Bipolar Disorder Flashcards
1
Q
What is mood?
A
a pervasive and sustained emotion or feeling tone that influences a person’s behavior and colors his/her perception of the world
-can be labile, fluctuating, or alternating rapidly between extremes
2
Q
Differentiate cyclothymia and dysthymia.
A
cyclothymia: mood swings between short periods of mild depression and hypomania
dysthymia: persistent depressive disorder
3
Q
What is bipolar disorder?
A
a chronic mood disorder subcategorized into bipolar I disorder and bipolar II disorder
4
Q
Differentiate BDI and BDII.
A
BDI: a distinct period of at least ONE week of a full manic episode (abnormally & persistently elevated mood and increased energy)
BDII: a current and/or past hypomanic episode AND a current and/or past major depressive episode
5
Q
Describe the epidemiology of bipolar disorder.
A
men=women
-men have more manic episodes, women more depressive or mixed
lifelong illness with variable course
6
Q
True or false: there is a cure for bipolar disorder
A
false
however, recovery/maintenance is possible
7
Q
What is the etiology of bipolar disorder?
A
multifactorial and many interrelated risk factors at play
-genetics
-neurobiological
-developmental
-psychologic
8
Q
What is the pathophysiology of bipolar disorder?
A
the exact cause of bipolar disorder is unknown
-several theories involving neurotransmitters and signal transduction have been proposed
9
Q
What are the risk factors for bipolar disorder?
A
drug or alcohol abuse
1st degree relative
period of high stress
major life changes
medical conditions (hyperthyroid, CVD, endocrine, CNS, hormonal)
10
Q
What are some secondary causes of mania that are medication/drug related?
A
antidepressants
-SNRI > TCA > SSRI > mirtazapine
-may need to abruptly d/c if severe mania and push through FINISH sx
DA-augmenting agents
-stimulants (caffeine, decongestants, amphet, cocaine)
-sympathomimetics
-DA agonists/releasers/reuptake inhibitors
NE-augmenting agents
alcohol and cannabis
thyroid preps
steroids (anabolic, corticosteroids)
11
Q
What is the average age of onset for bipolar disorder?
A
20-25
-2/3 people with BD have sx before age of 18
12
Q
What is the risk with those who develop bipolar disorder before the age of 19?
A
longer delay to treatment
greater depressive symptom severity
higher levels of anxiety/substance use and comorbidity
13
Q
Describe the prognosis for bipolar disorder.
A
with tx, illness usually includes periods of remission with risk of full or sub-syndromal relapses
Kindling Theory
-abnormalities lead to more abnormalities
-syndromal episodes increase vulnerability to more episodes
neurodegeneration (because of kindling)
-delayed functional recovery, increasing impairment, neurocognitive deficits
profound morbidity and mortality
-impairment, hospitalization, increased mortality
14
Q
What is the best predictor of functioning for someone with bipolar disorder?
A
medication adherence
-50% of patients d/c their meds due to AE’s
15
Q
What are some medical conditions that can worsen and/or make bipolar disorder difficult to treat?
A
anxiety (50-60%)
substance use disorder (60%)
-alcohol=most common
ADHD
PTSD
DM, dyslipidemia, CVD, obesity
16
Q
What is one of the leading causes of death in patients with bipolar disorder?
A
suicide
-20x higher risk than general population
-men at increased risk
-worldwide 43% of BD pts report suicidal ideation
17
Q
What should occur during any patient interaction regarding bipolar disorder?
A
suicide risk assessment
18
Q
What is the diagnostic criteria for mania?
A
abnormally and persistently elevated mood and energy with at least 3 of the following changes from usual behavior: DIGFAST
sx present nearly every day for at least one week
leads to significant functional impairment OR requires hospitalization OR includes psychotic features
episode not due to physiologic effects of a substance or medical condition
19
Q
What is the mnemonic to help remember the symptoms of mania?
