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PHAR 358 > Bipolar Disorder > Flashcards

Bipolar Disorder Flashcards

1
Q

What is mood?

A

It is the pervasive and sustained emotion or feeling tone that influences a person’s behaviour and colour his or her perception of the world

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2
Q

What is the impact of bipolar disorder on mood?

A

Mood can be labile, fluctuating, or alternating rapidly between extremes

ex. Laughing out loudly at one monet, tearful the next

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3
Q

What is the mood spectrum?

A

It describes a range of moods from psychotic depression to psychotic mania.

Patients with bipolar disease fluctuate between mood depression and mania

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4
Q

What are some examples of mood disorders?

A
  • Bipolar disorder
  • MDD (unipolar depression)
  • Cyclothymia (less severe mood swings)
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5
Q

What are the two main subtypes of bipolar disorder?

A

BD I and BD II

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6
Q

What is the diagnostic criteria for bipolar I disorder (BDI)?

A

A distinct period of at least one week of full manic episode: abnormally & persistently elevated mood and increased energy

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7
Q

What is the diagnostic criteria for bipolar II disorder (BDII)?

A

A current or past hypomanic episode and a current or past major depressive episode

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8
Q

How common is bipolar disorder in the population?

A

Less than 1% of people have been diagnosed with either BDI or BDII

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9
Q

What are the sex differences in symptoms associated with bipolar disorder?

A

Men have more manic episodes, women have more depressive or mixed symptoms

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10
Q

Is bipolar disorder an acute condition?

A

No, it is a lifelong illness with variable course

Full recovery is possible with appropriate drug therapy

A cure is not possible at this moment

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11
Q

Does bipolar disorder have a simple etiology?

A

No, it is multifactorial

  • Developmental
  • Psychologic (stresses, especially during development)
  • Genetic
  • Neurobiologic
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12
Q

What are some risk factors associated with bipolar disorder?

A
  • First degree relative with bipolar disorder
  • Period of high stress (traumatic experiences)
  • Major life changes (family deaths)
  • Medical conditions (hyperthyroidism, hormonal changes, CNS disorders, CVD)
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13
Q

What are some secondary causes of mania?

A
  • Alcohol intoxication
  • Antidepressants
  • DA-augmenting agents (amphetamines, cocaine, reuptake inhibitors)
  • Marijuana intoxication
  • NE-augmenting agents
  • Steroids
  • Thyroid preparations
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14
Q

What happens when a bipolar disorder patient on an anti-depressant experiences a mania episode?

A

Discontinue anti-depressanr abruptly (drug may be exacerbating mania)

Patient will have to endure withdrawal symptoms

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15
Q

What is the onset of bipolar disease?

A

Average age of onset is 20-25

2/3 of bipolar patients have some symptoms (usually depressive) before the age of 18

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16
Q

What is the prognosis of bipolar disorder?

A

With treatment, illness usually includes periods of remission with risk of full or sub-syndromal relapses (prevent remission and neurological deterioration)

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17
Q

What are some risks of leaving bipolar disorder untreated?

A

Kindling Theory
- Syndromal episodes increase vulnerability to more episodes

Neurodegeneration
- Persistent neurocognitive deficits, increasing impairment delayed functional recovery

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18
Q

What are some comorbid conditions with bipolar disorder?

A
  • Anxiety disorders (50-60%)
  • Substance use disorder (60%)
  • ADHD (20%)
  • PTSD
  • Medical comorbidities (diabetes, dyslipidemia, obesity, CV disease)
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19
Q

What is the leading cause of death in patients with bipolar disorder?

A
  • 6-7% of identified patients with bipolar disorder die by suicide (20x rate vs. general public)
  • 3% of BD patients report suicidal ideation (20-50% attempt suicide at least once)
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20
Q

What is the name of the suicide risk assessment tool?

A

Columbia Risk Assessment Tool

review slide 18

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21
Q

What is the DSM-5 diagnostic criteria for mania?

A

Persistantly and abnormally

Elevated mood (irritable or expanisve) and energy

With at least 3 of the following changes from usual behaviour:
- Grandiosity (god-complex)
- Decreased need for sleep
- Racing thoughts
- Increased talking/pressured speech
- Distractibility
- Increasing goal-directed or psychomotor agitation
- Excessive engagement in high risk behaviours

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22
Q

What is a good symptom mneumonic for mania?

