CANMAT Guidelines: Bipolar Disorder part 1 Flashcards
list the agents recommended as FIRST line treatment for acute mania
lithium
quetiapine
divalproex
asenapine
aripiprazole
paliperidone
risperidone
cariprazine
(alone or in combo)
list the FIRST line treatments recommended for acute bipolar depression
quetiapine
lurasidone + lithium or divalproex
lithium
lamotrigine
lurasidone
adjunctive lamotrigine
for those initiating or switching treatments during the maintenance phase, which medications would be considered FIRST line for this phase of bipolar disorder
lithium
divalproex
lamotrigine
asenapine
aripiprazole
(monotherapy or in combination)
which types of treatments should be tried first in bipolar disorder management
those that show efficacy across the spectrum of the illness, as BD is cyclical with different phases
i.e lithium
what is the estimated lifetime prevalence of illness across bipolar I, II and subthreshold bipolar disorder subtypes according to the world mental health survey
2.4%
(1.5% 12 month prevalence)
what is the lifetime prevalence of bipolar I
0.6%
(0.4% 12 month prevalence)
what is the lifetime prevalence of bipolar II
0.4%
(0.3% 12 month prevalence)
when does BD typically manifest
late adolescence and young adulthood
overall age of onset at 25 years
how many “age of onset” groups are there within bipolar disorder I
3
what are the 3 “age of onset” age ranges for BDI
early onset (large/42%)–> around age 17 +/- 3 years
middle onset (smaller/26%)–> 24 years +/- 5 years
late onset (34%)–> 32 +- 12 years
what comorbid conditions/symptoms are associated with earlier age of onset
longer delay to treatment
greater depressive severity
higher levels of anxiety and substance use
in which cases should organic mania be considered and investigated
when mania onset occurs after age 50
(though manic episodes can occur for first time after age 50)
for what % of their lives do people with BD tend to be symptomatic with syndromal or subsyndromal symptoms
about 50% of their lives
leads to signifiant impairment
for what % of the time are people with BD generally unable to maintain proper work role function
about 30% of the time or mroe
list the specifiers included in the DSM V for manic episodes
anxious distress
mixed features
psychotic features
catatonia
peripartum onset
remission
current episode severity
list specifiers included in the DSM V for depressive episodes
anxious distress
mixed features
melancholic features
atypical features
psychotic features
catatonia
peripartum onset
remission
current episode severity
list specifiers listed in the DSM V for illness course in BD
rapid cycling
seasonal pattern
why do we are about preventing mood episodes in BD
because on average the risk of recurrence increases with # of previous episodes
also–> number of previous episodes is associated with increased duration and symptomatic severity of subsequent episodes
also–> number of episodes is associated with lower threshold for developing further episodes
also–> increased risk of dementia with more episodes
what are the three broad clinical stages in the staging system for BD
- individuals at increased risk for developing BD due to family history as well as certain subsyndromal symptoms predictive of conversion to full BD
- patients with fewer episodes and optimal functioning in interepisodic periods
- patients with recurrent episodes as well as decline in functioning and cognition
*heterogeneity in BD has prevented clinical use of staging systems
what is the most frequent midiagnosis in bipolar disorder
MDD
b/c patients are more likely to present for tx of depressive symptoms
may not recall periods of mania or hypomania or may not interpret as pathological
list 10 features of depression that may increase suspicion of bipolarity
- earlier age of illness onset
- highly recurrent depressive episodes
- family history of BD
- depression with psychotic features
- psychomotor agitation
- atypical depressive symptoms
–hypersomnia
–hyperphagia
–leaden paralysis - postpartum depression and psychosis
- past suicide attempts
- antidepressant induced manic symptoms
- rapid cycling
what is the second most common misdiagnosis for BD
schizophrenia and other psychotic disorders –> occurs as initial diagnosis in asm any as 30% of patients
what is considered “early onset of first depression” and thus more suspicious of bipolarity
under age 25
which psychiatric disorders are often labelled incorrectly as BD
borderline PD
SUDs
ADHD
what is a good screening tool for flagging patients who may have signs/symptoms of BD
the Mood Disorders Questionnaire (MDQ)
this is a validated self report instrument
what is a limitation of questionnaires like the MDQ
poor sensitivity and specificity especially in community or in high comorbid settings
elevated risk of flagging those with borderline traits
*should only be used as adjunct for screening clinical populations and not for diagnostic or treatment purposes
what disorders are particularly common alongside BD (common comorbidities)
SUDs
impulse control disorders
anxiety disorders
personality disorders (esp cluster B)