A
DIGFAST
distractibility
irritability
grandiosity
flight of thoughts
activity/energy increased
sleep decreased
talkability
20
Q
What is the diagnostic criteria for a hypomanic episode?
A
same sx criteria as manic episode but only lasting up to 4 days
unequivocal change in functioning or mood that is uncharacteristic of the individual and/or observable by others
impairment in social/occupational functioning is not severe, no hospitalization, no psychosis
episode not attributable to physiological effects of a substance or medical condition
shorter time period, less severe
21
Q
Differentiate the diagnostic criteria for BDI and BDII.
A
duration of manic sx:
-BDI: > 7 days
-BDII: < 4 days
functional impairment:
-BDI: yes
-BDII: no
psychotic features:
-BDI: yes
-BDII: no
requires hospitalization:
-BDI: yes
-BDII: no
history of depression:
-BDI: no
-BDII: yes
22
Q
What is the diagnostic criteria for a major depressive episode?
A
5+ sx present nearly every day in the same 2 week period that result in change in functioning
-one or both of: depressed mood, anhedonia
SIG E CAPS
23
Q
What is an example of a patient rated scale for BDI/II?
A
mood disorder questionnaire (MDQ)
-used to screen for possible BD
-most specific for identifying BDI
-positive if “yes” to 7/13 items in Q2, “yes” to Q2, and “moderate or severe problem” to Q3
24
Q
What are the challenges in bipolar disorder diagnosis and treatment?
A
delay to diagnosis
-avg delay 8-12 yrs
-often pts do not recally hypomanic sx
-more likely to seek help for depression vs mania
misdiagnosis
-most common: depression
limited clinical trials
25
What are the goals of therapy for bipolar disorder?
1. eliminate mood episode with complete remission of symptoms, ongoing (acute treatment)
2. prevent recurrences or relapses of mood episodes, ongoing (maintenance treatment)
3. improve quality of life and optimize psychosocial functioning, ongoing
4. minimize harm to self and others (including prevent suicide), ongoing
5. maximize adherence and minimize adverse effects of pharmacotherapy, ongoing
6. identify and minimize risk factors for mood episode, ongoing
7. provide care for comorbid psychiatric, substance use, or medical conditions, ongoing
8. provide education to patient and family members, ongoing
26
Describe the timeline for improvement once medication is initiated for mania and depression.
mania:
-response 1-2 weeks
-full clinical benefit 3-4 weeks
depression:
-response 2-4 weeks
-full clinical benefit 6-12 weeks
27
List some of the non-pharm strategies for bipolar disorder.
exercise, healthy diet, adequate sleep
decrease substance use/alcohol/nicotine/caffeine
psychoeducation, psychotherapy, counselling
ECT
bright light therapy (more for depression)
relapse prevention plan
28
What are the most commonly used mood stabilizers?
lithium
valproic acid/divalproex
lamotrigine
29
Which mood stabilizers see limited use due to their adverse reactions and drug interactions?
carbamazepine
oxcarbazepine
30
Which mood stabilizers are rarely used due to lack of efficacy and poor tolerability?
topiramate
gabapentin
31
What are the indications for lithium?
bipolar disorder (acute mania tx, maintenance tx)
schizoaffective disorder
unipolar depression (antidepressant augmentation)
32
What is the MOA of lithium?
exact MOA not fully understood
*has multiple effects on cellular function*
33
Describe some important points about the absorption of lithium.
completely dissociates to lithium cation
-almost completely absorbed from small intestine
-small amount actively exchanged for sodium
F of liquid and regular release > extended release
34
Describe some important points about the volume of distribution of lithium.
initially distributes in extracellular space
then accumulates in various organs
distributes evenly in total body water space
35
What is the half-life of lithium?
normal renal function: 12-27 hours
elderly: 30-36 hours
36
Describe some important points about the elimination of lithium.