A

DIGFAST

D: distractibility
I: irritability
G: grandiosity
F: flight of ideas (racing thoughts)
A: activity increased
S: sleep decreased
T: talkativeness

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23
Q

What is the diagnostic criteria for hypomanic episodes?

A

Same symptoms as full blown mania, but only lasts up to 4 days

The episode is not linked to physiological effects of a substance or another medical condition

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24
Q

Review slide 26 for diagnostic criteria comparisons between BDI and BDII

A
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25
Q

What is the diagnostic criteria for MDD?

A
  • Depressed mood most of the day, nearly every day
  • Diminished interest or pleasure in all or most activities

Need to have atleast 3+ of the following symptoms
- Changes in sleep pattern
- Changes in interests and activity
- Feelings of guilt or worry
- Changes in energy
- Changes in concentration
- Changes in appetite
- Psychomotor disturbances
- Suicidal ideation

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26
Q

What are some challenges in bipolar disorder diagnosis and treatment?

A
  • Delay to diagnosis (average delay of 8-12 years, usually have history of MDD)
  • Misdiagnosis (3/4 of bipolar patients have been misdiagnosed with depression)
  • Limited clinical trails (not a lot of quality evidence due to heterogeneous illness, co-morbidities, manic symptoms, etc)
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27
Q

How quickly does therapy for mania result in improvement in mood?

A

Response: 1-2 weeks
Full clinical benefit: 3-4 weeks

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28
Q

How quickly does therapy for depression result in mood improvement?

A

Response: 2-4 weeks

Full clinical benefit: 6-12 weeks

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29
Q

What are some non-pharm approaches to managing bipolar disorder?

A
  • Exercise, adequate sleep, health diet, decrease substance use (general self care)
  • Bright light (good for depressive symptoms)
  • Relapse prevention plan (help support patient adjust doses during relapses)
  • Psychoeducation and therapy (can be unaccessible for some patients)
  • Medication adherance (identify barriers and help resolve)
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30
Q

What are the most commonly used mood stabilizers used in treatment of bipolar disorder?

A
  • Lithium
  • Valproic Acid/Divalproex
  • Lamotrigine
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31
Q

What are the official indications for lithium?

A
  • Bipolar disorder (acute mania treatment and prophylaxis)
  • Schizoaffective disorder
  • Unipolar depression (anti-depressant augmentation)
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32
Q

How does lithium distribute in the body?

A

Evenly into to the total body water space (can accumulate across the body, poses risk for toxicity)

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33
Q

How quickly is lithium cleared from the body?

A

Half-life is usually within 12-27 hours, longer in elderly due to lower clearance

95% renal clearance, remainder is perspiration

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34
Q

What are the therapeutic ranges for lithium?

A

Acute mania (1.0-1.2mmol/L)

Maintenance therapy (0.6 - 1.0mmol/L)

Elderly (0.6-0.8mmol/L)

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35
Q

Is lithium a narrow therapeutic index drug?

A

Yes, toxic ranges (over 1.5mmol/L) are close to therapeutic ranges(0.6-1.0mmol/L)

Need to monitor closely

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36
Q

When are lithium levels drawn?

A

Unlike other drug levels, serum levels are drawn 12 hours after dosing to capture complete absorption and distribution

Usually done in the morning after an evening dose

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37
Q

What is done if lithium drug levels are well above 1.2mmol (toxic levels)?

A

Hold dose as toxic levels of lithium can be fatal

Repeat plasma level next day (half-life is 24 hours)

Restart therapy when levels are within target range (0.6-1.0mmol/L)

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38
Q

Review slides 56 to 62 for lithium dose adjustment

A
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39
Q

What are some factors that can lower expected lithium levels?

A
  • Sodium supplement (can also be dietary)
  • Burns (increased total body water, dilutes lithium)
  • Caffeine (fluid)
  • Hemodialysis (increased clearance)
  • Pregnancy
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40
Q

What are some factors that can elevate expected lithium levels?

A
  • Dehydration
  • NSAIDs (reduces renal perfusion)
  • TZDs (Na+ reabsorption inhibited, body holds on to Na+ and Li+)
  • Sodium loss (body holds onto more Li+)
  • ACEi/ARBs (reduced GFR)
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41
Q

What are some drugs that interact with lithium?

