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Devon Anne Sherwood, PharmD, BCPPAssistant Professor, UNE College of PharmacyClinical Psychopharmacology Specialist, Spring Harbor Hospital

December 2, 2017

Identify the pathophysiologic mechanisms underlying bipolar disorder relating to the various presentations involved.

Describe the medication profile of mood stabilizers and recommend appropriate acute and chronic treatments

Analyze the pharmacology and side-effect profile of FDA approved treatments

Explain a general approach to treatment for special populations (ie. elderly, pediatric, pregnant patients)

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A lifelong disorder of periods of elevated mood, high energy, irritability, decreased need for sleep, grandiosity and euphoria◦ 1st episode is usually depressed ( or ) More men than women present as

manic first

80% experience multiple episodes

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Caused likely due to:◦Genetics, environmental triggers, and dysregulation of neurotransmitters, neurohormones, and second messenger systems in the brain

Epidemiology:◦ ~3-7% lifetime prevalence◦ Recent study = 4.5% BPD I = 1%, BPD II = 1.1% Average onset 15 – 30 years old

Kaplan & Saddock Comprehensive Textbook of Psychiatry, 9th edDrugs. 2009;69:2063–2101.

Up to Date 2017 Dipiro 10th Ed.4

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Chromosomal regions reported to be linked to bipolar and unipolar disorders

Kaplan & Saddock - Comprehensive Textbook of Psychiatry 9th ed. Volume 1 - Table 13.3-5

Pathophysiology: Genetic influence80% concordance in identical twin80-90% have a biological relative with a mood disorder• Family, twin and adoption studies report lifetime prevalence

risk among 1st degree relatives

Neurotransmitter alterations in the CNS:◦ Monoamine hypothesis

Functional deficit of NE, DA, and/or 5-HT in depression and excess of NE and DA in mania

◦ Permissive hypothesis

CNS 5-HT is low in mania & depression, and superimposed low NE = depression & high NE = mania

◦ Dysregulation hypothesis

Mood disorders may be caused by a dysregulation between NT systems

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◦ GABA deficiency hypothesis

Relates to the sensitization-kindling theory for mood disorders. GABA is the main inhibitory NT in the CNS

◦ Glutamate

Excitatory NT

◦ Ach deficiency hypothesis

Aka Cholinergic-adrenergic imbalance

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Neuroimaging studies:◦ Shown abnormalities in neurochemical, anatomical

and functional abnormalities

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http://www.bipolar-lives.com/bipolar-brain-imaging.html

Environmental & Psychosocial stressors

Others:◦ Second messenger theories◦ Infections◦ Immunological reactions◦ Nutritional deficiencies◦ Sleep deprivation◦ Disruption of circadian rhythms◦ Endocrine abnormalities (ie, hormonal disturbances, thyroid)◦ Hypocalcemia / hypercalcemia

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DS

M 5, 2013

ANXIETY

Panic

GAD

OCD

PSYCHOTICSchizophrenia

Schizoaffective

MOOD

Major Depression

Bipolar Disorder

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Am J Psychiatry 2002;159(4):iv,1-50.Mahli GS et al. CNS Drugs 2003;17:9-25Kaplan & Saddock Comprehensive Textbook ofPsychiatry, 9th edDSM-5

46% of patients abuse EtOH◦ Attempt to self-medicate

41% of patients use other drugs◦ Illicit and prescription

25 - 50% attempt suicide◦ 10-15% succeed

◦ 30 times greater when depressed

Primary mania without treatment◦ 50% remission in 20 weeks

◦ 100% remission in 40 weeks

Overall◦ 50% relapse rate if

untreated in 1 year

Mixed mania or depressive phase◦ 45% remission in 1 year

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Bipolar I Disorder

Bipolar II Disorder

Cyclothymic Disorder

Substance/Medication-Induced Bipolar and Related Disorder

http://dsm.psychiatryonline.org.une.idm.oclc.org/doi/full/10.1176/appi.books.9780890425596.dsm03

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Bipolar I Disorder :

◦ “requires at least one Manic or Mixed episode, but there may be episodes of Hypomania, MajorDepression, or mixed features. (This diagnosis conforms to the classic concept of manic depressive illness.)”