95% renal, 4% perspiration
not metabolized, primarily excreted renally as free cation
not protein bound --> freely filtered by glomerulus like Na and K = 80% reabsorbed in proximal tubule
37
What are some scenarios that can lead to decreased clearance of lithium?
hyponatremia
dehydration
renal failure/dysfunction
decreased renal blood flow
38
What kind of PK does lithium show?
linear, dose-proportional PK
39
When should a lithium sample level be taken?
12 hour post dose level
-in AM after evening dose (allows complete absorption and distribution)
*STAT if toxicity or non-adherence is suspected*
40
How frequent should lithium sample levels be taken?
5-7 days after starting therapy or changing dose
then once weekly until stabilized dose x 2 weeks, then monthly for up to 3 months, then at least every 6 months
41
How is lithium typically initiated during acute mania?
higher initial doses
-increases likelihood of GI side effects
*subsequent doses guided by plasma level and clinical response*
42
How can we help minimize the GI side effects experienced when initiating lithium?
take with food and/or divide dose BID
43
How is lithium typically given once the patient is stabilized?
once daily
-usually given at night to improve compliance
44
What are some benefits that some trials have shown with the once daily evening dosing of lithium?
decrease in urine volume and decreased renal toxicity
45
What could a potential solution be for a patient experiencing peak related side effects to lithium?
change to extended release formulation
46
What should be done when toxic levels of lithium are suspected?
hold dose
repeat plasma level the next day
restart therapy once within target range
47
What are some factors that might decrease lithium levels?
caffeine
pregnancy
sodium supplement
burns
hemo/peritoneal dialysis
theophylline
acetazolamide
sodium bicarb
48
What are some factors that might increase lithium levels?
ACEI/ARBs
NSAIDs
thiazide diuretics
dehydration
strenuous exercise
SSRI/SNRI
chronic lithium use
renal impairment
increased age
sodium loss
cirrhosis
49
What are the drug interactions with lithium?
diuretics
-may have mixed effects
NSAIDs
-decreased lithium clearance=increased lithium levels
ACEI/ARBs
antipsychotics
-additive risk of neurotoxicity
antidepressants
-theoretical risk of serotonin syndrome (monitor)
50
What are the common side effects of lithium?
increased thirst and urinary frequency
-dose related
fine tremors in hands/arm
-dose related
-usually symmetrical
headache, sedation, weakness
-dose related
GI upset
-dose related
-usually one of first signs of toxicity
skin changes
-acne, psoriasis
-dose related
alopecia
weight gain
-avg 4-6kg in first 2y
51
What are the serious side effects of lithium?
hypothyroidism
renal injury
-interstitial nephritis, renal failure, ESRD
blood dyscrasias
bradycardia or conduction abnormalities
nephrogenic diabetes insipidus
52
In addition to typical counselling pieces, what else should be discussed with lithium?
may take several weeks to see benefit
maintain adequate hydration and consistent salt/caffeine intake
avoid NSAIDs; talk to pharmacist before starting new med
consider contraception if child-bearing age
will require regular blood level monitoring
regularly check elytes, renal, thyroid, serum level
if tolerated + stabilized, consider OD dosing hs (less AE and less renal risk)
53
How can the common side effects of lithium be managed?
thirst: drink water, hard candies (should subside)
sedation: take hs, dont drive
nausea: take with food; consider ER if doesnt subside
acne: talk to pharmacist or MD for tx
tremor: talk to MD if it doesnt subside
54
What is the difference between valproic acid and divalproex?
divalproex is the prodrug of valproic acid
55
What are the indications of valproic acid?
seizures: generalized tonic-clonic, partial onset, absence
-broad spectrum antiepileptic activity
bipolar disorder: acute mania tx, maintenance tx
56
What is the MOA of valproic acid?
exact MOA is unknown
possible mechanisms:
1. inhibition of voltage-gated Na+ channels
2. increasing action of GABA
3. modulates signal transduction cascades and gene expression
4. may effect neuronal excitation mediated by NMDA subtype of glutamate receptors
5. also effects 5HT, DA, aspartate, and T-type Ca2+ channels
57
Is valproic acid well absorbed or poorly absorbed?
well absorbed from all oral dosage forms but rate of absorption varies
-F: 0.9-1.0
58
Describe the protein binding of valproic acid.
