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4. Mood Disorders > CANMAT Guidelines: Bipolar Disorder Part 2 > Flashcards

CANMAT Guidelines: Bipolar Disorder Part 2 Flashcards

1
Q

which is often more debilitating for patients with BD, the depressive or manic states

A

the depressive

*depressed mood accounts for estimate 2/3 of the time spent unwell, even with treatment

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2
Q

what % of suicide deaths and suicide attempts in those with BD occur during the depressive phase

A

over 70%

*depressive episodes with mixed features are particularly risky with even higher short term risks of suicide and death

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3
Q

what are the most common medication classes ingested at lethal levels in suicide attempts in BD

A

opioids and benzos

*there were fewer deaths due to lethal lithium levels than lethal carbamazepine levels

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4
Q

are there any first line psychosocial treatment options for acute bipolar depression

A

no

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5
Q

what is a mnemonic for remembering first line treatments for acute bipolar depression

A

Quivering Ladies Languish Losing Loud Laughter

Quietiapine

Lurasidone + Li/DVP

Lithium

Lamotrigine

Lurasidone

Lamotrigine (Adj)

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6
Q

Name the two agents that are first line for acute bipolar depression that treat all of the following: acute depression, acute mania, prevent both mania and depression

A

quetiapine + lithium

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7
Q

does lamotrigine treat acute mania

A

no–we have evidence it does NOT

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8
Q

does lurasidone + Li/DVP or lurasidone alone treat acute mania?

A

we dont have the data

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9
Q

which first line agent for acute bipolar depression have the most safety concerns in the acute period

A

lamotrigine

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10
Q

which two first line agents for acute bipolar depression have the most tolerability concerns in the acute phase

A

quetiapine and lurasidone + Li/DVP

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11
Q

list second line agents for acute bipolar depression in order

A

Divalropex

SSRIs/buprioprion (adjuvant)

ECT

Cariprazine

olanzapine-fluoxetine

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12
Q

what is a mnemonic to remember second line treatment for acute bipolar depression

A

Deep Sleep Eludes Crying Octopi

Divalproex

SSRIs/buproprion

ECT

Cariprazine

Olanzapine-Fluoxetine

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13
Q

list the 4 mnemonics for 1st and 2nd line treatments for acute mania and acute bipolar depression

A

Acute Mania:
1st mono: Love Quiet Days At A Placid Rustic Cabin

(lithium, quetiapine, Divalproex, Asenapine, Aripiprazole, Paliperidone, Risperidone, Cariprazine)

1st combo: Quietly Arguing with Righteous Assholes (QARA)

Quetiapine, Aripiprazole, Risperidone, Asenapine + Li/DVP)

2nd: Only Cows on LSD Zipline Happily Evermore

(olanzapine, carmabazepine, olanzapine + lithium/divalproex, lithium + divalproex, ziprasidone, haloperidol, ECT)

Acute bipolar depression:
1st: Quivering Ladies Languish Losing Loud Laughter

(Quetiapine, Lurasidone + Li/DVP, Lamotrigine, Lurasidone, Lamotrigine (adj))

2nd: Deep Sleep Eludes Crying Octopi

(Divalproex, SSRIs/buproprion, ECT, Cariprazine, Olanzapine + fluoxetine)

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14
Q

which second line med for acute bipolar depression has the most safety concerns in maintenance phase

A

olanzapine + fluoxeitne

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15
Q

which 1st or second line meds for acute bipolar depression have the greatest risk for manic switch

A

SSRIs/buproprion (adj) and olanzapine + fluoxetine

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16
Q

which first line treatment for acute bipolar depression has level 1 evidence

A

quetiapine

(lurasidone has level 1 as an adjuvant but level 2 as monotherapy)

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17
Q

what trough serum level of lithium is recommended by the guidelines for clinical effectiveness in treating acute bipolar depression

A

0.8-1.2 mEq/L

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18
Q

what medication should you consider adding in management of BD in lithium nonresponders

A

lurasidone or lamotrigine

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19
Q

what dose of quetiapine does the guidelines reocmmend

A

quetiapine 300mg daily

*clinical trials have shown that there is “no difference” in efficacy between quetiapine 300mg and 600mg daily doses (lower doses have not been studied)

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20
Q

what is the minimum target dose of lamotrigine

A

minimum 200mg/day

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21
Q

is there good data for efficacy of adding antidepressant to a mood stabilizer or AP in treatment of acute bipolar depression?