A
  • Diuretics (effect depends on quantity of fluid in the patients body)
  • NSAIDs (reduced lithium clearance, and lithium accumulation)
  • ACEi/ARBs (reduced renal perfusion, reduced lithium clearance, increased lithium levels)
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42
Q

Review slides 65 to 70 for managing lithium drug interactions

A
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43
Q

What are some characteristic lithium adverse effects?

A
  • Increased thirst and polyuria
  • Fine tremors to hands/arms
  • GI upset (first signs of toxicity)

Serious
- Renal injury (can be irreversible)
- Hypothyroidism
- Bradycardia

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44
Q

Review slide 73 for lithium monitoring tips

A
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45
Q

What are some important points to discuss during patient counselling for lithium?

A
  • May take several weeks to see benefit
  • Ensure adequate hydration and keep salt/caffeine intake stable
  • Self-monitor for signs of toxicity
  • Will require regular blood level monitoring
  • Avoid NSAIDs
  • Consider birth control if the patient has child-bearing potential
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46
Q

What are the officially indicated indications for valproic acid?

A

Seizures (broad-spectrum anti-epileptic activity)

Bipolar disorder (acute mania treatment and maintenance/prophylaxis)

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47
Q

What are some potential mechanisms of action for valproic acid in treating bipolar disorder?

A
  1. Inhibition of volage gated Na+ channels (reduces released of glutamate)
  2. Increasing action of GABA
  3. Modulates signal transduction cascades and gene expression

4 May effect neuronal excitation mediated by the NMDA subtype of glutamate receptors

  1. Also effects serotonin, dopamine, aspartate, and T-type Ca2+ channels
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48
Q

What is an important drug interaction consideration for valproic acid?

A

Valproic acid is highly protein bound, and concommitant use with other highly protein bound drugs may result in overdosing at normal doses

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49
Q

How is valproic acid cleared?

A

More than 95% is hepatically cleared (metabolites can cause liver toxicity)

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50
Q

What is the therapeutic range for valproic acid in bipolar disorder?

A

Total 350-700umol/L, free levels are not readily available. Need to inference free levels from total levels and impact of potential drug interactions

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51
Q

How are valproic acid levels monitored?

A

A blood sample is taken at steady state trough, usually 3-4 days following initial therapy and then 1-2 weeks later to check dose level stability

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52
Q

How are valproic acid doses adjusted in patients with hepatic dysfunction?

A

These patients show lower protein binding and clearance of valproic acid, so it is best to avoid this drug in these patients

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53
Q

How are valproic acid doses adjusted in elderly patients?

A

Elderly patients have lower protein binding and hepatic clearance, so use lower initial doses

54
Q

How are valproic acid doses adjusted in patients with renal dysfunction?

A

No dosage adjustment required

Valproic acid is almost only cleared by the liver, minimal involvement in clearance from the kidneys

55
Q

What are the most common formulations of valproic acid?

A
  • Syrup (Valproate Sodium)
  • Capsules (Valproic acid)
  • Enteric coated tablets (Divalproex sodium, pro-drug)
56
Q

Which drugs are known to increase valproate levels?

A
  • Macrolides (clarithro, erthro)
  • ASA/salicylates (increase unbound VPA)
57
Q

Which drugs are known to decrease valproate levels?

A
  • Carbapenems (erta, imi, mero)
58
Q

Which drug has its levels increased when used concommittantly with valproate?

A

Lamotrigine (decrease LTG dose by 50% when used with VPA)

59
Q

Review slides 92 to 95 for divalproex prescribing patient case

A
60
Q

What are some adverse effects associated with valproate?

A
  • GI (lower with divalproex vs valproic acid)
  • CNS (tremor, sedation, ataxia, dizziness)
  • Skin rash (especially if used in combo with lamotrigine)
  • Weight gain (chronic use in 60% of patients, more than lithium)
61
Q

Is valproate a good option for treating bipolar disorder in pregnant women?

A

No, valproate is teratogenic, so birth control should be considered in women of child bearing age

62
Q

What are some counselling points for valproate?

A
  • May take several weeks to see benefit
  • Check with pharmacist or physician before starting any new drugs (concern about starting highly protein binding drugs)
  • Use reliable contraception if child-bearing potential
  • Avoid excessive alcohol use due to hepatic injury
63
Q

What are the indications for lamotrigine?