85-90% bound to serum albumin
saturable protein binding occurs within therapeutic range
-at 500umol/L VA is 90% bound to albumin
- >500umol/L binding saturates and there is increased free
58
Describe the elimination of valproic acid.
>95% hepatic metabolism
-majority by glucuronidation and oxidation
-minority by CYP
-4-ene-VA metabolite can cause liver toxicity
59
True or false: valproic acid is a low extraction drug
true
Cl is independent of hepatic blood flow but directly dependent on free fraction
60
What is the half-life of valproic acid?
12-18 hours
-closer to 12 hours if taking enzyme inducing drugs
61
What is the therapeutic range of valproic acid?
total 350-700umol/L (50-150mcg/ml)
*TR is a guideline only and must be individualized*
62
When should valproic acid levels be taken?
3-4 days after initial therapy (trough)
signs and sx of VA toxicity
suspected non-adherence
addition or withdrawal of enzyme inducing drugs
63
What are some dosing principles with valproic acid?
hepatic disease: decreased protein binding and clearance
-avoid in hepatic disease
-unbound drug may increase while total [ ] may remain unchanged
elderly: decreased protein binding and and clearance
-use lower initial doses
renal impairment: no dosage adjustment necessary
64
What are the two main types of drug interactions with valproic acid?
VA is an enzyme inhibitor
-most commonly seen with drugs metabolized by 2C9, UDPGT, epodixe hydroxylase
due to high protein binding, VA is subject to displacement interactions with other drugs and endogenous substances
65
What are some drugs that are reported to increase valproic acid levels?
macrolide antibiotics
-use alt antibiotic if possible
-monitor VA levels after start and stop antibiotic
topiramate
-may enhance hepatotoxic effect of VA
-monitor VA level and signs of hepatic dysfunction
isoniazid
-monitor VA levels after start and stop isoniazid
ASA/salicylates
-may increased unbound VA
-monitor for toxicity
66
What are some drugs reported to decrease valproic acid levels?
carbapenem antibiotics
-monitor VA levels before and after
anticonvulsants
rifampin
67
What are some drugs who's levels are reported to increase when used with valproic acid?
anticonvulsants
-*lamotrigine: decrease LGT dose 50% and double titration period
warfarin
TCAs
68
Which mood stabilizer is a good option for patients with bipolar who have mania and alcohol use disorder?
divalproex
69
What are the dose related side effects of valproic acid?
GI: NVD, constipation, anorexia
-reported to be lower with divalproex vs VA
CNS: sedation, tremor, ataxia, dizziness
thrombocytopenia
70
What are the idiosyncratic side effects of valproic acid?
increased transaminases and LDH (may be dose related)
-adjust therapy if liver enzymes > 3x ULN
hepatoxicity (4-ene metabolite)
pancreatitis
leukopenia
hyperammonia
skin rash (SJS, DRESS, TENS) *increased risk with lamotrigine*
hyponatremia
71
What are the chronic side effects of valproic acid?
weight gain
-up to 60% of patients, mean 8-14kg
alopecia
menstrual disturbances, polycystic ovaries
72
What is an important consideration with valproic acid for women of child-bearing age?
teratogenic
-best practice=use contraception
73
What are some monitoring parameters for valproic acid?
sedation: ongoing
CBC with diff and platelets, LFTs: baseline, monthly x 3mo, then q4-6 mo
ammonia: if unexplained lethargy/confusion/vomiting
rash: ongoing
valproate level: 2-4d after dose change or DDI started then in 1-2w to ensure stable, then prn
74
What are some pieces of information that should be provided during a valproic acid counsel in addition to the typical counselling points?
may take several weeks to see benefit
avoid excessive alcohol
self-monitor for sx of liver failure or pancreatitis
use reliable contraception if child-bearing potential; take folic acid supplementation
DI check every time starting or stopping VA/DVP
check with Ph/MD before starting new Rx or OTCs
75
What are management strategies for the common side effects of valproic acid?