A

no, actually relatively weak efficacy data (which is why downgraded to second line from first line)

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22
Q

in which patients with acute bipolar depression should antidepressants be ideally avoided or used cautiously if necessary

A
  1. those with history of antidepressant induced mania or hypomania
  2. those with current or predominant mixed features
  3. recent rapid cycling
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23
Q

should antidepressant monotherapy be used for treatment of bipolar I depression

A

NO

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24
Q

in which patients might you consider doing ECT for acute bipolar depression

A

treatment refractory patients

those for whom rapid response is needed ( i.e severe depression with imminent suicide risk, catatonia or psychotic depression)

when rapid response needed for medical stabilization

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25
Q

is aripiprazole monotherapy recommended for treatment of acute bipolar depression

A

no (negative evidence)

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26
Q

what type of light therapy is recommended as a third line tx for acute bipolar depression

A

bright light delivered midday

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27
Q

list some other third line or ancillary treatments for acute bipolar depression (adjunctive)

A

eicosapentaenoic acid (EPA)

N-acetylcysteine

light therapy

ketamine IV

aripiprazole

asenapine

levothyroxine

modafinil

armodafinil

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28
Q

what treatment options may be preferentially used in treatment of acute bipolar depression if a rapid response is needed

A

quetiapine

lurasidone

ECT

cariprazine

olanzapine-fluoxetine

(start to separate from placebo within/by one week)

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29
Q

what agent might be avoided in the treatment of acute bipolar depression if rapid response is required

A

lamotrigine (due to need for slow titration)

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30
Q

what are the risks associated with an overly rapid titration of lamotrigine

A

skin rashes

stevens-johnson syndrome

toxic epidermal necrolysis

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31
Q

once the titration is completed, is lamotrigine well tolerated

A

yes–> and effectiveness may be even more pronounced in those with depressive cognitions and psychomotor slowing

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32
Q

which agents may be preferentially used in the treatment of acute bipolar depression if anxious distress is prominent

A

quetiapine

olanzapine-fluoxetine

lurasidone

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33
Q

which agents used in the treatment of acute bipolar depression seem to have limited efficacy on anxious distress

A

divalproex

risperidone

lamotrigine

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34
Q

what type of med has been shown to alleviated mixed features in bipolar depression

A

atypical antipsychotic have a class effect

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35
Q

ECT is very effective (according to clinical experience) in what type of patient with acute bipolar depression

A

those with melancholic features

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36
Q

what % of inpatients experience psychosis in the context of an acute bipolar depression

A

up to 20%

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37
Q

is lamotrigine recommended for those with rapid cycling BD

A

no

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38
Q

why is it important that comprehensive treatment for BD be initiated even after a first episode

A

in a subset of patient BD may be a NEUROPROGRESSIVE disease

–recurrences associated with reductions in brain grey and white matter volumes

–worsening cognitive impairment

–decrease in inter-episodic recovery and functioning

–higher rate and severity of relapse

–reduced rate of treatment response to both pharmacological and psychotherapeutic strategies

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39
Q

what effect does effective early treatment have on the brain of someone with BD

A

reverses cognitive impairment

preserves brain plasticity

*particularly in those who remain episode free

*may lead to improved prognosis and minimization of disease progression

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40
Q

between lithium and quetiapine, which seems to be superior in both volumetric and cognitive outcomes after a first BD episode

