PSYC 17/18 Bipolar Disorder

1) Lifetime prevalence of bipolar disorder is: ___%

2) Age of onset (+1 caveat)

3) More in males or females?

4) What’s the long term impact? (In terms of a) returning to normal life functioning 1 year after hospitalization and b) work wise)

5) Common medical co-morbidities (4)

6) Common psychiatric co-morbidities (4)

7) ___ year reduction in life expectancy

8) ___% of patients die by suicide 

1) 1-2%

2) 15-25 (late adolescence; early adulthood)

• —> May have later onset at around 45-54 years-old

3) Similar prevalence in both males and females

4) Only 24% return to normal life functioning 1 year after hospitalization

• —> 57% unable to work (33% work full time; 9% work part time)

5) MEDICAL CO-MORBIDITIES

• Metabolic Syndrome

• Migraine

• Obesity

• T2DM

6) PSYCHIATRIC CO-MORBIDITIES

• Anxiety disorders

• Substance use disorders 

• Personality disorder

• ADHD 

7) 10 year reduction

8) 6-7% die by suicide

DSM Criteria for: MANIC DISORDER

1) At least ___ week(s) of abnormally ____, ____, or ___ mood AND increased ___ ___ ___ or energy

2) Must have ___ symptoms from the list

3) List the symptoms + Acronym to remember (7)

4) Question 2 gets changed to ___ symptoms from the list if ONLY MOOD is ____ 

5) Patient must have at least ___ past or current manic episode

6) Manic and MDD episode(s) is not better explained by other disorders such as _____ or ____ ____

7) Causes significant _____ in social or occupational functinoing, or requires ______

8) Episode not due to ____ or other ____ conditions

1) 1 week; elevated, expansive, irritable; goal-directed activity

2) 3

3) Symptoms + Acronym = DIG FAST

• Distractibility + easy frustration

• Irresponsibility and erratic, uninhibited behaviours

• Grandiosity. inflated self-esteem

• Flight of ideas

• Activity increased / psychomotor agitation

• Sleep decreased

• Talkativeness

4) 4+ only if mood is only irritable 

5) 1

6) Schizophrenia; schizoaffective disorder

7) Significant impairment; hospitalization

8) Substances; other medical condition

DSM-5 Criteria: HYPOMANIC episode

1) Duration

2) Same as ____ but ___ symptoms (no ____ symptoms)

3) How can you describe ^

4) ____ or ____ hypomanic episode + MDD episode

5) No history of ___ episodes

5) Episode not better explained by other disorders such as ____ or _____

1) 4 days

2) Manic, milder symptoms (no psychotic symptoms)

3) Description:

• Symptoms not severe enough to cause marked impairment in social or occupational functioning or necessitate hospitalization

4) Past or current

5) No history of MANIC episodes

6) Schizophrenia / Schizoaffective disorder

Diagnostic Challenges:

1) Prevalence of ____ symptoms is higher than ____ symptoms, so it often goes diagnosed as _____ _____

2) Delay between illness onset and diagnosis (mean delay is ____ years)

1) Depressive symptoms > Manic symptoms; often misdiagnosed as unipolar depression

2) 5-10 year delay

1) What is mixed episode / features

• ____ for hypomamia with ≥ (#)___ ____ symptoms

2) What is cyclothymic disorder

• Numerous ______ episodes over ___ years

3) What is rapid-cycling

• ≥ __ episodes within __ year

1) Mania for hypomania with ≥ 3 depressive symptoms

2) Numerous Sub-syndromal episodes over 2 years

3) ≥ 4 episodes within 1 year

Pathophysiology of BD

1) Is UNKNOWN… but likely involves a combination of ___ and ___ factors

2) Proposed biological mechanisms (5) [MMISC]

1) Genetic + Environmental Factors

2) Proposed biological mechanisms:

• Monoaminergic systems (DA, NE, 5-HT)

• Signaling cascade dysfunctions

• Mitochondrial dysfunctions

• Circadian rhythm dysfunctions

• Immune-mediated dysfunctions

Goals of therapy for bipolar disorder (7)