GI upset: take with food, use DVP, use H2RAs
sedation: take higher dose at hs
76
What are the indications of lamotrigine?
seizures
-partial seizures (adjunctive)
-absence seizures (monotherapy)
-generalized tonic-clonic (monotherapy)
bipolar disorder
-acute bipolar depression
-maintenance in BDI/II
77
Describe the pharmacology of lamotrigine.
alters signal transduction via
-binding to the open channel conformation of the voltage-gated Na+ channels
-reducing release of glutamate
weak 5HT3 receptor inhibitory effects
78
What is the half-life of lamotrigine?
25-33 hours (adults, with no interacting drugs)
79
How is lamotrigine eliminated?
hepatic and renal metabolism
80
True or false: the therapeutic range of lamotrigine is well established and therapeutic drug monitoring is done in the clinical setting
false
no established level for the the therapeutic range and not done clinically
81
What is absolutely essential when initiating lamotrigine?
slow titration = very very important
-high risk of rashes like SJS and TENS which can lead to end organ failure
82
What needs to be done when a patient misses a dose for 5 days during their lamotrigine titration?
they must restart the titration
83
What are the common side effects of lamotrigine?
sedation
headache
nausea
dizziness
*in general it is well tolerated*
84
What are the less common side effects seen with lamotrigine?
dyspepsia
diarrhea
anxiety or emotional lability
chest pain
peripheral edema
dysmenorrhea
ataxia
rash (non-serious)
85
What are the rare and serious side effects of lamotrigine?
risk of SJS (if titrated too quickly)
aseptic meningitis
blood dyscrasias
hepatotoxicity
86
What are the principle monitoring parameters for lamotrigine?
baseline: hepatic and renal function
ongoing: rash
no serum levels necessary
no lab monitoring required other than standard blood work
87
What are the important drug interactions to keep in mind with lamotrigine?
VA/DVP:
-can increase LTG levels two-fold or more
phenytoin, CBZ, phenobarb, topiramate:
-can decrease LTG levels (by 30-50% from CBZ)
-LTG can increase CBZ toxicity
oral contraceptives (estrogen):
-can decrease LTG levels by 50%
88
What are some counselling essentials and therapeutic tips for lamotrigine?
may take several weeks to see benefit
take without regard to food and time of the day
adherence is important, contact MD if missed more than 5 days as may need to restart titration
common AE management: usually well tolerated
self monitor for skin rash, if any skin abnormalities develop seek out medical attention and stop lamotrigine
watch out for enzyme inhibitors (esp VA and CBZ)
89
What are the indications of carbamazepine?
seizures: generalized tonic-clonic, partial-onset
bipolar: acute mania tx, maintenance
neuropathic pain (off-label)
trigeminal neuralgia
90
Describe the pharmacology of carbamazepine.
signal transduction modulation and anti-kindling properties
-blocks voltage-dependent Na+ channels
-blocks NMDA glutamate receptor and decreases Ca2+
-modulates aspartate and glutamate release
-may depress activity in thalamus or decrease synaptic transmission
stimulates release of ADH and potentiates its action in promoting reabsorption of water
91
Describe the elimination of carbamazepine.
> 99% hepatic metabolism via CYP enzymes
-3A4 (major), 2C8 (minor), 1A2 (minor)
induces its own metabolism via the epoxide-diol pathway
-autoinduction
92
True or false: carbamazepine forms an active metabolite that has therapeutic and toxic effects
true
epoxide is the major metabolite
93
Describe the autoinduction of carbamazepine.