A

lithium

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41
Q

what % of the following populations will experience a recurrence every year:

  1. with treatment
  2. without treatment
A
  1. with treatment–> 19-25%
  2. without treatment–> 23-40% (of those on placebo)
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42
Q

list risk factors for recurrence of a mood episode in BD

A

younger age at onset

psychotic features

rapid cycling

more/more frequent previous episodes

comorbid anxiety

comorbid SUD

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43
Q

how quickly do patients with BD discontinuing lithium experience a recurrent mood episode

A

50-90% experience a recurrence within 3-5 months

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44
Q

list some risk factors for partial or nonadherence to medications in BD

A
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45
Q

what is a mnemonic for the first line maintenance treatments for BD

A

Lengthy Questions Distress Ladies Awaiting Quiet And Appropriate Activities

Lithium

Quetiapine

Divalproex

Lamotrigine

Asenapine

Quetiapine + Li/DVP

Aripiprazole + Li/DVP

Aripiprazole

Aripiprazole OM

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46
Q

What is a mnemonic for second line agents for maintenance treatment of BD

A

Only Really Ragged Children Pet Little Zebras

(Olanzapine, Rispridone LAI, Risperidone LAI (adj), Carbamazepine, Paliperidone, Lurasidone + Li/DVP, + Ziprasidone Li/DVP)

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47
Q

is long term antidepressant use recommended?

A

no–> only included in recommendations for acute treatment of bipolar depression HOWEVER if someone is stable on combo that includes antidepressant, withdrawing them may contribute to destabilization

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48
Q

how might dose be adjusted once the acute episode resolves and the patient enters maintenance treatment

A

may be necessary to lower the dose

patients often experience greater side effects once out of the acute episode

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49
Q

does combo treatment of AP + Li/DVP reduce risk of recurrence?

A

yes there is evidence for this –> continuing the AP for the first 6 months following response offers clear benefit in reducing risk of mood episode recurrence

reevaluate AP use after 6 months

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50
Q

which is more effective at preventing any mood or manic episode, paliperidone or olanzapine

A

olanzapine

but olanzapine does have more safety concerns

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51
Q

why is cariprazine not included in the maintenance recommendations

A

only currently have evidence for efficacy in acute mania and depression

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52
Q

why are TCAs not recommended as adjunctive therapy in BD

A

increased risk of manic switch

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53
Q

why is perphenazine not recommended for maintenance treatment of BD

A

those on perphenazine + mood stabilizer more likely to have emergent depressive sx and intolerable side effects

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54
Q

list factors associated with overall good prognosis with BD

A

good treatment adherence

lack of early adversity

intermediate age at onset

good social support

absence of spontaneous rapid cycling

absence of features of a personality disorder

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55
Q

what is the gold standard of maintenance treatment of BD? why?

A

lithium

b/c effective at preventing both manic and depressive episodes and appears to have anti suicidal effects

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56
Q

how heritable is lithium-responsiveness in BD

A

you are about twice as likely to respond to lithium if you have a lithium responding parents vs if you dont

patients who have a lithium responding relative have a 67% likelihood of also being lithium responsive

(vs 35% of those without a responsive relative)

(“The neurons from people with BD were hyperexcitable and their activity was selectively modified by in vitro lithium in accordance with clinical response”)

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57
Q

who tends to respond to lamotrigine

A

predominantely depressive polarity + comorbid anxiety

58
Q

who is more likely to respond to carbamazepine

A

atypical illness

BDII

schizoaffective disorder

59
Q

in which type of patients might you consider genotyping for CYP450 enzyme like 2D6 and 3A4

A

patients with refactory BD who have not responded to high doses of various first, second and third line agents or their combos

goal to exclude possibility of ultra rapid metabolizers

60
Q

what is the prevalence of BDI in canada

A

0.87%

61
Q

what is the prevalence of BDII in canada

A

0.67%

62
Q

how does the disability and economic burden of BDII compare to that of BDI

A

disability is comparable

economic burden is up to 4x higher for BDII

–> patients with BDII spend as much time symptomatic as those with BDI with mood symptoms mostly in depressive phase

63
Q

how do rates of suicide in people with BDII vs BDI compare

A

similar for both attempts and completed suicides

64
Q

what % of those with BDII attempt suicide over the course of their illness? complete?