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Bipolar II Disorder:

◦ “requires neither a Manic nor a Mixed Episode, but does require at least one episode of hypomania in addition to an episode of Major Depression”

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Complete history ◦ PMHx/PSurgHx

◦ Past Psych Hx

◦ Family

◦ Social

◦ Medication

Physical & neurologic exam◦ Include vitals & ECG in initial workup

Labs ◦ CBC, CMP (Chem7, LFT’s), fasting glucose, lipids,

renal fxn, thyroid panel, Utox, UA, pregnancy

Mental Status Examination

2-agonists (withdrawal) Anticonvulsants

Antidepressants

Baclofen (Lioresal®)

BZDs and Alcohol

Bronchodilators

Calcium replacement

Cimetidine (Tagamet®)

Decongestants ◦ Sympathomimetics

Disulfiram (Antabuse®)

Dopaminergic agents

19Dipiro et al. Pharmacotherapy 10th ed.

Hallucinogens: LSD, phencyclidine

Interferon (withdrawal)

Isoniazid

NSAIDs (ie. Motrin®, Aleve® )

Procainamide

Quinacrine

Steroids

◦ Anabolic, corticosteroids, ACTH

Stimulants

Xanthines

Yohimbine

20Dipiro et al. Pharmacotherapy 10th ed.

Mood◦ Euphoric◦ Elated/happy◦ Irritable

Cognitive◦Grandiose◦ Flight of ideas/racing thoughts◦Hallucinations and delusions◦ Ideas of reference

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Activity and behavior◦ Aggressiveness/

violence/outbursts◦ Insomnia/

constant motion◦ Impulsiveness◦ Pressured speech◦ Increased sexual activity◦ Increased artistic abilities

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Bipolar I:◦ Lifelong mood stabilizer therapy is recommended for patients

with 2 manic episodes, 1 severe manic episode, a strong family BPD hx, more than1 manic episode per year, or rapid onset of manic episodes.

Bipolar II:◦ Long-term prophylaxis for patients is recommended after three

hypomanic episodes or if the patient required an antidepressant but became hypomanic.

Breakthrough episodes ◦ Short-term BZD’s or AP’s for mania

◦ Short-term Antidepressants for depression??? – controversial!!

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Hypomanic episodes may not require treatment unless there is a hx of mania

Acute manic episodes can be treated with a mood stabilizer (Lithium, CBZ or VPA) with adjunctive BZD for anxiety/insomnia. ◦ Severe episodes with psychosis and agitation require

antipsychotics + BZD’s along with the mood stabilizer.

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If no response w/in 2-4weeks, a second mood stabilizer can be added. If patient is still nonresponsive, the mood stabilizer should be switched to another agent, or ECT may be used.

After remission, adjunctive agents are tapered and discontinued over 2-6 months

After response, patients with only one manic episode should continue on a mood stabilizer for 12 months

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Largest BPD trial to date– NIMH study offering several findings since 2003

Standard Care Pathway◦ Mood Stabilizers:

Anticonvulsants

Antipsychotics

Role of Antidepressants?

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Sachs G, et al. Acta Psychiatrica Scandinavica 2004;110(suppl. 422):7-17).Sachs G, et al. Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression: A Double-blind Placebo-controlled Study . New England Journal of Medicine. online 28 Mar 2007.

Concomitant antidepressant therapy (not monotherapy!)

◦ 35% of rapid cyclers will switch

◦ 26% have rate of cycling (incl. depression)

◦ SSRIs reported to cause up to 27% mania

◦ Lithium can reduce switching

◦ Bupropion may cause less switching vs. other antidepressants

Many patients require polypharmacy

Rapid medication discontinuation

◦ ’s relapses by 250%

◦ Meds should be tapered over 2-4 week

Prim Care Companion CNS Disord. 2014; 16(5) 10

NICE Guidelines

Arch Gen Psychiatry 2000;57:490-2

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MANIA MAINTENANCE DEPRESSION

Lithium 1970 1974

Thorazine 1973

Depakote 1995

Zyprexa 2000 2003

Lamictal 2003

Risperdal 2003

Seroquel 2004 2008 2006

Abilify 2004 2005 2007

Geodon 2004

Symbyax 2009 2004

Equetro 2004

Tegretol XR 2004

Saphris 2009 2010

Latuda 2013

Vraylar 2015

Pregnancy◦ Use lowest effective dose (ie. try to dose reduce if

possible) for any medication used treating bipolar disorder in pregnancy

◦ Haldol often still preferred for acutely manic symptoms or as mood stabilizer – most commonly used in this population

