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Therapeutics (Fall 2024) > Bipolar Disorder > Flashcards

Bipolar Disorder Flashcards

1
Q

What is considered Cyclothymia?

A

Between Dysthymia and Sub-threshold mania

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2
Q

What is bipolar I disorder or 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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3
Q

What is Bipolar II Disorder (BDII)?

A

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

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4
Q

What prevalence and epidemiology of Bipolar disorder?

A

Men have more manic episodes, women more
depressive or mixed

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5
Q

Risk factors contributing to Bipolar Disorder?

A

Drug/Alcohol abuse,
First degree relative
High stress
Major life events
Some medicaiton conditions

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6
Q

What are the medication related causes that can induce mania?

A

LOTS (List is not inclussive)

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7
Q

What is the avg age of onset with bipolar?

A

20-25

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8
Q

What is the clinical presentation of bipolar disorder?

A
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9
Q

What is the prognosis of bipolar disroder?

A

Untreated it has a high mortality rate, significant impairment, disruptive courses of hospitalization,

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10
Q

What conditions may worsen existing BD?

A
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11
Q

What is some of the diagnostic criteria of mania?

A
  1. Grandiosity or inflated self-esteem
  2. Decreased need for sleep
  3. Racing thoughts
  4. Increased talking/pressured speech
  5. Distractibility
  6. Increased goal-directed or psychomotor agitation
  7. Excessive engagement in high risk behaviours
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12
Q

How many specific symptoms are required for someome to be considered manic?

A

3+ and occur nearly every day for 1 week

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13
Q

What is a pnemonic for helping with mania symptoms?

A

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

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14
Q

What is required for diagnosis?

A

Manic episode

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15
Q

What is a hypomanic episode?

A

Same DIGFAST symptoms, but lasting up to 4 days

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16
Q

What is Bipolar II disorder?

A
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17
Q

What is the general differneces of diagnostic between BDI and BDII?

A
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18
Q

What is considered a “Major depressive episode”?

A
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19
Q

What is the MDQ?

A

This is a patient rated scale used to screen for possible BD.

3 questions, 13 item.

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20
Q

What is the challenged with BD diagnosis?

A

Delay to diagnosis 8-12 years, Misdiagnosis, limited clinical trials

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21
Q

What is expected medicaiton response in MANIA?

A
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22
Q

What is the expected medication response in BD depression?

A
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23
Q

What are some non-pharm therapy for BPD?

A
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24
Q

What are the most commonly used mood stabilizers?

A

Lithium
Valproic acid
Lamotrigine

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25
Q

What are the indications of lithium?

A

Acute mania treatment
Prophylaxis/maintenance

Schizoaffective disorder

Unipolar depression

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26
Q

What is the MOA of lithium?

A

Not fully known

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27
Q

What is the general Vd of lithium?

A

Distirbutes evently in the total body water space

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28
Q

What is the approximate T1/2 of lithium/

A

Assuming normal renal funciton 12-27 hours range

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29
Q

What is the general elimination of lithium?

A

95% renal

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30
Q

What is special about the elimination of lithium?

A

Not protein bound→ freely filtered by glomerulus like sodium and potassium
80% reabsorbed in the proximal tubules (with sodium)

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31
Q

Regarding clearance what does lithium follow?

A

Follows linear dose proportional pharmacokinetics, Decreased clearance when hyponatremia, dehyradtion,. renal failure, or dysfunction

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32
Q

What is the lithium therapeutic range for acute mania?

A

1.0-1.2 mmol/L

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33
Q

What is the lithium TR for maintenance therapy?

A

0.6-1.0 mmol/L

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34
Q

What is the Lithium therapeutic range for elderly?

A

0.6-0.8 mmol/L

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35
Q

When do we sample lithium levels?

A

12 hour post dose level

Stat if toxicity or non adherence is suspected

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36
Q

What is the target range for lithium for maintenance

A

0.8-1.2 mmol/L some guideliens do go upwards of 1.4-1.5 mmol/L

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37
Q

What is the usualy odsage of lithium?

A

900-2100 mg/day either HS or divided dose

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38
Q

What is the general starting dose of lithium?

A

starting dose of 300mg/day

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39
Q

What is the target plasma level for maintenance therapy?

A

0.6-1 mmol/L

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40
Q

When can we go HS dosing of lithium?