A

Seizures

Bipolar disorder

64
Q

What is the half-life for lamotrigine?

A

Half-life is 25-33 h for adults and no interacting drugs

65
Q

What is the primary organ that eliminated lamotrigine from the body?

A

Hepatic and renal metabolism are both important

66
Q

What is an important consideration for lamotrigine dosing?

A

Slow titration due to risk of severe skin reactions (rash, SJS, and TEN)

Due to skin rash risk, so not start new shampoo, detergents, and perfumes

67
Q

What is the dosing protocol for missing lamotrigine doses?

A

If the patient has missed doses for more than 5 days (5 half-lives), then they must restart titration to safely resume therapy

68
Q

What are some common adverse effects associated with lamotrigine?

A

Sedation
Headaches
Nausea
Dizziness

69
Q

What are some rare/serious adverse effects associated with lamotrigine?

A

Risk of SJS (especially if titrated too quickly), asceptic meningitis, blood dyscrasias, hepatoxicity

70
Q

What are some good variables to monitor for patients on lamotrigine?

A

Baseline: Hepatic and renal function
Ongoing: Rash

No serum lamotrigine levels necessary

No lab monitoring required other than regular blood work

71
Q

What is the drug interaction between valproate and lamotrigine?

A

VPA/DVP increase lamotrigine levels two-fold or more

72
Q

What is the drug interaction between carbamazepine, pheny, phenobarb, and topiramate and lamotrigine?

A

These drugs can decrease lamotrigine levels by 30-50%

73
Q

What is the drug interaction between oral contraceptives (estrogen) and lamotrigine?

A

Estrogen contraceptives can reduce lamotrigine levels by 50%

74
Q

Review slides 111 to 114 for case example of managing drug interactions and titration of lamotrigine

A
75
Q

What are some important counselling for lamotrigine?

A

May take several weeks to see benefit in mood

Adherence is important, may need to repeat titration if doses are missed for more than 5 days

Self-monitoring for rash is very important (stop taking lamotrigine if you see any signs of skin abnormalities, seek ER if rapid development)

Watch out for enzyme inhibitors like VPA and carbamazepine

76
Q

Which drug class is carbamazepine structually similar to?

A

TCAs, and carbamazepine can cause false positives for TCAs and may confer similar effects due to receptor binding

77
Q

What are the indications for carbamazepine?

A

Seizures

Bipolar disorder

Neuropathic pain (off-label)

Trigeminal neuralgia

78
Q

What is the general MOA for carbamazepine?

A
  • Blocks voltage-dependent Na+ channels
  • Blocks NMDA glutamate receptor
  • Decrease synaptic transmission
  • Stimulates release of ADH which promotes water resorption (can cause hyponatremia and fluid overload)
79
Q

What is autoinduction in the context of carbamazepine metabolism?

A

Induces its own metabolism, which can make titration to therapeutic doses a longer and more tedious process

As a result, clearance and half-life are variable

80
Q

What is the therapeutic drug level of carbamazepine?

A

17-51 umol/L

Taken 1 hour after dose as a trough level

81
Q

How often are carbamazepine levels monitored?

A

During initiation and auto-induction, monitor every 1-2 weeks until on stable regimen

82
Q

What are some carbamazepine dosing principles?

A
  • Initiate slowly due to avoid side effects
  • Best to give in divided doses, usually Q12h or Q8h instead of a single dose
  • Dose at meal time
  • Not recommended in patients with decompensated liver disease
83
Q

What is the main type of drug interaction with carbamazepine?

A

Carbamazepine levels are significantly impacted by co-administration with CYP3A4 inhibitors and inducers

84
Q

Which drug classes cause carbamazepine levels to be elevated?

A

Macrolides (erythro, clarithro)

Azoles (fluco, keto, itra)

CCBs (diltiazem and verapamil)

Grapefruit juice

85
Q

Which drug classes cause carbamazepine levels to be lower than expected?

A

Anticonvulsants (pheny, phenobarb)

Rifampin

86
Q

What are the two most important drugs whose levels are decreased by concomittant use with carbamazepine?

A

Warfarin

DOACs (should not be used with carbamazepine)

87
Q

What are some other drugs that are decreased by carbamazepine?