◦ SGA’s = limited studies, watch for gestational diabetes

◦ Benefit vs. Risk??? Lithium Lamotrigine Carbamazepine Valproic acid/Divalproex Sodium

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Pediatrics◦ Lithium, carbamazepine & valproic acid all used

◦ Lithium FDA approved over 12yo

◦ Aripiprazole & risperidone approved in 13-17yo, mania

◦ Quetiapine approved in 10-17yo, monotherapy or adjunct to lithium or valproic acid

◦ Olanzapine is approved in 13-17yo, mania or mixed

Elderly◦ Lithium elimination T½ increase as renal clearance

decreases (can double)

◦ Valproic acid T½ increases with aging

◦ Elderly may be more sensitive to side effects of mood stabilizers and antipsychotics, especially with dementia

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All can take days toweeks to work

◦ Lithium

◦ Anticonvulsants Depakote, Tegretol,

and Lamictal

Oxcarbazepine

◦ Antipsychotics AtypicalsFDA approved:

Zyprexa, Risperdal, Seroquel, Geodon, Abilify, Saphris, Latuda, Vraylarand Clozaril

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A. Risperidone

B. Lithium

C. Valproic Acid

D. Carbamazepine

E. Lamotrigine

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Equally effective in preventing both manic and depressive episodes 20 - 30% patients do NOT respond or can’t tolerate

~70% effective for acute manic episode 80-90% effective for prophylaxis◦ Less effective in rapid cycling and mixed BPD ◦ 20-50% relapse rate over 2 years

Half-life ranges from 18 to 36 hours◦ Dependent on renal function, disease state and concomitant

drug use

Caution in pregnancy and breast-feeding◦ Can cause Epstein’s Anomaly

Toxicity can be fatal

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Absorption◦ Readily absorbed from GI tract

◦ Peak serum levels occur in 2-4 hours

◦ Complete within 8 hours

◦ Slow release formulation have a slower and more variable absorption rate

Elimination◦ >95% renally excreted

◦ 80% reabsorbed at proximal tubule

◦ 20% is excreted in urine

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Dosage◦ 300mg BID up to 900mg TID

◦ Dose according to blood levels

Acute phase = 0.8 - 1.2 mEq/L (up to 1.4 severe)

Maintenance phase = 0.4 - 1.0 mEq/L

Initiation◦ Start low and titrate up slowly (Usually 300mg bid)◦ Observe for clinical improvement while monitoring level range

(acute vs maintenance phase)

Steady State serum level determination◦ Steady state should be reached after 4-5 days of dose change◦ Draw levels 12 hours post dose◦ Once maintenance therapy achieved, monitor every 2-3 months

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Fine hand tremor (50%)

◦ Tx. with -blockers!

Polyuria

Polydipsia

Weight gain (20%)

Goiter / hypothyroidism

◦ 5-15% of patients

◦ May develop after years

◦10 X more likely in women

◦ Mostly irreversible

Leukocytosis

EKG changes

Neurologic

Dermatologic

libido

Metallic taste

Urinary incontinence

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(>70%)

Side Effects

◦ Early GI disturbances

Muscle weakness, lethargy

Sedation

HA, confusion, ↓ memory, ↓ concentration

Tremor

Dry mouth

Leukocytosis

Late◦ Nephrogenic diabetes insipidus◦ Hypothyroidism

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Toxicity - Related to plasma levels◦ Diarrhea◦ Severe nausea and vomiting◦ Coarse hand tremor◦ Hyperreflexia◦ Drowsiness, lethargy◦ Muscular weakness, lack of coordination, ataxia◦ Blurred vision, dry mouth◦ Large output of dilute urine◦ Confusion, CNS irritability◦ Slurred speech◦ Cardiovascular (arrhythmias, hypotension)◦ Seizures, coma, death Intermittently dialyze if blood levels > 3.5mEq/L

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Lavage (for acute ingestion)

Correct / Maintain fluid and electrolyte balance

Maintain adequate fluid and salt intake, especially in situations of dehydration.◦ BEST TREATMENT: NaCl 0.9% IV

Monitor cardiac and respiratory fxn

Seizure precaution

Monitor Li+ conc. (Q 3-4 hours)

Dialysis ◦ Li+ is the only psychotropic that is dialyzable!

