Pharmacotherapy of Bipolar Disorders

Question 1

Bipolar Disorders

Answer 1

• Bipolar I Disorder: Mania (and usually major depression)
• Bipolar II Disorder: Hypomania and Major Depression
• Cyclothymic Disorder: subthreshold hypomania and subthreshold depression
• Substance/Medication Induced Bipolar Disorder
• Bipolar Disorder due to another medical condition

Question 2

Mania

Answer 2

• Distinct period
• Abnormal and persistent
• Elevated, expansive, or irritable mood
• Increased activity or energy
• 1 Week (or any duration if hospitalization needed)
• Most of the day nearly every day

Question 3

Mania Symptoms

Answer 3

• Inflated self-esteem or grandiosity
• Decreased need for sleep
• More talkative than usual/pressured speech
• Flight of ideas/racing thoughts
• Distractability
• Increased goal directed activity
• Excessive involvement in high risk activity: buying sprees, sex, foolish investments
• Marked impairment or hospitalization or psychosis
• Exclude other causes

Question 4

Hypomania

Answer 4

Mania Criteria Except

• 4 days
• Unequivocal change in functioning
• Observable by others
• Not severe enough to cause impairment or hospitalization
• No psychosis

Question 5

Specifiers

Answer 5

• Rapid Cycling: 4 or more distinct mood episodes per year
• Mixed Features: presence of depressive symptoms in mania or vice versa
• With Psychotic Fetures
• With Anxious Distress
• Seasonal Pattern
• Peripartum Onset

Question 6

Screening for Bipolar Disorders

Answer 6

• MDQ >= 7 (Sensitivity 58%, Specificity 93%)
• Self Report Scale
• > =7 symptoms occuring at same time
• Moderate or serious

Question 7

Acute Phase Treatment Goals

Answer 7

• 1-3 months
• Non-response: <25% reduction in symptoms
• Partial Response: 25-50% reduction in symptoms
• Response: >50% reduction in symptoms
• Remission: Absence of mood symptoms for over 2 months

Question 8

Maintenance Phase Treatment Goals

Answer 8

• 3 months - lifetime

- Prevent relapse to any mood episode

Question 9

Bipolar Disorder Treatments

Answer 9

• Bipolar Mania: Medication SMD 0.42
• Bipolar Depression: Medication SMD 0.24
• Bipolar Maintenance: Medication SMD 0.41
• Psychotherapy: not for monotherapy, possibly effective for augmentation

Question 10

First Generation Antipsychotics (D2 Antagonist)

Answer 10

• High Potency: Haloperidol*, Fluphenazine
• Mid Potency: Perphenazine
• Low Potency: Chlorpromazine, Thioridazine*

Question 11

Second Generation Antipsychotics (D2/5HT2 Antagonist)

Answer 11

• High Potency: Risperidone, Olanzapine, Asenapine, Paliperidone, Iloperidone
• Mid Potency: Ziprasidone*, Lurasidone
• Low Potency: Quetiapine, Clozapine

Question 12

Second Generation Antipsychotics (D2 Partial Agonist/5HT2 Antagonist)

Answer 12

• Aripiprazole
• Brexpiprazole
• Cariprazine

Question 13

Theories of Atypicality

Answer 13

• Minimal Neuroleptic Potential: Clozapine, Quetiapine
• 5HT2 Antagonism/D2 Disinhibition: all second generation
• Fast Off/Kiss-and-Go: Clozapine, Quetiapine, Olanzapine
• D2 Partial Agonism: Aripiprazole, Brexpiprazole, Cariprazine

Question 14

Antiepileptics

Answer 14

• Valproic Acid/Divalproex 25-60 mg/kg/day
• Carbamazepine 400-800 mg PO BID
• Lamotrigine 200 mg PO QD

Monitoring

• Baseline: CBC, Chem7, LFTs, lipase, HCG
• Follow-up: Troughs and the baselines

Question 15

Lithium

Answer 15

• 900-1800 mg/day
• Conduction blocks, delirium, ataxia, coma, seizures, death at toxicity

Monitoring

• Baseline: Chem7, Ca+, TSH, HCG
• Follow-up: Baselines and trough levels

Question 16

Strong Suicide Risk Factors

Answer 16

• History of attempts
• Age >65 y.o.
• <5 years since psychiatric hospital discharge
• Severe pain

Question 17

Moderate Suicide Risk Factors

Answer 17

• Access to firearms
• PHQ-9 question 9
• Prior psychiatric hispitalization
• High dose benzos
• Hopelessness
• Seizure disorder
• Alcohol abuse
• Manic depressive disorder
• Family history of suicide

Question 18

Weak Suicide Risk Factors

Answer 18

• Depressive disorder
• Anxiety disorder
• CHF
• COPD
• Moderate pain
• Ever prescribed a benzo
• Male sex
• White race

Question 19

Ideal Mood Stabilizer

Answer 19

• Treats all phases of bipolar disorder

- Includes acute mania/depression and maintenance

Question 20

Ideal Mood Stabilizer Examples

Answer 20

• Olanzapine/Fluoxetine
• Olanzapine
• Quetiapine
• Valproate
• Lithium + Valproate
• Lithium (?)
• ECT (probably)

Question 21

Antiepileptics + Lithium

Answer 21

• Inhibits phosphoinositide hydrolysis
• Inhibits glycogen synthase kinase
• Inhibits histone deacetylases
• Decreases PKC Activity
• Facilitates GABA transmission

Question 22

Bipolar Depression Treatments

Answer 22

• Olanzapine/Fluoxetine
• Valproate
• Quetiapine
• Lurasidone
• Olanzapine

Off-Label
-Augmentation of mood stabilizer: Armodafinil or pramipexole

Question 23

Weight Gain + Antipsychotics

Answer 23

• Olanzapine
• Gabapentin
• Amitriptyline
• Mirtazapine
• Quetiapine
• Risperidone

Question 24

Weight Loss + Antipsychotics

Answer 24

• Topiramate
• Buproprion
• Fluoxetine

Question 25

Bipolar Medications + Preggo/BF

Answer 25

- Lithium: Category D, excreted in breast milk, heart defects - Valproate: Category D, excreted in breast milk, neural tube defects - Carbamazepine: Category D, excreted in breast milk, facial dysmorphism and fingernail hypoplasia - Lamotrigine: Category C, excreted in breast milk - Antipsychotics: Category C, excreted in breast milk, low birth weight - ECT: SAFE in pregnancy