ddx BD
MDD
PDD
BD related to another medical condition
substance or med induced BD
cyclothymic disorder
psychotic disorders
borderline PD
narcissistic PD
antisocial PD
what % of identified patients with BD die by suicide
6-7%
what % of patients with BD worldwide report SI
43%
21% have plan
what % of patient with BD have attempted suicide in the past year worldwide
16%
which gender of people with BD have higher risk of dying by suicide
men
how does risk of suicide attempt + risk of fatality differ in those with BD
risk of suicide is substantially higher in BD (10.7 per 100 000 per year)
fatality of attempts is higher in BD
list 9 factors that have been significantly associated with suicidal ATTEMPT in BD
- female sex
- younger age of illness onset
- depressive polarity of first illness episode
- depressive polarity of current or more recent episode
- comorbid anxiety disorder
- comorbid SUD
- comorbid cluster B/borderline PD
- first degree family history of suicide
- previous suicide attempts
what are the only two risk factors that have been significantly associated with suicide DEATHS in BD
- male sex
- first degree family history of suicide
*older age also results in a higher degree of lethality of attempts with higher ratio of death:attempts
what periods of time are associated with higher risk of suicide in BD
periods during and following hospital admission
what % of suicides in BD occur DURING an inpatient stay
14%
what % of suicides in BD occur within 6 weeks of discharge
26%
what % of suicides in BD occur within the 6 weeks after an inpatient stay
26%
what medication used in BD has been shown to preventing suicide attempts + deaths
lithium
+anticonvulsants to a lesser extent
(limited data on APs and antidepressants)
what is the most common method of suicide in BD
self poisoning
what are the initial and foundational steps for all patients being treated for BD
patient health education + pharmacotherapy
(after basic clinical management like attention to dx, comorbidity, medical health)
what tool can patients use to monitor their symptoms and identify early warning signs of relapse
the NIMH Life Chart Method-Self Rating Scale
*has been shown to improve treatment but regular completion can be a burden
what is a phone app that might be an alternative to the NIMH Life Chart Method–Self Rating Scale if that is too cumbersome
the SIMPLE phone app
(self monitoring and psychoeducation in bipolar patients)
are there any specific recommendations for psychosocial interventions in acute mania?
no–> no evidence exists, and thus there are no recommendations
for which psychosocial interventions is there positive evidence in the maintenance phase of BD
CBT (2nd line)
family focused therapy (2nd line)
interpersonal and social rhythm therapy (3rd line)
peer support (3rd line)
what psychosocial intervention is first line in maintenance phase of BD
psychoeducation
name two models of psychoeducation delivered in a group format to euthymic people with BD that have published manuals and substantial research support
- Barcelona BDs program (21 sessions over 6 months)
- Life Goals Program (phase I has 6 weekly sessions)
*both have level 2 evidence for prevention of relapse
how many sessions of individual psychoeducation would be required to be a first line intervention for relapse prevention in BD?
at least 5 sessions
level 2 evidence for relapse prevention
is psychoeducation + pharmacology improve illness course compared to pharmacology alone
yes–> striking overal improvement
*no clear evidence in either acute mania or depression, but has good evidence in maintenance
is CBT recommended in acute bipolar depression
yes–> second line–> level 2 evidence
how does interpersonal and social rhythm therapy differ from IPT
includes regulation of social and sleep rhythms specifically targeted to the bipolar population
24 individual sessions over 9 months
in which types of patients with BD is agitation particularly common
those with mixed features
what is the DSM V definition of agitation
“excessive motor activity associated with feeling of inner tension”
list the 4 first line agents recommended for management of agitation in BD
aripiprazole IM (9.75 mg)
lorazepam IM (2mg)
loxapine inhaled (5mg)
olanzapine IM (2.5mg)
list 6 second line agents (or combinations) recommended for managing agitation in mania
asenapine
haloperidol IM
haloperidol + midazolam
haloperidol + promethazine
risperidone
ziprasidone
is loxapine IM first line for management of agitation in mania
no–> IM is third line, inhaled is first line
*absence of evidence does not constitute lack of efficacy
how should you approach pharmacological treatment of acute mania when looking at the list of first and second line agents in CANMAT guidelines
they are listed HIERARCHICALLY
the implication is that those listed higher up in the table should be considered FIRST before moving on to the next on the list, unless other factors such as hx of previous non response or patient preference preclude such a strategy in a given patient
should monotherapy be tried before combination therapy?