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NSAIDs ( Li+)◦ Decrease renal function

Diuretics ( Li+)◦ K-Sparing, Thiazides

Antipsychotics / Antidepressants

Xanthines (i.e. Theophylline, Caffeine) ( Li+)

Cardiovasculars ( Li+)◦ i.e. ACE inhibitors

Sodium Chloride ( Li+)◦ Inversely related to lithium concentrations

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65-70% response in mania

Less toxicity with this agent than lithium◦ Much wider therapeutic window

Highly protein bound

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Mixed / dysphoricbipolar

Rapid cycling

Migraine headaches

Neurological findings

Organic mania

Lithium treatment failures

Co-morbid substance abuse

Co-morbid psychiatric illnesses◦ Anxiety, Panic disorder

Irritability, aggression, and impulsive behavior

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◦ Dose range is 500 to 3000 mg/day, divided

Start at 250 - 500 mg BID to TID

Max. = 60mg/kg/d

Give with food to minimize GI symptoms

Fast crisis stabilization regimen◦ Add a “0” to patient’s weight (lbs)

Plasma concentration monitoring ◦ 50-125mcg/ml for acute bipolar treatment

Up to 150mcg/ml have been used if needed NOTE: For epilepsy, range is 50-100mcg/ml

Toxicity is seen at levels above 100!

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Neurologic◦ Ataxia, dizziness, drowsiness, tremor

Gastrointestinal◦ Nausea and vomiting◦ Give with food to minimize GI SEs

Hematologic◦ Prolonged bleeding times◦ Thrombocytopenia

Hepatologic◦ Transient s in LFTs◦ Liver failure reported

Dermatologic◦ Rash, alopecia, hair changes

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Weight gain

Caution with pregnancy and breast-feeding◦ Formerly Category D - all trimesters

◦ Causes congenital malformations (neural tube defects)

In first trimester associated withspina bifida

Lower IQ well documented in in-utero exposed children

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Enzyme inhibitor of metabolism

◦ MAJOR interaction with Lamictal®!

Lithium may increase VPA concentrations

Oral anticoagulants / Aspirin◦ Can cause bleeding times

Highly protein bound drugs

CNS depressants◦ Additive drowsiness

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>60% effective for acute mania◦ Better efficacy in rapid cycling, mixed episodes,

and severe mania (with Lithium)

60-75% effective for prophylaxis

Time to response may be up to 1-3 weeks

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Dosing◦ Initiate at 200-400mg/day◦ Increase by 200mg every 3-5 days up to 600-

1200mg/day in divided doses

Plasma concentration range is 4-12mcg/ml◦ Steady state is in 5 to 7 days◦ Draw levels 12 hours post-dose◦ Check biweekly for 2 months, then q 2-4 months if necessary Auto-induction takes about 4-5 weeks

May need to adjust dose upward to compensate

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Neurologic (60% of patients)◦ Drowsiness, dizziness, diplopia

Gastrointestinal (15% of patients) Dermatologic◦ Rash, photosensitivity

Hematologic (25% of patients)◦ Rare risk of agranulocytosis and aplastic anemia

8 patients per 1 million patients per year exposure◦ Transient in WBC’s

Hyponatremia (Rare SIADH) Hepatologic (Transient s in LFTs) Caution in pregnancy and breast-feeding◦ Formerly classified Category D

Neural tube (folate antagonist), cardiovascular, and urinary tract defects

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Enzyme inducer of CYP 1A2 & 3A4enzymes

◦Will metabolism of other drugs & itself Result is a in other drugs’ blood levels

Caution with critical drugs

ie. birth control pills, antibiotics, anticonvulsants, anticoagulants, etc.

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FDA approved for maintenance of Bipolar I◦ “The effectiveness of LAMICTAL in the acute treatment

of mood episodes has not been established”

May be best used in bipolar depression and maintenance prophylaxis◦ If acutely manic – may be used as an adjunct

Maintenance efficacy proven in 2 – 18 month studies after acute stabilization◦ Time until depression or manic relapse prolonged

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◦ Concerns: RASH in 0.08 – 10% of adults, up to 14% pediatrics

◦ Higher incidence in children; MUST discontinue drug at first sign of rash

◦ Dosing properly is critical to reduce risk of rash

◦ STEVEN’S JOHNSON’S SYNDROME!!