A

Lurasidone (antipsychotic)

Anti-retrovirals (HIV treatment)

88
Q

What are some common adverse effects associated with carbamazepine?

A

GI: nausea, vomiting, constipation

CNS: sedation, incoordination, ataxia

CV: Tachycardia, hypotension

89
Q

What are some concerning adverse effects associated with carbamazepine?

A

SIADH/hyponatremia

Blood dyscrasias

Rash (10% of patients get morbiloform rashes and hypersensitivity reactions)
- especially in patients with Asian & pos. HLA-B1502 and Caucasian & HLA-A3101

90
Q

What are the contraindications for carbamazepine use?

A

History of hepatic disease, CVD, blood dyscrasias (esp when used with clozapine), bone-marrow depression

91
Q

What should be monitored in regular blood work for patients on carbamazepine?

A

Determine baseline, then monthly for 3 months, then q6-12 months once stable

CBC with diff and platelets
Electrolytes
LFTs
Renal function

92
Q

Review slides 137 and 138 for carbamazepine-induced SIADH case example

A
93
Q

What are some good counselling points for carbamazepine?

A
  • Take with food to minimize GI upset
  • Report rash or flu-like symptoms
  • Carbamazepine will decrease efficacy of estrogen or progestin based contraception
  • Drug interactions with CYP3A4 inducers and inhibitors
  • HLA-B*1502 testing in Asian patients to avoid uneccessary skin reactions
94
Q

What is the primary MOA for antipsychotics?

A

Dopamine blockade, can be useful for resolving mania

95
Q

What is the main therapeutic difference between atypical and typical antipsychotics?

A

Atypicals have lower risk of extra-pyramidal symptoms (pseudo-parkinson’s)

Typicals are very rarely used for bipolar

96
Q

What are some adverse effects associated with antipsychotics?

A

EPS (extra-pyramidal syndrome, psuedo-parkinson’s)

Hyperprolactinemia, sexual dysfunction

Metabolic disturbance (weight gain, dyslipidemia, DM, CVD)

Sedation

QT prolongation

Seizures

97
Q

What are some common lab values monitored in patients on antipsychotics?

A

BMI, vitals

A1c, lipids

ECG

Liver function, renal function, lytes, CBC

Prolactin

98
Q

What is the role of antidepressants in bipolar disorder?

A

Increased risk of switching patients to mania, but bipolar depression can be difficult to treat

Avoid antidepressant monotherapy without antimanic agent and d/c during acute manic episode

Use short courses (3-4 months) of therapy

99
Q

What are the preferred antidepressants for bipolar depression?

A

Citalopram, Escitalopram Fluoxetine, Sertraline

Trazodone, Mirtazipine, Bupropion, Vortioxetine

100
Q

Review slides 150 to 152 for strategy of treating bipolar disorder with mood stabilizers

A
101
Q

What are some things that clinicians for assess before treating acute mania (imp. question)?

A
  • Risk of aggressive behaviour or violence to others
  • Risk of suicide
  • Degree of insight
  • Ability to adhere to treatment
  • Co-morbidities
  • Substance use
  • Physical condition & lab tests
  • Most appropriate treatment setting (inpatient vs outpatient)

Review slide 159

102
Q

What drugs should be discontinued on the onset of acute mania?

A
  • Antidepressants
  • Stimulants (caffeine, amphetamines)
  • Alcohol
  • Nicotine (gradually d/c)
103
Q

What are some things that need to be ruled out when diagnosing acute mania?

A
  • Prescribed medication
  • Illicit-drug use/abuse
  • Endocrine disorder
  • Neurological disorder
104
Q

Review slides 160 to 163 for antidepressant-induced mania case example

A
105
Q

What are the first line monotherapies for acute mania?

A

Lithium, quetiapine (and other atypical antipsychotic), divalproex

50% of patients will respond to monotherapy with improvement in 3-4 weeks (earlier with DVP and APs)

106
Q

What is the first line combo therapy options for acute mania?

A

Lithium + atypical antipsychotic

OR

Divalproex + atypical antipsychotic

107
Q

What is the advantage of lithium over other options for treatment of acute mania?

A

Preferred in patients with classical euphoric grandiose mania, few prior episodes of illness, family history of BD, and family history of responding to lithium

108
Q

What is the advantage of divalproex over other options for treatment of acute mania?