A

attempt–> 30%

complete–> 1/25

65
Q

why is it harder to generate recommendations for treatment of BDII

A

because there is a relative paucity of large, methodologically sound clinical trials in BDII

66
Q

has lithium been studied in acute hypomania

A

no

67
Q

what four medications have been studied in placebo controlled trials for acute hypomania

A

divalproex

N-acetylcysteine

quetiapine

risperidone (open label)

*all generally suggested efficacy but had significant weaknesses

68
Q

what does clinical practice suggest in terms of the management of acute hypomania

A

when its frequent, severe or impairing enough to require treatment–> consider mood stabilizers like lithium or divalproex and/or atypicals

N-acetylcysteine may also be of benefit but needs more studies

69
Q

what is the only first line agent for BDII depression listed in the guidelines

A

quetiapine

70
Q

list the second line agents for BDII depression

A

Lithium

Lamotrigine

Buproprion (adj)

ECT

Sertraline

Venlafaxine

71
Q

list some of the third line agents for bipolar II depression

A

agomelatine (adj)

divlaproex

EPA (adj)

N-acetylcysteine (adj)

T3/T4 thyroid hormones

ziprasidone

ketamine (adj)

fluoxetine

72
Q

what SSRI is NOT recommended in BDII depression

A

paroxetine

73
Q

which antidepressants are associate with manic switch in BDI in particular

A

venlafaxine

TCAs

74
Q

how do the rates of manic switch compare between BDI and BDII

A

lower rates of switch in BDII–> even when on antidepressant monotherapy and with agents known to be higher risk for switch in BDI

*risk benefit ratio of antidepressants is more favorable in BDII depression than BDI depression

75
Q

how does the efficacy of sertraline compare to lithium in treatment of BDII depression

A

as effective as both lithium monotherapy and lithium + sertraline therapy

76
Q

how does the efficacy of venlafaxine compare to lithium in treatment of BDII depression

A

venlafaxine monotherapy was shown to be more effective than lithium

theres also maintenance data for venlafaxine in preventing relapses

*also–> buproprion was shown to be as effective as sertraline and venlafaxine

77
Q

can findings about, say, sertraline be generalized to other antidepressants in treatment of BDII depression

A

no–> and in fact safety issues have not been well studied

78
Q

list the 3 agents recommended for first line maintenance of BDII

A

quetiapine

lithium

lamotrigine

79
Q

what agent is recommended second line for BDII maintenance

A

venlafaxine

80
Q

list agents recommended third line for BDII maintenance

A

carbamazepine

divalproex

escitalopram

fluoxetine

other antidepressants

risperidone

81
Q

how much does ongoing maintenance therapy with quetiapine monotherapy reduce the risk of relapse in BDII patients if used for maintenance

A

67% reduction in risk of relapse into any mood episode

72% reduction in risk of relapse into depression

(less robust risk reduction for relapse into hypomania)

82
Q

how might atypical antipsychotics interfere with fertility

A

may increase serum prolactin levels and thus interfere with ovulation and decrease fertility

83
Q

in which BD patients might you consider tapering psychotropic medications before pregnancy

A

clinically stable x 4-6 months prior and considered at low risk of relapse

84
Q

which anticonvulsants have been known to affect the pharmacokinetics of oral contraceptives

A

carbamazepine

topiramate

lamotrigine

85
Q

according to health canada, in which populations should valproate products not be used

A

should not be used in:

–female children

–female adolescents

–women of childbearing potential

–pregnant women

UNLESS alternative treatments are ineffective or not tolerated

86
Q

why should valproate products be avoided in women of childbearing potential etc…

A

high teratogenic potential

risk of developmental disorders to exposed infants

87
Q

what % of pregnant women with BD had a recurrence of a mood episode:

  1. when they discontinued their mood stabilizer during pregnancy
  2. when they continued their mood stabilizer during pregnancy
A

in a tertiary center:

  1. when discontinued–> 85% recurrence during pregnancy
  2. when continued–> 37% recurrence during pregnancy

*usually depressive or mixed episodes

*50% of recurrences happened in 1st trimester

*lower rates in community

88
Q

are there any medications used for tx of BD for which we have evidence of controlled studies showing no risk in pregnancy

A

no

89
Q

name two medications used to treat BD (I or II) with evidence level B (no evidence of risk in humans) during pregnancy

A

clozapine

buproprion

90
Q

what level of evidence do we have for safety of most agents used in the tx of BD during pregnancy

A

C or D–> either risk cannot be ruled out or positive evidence of risk (benefit may outweigh risk)

91
Q

lithium has what risk category in pregnancy

A

D

92
Q

lamotrigine has what risk category in pregnancy

A

C

93
Q

aripiprazole has what risk category in pregnancy

A

D

94
Q

valproate has what risk category in pregnancy

A

D

95
Q

olanzapine has what risk category in pregnancy

A

C

96
Q

quetiapine has what risk category in pregnancy

A

C

97
Q

sertraline has what risk category in pregnancy

A

C

98
Q

what risks are there to the fetus of using divalproex/valproate in pregnancy

A

neural tube defects

+ other abnormalities

evidence of “striking degrees” of neurodevelopmental delay in children at 3 years of age

loss of avg. 9 IQ points

99
Q

what is the risk of neural tube defects in infants exposed to valproate products in utero

A

up to 5%

100
Q

are pregnant women more likely to require higher medication doses in the first, or in the second + third trimesters

A

second + third due to increased plasma volume, hepatic activity, renal clearance

101
Q

what dose of folic acid should women with BD take during pregnancy

A

5mg/day

102
Q

prenatal vitamins containing what compound have been recently recommended as possibly preventive of the later development of schizophrenia

A

prenatal vitamines containing CHOLINE

103
Q

what is the concern about very high materal folate levels

A

?risk of autism spectrum disorders

104
Q

what % of women with BD who were medication free experience a recurrence inthe post partum period

A

66%

(compared to 23% who were maintained on medication)

105
Q

risk or recurrence is highest in which women in the post partum period

A

highest in those who experiened a recurrence of their BD during pregnancy
+
those who were not on prophylactic tx

106
Q

for which agents do we have evidence for efficacy in tx of postpartum bipolar depression

A

quetiapine

107
Q

for which agents do we have evidence for efficacy in tx of postpartum bipolar mania

A

benzos

antipsychotics

lithium

108
Q

what website may be useful for choosing which medications to use for BD in pregnancy and lactation

A

the FDA PLLR

“pregnancy and lactation last rule”

109
Q

what two medications used in the treatment of BD may be preferred choices for lactating mothers

A

quetiapine

olanzapine

*due to relatively lower infant dosages

110
Q

how does comorbidity with PMDD (premenstrual dysphoric disorder) affect course of BD

A

earlier illness onset of BD

more comorbid axis I disorders

higher number of manic/hypomanic + depressive episodes

higher rates of rapid cycling

111
Q

do PMS and PMDD occur more or less frequently in people with BD

A

more frequently

112
Q

how does menopause affect the course of BD

A

increased rates of depressive, but not manic, episodes during menopause transition

*more data needed

113
Q

what % of people with BD experience their first mood episode during childhood or adolescence

A

between 1/3 (community) to 2/3 (clinical samples)