Common – GI: N/V/D, Abdominal pain

Neuro: Asthenia, Ataxia, Coordination problems, Dizziness, Headache, Insomnia, Somnolence, Tremor, Vertigo, Pain

Ophthalmic: Blurred vision , Diplopia

Psychiatric: Anxiety, Depression

Reproductive: Dysmenorrhea

Serious - Erythema multiforme , Stevens-Johnson Syndrome, Toxic

Epidermal Necrolysis, Anemia, Disseminated Intravascular Coagulation, Eosinophilia, Leukopenia . Thrombocytopenia, Liver failure, Aseptic Meningitis, Angioedema

Formerly Pregnancy Category C (D1 AUS): Increased cleft lip noted, decreased folate in rat pups 1st trimester

Respiratory: Rhinitis

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As

monotherapy

With Valproic

acid

With an

EIAED*

Weeks 1&2 25mg QD 25mg QOD 50mg QD

Weeks 3&4 25mg BID 25mg QD 50mg BID

Weekly dose

↑ thereafter25 or 50mg 25mg 100mg

Average

maintenance

dose

200mg QD100-200mg QD

(or BID)

300-500mg

( BID)

If a patient misses a few days of medication, a careful titrationback to the maintenance dosage is recommended

* carbamazepine, phenytoin, phenobarbital, and primidone

A. Lithium

B. Lamotrigine

C. Valproic Acid

D. Quetiapine

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FDA approved as monotherapy or adjunct to other mood stabilizers◦ Adjunctive therapy results in faster and better

remission rates

Significant symptom improvements can be seen in 3 to 7 days

Expert Consensus Guidelines changed from 1999 to 2004 to include atypicals as first-lineagents

Bipolar Depression: Seroquel, Abilify, Latuda(and Symbiax) are FDA approved

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A. Ziprasidone

B. Paliperidone

C. Quetiapine

D. Iloperidone

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Drug Weight

Gain

Sedation EPS Cardio GI

Olanzapine +++ ++ + 0 +

Risperidone ++ + ++ 0 +

Ziprasidone + + + + +

Quetiapine ++ ++ 0 0 +

Aripiprazole + + + 0 ++

Clozapine +++ ++ 0 + +

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0= none known (placebo rate); +=minimal; ++=moderate or occasional; +++= severe or

common; Strakowski SM, et al. CNS Drugs. 2001;15:701-708; Strakowski SM, et al. Expert Opin

Dosage: ◦ Initial 2-3mg po daily (still can give BID to minimize

ADR)

◦ Avg dose 4-6mg/day; doses above 6mg/day not evaluated in BPD

◦ Risperdal Consta - dosing same as for schizophrenia

(25mg – 50mg IM q2weeks)

Common Side Effects◦ Drowsiness / Somnolence

Titration necessary to minimize orthostatic hypotension

◦ Orthostatic hypotension / Dizziness

◦ Little EPS at low doses / s at hi doses

◦ Medium weight gain (mostly in adolescents)

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Dosing range: 5-20mg QD at bedtime◦ Zyprexa Zydis® (orally disintegrating tablet) & Zyprexa

IM (injection) available for agitation Agitation – Bipolar I Disorder: 10mg ODT/IM q2-4hrs

(range 2.5 – 10mg; up to 10mg IM x 3 doses q2-4hrs max in 24hrs)

Common Side Effects◦ Drowsiness

◦ Dizziness

◦ Akathisia

◦ Weight gain (avg. > 10 lb.)

Occurs early in tx. and continues avg. 9 months

◦ Hyperglycemia / Diabetes

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FDA approved for bipolar depression Dosing◦ Begin with 6mg/25mg QHS◦ Adjust dose every 2 to 4 weeks as needed

How supplied:

6mg/

25mg

6mg/

50mg

12mg/

25mg

12mg/

50mg

olanzapine

equivalent 6 6 12 12

fluoxetine

equivalent 25 50 25 50

Clozapine analog◦ Half-life =

Immediate release: T1/2 = 6 hours (longer in some elderly pts.)

Extended release: T1/2 = 7 hours

N-desalkyl quetiapine (extended release): T1/2 = 9-12hrs

◦ Metabolized partially by CYP3A4

Phenytoin increases clearance up to 500% May need to dose of quetiapine

Medium weight gain observed◦ Dizziness and somnolence seen

◦ No EPS or prolactin at any dose studied Believed due to transient binding at D2 receptors

Usual doses are 400-800mg/d divided◦ Higher doses well tolerated

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Average half-life is 7 hrs.