1. Achieve Euthymia / Baseline symptoms

2. Prevent subsequent episodes

3. Reduce residual symptoms

4. Restore/Improve functioning

5. Improve quality of life

6. Minimize SEs of treatmet

7. Educate patient + caregiver

In bipolar disorder, is pharmacological therapy or psychotherapy first line

Pharmacotherapy

• Long term treatment required to prevent subsequent episodes

• Tailor treatment to patient presentation (manic, hypomanic, depressive)

Psychological therapies used for bipolar

• Evidence based psychoeducation

• Cognitive behavioural therapy (CBT)

• Family-focused therapy (FFT)

• Interpersonal and Social Rhythm Therapy (IPSRT)

Lifestyle interventions for Bipolar Disorder

• Structure and routine

• Limit activity

• Sleep hygiene

• Regular exercise

• Diet (reduce alcohol / drug / caffeine use)

• Education (patient + caregiver)

  • Early recognition of symptoms

  • Self-care

  • Reduce self-stigmatization

  • Importance of medication adherence

• Social support (activity, housing, avoid isolation, identify family/friends as support)

• Risk/safety assessment (relapse prevention plan, safety plan)

LITHIUM

1) MOA is unknown but it may target:

1. Inhibition of ____ synthase ___ 3

2. ___ of inositol phosphatases 

3. Modulation of ___ receptors

4. Modulation of ___ of collapsin response mediated proteon-2 (___)

2) Therapeutic Actions:

1. ___ management of mania and depression

2. Prevention of ___ and ____

3. Adjunctive treatment for ___ ____ (used w/ ____)

4. Reduces risk of _____

3) Dosing Consideration for whom (2)

4) Drug Interactions:

1. Causes increased levels of lithium (3 drug + 1 non-pharm)

2. Causes decreased levels of lithium (2)

3. Additional considerations (3)

5) Side Effects of Lithium (7) (NDPP WTH!)

6) Lithium Can Induce ___ by causing ___

7) Monitoring (6) + how often

8) Therapeutic ranges:

• Mania

• Depression

• Age 60-79 y/o

• Age 80+

9) Critical alert for levels above ____ is bad, ____ is hospitalization

1) MOA:

1. Inhibition of glycogen synthase kinase 3

2. INHIBITION of inositol phosphatases 

3. Gluatamate

4. Phosphorylation (CRMP2)

2) Therapeutic Actions:

1. Acute

2. Mania and depression 

3. Unipolar depression (antidepressants)

4. Suicide / Suicidal Ideation 

3) Dosing Consideration 

• Renal function

• Patient age 

4) Drug Interactions

1. NSAID, ACE-I, Diuretics, Dehydration

2. Caffeine, Sodium

3. Food insecurity, heat warning, dehydration 

5) Side Effects of Lithium (7+1)

1. Nausea

2. Diarrhea

3. Polydipsia (thirst)

4. Polyuria / Nephrogenic diabetes insipidus (urinating lots but low urine [])

5. Weight gainTremor

6. Tremor

7. Hypothyroidism

6) Can induce CKD by causing Interstitial Nephritis 

7) Monitoring:

• CBC differential

• Thyroid function

• Renal function

• Calcium

• Weight 

• Pregnancy Status

  • Repeat the above workup every 1-3 months

8) Therapeutic Ranges

a) Mania = 0.6 - 1.0

b) Depression = 0.6 - 0.8

c) Age 60-79 = 0.4 - 0.8

d) Age 80+ = 0.4 - 0.7

9) 1.5 = bad , 2.0 = HOSPITALIZATION

Valproic Acid / Divalproex

1) MOA

Thought to ___ ___ neuronal impulses through ____ of ___- ___ ___+ channels AND increase brain ____ concentrations 

2) Therapeutic actions (2)

• Acute management of what? (If any)

• Prevention of what? (If any)

3) Drug Interactions 

4) Side effects (11) C 3H (NP) RS TTW

5) Monitoring; Baseline Workup + Follow-Up (6)

6) Therapeutic Ranges

1) MOA:

• Slow down; inhibition of voltage gated Na+; increase GABA 

2) Therapeutic Actions:

• Acute management of mania and BD depression

• Prevention of mania (less evidence) and BD depression

3) Increases levels of lamotrigine

4) Side effects: C 3H (NP) RS TTW

1. Changes in menstrual cycle

2. Hair loss / thinning 

3. Hepatotoxicity 

4. Hyperammonemia

5. Nausea

6. Pancreatitis

7. Rash

8. Sedation / confusion

9. Tremor

10. Thrombocytopenia

11. Weight gain 

5) Monitoring; Baseline Workup + Follow-Up

• CBC differential

• Weight

• Pregnancy status

• Menstrual history

• Liver function

• Lipid panel

  • Monthly for 3 months, then every 3-6 months

6) Therapeutic range = 350-700 umol/L

Lamotrigine

1) MOA

• Thought to reduce ____ transmission and ____ voltage-sensitive sodium channels

2) Therapeutic actions (2)

• Acute management of ____

• Prevention of ___ and _____

3) Drug Interactions 

4) Side effects (5) + one caveat to remember 

5) Monitoring; Baseline Workup + Follow-Up?

6) Therapeutic Ranges?

1) Reduce glutamatergic transmission + inhibit Na channels

2) Therapeutic actions:

• Acute management of BD depression

• Prevention of mania and depression

3) Drug interactions:

• Valproic acid increases levels of lamotrigine 

4) Side effects:

• Dizziness

• Tremor

• Headache

• Somnolence

• Rash / SJS / TEN

  • STOP at first sign of rash

5) Not required

6) Not required

For which bipolar medication is baseline monitoring workup AND therapeutic ranges NOT required

Lamotrigine (baseline monitoring)

Carbamazepine

1) MOA

• Thought to reduce ____ transmission and ____ voltage-sensitive sodium channels

2) Therapeutic actions

• Acute management of ____

3) Side effects

4) Monitoring; Baseline Workup + Follow-Up? (6)

5) Therapeutic Ranges?

1) Thought to reduce glutamatergic transmission and inhibit voltage-sensitive sodium channel 

2) Acute management of mania

3) Side effects:

• Blurred vision, diplopia, nystagmus

• Ataxia

• Rash, SJS

• Leukopenia / Transaminitis 

• Menstrual disturbances

• Hyponatremia,

• Polydipsia 

• Sedation

4) Monitoring baselin workup:

• CBC differential

• Liver function

• Renal function

• Electrolytes

• HLA-B*1502 / HLA-A*3101

• Pregnancy status

  • Repeat monthly x 3 months, then every 3 months

5) Therapeutic range = 17 - 51 umol/L

Valproic Acid / Divalproex Follow Up:

1) Which tests do you want to repeat

2) How often

Repeat CBC differential + liver function

• Monthly for 3 months, the q3-6 months

Which two drugs are good for acute management of mania and BD depression

Lithium

Valproic Acid / Divalproex

Which medication is good for acute management of BD depression

and MAINTENANCE of mania and depression

Lamotrigine

Which medication is only good for acute management of mania? (Not even for prevention)

Carbamazepine (mania)

Which medication(s) requires THYROID FUNCTION panel AND Calcium

Lithium

Which medication(s) require renal function baseline workup

Lithium, Carbamazepine

Which medication(s) require hepatic function baseline workup

Valproic Acid

Carbamazepine

Which medication(s) require:

1. HLA-B*1502 / HLA-A*3101 AND

2. ELECTROLYTE baseline workup

Carbamazepine (monitoring)

Which medication(s) require weight baseline workup

Lithium, valproic acid 

Which medications require Lipid panel + Menstural Hx

Valproic Acid

Which medication(s) should patients be instructed to monitor for rash

• Lamotrigine

• Valproic Acid / Divalproex

• Carbamazepine 

Which medications can cause menstrual disturbances

• Valproic acid / Divalproex

• Carbamazepine

(Menstural)

Treatment of Acute Mania

1) _____ week(s) at therapeutic dose then reassess. Full response may take ____ to ____

2) What medication do you want to discontinue

3) Combination treatment has ____ response rate but more ___ ___.