*earlier age of onset characterized by increased symptom burden and comorbidity

114
Q

should the same set of symptoms be used to diagnose BD in kids and adults

A

yes

115
Q

what other conditions are often confused for BD in kids and adolescents

A

ADHD

DMDD

ODD

substance use

personality disorders

GAD

116
Q

what is one way to distinguish ADHD from BD

A

ADHD is ongoing whereas BD is episodic

decreased sleep, hypersexuality, hallucinations, delusions, HI and SI are rare or absent in uncomplicated ADHD

117
Q

what is the relationship between DMDD and BD

A

The recent DSM‐5 diagnosis DMDD—which includes chronic irritability as a defining feature—lists BD as an exclusion criterion. However, the DMDD phenotype is evident in about 25% of adolescents with episodic BD, and is associated with factors such as greater family conflict and ADHD comorbidity.571 Classical BD and chronic irritability are therefore not mutually exclusive, the nonspecific nature of the latter notwithstanding.

118
Q

what % of children or youth with MDD will go on to develop BD

A

28%

(about a third)

119
Q

list risk factors for switch to mania in child with MDD

A

family history of mood disorders

emotional and behavioural dysregulation

subthreshold manic symptoms

cyclothymia

atypical depression

psychosis

120
Q

what were the three most potent predictors of switch to mania in youth with MDD

A

family history

earlier age of onset

presence of psychotic symptoms

121
Q

are kids and teens more or less susceptible or the metabolic side effects of psychiatric medications

A

more susceptible

(especially atypical APs)

122
Q

risperidone may be preferable to lithium for treatment of BD in what type of kids/teens

A

non obese youth

youth with ADHD

123
Q

list first line treatment for mania in kids/teens

A

lithium

risperidone

aripiprazole

asenapine

quetiapine

124
Q

second line treatments for mania in kids/

A

olanzapine

ziprasidone

quetiapine adj.

125
Q

first line for tx of bipolar depression in kids/teens

A

lurasidone (has RCT data)

126
Q

second line for tx of bipolar depression in kids/teens

A

lithium

lamotrigine

(no data in kids but ++ in adults)

127
Q

third line for tx of bipolar depression in kids/teens

A

olanzapine-fluoxetine combo (has RCT data but ++ metabolic concerns + limited clinical experience in youth)

quetiapine

128
Q

first line for BD maintenance in kids/teens

A

aripiprazole

lithium

divalproex

129
Q

can stimulants be used to treat comorbid ADHD in kids/teens

A

yes–> in stable/euthymic youth taking optimal doses of antimanic medications

130
Q

what is the lifetime prevalence of late life BD

A

1-2%

*though 90-95% of older adults with BD will have their initial episode before age 50

131
Q

what are the most often comorbid conditions with late life BD

A

anxiety and SUDs

132
Q

what is the reduction in life expectancy in older adults with BD compared to non-psychiatric populations

A

reduction in life expectancy of 10-15 years

133
Q

older adults with BD have an average of how many medical comorbidities

A

3-4

134
Q

what are the most common medical comorbidities of older adults with BD

A

metabolic syndrome

HTN

diabetes

CV disease

arthritis

endocrine abnormalities

135
Q

what side effects can be seen with LITHIUM in particular for older adults with BD

A

adverse neurological effects

renal disease

136
Q

what side effects can be seen with DIVALPROEX in particular for older adults with BD

A

motor side effects

metabolic effects (weight gain and DM)

137
Q

what side effects can be seen with CARBAMAZEPINE in particular for older adults with BD

A

induces CYP450

138
Q

what medications should be monitored closely in older adults when also prescribed lithium

A

NSAIDs

ARBs

ACEIs

thiazide diuretics

139
Q

how often should you do lithium levels and renal monitoring in older adult populations with BD

A

Li level and renal monitoring:

q3-6 months
+
5-7 days after lithium dose adjustment or adjustment of NSAID/ARB/ACEI/ thiazide diuretic

140
Q

what two medications are listed as first line for acute mania in older adults

A

lithium

divalproex

4. Mood Disorders (17 decks)

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