A
  • Only if able to tolerate
  • Usually given at night to improve compliance
  • Some trials show a  in urine volume and  renal toxicity with once daily
    evening dosing
  • Patients sensitive to peak related side effects (e.g. tremor, urinary frequency,
    nausea) may respond to extended release formulation
  • When lithium changes from multiple daily dosing to once daily dosing, can
    expect ~10-25% increase in 12hr Lithium level
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41
Q

Why would we change soemone to the extended release lithium tablets?

A

Experiencing adverse reactions from capsules

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42
Q

What factors can decrease lithium levels?

A

Sodium supplement

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43
Q

Low serum sodium will increase or decrease serum lithium?

A

Increased because our body will try and hold onto serum sodium and doesnt have the necessary “Senses” to detect lithium levels.

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44
Q

What can increase lithium levels?

A

Sodium loss
NSAIDs
Thiazide Diuretics
Ace/Arbs

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45
Q

What are the ranges that lithium toxicity can occur?

A

> 1.5

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46
Q

What can severe lithium poisoning result in?

A
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47
Q

What labs are importnat for monitoring with regards to lithium

A

Monitor serum level, renal, lytes, thyroid regularly

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48
Q

What are some common side effects for lithium?

A
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49
Q

What is valproic acid used to treat?

A
  • Seizures:
  • generalized tonic-clonic (grand mal), partial-onset,
    absence
  • Has broad-spectrum anti-epileptic activity
  • Bipolar disorder
  • Acute mania treatment
  • Maintenance (prophylaxis)
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50
Q

What is the high level MOA of valproic acid?

A

Inhibiton of voltage gated sodium channels,
Increasing the action of Gaba,

Modulate signal transduction and gene expression

Effect neuronal exictaiton mediated by the NMDA subtype of glutamate receptors

Effects on serotonin dopamine aspartate and t-type calcium channels

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51
Q

WHat is the general protein binding of valproic acid?

A

85-90% to serum albumin

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52
Q

What is the elinmination mechanism of valporic acid?

A

> 95% hepatic metabolism via glucoronidation, B-oxidation, alpha-
hydroxylation
* Major meta

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53
Q

What are the main metabolizers of valproic acid?

A

UDPGT-catalyzed glucoronidation and B-oxidation

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54
Q

What part of valproic acid can lead to toxicity?

A

4-ene-valproic acid metabolite can cause liver tox

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55
Q

What is the therapetuic range of Valproic acid?

A

350-700 umol/L. Note that free valproic acid levels are not available

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56
Q

What is the typical dosing of Valproic acid?

A

20-30mg/kg/day PO load

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57
Q

What is the general maintenance dose of valproic acid?

A

Generally 250mg po BID upawrds to 1500-2500mg/day though

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58
Q

What is generally the max dose of valproic acid?

A

60mg/kg/day

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59
Q

What can increase valproic acid levels?

A

Hepatic disease

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60
Q

Does renal impairment effect valproic acid?

61
Q

What antibiotics can interact with valproic acid?

A

Clarithromycin, Erythromycin, Telithrimycin

62
Q

How do antibiotics affect valproic acid levels?

A

Increase and decrease dpeends on the ones!

63
Q

What can increase valproic acid levles?

64
Q

What antibiotics decrease valproate levels./

65
Q

What drugs can be increase with valproate acid?

A

Lamotrigine

66
Q

What is important about the lamotrigine interaciton with valproic acid?

A

Recommends 50% reduction in dose when used with valproate due to its competitive binding for albumin.

67
Q

What are some dose related side effects of valproate?

68
Q

What should be monitored with valproic acid?

69
Q

What are the indications of lamotrigine?

70
Q

What is the MOA of lamotrigine?

71
Q

What is the half life of valproic acid?

72
Q

What is the half life of lamotrigine?

73
Q

When is peak plasma levels achieved following lamotrigine dose?

74
Q

How is lamotrigine eliminated?

A

Hepatic and renal metabolism Glucuronidation and UGT enzymes

75
Q

What are the common side effects of lamotrigine?

76
Q

What should be monitored with Lamotrigine?

77
Q

What are the rare/serious AE of lamotrigine?

78
Q

What are important counselling points of lamotrigine

A

Titration is necessary to avoid possible rash. Dont start any new skin care stuff

79
Q

What are some key drug interactions with lamotrigine?

80
Q

What are the monitoring parameters of lamotrigine

A

MONITORING:
Baseline: hepatic and renal function
Ongoing: rash
No serum levels necessary
No lab monitoring required other than standard/annual blood work

81
Q

What is the serious reaction we worry about with lamotrigine

A

Skin rashes

82
Q

Lamotrigine drug interacitons

83
Q

What is imporatnt with lamotrigine when first starting?