5HT/NE reuptake inhibition

Metabolized by CYP 3A4◦ Carbamazepine – Can ziprasidone by 36%

(need more Geodon®)

◦ Ketoconazole – Can ziprasidone by 33% (need less Geodon®)

Side effects◦ Rare QTc prolongation (EKG recommended); avoid

concomitant QTc prolonging medications or patients with EKG abnormality

◦ Drowsiness / insomnia, akathisia

Little weight gain or hyperglycemia observed

Dosing: 20mg-80mg BID with food◦ Up to 240mg/d clinically has demonstrated benefit in BPD

Rapid I.M. injection available (10-20mg)

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Doses range from 10 to 30mg a day

◦ Bipolar studies used 30mg/d

◦ Once daily dose appropriate (T½=75hrs)

Also Approved for atypical depression◦ Suggests for those in the depressed phase, may be especially

useful if fear of switching to mania with an

antidepressant

ADR:◦ Less risk of metabolic side effects than other 2nd

generation/atypical antipsychotics – weight increased noted more in pediatrics (~7%, rates 2.5-21.5%)

◦ May cause akathisia (2-25%), other EPS reported

◦ Headache, insomnia, GI upset (N/V) usually transient

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Maintenance dose from 5 – 10mg SL BID◦ Monotherapy start & max = 10mg SL BID

◦ Adjunctive therapy start 5mg SL BID Dosed BID due to sedation

(T½=24hrs)

Watch for drug interactionswith strong CYP 1A2 inhibitors

Adverse Effects◦ Somnolence, dizzness,

EPS, weight increase

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Approved for Bipolar Depression only

Doses range from 20 – 120mg/day◦ 80-120mg/d no additional benefit in studies

◦ Take with food (at least 350 calories)

◦ Side effects: akathesia, EPS, somnolence

◦ PK: 3A4 Substrate

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Newest approved agent for Bipolar I manic & mixed type, schizophrenia (Fall 2015)

Long T½ -◦ Parent 2-4 days, but active metabolite didesmethyl

cariprazine (DDCAR) 1-3 weeks

Severe hepatic or renal impairment - Do not use!◦ Mild or moderate, no adjustment necessary

Strong inhibitors of CYP 3A4 – Decrease dose 50%!

CYP 3A4 inducers = Do not use!

Most common ADR = EPS (including akathesia)

Starting dose = higher than schizophrenia◦ Bipolar Mania (maintenance) = 3-6mg

(schizophrenia maintenance= 1.5 – 6mg)

Indicated for treatment resistant schizophrenia AND bipolar disorder◦ Used for resistant bipolar disorder only

Many unpleasant side effects◦ Drooling, weight gain, seizures,

cardiovascular effects, diabetes, orthostasis, agranulocytosis, etc.

◦ Requires monitoring in REMS program

Costly lab monitoring

Dose titration (same as for schizophrenia)& national registry paperwork required

Arch Gen Psychiatry 2003;60:82-91

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Lithium

VPA, CBZ, LTG

(Note: both answers are drugs, not classes. There may be more than one correct answer!)

Benzodiazepines◦ Can help with insomnia and anxiety

◦ Clonazepam and lorazepam studied

◦ Only to be used short-term

◦ Can be combined with an antipsychotic

◦ NOT CONSIDERED MOOD STABILIZERS

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All antipsychotics can be used

Calcium Channel Blockers◦ Verapamil (Calan®, Isoptin®)

◦ Nifedipine (Procardia®, Adalat®)

◦ Nimodipine (Nimotop®) Has anticonvulsant effects

May be safer in pregnancy

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Antihypertensives◦ Clonidine◦ Propranolol

Other Anticonvulsants –◦ Oxcarbazepine (Trileptal®)◦ Gabapentin (Neurontin®)◦ Topiramate (Topamax®)◦ Tiagabine (Gabitril®)◦ Many others in study

Electroconvulsive therapy (ECT)

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Studies have shown lack of efficacy!!!!

No perfect mood stabilizer exists yet

Some may need 3 or 4 medsto “stabilize” their mood

Must consider benefits & risks, side effects, and outcomes◦ Patient must make an informed

decision with their medication

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