A

Equally effective in treating classical and dysphoric mania

Multiple prior mania episodes

Predominant irritable or dysphoric mood

Comorbid substance abuse

History of head trauma

109
Q

Review slides 167 to 169 for treatment of mania

A
110
Q

What are the second-line monotherapies for acute mania?

A

Olanzapine, carbamazepine, ziprasidone, haloperidol

111
Q

What is the second-line combo therapy for acute mania?

A

Olanzapine + lithium or divalproex

112
Q

What is the role of electroconvulsive therapy in treating acute mania?

A

Limited number of controlled clinical trials, but suggets up to 80% of patients see marked clinical improvement

113
Q

Is lamotrigine recommended in acute mania treatment?

A

No, it does not help with mania specifically

114
Q

What factors should clinicians assess when treating bipolar I depression?

A
  • Severity of depression
  • Risk of suicide/self-harm behaviour
  • Ability to adhere to treatment
  • Psychosocial support network
  • Ability to function
  • Previous treaments
  • Outpatient vs. inpatient
115
Q

Which drugs should be discontinued when treating bipolar I depression?

A

Stimulants (nicotine, caffeine), drug, and alcohol use

116
Q

What conditions need to be ruled out before diagnosing a patient with bipolar I depression?

A
  • Symptoms due to alcohol/drug abuse, medication adverse events, other treatments
  • General medical condition
117
Q

What is the first line monotherapy for bipolar I depression?

A

Quetiapine/lurasidone + lithium/DVP

or

lithium alone

or

lamotrigine monotherapy/adjunct

or

lurasidone monotherapy

118
Q

What is the second line treatment for bipolar I depression?

A

Divalproex

119
Q

What is the second line add-on therapy for bipolar I depression?

A

Adjuntive SSRI or bupropion (added to lithium/divalproex or atypical antipsychotic)

Olanzapine-fluoxetine

120
Q

Review slide 183 to 185 for treatment optimization for bipolar disorder with suicidal ideation

A
121
Q

What is the purpose of bipolar I maintenance therapy?

A

Effective maintenance treatment early in illness, even after first episode:
- Reverse cognitive impairment
- Preserve brain plasticity
- May lead to improved prognosis and minimization of illness progression

122
Q

What are risk factors for reccurent episodes of bipolar I?

A
  • Younger age at onset
  • Psychotic features
  • Rapid cycling
  • More previous episodes
  • Comorbid anxiety
  • Comorbid substance use
123
Q

What is the role of psychosocial therapy in bipolar I maintenance therapy?

A

Pharmacotherapy may be the foundation to BD maintenance therapy, but alone is often ineffective to prevent recurrence

Adjunctive psychosocial treatment decreases recurrence rates by 15%

124
Q

What are some factors that should be assessed before starting bipolar I maintenance therapy?

A
  • Are medications effective in acute phase (only use antidepressants for 4-8 weeks until depressive symptoms subside)
  • History (clinical course, response to previous therapy, family history)
  • Psychiatric comorbidities
  • Predominant illness polarity
  • Polarity of most recent illness
125
Q

What drugs should be discontinued before starting bipolar I maintenance therapy?

A

Stimulant, nicotine, caffeine, drug, and alcohol use

126
Q

What drug has the most real-world evidence in bipolar disorder maintenance therapy?

A

Lithium

127
Q

How long should adjunt atypical antipsychotics be used with lithium maintenance therapy?

A

Up to 6 months, benefits are not significant past that point

128
Q

For patients experiencing manic and depressive bipolar symptoms, what is the best course of action from a pharmacological standpoint?

A

d/c antidepressants (can worsen mania)

Monotherapy: atypical antipsychotic (fast acting)

Combination therapy (lithium or divalproex + atypical antipsychotic)

129
Q

For pregnant patients with bipolar disease, what are some treatment tips?

A

Avoid DVP/VPA and carbamazepine because they are teratogens

Lithium has lower risk

Lamotrigine seems to be the safest option while maintaining adequate bipolar maintenance treatment

130
Q

What is the best agent for bipolar patients experiencing suicidal ideation?

A

Lithium has the most evidence to reduce the risk of suicide in patients with bipolar disorder

ECT can be used as adjuct in cases of high risk of suicide

PHAR 358 (3 decks)

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