ic13 bipolar disorder Flashcards
what treatment can induce bipolar disorder
1) antidepressants may induce mania in the initial few days - 2 weeks.
2) ECT
medications that may induce mania
drugs of abuse: eg alcohol
drug withdrawal states (from BZP, barbiturates, antidepressants, alpah2 agonists, opioids)
antidepressants
DA or NE augmenting agents
steroids (inc corticosteroids, anaboic…)
thyroid prep (t3, t4)
xanthine (caffeine, theophylline)
decongestants (pseudoephedrine)
otc weight loss (ephedra)
herbal (st john wort)
presentation of mania/hypomania
abnormal and persistently elevated/expansive/irritable mood.
DIGFAST
distractibility & easily frustrated
irresponsible/erratic uninhibited behaviour
grandiosity
flight of ideas
activity increase
sleep (need is decreased)
talkativeness
descriptors for mood episodes
major depressive: sx >2 wks + functional impairment
manic: sx ≥1 wk + functional impairment
hypomanic: ≥4 days (no functional impairment or psychosis)
criteria for manic episode
at least 3 sx
+
elevated/expansive mood
(4 if mood is only irritable)
non phx tx for bipolar
1) psychoeducation about disorder, tx, monitoring for pt and caregiver
- recognising early s/sx of mania/depression
- charting mood changes
2) psychotherapy (group, individual, family), CBT
3) stress reduction techniques, relaxation therapy
4) sleep hygiene (regular sleep schedule, avoid alcohol/caffeine prior to bedtime)
5) nutrition (regular intake of protein rich foods, essential fatty acids, supplements, vitamins…)
6) exercise (regular aerobic and weight training at least 3 times a week)
treatment algorithm for bipolar disorder?
include mania vs depression
1) short course PRN benzodiazepines
- to help the patient sleep and relax
- onset within hours
eg lorazepam 0.5mg DS max 10mg.day
or clonazepam 0.25mg BD max 4mg/day
2) mood stabiliser for acute treatment
for mania: either
(a) SGA: olanzapine, quetiapine, risperidone, ariprazole or FGA: haloperidol
(b) lithium (1st line for maintenance and suicide prevention)
(c) valproate (3rd line)
(d) carbamazepine (4th line)
for depression either
(a) lithium
(b) SGA: quetiapine, olanazapine + fluoxetine, OR lurisdone, capirazine
(c) lamotrigine
what is the MOA of lithium
inhibits secondary messengers in the phosphatidylinositol system
may reduce protein kinase c
decrease 5ht reuptake and dopamine release.
what labs to monitor for lithium?
TFT
electrolytes (ca2+)
renal function
FBC
physical exam: ( pregnancy test, urinalysis, ECG)
ECG important esp if >40y/o OR cardiac disease.
- watch for rashes*
what is the target level of lithium (USUALLY how many days) and sampling time
should reach steady state in 5 days
for acute mania: 0.8-1.0 mEq/L
for maintenance: 0.6-1.0mEq/L
take 12h after previous dose, 5-7 days after initiation OR dose/formulation change OR introducing interacting medication
FOR 2 WEEKLY in acute stage until stable.
then q3 months in first year
q3-6 months afterwards.
HIGHEST 1.2
side effects of lithium
acne,
tremors (fine to coarse),
polyuria (urinate more than normal),
hypothyroidism,
ECG changes,
nausea,
weight gain,
fatigue,
cognitive impairment,
diabetes insipidus (frequent thirst and urination
more common at >0.8mEq/L
drug and disease interactions with lithium?
lithium toxicity with (lithium resembles sodium and may cause reuptake in low fluid status)
(i) condition
- decreased sodium
- dehydration
(ii) drug
- thiazides
- acei/arb
- nsaids
neurotoxicity with
- anticonvulsants (CBZ, phenytoin, diltiazem)
- antihypertensive (lorsartan, methyldopa, verapamil)
- metronidazole
enhanced renal elimination
- caffeine and theophylline
different levels of lithium toxicity?