not necessarily–> treating clinician makes the decision for mono or combo therapy
*based on rapidity of response needed, whether hx previous partial response to monotherapy, severity of mania, tolerability concerns with combo therapy and willingness of patient to take combo therapy
which works faster for acute mania, mono or combo therapy
combo
what factors play into how first and second line treatments for acute mania are ranked
efficacy for acute mania
efficacy in preventing mania or depression
treating bipolar depression
safety/tolerability
risk of tx emergent switch
what is the top ranked treatment for acute mania per the guidelines
lithium
list the first line monotherapy treatments for acute mania IN ORDER per the guidelines (theres 8 on the list)
- lithium
- quetiapine
- divalproex
- asenapine
- aripiprazole
- paliperidone (above 6 mg)
- risperidone
- cariprazine
what is a mnemonic for remembering the first line monotherapy treatments for acute mania
Love Quiet Days At A Placid Rustic Cabin
Lithium
Quetiapine
Asenapine
Aripiprazole
Paliperidone
Risperidone
Cariprazine
List the 4 first line combination therapies for acute mania IN ORDER
- Quetiapine + lithium/divalproex
- Aripiprazole + lithium/divalproex
- Risperidone + lithium/divalproex
- Asenapine + lithium/divalproex
what is a mnemonic for the 4 first line combination therapies for acute mania
Quiet A Righteous Asshole
Quetiapine
Aripiprazole
Risperidone
Asenapine
+lithium/divalproex
list second line treatments (combo + mono) for acute mania IN ORDER
- olanzapine
- carmabazepine
- olanzapine + lithium/divalproex
- lithium + divalproex
- ziprasidone
- haloperidol
- ECT
what is a mnemonic for second line treatments for acute mania
Only Cows On LSD Zipline Happily Evermore
with which treatment for acute mania is there a concern for depressive switch
haldol
does aripriprazole treat acute bipolar depression
no
which first line treatments for acute mania have data for treating acute depression as well
lithium
quetiapine
divalproex
cariprazine
which first line treatments for acute mania have data for preventing depression
lithium
quetiapine
divalproex
asenapine
which first line agents for treatment of acute mania have evidence for preventing mania
all EXCEPT cariprazine
which first line agent for acute mania has the most tolerability concerns in the acute period
quetiapine
which first line agents for acute mania (3) have the most safety concerns in the maintenance period
lithium
quetiapine
divalproex
which first line agents for acute mania (4) have the most tolerability concerns in the maintenance period
lithium
quetiapine
paliperidone
risperidone
which first line combination therapies for acute mania have the most safety concerns in the maintenance period
quetiapine + lithium/divalproex
risperidone + lithium/divalproex
*significant impact on treatment selection
which combination therapy for acute mania seems to have the best tolerability and safety profile in the maintenance period
asenapine + lithium/divalproex
*but this is also ranked fourth in the combo ranking
the next safest/most tolerable is aripiprazole + lithium/divalproex followed by the quetipaine and risperidone combos
does lithium treat and/or prevent bipolar deprssion
yes it both treats and prevents
does olanzapine treat and/or prevent bipolar deprssion
yes it both treats and prevents
does ziprasidone treat and/or prevent bipolar deprssion
no data for prevention
data shows it does NOT treat bipolar depression
does ECT treat and/or prevent bipolar deprssion
it seems to do both (level 4 evidence)
does haloperidol treat and/or prevent bipolar deprssion
data suggests it does NOT prevent
no data with regard to treating bipolar depression
which 3 second line agents for acute mania have the most safety concerns in the maintenance period
olanzapine
olanzapine + li/dvp
haloperidol
which second line treatment for acute mania appears to be best tolerated in the maintenance phase
ziprasidone
when should efficacy of treatment for acute mania be evaluated
at the end of weeks 1 and 2 and then treatment options modified accordingly
what do you do if a patient presents manic, but is currently on antidepressants
stop the antidepressants
if this is first presentation of mania, then should observe patient for a period of time after antidepressant discontinuation before starting antimanic therapy and obtain collateral
what % of patients presenting with acute mania will respond to monotherapy? in what time frame?
