjust dose in renal impairment

• Monitoring – Only Electrolytes


• (↑Hyponatremia risk > Carbamazepine)
Oxcarbazepine (Trileptal) Monitoring
Baseline Q6-12 months

Physical Exam and General Chemistry X

Hematologic tests

Metabolic tests

Liver function tests

Renal function tests

Thyroid function tests

Serum Electrolytes X X
(HIGHER RISK OF HYPONATREMIA
THAN CARBAMAZEPINE)
Dermatological tests
Oxcarbazepine (Trileptal) ADR
• Dose-related ADR:
• Dizziness and sedation
• HA
• Ataxia and fatigue
• Vertigo
• Abnormal vision and diplopia
• Vomiting and abdominal pain
• Hyponatremia!
• MC w/Oxcarbazepine than Carbamazepine
• Can be severe (<125 mEq/L →↑RISK OF SEIZURE)
• MC in first 3 months
• Symptoms: confusion, HA, lethargy, malaise
• Hypersensitivity reactions
• Cross-reativity with Carbamazepine hypersensitivity
Oxcarbazepine (Trileptal) DDI’s
• Inhibits 2C19 → ↓metabolism of phenytoin
• Induces 3A3 and 3A4
• ↑metabolism of oral contraceptives → ↓[oral
contraceptives]
• Like Carbamazepine (Tegretol)
• Oxcarbazepine + diuretics → ↑risk of hyponatremia (∴↑RISK
OF SEIZURE)
2nd Generation Antipsychotics
• Treatment of acute mania in BPD
• Quetiapine (Seroquel)
• Treatment of manic/mixed states of BPD
• Aripiprazole (Abilify)
• Asenapine (Saphris)
• Olanzapine (Zyprexa)
• Risperidone (Risperdal)
• Ziprasidone (Geodon)
• Cariprazine (Vraylar)
• Maintenance treatment of BPD
• Aripiprazole (Abilify)
• Quetiapine (Seroquel)
• Risperidone IM (Risperdal)
• Ziprasidone (Geodon)
• Bipolar Depression
• Quetiapine (Seroquel)
• Lurasidone (Latuda)
• Olanzapine/Fluoxetine combo
How To Assess Severity of Symptoms?
• Depression
• PSQ-9 – can use to measure severity at baseline and response to treatment
• Mania
• Young Mania Rating Scale (YMRS)*
• GOLD STANDSRD
• 11 items clinician rated scale of symptoms in past 48hr
• 0-4
• elevated mood
• energy levels
• sexual interest
• sleep
• language-thought disorder
• Appearance
• Insight
• O-8
• irritability
• rate and amount of speech
• content of speech
• behavior
• Goal ≤12 → remission of symptoms
• Higher the score = more manic
• 10 = some elevation but not full manic episode
Back To Our Patient: ah
Recap of Our Patient: AH
• CC: “There are hundreds of vampires in this city, and I have documents to prove
it.”
• HPI:
• AH is a 25 year-old male seen today in the Crisis Center.
• According to his neighbors who called the police, the patient has been acting
increasingly strange. The lights in the house are left on all night long, and
spiritual music is played at all hours.
• Last evening, he dug a trench around his front yard with an electric lawn
edger and filled it with garlic cloves
• This evening, he painted crosses on the front of the house and threw
furniture into his front yard and the street. When approached by neighbors,
he apparently began screaming and preaching at them. When the police
arrived, they found the patient standing naked on the dining room table in his
front yard preaching. When the police approached him, he began throwing
garlic tablets at them and screaming, “Become naked in the eyes of the Lord
and you will be saved.” He became increasingly hostile during the arrest
shouting, “Don’t hate me because I’m beautiful.” He then tried to bite one of
the officers.
Patient
• PMHx:
Case Continued…
• Manic episodes first occurred while he was in college, leading to psychiatric
admissions at ages 21 and 23 for acute mania
• Patient was treated with haloperidol 5 mg by mouth once daily, and lithium
600 mg by mouth each morning and 900 mg by mouth at bedtime, with
adequate response and discharged on both occasions after about one month
• Medical problems include migraine headaches
• FHx:
• Father has a history of depression
• Paternal grandmother was placed in an “asylum” for hysteria secondary to
childbirth
• Mother and brother have Type II diabetes
• SHx:
• Recently fired from his job as a nurse at a hospital
• Patient is a single homosexual
• Religious upbringing as a Southern Baptist
• Smokes 1 ppd for 5 years
• Medications:
• Ibuprofen PRN for migraine headaches
• (interaction with Li – tell pt to use APAP)
• Allergies: None
Question #1
Question #2
Question #3
Pain Management

Patient FT is started on lithium and is undergoing an orthopedic


consultation for ankle pain. Ankle fracture is ruled out with an x-ray and
physician asks for a pharmacologic option for pain control. What
medication would be best recommendation?
a. Duloxetine 60 mg by mouth once daily (neuropathic pain)
b. Ibuprofen 800 mg by mouth 3 times a day as needed for pain (NSAID)
c. Naproxen 500 mg by mouth 2 times daily until pain is gone (NSAID)
d. Acetaminophen 1000 mg by mouth 3 times a day as needed for pain
(3000mg MDD)
Study Pointers from Gretchen

• Know MOA for Antidepressants, Anxiety and Panic Agents


• Know Therapeutic Class for mood stabilizers (only know MOA for Li)
• No dosing on ANY drugs for this module!
• Know which agents are most likely to have DDIs (not specific Dis)
• Know Drug –food interaction with MAOIs and tyramine containing
foods
• Know first line options highlighted in attached slides
VPA Monitoring Parameter

Baseline laboratory screening before starting valproate should include


which of the following?
a. Ammonia (not standard baseline screening)
b. Liver function tests (CYP enzyme inhibition)
c. HLA-B*1502 variant (Asian pt for Carbamazepine (Tegretol))
d. Thyroid function tests (Li)
In Conclusion
• Bipolar disorder (BPD) is a chronic, cyclic mental illness that is
characterized by recurrent fluctuations in mood, energy, and
behavior
• There are many different types of BPD
• The healthcare team must accurately diagnosis the patient and
determine the appropriate therapy/therapies
• For the pharmacological treatment options for BPD, there is a high risk of
toxicity, especially with those medications that have a narrow
therapeutic index
• Be aware of the therapeutic serum drug levels, drug-drug
interactions, the symptoms of toxicity, and how to properly treat
toxicities!

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