increasing GI and CNS side effects
mild: 1.5-2.0
- GI: N/V/D
- CNS: lethargy, confusion, coarse hand tremors, drowsy, lightheaded
moderate: 2.0-2.5
- GI: similar
- CNS: profound lethargy, worsening confusion, ataxia, apathy, sensory disturbances (slurred speech, blurred vision, tinnitus)
severe >3.0
- GI: similar
- CNS: seriously impaired consciousness, increased deep tendon reflexes, stupor, coma, seizure, death.
what is the metabolism of lithium
100% renally cleared
not affected by the liver.
sodium valproate labs to monitor
LFTs,
FBC (watch for thrmobocytopenia),
metabolic (FBG, lipids, BMI)
general (pregnancy, rahs, SJS/TEN)
sodium valproate PK
undergoes hepatic metabolism,
no need for dose adjustment in renal impairment… can be used if renally impaired.
sodium valproate TDM range and sampling time
50 - 125 mcg/ml
ss in 3-5 days
take trough sample before 1st dose of the day, at least 2-3 days after initiation or changing dose.
TDM not routinely required.
SE of sodium valproate
rash, SJS/TEN
common:
N/V, weight gain, ataxia (no coordination), tremors. dizziness, somnolencence
other:
hepatotoxicity, thrombocytopenia, pancreatitis, hyperammonemia, alopecia
neonatal birth defects.
drug interactions w/ valproate
SJS risk w lamotrigine
cyp interactions with valproate
substrate: 2c19
inhibitor: 2c9, 2d6, 3a3, 3a4
target CBZ TDM? and sampling time
4-12 mg/L in 4 weeks
>7mg/L for bipolar
take trough sample before first dose
TDM q6 monthly in the first year, then annually.
SE of CBZ
GI and CNS toxicity
hyponatremia
blood dyscrasia (incl leukopenia , agranulocytosis).
rash
SLE/TEN
what to avoid adding with CBZ
CLOZAPINE
risk of agranulocytosis
CBZ labs
FBC (agranulocytosis)
LFT
electrolytes (hyponatremia, monitor na+ at baseline, then repeat 2wk after initiation, then monthly for 1st three months)
general (pregnancy, agranulocytosis, rash, SJS/TEN)
hla*b1502
cyp interactions with CBZ (inducer, substrate, inhibitor)
INDUCER of
1A2
2C9
2C10
3A3
3A4
SUBSTRATE of 2c8,
3a3
3a4
CBZ pk?
hepatic metabolism
induces metabolism (of itself and other drugs)
lamotrigine SE (and special considerations)
rash esp in initial 8 weeks
less sedation and weight gain effects
max 100mg if combined with VPA
lamotrigine labs
LFT
FBC
Physical exam: rash, SJS/TEN
what is the approach to manage poor response
if no response after 2-4 weeks, then augment with a second first like agent or SGA
consider ECT if severe or treatment resistant (stop lithium, anticonvulsants, benzo at least 12h before ECT).
MANAGEMENT of bipolar disorder with rapid cycling (define also)
≥4 mood episodes per year
avoid antidepressants/stimulants in rapid cycling (or if patient has PMH for antidepressant induced mania).
evaluate and treat any underlying conditions: hypothyroid, hormonal imbalance, substance abuse…
- optimise mood stabiliser tx.
treatment considerations for pregnancy?
weigh risk vs benefits, gradually taper off medications
avoid lithium, valproate, CBZ
can consider SGA or FGA but monitor for side effects (gestational diabetes)
OR ECT
treatment considerations for breastfeeding?
weight risk vs benefits as all mood stabilisers are secreted into breast milk
treatment considerations for cardiac disease
consider valproate
monitor increase BP, HR, peripheral oedema
treatment considerations for liver impairment
lithium
treatment considerations for renal impairment
valproate
monitor serum levels closely
treatment considerations for children/adolescents
lithium
valproate
treatment considerations for elderly
consider lamotrigine
all psychotropics increase risk of side effects
avoid renally excreted drugs,
treatment considerations for aggression/violence
optimise dose and levels of lithium or valproate.
consider adding antipsychotic