50% within 3-4 weeks
how does efficacy compare in acute mania treatment between the first line monotherapy agents
comparable efficacy
despite having level 1 evidence for efficacy, why are carmabazepine, olanzapine, ziprasidone and haloperidol downgraded to second line treatments for acute mania
due to safety/tolerability risks
why is combination therapy preferred to mood stabilizer monotherapy in acute mania
on average, about 20% more patients will respond to combo therapy
*though there are fewer trials, there is also evidence for combo therapy compared to atypical antipsychotic monotherapy for efficacy
which is associated with more adverse events, combo or monotherapy (in acute mania)
combo
after how long did almost all anti-manic agents separate from placebo in trials
after one week
therefore, expect some therapeutic response to antimanic agents within 1-2 weeks
which first line anti manic agents that are recommended for monotherapy are NOT recommended for combination therapy
paliperidone and ziprasidone
due to lack of evidence for additional efficacy
what % of patients is it estimated will respond to ECT as antimanic treatment
up to 80%
what type of ECT has been used for treating mania
brief pulse therapy with 2-3 treatments per week
bifrontal electrode placement preferred over bitemporal
why is bifrontal electrode placement preferred in ECT for treatment of mania rather than bitemporal
assoc with faster treatment response and fewer cognitive side effects
what non-AP or mood stabilizer has level 2 evidence for treatment of acute mania and is third line
tamoxifen
(downgraded because of the risk of uterine cancer and lack of clinical experience DESPITE EVIDENCE FOR EFFICACY)
what neurostimulation therapy, other than ECT, can be considered as third line in treatment of acute mania
rTMS
is lamotrigine indicated for treatment of acute mania
no
name a non pharmacologic intervention that has level 3 evidence for treatment of acute mania when combined with other anti manic agents
glasses that block blue light
list 3 “nutraceuticals” that have shown indications of efficacy when used adjuctively with other antimanic agents
folic acid (level 2 evidence)
blocked chain amino acids (level 3 evidence)
L-tryptophan (level 3 evidence )
when would you usually choose lithium over divalproex when treating mania
- those who display classical euphoric grandiose mania
- few episodes of prior illness
- a mania-depression-euthymia course
and/or
- those with family history of BD (especially if family hx of lithium response)
when would you usually choose divalproex over lithium when treating mania
- person has multiple prior episodes
- predominant irritable or dysphoric mood
- comorbid substance use
and/or
- those with hx head trauma
in what population must care be taken with divalproex
women of childbearing age–> teratogenic
which two antimanic agents may be particularly considered in those with a history of head trauma
divalproex
carbamazepine
does the presence of anxious distress during a manic episode give any prognostic information
yes–>
predictor of poor outcome
i.e greater severity of manic symptoms, longer time to remission, more reported side effects of medication
are there specific agents recommended to treat anxious distress is mania
not studies specifically examining this–> anxious distress tends to improve as the mood episode improves
post hoc analyses:
divalproex
quetiapine
olanzapine
may be helpful
in what % of cases do depressive symptoms CO-OCCUR alongside mania
10-30%
does the presence of mixed features give clues as to prognosis
indicative of more SEVERE and DISABLING course
HIGHER RATE OF SUICIDE
what pharmacologic treatment plan is preferred in patients presenting with BD with mixed features
preferential use of atypical APs + DIVALPROEX combo therapy
what % of manic episodes are characterized by the presence of psychosis
at least HALF
does it matter whether psychotic symptoms are mood congruent or incongruent in BD
if psychosis is mood incongruent seem t have more severe illness with poorer long term prognosis
is there any evidence of superiority of any first line antimanic monotherapy compared to any other when psychotic features are present?
no
also no evidnece that any particular combo therapy is better for psychotic features
**clinical experience suggests combo therapy of atypical AP + li/dvp more appropriate for manic patients with mood-incongruent psychotic features
what is the definition of rapid cycling BD
course of illness that includes four or more mood episodes in a year
what % of patients with bipolar I have rapid cycling BD
about 30%
what three other factors are often associated with rapid cycling in BD
hypothyroidism
antidepressant use
substance use
what should you try if your patient is rapid cycling
check thyroid function
stop antidepressants, stimulants or other psychotropic agents that may be contributing to cycling
consider withdrawing substances