CBZ induces its own metabolism
-onset within 1-5 days
-time to completion 1-5 weeks
-dose related (each dose increase results in further autoinduction)
-results in increased Cl and decreased t1/2
94
What is the therapeutic range of carbamazepine?
17-51 umol/L
-TR is a guideline and must be indiviudalized
-extrapolated from seizure guidelines and does not correlate well to efficacy in bipolar
95
What should the time of sampling carbamazepine levels be?
trough within 1h prior to dose
96
How frequently should carbamazepine levels be taken?
until stabilized at target dose
-during auto-induction (q1-2w until on stable regimen)
-steady state trough (after 5 weeks)
97
Is routine monitoring of carbamazepine levels necessary?
not necessary, consider if:
-suspected toxicity
-suspected non-adherence
-potential DI's or altered PK
-switching between dosage forms
-to establish what [] resulted in mood stability
98
What are the dosing principles for carbamazepine?
initiate slowly due to early long t1/2 in order to minimize AE
can initiate with any dosage form
best to give in divided doses (usually q12h or q8h)
dosing best at mealtime
elderly: decreased hepatic clearance, lower initial dose and smaller dose increases
liver disease: not recommended in decompensated liver dx, dose reduce if needed in pts with stable liver disease
renal impairment: no dosage adjustment necessary
99
What is the primary mechanism of drug interaction with carbamazepine?
co-administration of CYP 3A4 inhibitors and inducers:
-increased and decreased CBZ levels
co-administration of drugs metabolized by CYP 450 isoenzymes
-CBZ induces multiple enzyme systems
100
What are some drugs reported to increase carbamazepine levels?
macrolides (use alt abx, checks levels before + after)
azoles (check levels before + after)
CCBs (use alt agent if possible, check levels)
anticonvulsants
grapefruit juice (avoid, dont alter ingestion level)
101
What are some drugs reported to decrease carbamazepine levels?
anticonvulsants
antituberculosis
102
What are some examples of drugs whos levels are decreased by carbamazepine?
DOACs (use not recommended)
warfarin (adjust per INR)
anticonvulsants
antiretrovirals
103
What are the dose related side effects of carbamazepine?
GI: nausea, vomiting, anorexia, constipation, dry mouth
CNS: sedation, dizziness, lethargy, tremor, diplopia, ataxia, incoordination, blurred vision
CV: tachycardia, hypotension, conduction abnormalities
104
What are the idiosyncratic adverse reactions of carbamazepine?
SIADH/hyponatremia
blood dyscrasias
hepatic (increased GGT, usually benign)
abnormal thyroid tests
diploplia, nystagmus
menstrual disturbances
weight gain
photosensitivity
rash and hypersensitivity reactions
105
Which patients should undergo genetic testing when starting on carbamazepine?
Asian ancestry: HLA-B*1502
Caucasian: HLA-A*3101
*to assess rash risk*
106
What are some chronic adverse effects of carbamazepine?
osteomalacia
vitamin D deficiency
107
What are the contraindications of carbamazepine?
history of hepatic dx, CVD, blood dyscrasias, bone-marrow depression
concurrent use with clozapine
108
What are some counselling essentials and therapeutics tips for carbamazepine?
take with food to minimize GI upset
report rash or flu like sx right away
CBZ will decrease efficacy of estrogen or progestin based contraception (use alt: copper IUD or condoms)
all the DDIs
strong recommendation to test for HLA-B*1502 allele in anyone of Asian ancestry
recommend Ca and Vit D supplementation
109
What is the primary mode of action of antipsychotics?
dopamine blockade
110
What is the difference between atypical and typical antipsychotics?
atypicals generallly lower risk of EPS and hyperprolactinemia
typicals very rarely used for bipolar
111
How are antipsychotics dosed for bipolar?
lower doses than for psychosis
112
What are the general adverse effects of antipsychotics?