84
Q

What are the indications of carbamazepine?

A
  • Seizures:
  • generalized tonic-clonic (grand mal), partial-onset
  • Bipolar disorder
  • Acute mania treatment
  • Maintenance
  • Neuropathic pain (off-label)
  • Trigeminal neuralgia
85
Q

What is the MOA of carbamazepine?

A

Signal transduction modulation (decrease repetitive
action potential firing) and anti-kindling properties

Release of ADH and potentiates its aciton in promoting reabsorption of water

86
Q

What is interesting about hte elimination of Carbamazepin?

A

Hepatic metabolism via CYP enzymes *Cyp3A4)

Induces its own metabolism

87
Q

What is the target therapeutic range of carbamazepine?

A

17-51 umol/L

88
Q

What is the typical dose of carbamazepine?

A

Bipolar disorder 100-200mg po BID

89
Q

Typical dosing range of carbamazepine?

A

300-1600mg/day absolute max of 1800/d

90
Q

What are some of the dosing principles of carbamazepine?

A

Inititate slowly,
Divided doses
Mealtime dosing

Hepatic considerations, no renal considerations

91
Q

What are the important antibiotic interactions that increase carbamazepine levels/

A

Erythromycin, clarithromycing, telithromycin

92
Q

What are the antifunglas that increase carbamazepine levels?

A

Itraconazole, fluconazole, ketoconazole

93
Q

What cardiovascular medicaitons increase carbamazepine?

A

Diltiazem
Verapamil

94
Q

What are some of the other items that can increase carbamazepine?

A

Grapefruit juice

95
Q

What are some of the drugs that can decrease carbamazepine?

A

WArfarin, Doacs specifically, Antiretrovirlas (NNRTIs) and lurasidone

96
Q

WHat are the three idiosyncratic reactions that may occur?

A

Syndrome of inappropriate antidiuretic hormone secretion (SIADH), bloood dyscrasias, rash

97
Q

What is the allele for asian ancestry that can increase hypersensitivity?

A

HLA-B*1502

98
Q

What is the genetic test for caucasian ancestry?

A

HLA-A*3101

99
Q

What are the CI of Carbamazepine?

A

History of hepatic disease, CVD, blood dyscrasias, bone marrow depression and CONCURRENT USE WITH CLOZAPINE

100
Q

What are the monitoring parameters of carbamazepine?

A

CBC with diff and platelets and electrolytes
LFTs
Renal function

101
Q

What are some of the counselling essentials and TT for Carbamazepine?

102
Q

What is the primary MOA of antipsychotics?

A

Dopamine blockade

103
Q

WHat is EPS?

A

Extrapyramidal Symptoms
Parkinsonian-like symptoms (stiffness, tremor, shuffling gait), acute dystonia (abrupt spasms of head and neck), and akathesia (physical restlessness).

104
Q

What is the difference between typical and atypical antipsychotics?

A

Atypicals (or SGAs) generally have lower risk of EPS and
hyperprolactinemia

Typical antipsychotics are very rarely used for bipolar

105
Q

What are bipolar patients more likely tho show with regards to antipsychotic doses?

A

Bipolar patients are more likely to show EPS when treated
with comparable doses of antipsychotics compared to
patients with psychosis

106
Q

What are the general adverse effects of antipsychotic therapy?

A
  • EPS
  • Hyperprolactinemia, sexual dysfunction
  • Metabolic disturbance (weight gain, dyslipidemia, DM, CVD)
  • Anticholinergic: sedation, constipation, dry mouth, blurred vision, confusion
  • Antihistaminergic: sedation
  • Alpha1 blockade: hypotension, reflex tachy, dizziness, sedation
  • QT prolongation
  • Seizures
107
Q

What are the monitoring parameters of antipsychotics?

108
Q

What is the risk with using antidepressants in bipolar?

109
Q

What was the landmark bipolar clinical trial that looked at antidepressants?

110
Q

What were the interventions of the Step BD trial?

A

Intervention/Comparator:
- Mood stabilizer (lithium, divalproex, or carbamazepine) + paroxetine or bupropion OR
- Mood stabilizer + placebo

111
Q

What were the findings of the BD trial?

A

Primary Outcome:
- Durable recovery (euthymia for minimum of 8 weeks):
- No significant difference between groups (combo 23.5% vs mono 27.3%, p=0.4)

  • Combo of antidepressant + mood stabilizer no more effective than mood stabilizer
    alone
112
Q

What were the secondary outcomes of hte BD trial?