4) Out of the 4 drugs: lithium, valproic acid/divalproex, lamotrigine, carbamazepine, which are considered first line

5) Which antipsychotic drugs are considered first line (5)

6) Combination therapy: antipyschotic drug + which medications

1) 1-2 weeks ; may take weeks to months

2) Antidepressants

3) Greater response rate, but more side effects

4) Lithium + Divalproex (valproic acid)

5) Antipsychotics

• Cariprazine

• Aripirazole

• Quetiapine XR

• Asenapine

• Risperidone / Paliperidone

6) Lithium or divalproex

Treatment of Acute BD Depression

1) _____ week(s) at therapeutic dose then reassess

2) Monotherapy use of antidepressants in bipolar 1 is ____ ____

3) Adjunctive therapy w/ antidepressants recommended? (What line)

4) Two most important POTENTIAL RISKS w/ antidepressants

5) Who do you want to avoid antidepressants in

6) What are the drugs of choice for treating BD depression (4)

7) What is the combination drug therapy of choice for treating BD depression

1) 2-4 weeks

2) NOT recommended

3) No good evidence (2nd line)

4) RISKS:

• Treatment emergent mania (increase risk w/ monotherapy)

• Accelerated mood switches

5) People with rapid cycling & mixed episode subtypes

6) Drugs to use:

1. Lithium

2. Lamotrigine

3. Quetiapine

4. Lurasidone

7) Lurasidone + Lithium or Divalproex

Maintenance Treatment

1) _____% recurrence risk per year on placebo

2) Are acute phase treatments generally continued in maintenance? When should you reassess?

3) What are the three mood stabilizers that we use in maintenance

4) What are the 3 antipsychotics we use for stabilizing

5) What combos do we use (2)

1) 23-40%

2) Yes —> Reassess if receiving SSRI/SNRI

3) Lithium, divalproex, lamotrigine 

4) Quetiapine, Aripiprazole, Asenapine

5) Quetiapine or Aripiprazole with Lithium or Divalproex

Bipolar and Pregnancy:

1) What should you counsel on (2)

2) If pregnant, what additional NHP might the patient need

3) Should you discontinue meds? Why?

4) Which drug should you AVOID due to teratogenicity

5) Which drug should you avoid but if can’t avoid, increase folate supplementation to ≥ 4 mg/day

6) Which drug should you avoid in 1st trimester and get a detailed ultrasound in 2nd trimester

7) Which drug should you screen for gestational diabetes

1) Effective contraception + family planning

2) Folic acid

3) NO!! Associated w/ 3x higher relapse rate

4) Valproic acid

5) Carbamazepine

6) Lithium —> Monitor levels during pregnancy / postpartum

7) Antipsychotics

What is the screening tool we use for bipolar 1 and a score of ____ indicates positive screen for bipolar 1 disorder

Rapid mood screener

≥ 4

For patients with bipolar 1 disorder, can psychotic symptoms be present and during which stage(s)

Yes —> In both manic or depressive states

Genetics:

1) ___ fold increase risk if a first-degree relative has bipolar illness

2) ___% of patients have family history of bipolar illness

1) 7-fold

2) 50%

Bipolar 1 Disorder:

1) What % of time in depression

2) What % of time in mania

3) What % of time in euthymic

1) 30-35%

2) 10%

3) 50%

Which medication reduces risk of suicides/suicidal ideations

Lithium (suicide)

1) Lithium half-life

2) What to consider as you age

1) 18-36 hours

2) As you age, renal function declines, therefore t1/2 GETS LONGER

Lithium Mild toxicity

• Score

• Symptoms

1.5-2

• Ataxia

• Coarse tremor

• Confusion

• Slurred speech

Lithium Moderate/Severe Toxicity (hospital)

2.0+

• Fluctuating consciousness

• Coma

• Stupor

• Seizures

• Rigidity

• Hyperreflexia

• Hypertension of limbs

• Cardiovascular instability

Monitoring lithium levels

• Trough level ___ hours post dose

• ______ days after dose adjustment

• Once every ______ months

• Or in clinical changes

12 hours post dose

3-7 days after dose adjustment (ideal = 5)

3-6 months

Which medication has a risk of 

• Fetal malformations

• Risk of intellectual disability and behavioural disorders in offspring

Divalproex / Valproic acid

Dosing for antipsychotics in schizophrenia vs bipolar; which condition gets a higher dose

Bipolar

Best antipsychotics that work for both mania and deprssion

Quetiapine + Cariprazine

Bipolar 2 therapeutics

1) CANMAT 1st line therapeutics

2) Maintenance (3)

1) Quetiapine

2) Quetiapine, Lithium, Lamotrigine

Most common substance use disorder with bipolar

Alcohol use disorder