EPS
hyperprolactinemia, sexual dysfunction
metabolic disturbances (weight gain, dyslipidemia, DM, CVD)
anticholinergic: sedation, constipation, dry mouth, blurred vision, confusion
antihistaminergic: sedation
alpha 1 blockade: hypotension, reflex tachy, dizziness, sedation
QT prolongation
seizures
113
What is the name of the landmark trial that assessed the use of antidepressants in bipolar? What was found?
STEP-BD
-combo of AD (bupropion or paroxetine)+ mood stabilizer no more effective than mood stabilizer alone in reducing sx of bipolar depression
-no difference between affective switch but it was only 8 wk trial
114
What is the consensus on antidepressant use in bipolar disorder?
avoid AD monotherapy without antimanic agent
use with caution in people with history of AUD-induced mania, mixed features, or rapid cycling
dc during acute manic episode (taper or abrupt if severe mania)
consider tapering off once depression sx eliminated for 3-4 months
115
If using an antidepressant in bipolar, which ones should be avoided?
TCA > SNRI
116
What is a good analogy for the use of mood stabilizers for bipolar?
using mood stabilizers to treat bipolar is like tuning a musical instrument
-want to find the fine place where they are not too low and not too high
117
How are the medications for bipolar ranked in the CANMAT/ISBD 2018 Bipolar Guidelines?
based on level of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, treatment emergent switch risk
118
What is the approach to treatment in any phase of bipolar disorder?
1. review general principles and assess medication status
-e.g., substance use, adherence, change in medical status/meds
2. initiate or optimize therapy
-assess if dose is optimized, reasonable trial
3. add-on or switch
4. monitor/maintain
119
What are some key points to assess before initiating treatment for acute mania?
degree of insight
risk of aggressive/violent behavior
ability to adhere to tx
appropriate tx setting
risk of suicide
physical condition, lab lests
comorbidities
substance use
120
What should be discontinued before initiating treatment for acute mania?
alcohol
nicotine (gradual)
antidepressants
stimulants (caffeine, amphetamines)
121
What are some things that should be ruled out before initiating treatment for acute mania?
illicit drug use
neurological disorder
endocrine disorder
prescribed medication
122
What are the first line monotherapy options for acute mania?
lithium
quetiapine
divalproex
aripiprazole
paliperidone (dose > 6mg)
risperidone
*comparable efficacy, small-medium effects*
123
What are the benefits of the first line monotherapy options for acute mania?
50% will respond to monotherapy with significant improvement in mania in 3-4 weeks
some improvement to mania should be seen in 1st week (especially with DVP or APs)
124
What are the first line combo therapy options for acute mania?
lithium or DVP + quetiapine (L1), asenapine (L2), or risperidone (L1)
125
What are the benefits of combo therapy for acute mania?
greater efficacy than monotherapy with lithium or divalproex alone, especially in more severe illness
-clinical trials suggest that on avg about 20% more patients will respond to combo therapy
-lithium + quetiapine superior to quetiapine alone
125
When is combo therapy recommended as 1st line for acute mania?
when a response is needed faster, in patients judged at risk, who have had a previous history of partial acute or prophylactic response to monotherapy or in those with more severe manic episodes
126
What are some patient specific factors that may lead you to choosing lithium over divalproex for acute mania?
classical euphoric grandiose mania
few prior episodes of illness
mania-depression-euthymia course
family history of BD (esp if family hx of lithium response)
127
What are some patient specific factors that may lead you to choosing divalproex for acute mania?
equally effective in classical and dysphoric mania
predominant irritable or dysphoric mood
multiple prior episodes
comorbid substance abuse
history of head trauma
128
What are some patient specific factors that may lead a patient to responding to carbamazepine for acute mania?
history of head trauma
neurologic symptoms
comorbid anxiety or substance use
schizoaffective presentations with mood-incongruent decisions
negative history of bipolar illness in 1st degree relatives
129
What are the options for acute mania with mixed features?
DVP or APs (especially AP + DVP)
130
When is it recommended to add on or switch for acute mania?