A

Secondary Outcome:
- Treatment emergent affective switch (change to mania/hypomania):
- No significant difference between groups (combo 10.1% vs mono 10.%, p=0.84)

113
Q

What was the caveate of the BD trial?

A

Only investigated 8 weeks while bipolar is a life long disease

114
Q

What is the general conensus of AD use as of Sept 2024?

115
Q

Which class of antidepressants may be use for BD-MDD?

116
Q

What are the 4 general principles to approaching therapy treatment for depression?

A

1.Review general principles and assess medication
status
* E.g. Substance use, adherence, change in medical status
or medications

2.Initiate or optimize therapy
* Assess if dose is optimized, reasonable trial

3.Add-on or switch therapy: other first-line agents
* Add-on or switch therapy: second-line agents
* Add-on or switch therapy: third-line agents

4.Monitor/Maintain

117
Q

What should we assess for acute mania?

118
Q

What should we discontinue for acute mania?

119
Q

What should we rule out for acute mania?

120
Q

What are our first line options for 1st line monotherapy with regards to acute mania?

121
Q

What are our first line combinatiosn with regards to acute mania?

122
Q

What are the patient specific factors with regards to Initiating or optimizing therapy acute mania? LITHIUM

A

Lithium is preferred over divalproex for individuals who display classical euphoric
grandiose mania (elated mood in the absence of depressive symptoms), few prior
episodes of illness, a mania-depression- euthymia course, and/or those with a family
history of BD, especially with a family history of lithium response.

123
Q

What are the patient specific factors with regards to Initiating or optimizing therapy acute mania? Valproic acid

A

Divalproex is equally effective in those with classical and dysphoric mania. It is
recommended for those with multiple prior episodes, predominant irritable or dysphoric
mood and/or comorbid substance abuse or those with a history of head trauma

124
Q

What are the patient specific factors with regards to Initiating or optimizing therapy acute mania? Carbamazepine

A

Patients with specific factors such as a history of head trauma, neurologic symptoms,
comorbid anxiety and substance abuse, schizoaffective presentations with mood-
incongruent delusions, or negative history of bipolar illness in first-degree relatives may
respond to carbamazepine.

125
Q

With those with mixed features of a acute manic episode what are treatment options

A

DVP or APs, especially AP + DVP.

126
Q

What is the general therapeutic response expected with agents in acute mania?

A

Some therapeutic response is expected within 1-2 weeks after starting
1st line agent . If no response is observed within 2 weeks with
therapeutic doses of antimanic agents, and other contributing factors
are excluded, then switch or add-on strategies should be considered.

127
Q

What are the first line agents for acute mania?

128
Q

What are the Add on or Switch agents for acute mania?

129
Q

What are the agents that are not recommended for acute mania?

130
Q

For Bipolar I depression assessment are what are the assess factors?

131
Q

For Bipolar I depression assessment are what are the Rule out factors?

132
Q

For Bipolar I depression assessment are what are the discontinue factors?

133
Q

What are the 1st line monotherapy options for Bipolar I with depression?

134
Q

With regards to Bipolar I depression what is a caveatte with the clinical response?

A

Generally takes longer up to 4-6 weeks, some improvement after 2 weeks though

135
Q

What is imporant to reassess in bipolar i depression?

A

Dose optimization, adherence

136
Q

What are hte fitst line options for Bipolar I depression?

137
Q

Why is quetiapine higher than lithium for bipolar I depression?

A

Evidence, but only 8 weeks of the study and they comparred to placebo in some cases…

Clinical experience Lithium+quetiapine

138
Q

What for Bipolar I depression is 2nd line monotherapy?

A

Divalproex

139
Q

What is 2nd line add on therapy for bipolar I depression?

140
Q

What agents should you not recommend for acute bipolar depression

A

Antidepressant monotherapy

141
Q

What is the Bipolar I maintenance

A

Effective maintenance treatment early in illness even after first episode

  • Reverse cognitive impairment
    Preserve brain plasticity
    May lead to improved prognosis and minimzation
142
Q

What is foundational for the maintenance of bipolar disorder I

A

Pharmacotherapy

143
Q

What is bipolar I maintenance therapy?

144
Q

What was the Balance 2010 trial?

A

To assess if lithium + valproic acid is better than either drug as monotherapy for relapse prevention in BDI

145
Q

What were the findings of the Balance 2010 trial?

146
Q

What are the bipolar I maintenance add on or switch therapy?

147
Q

What are the special situations for

148
Q

Which therapy has the most evidence for suicide prevention?

A

Lithium has the most evidence

Therapeutics (Fall 2024) (11 decks)

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