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 should be considered
-remember a therapeutic response is expected within 1-2 weeks after starting a 1st line agent
131
Which agents are not recommended for acute mania?
lamotrigine
gabapentin
topiramate
omega 3 fatty acids
132
What are some key things to assess for before initiating treatment for bipolar I depression?
risk of self harm/suicide
depression severity
psychosocial support
ability to adhere to tx
ability to function
previous treatments
decide appropriate tx setting
133
What are some things that should be discontinued before initiating treatment for bipolar I depression?
nicotine
caffeine/stimulants
drugs
alcohol
134
What are some things to rule out before initiating treatment for bipolar I depression?
sx due to alcohol/drugs, meds, other treatments
general medical condition
135
What are the 1st line monotherapy options for bipolar I depression?
quetiapine (L1)
lurasidone + Li/DVP (L1)
lamotrigine monotherapy or adj (L2)
lithium (L2)
lurasidone (L2)
*lithium + quetiapine combo often used in practice*
136
How long might it take before seeing initial improvements in symptoms of bipolar I depression?
4-6 weeks but may take longer for full resolution
137
True or false: the clinical response for bipolar depression is faster than acute mania
false
slower response than acute mania
138
Which agents are not recommended for acute bipolar depression?
antidepressant monotherapy
-available trials do not support their efficacy
-safety concern = mood switching
aripiprazole monotherapy
ziprasidone mono/adjunctive therapy
lamotrigine with folic acid
mifepristone adjunctive
139
What kind of treatment do almost all individuals with BD require?
maintenance treatment to prevent subsequent episodes, reduce residual sx, and restore funcitoning
140
What might recurrences of BD be associated with?
decreased brain matter volume
worsened cognitive impairment
decreased inter-episodic function
higher rates and severity of relapse
reduce rate of tx response to pharmacotherapy and psychotherapy
141
What are the benefits of maintenance treatment?
reverse cognitive impairment
preserve brain plasticity
may lead to improved prognosis and minimization of illness progression
142
What are the risk factors for recurrence of BD?
younger age at onset
psychotic features
rapid cycling
more previous episodes
comorbid anxiety
comorbid substance use
143
What is the benefit of psychosocial interventions for maintenance therapy of bipolar disorder?
decreases recurrence rate by ~ 15%
-pharmacotherapy is the foundation to BD maintenance therapy but alone is ineffective to prevent recurrence
144
What is the only first line psychosocial intervention for maintenance therapy that should be offered to all patients?
psychoeducation
145
Which drug is typically used for the maintenance phase of BDI?
the medication used in the acute phase (assuming it was effective)
the following have L1 evidence for prevention of mood episode:
-quetiapine
-lithium
-divalproex
-lamotrigine
-quetiapine + lithium/DVP
146
What is the study that assessed if lithium + VA is better than either drug as monotherapy for relapse prevention in BDI?
BALANCE
147
What were the findings of the BALANCE trial?
statistical analysis significantly favoured combo over VA & Li over VA
lithium superior to VA for maintenance of BDI
no significant differences in AEs
148
What is the recommended pharmacotherapy for mixed episodes?
discontinue antidepressants
monotherapy: atypical antipsychotic
combo: Li/DVP + AAP
149
Which mood stabilizers should be avoided in pregnancy?
DVP/VA and CBZ
-risk of neural tube defects
150
Which mood stabilizer poses a small increased risk during 1st trimester?
lithium
151
Which mood stabilizer has the least risk/appears safe in pregnancy?
lamotrigine
152
What is the evidence for use of antipsychotics in pregnancy?
least studied
risk neutral for quetiapine, aripiprazole, risperidone, olanzapine
153
Which mood stabilizer has the most evidence that it can reduce the risk of suicide in patients with bipolar?
lithium
-anticonvulsants have some evidence for protective effects
-antidepressants are controversial
-AP's: clozapine + evidence but for schizophrenia, AP's do not have anti-suicide effects
