Case 8 - Bipolar Flashcards
what is bipolar 1 disorder
manic episodes typically alternate with depressive episodes during the course of illness
there is a recurrent mania subtype which is rare
what is bipolar II disorder
lifetime experience of at least one major depressive and one hypomanic episode - not manic
often depressive episodes become predominant over time and are very functionally impairing
hypomanic episodes do not usually cause impairment, often improve productivity at home and work and sometime are not disclosed because they are not seen as a problem by the patient
usual cause of presentation is depression or unpredictability of mood
BPII can be mistaken for recurrent MDD if you don’t look for a past history of hypomania
what is a manic episode
A. a distinct period of abnormally and persistently elevated, expansive or irritable mode and abnormally and persistently increased activity or energy lasting at least one week and present most of the day nearly every day
B. during A, 3 or more of the following (4 if mood is only irritable) are present to a significant degree and represent a noticeable change from usual behaviour
- inflated self esteem
- decreased need for sleep
- pressure of speech
- flight of ideas or subjective experiences that thoughts are racing
- distractibility
- excessive involvement in pleasurable activity that have high potential for painful consequence
C. sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalisation or there are psychotic features
D. not attributable to the physiological effects of a substance or another medical. condition
what is hypomania
A. a distinct period of abnormally and persistently elevated, expansive or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 xonsectuve days and present most of the day, nearly every day
B. during A, 3 or more of the following (4 if mood only irritable) have persisted, represent a noticeable change from usual behaviour and have been present to a significant degree: same 7 features as mania
C. episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic
D. the disturbance in mood and the change in functioning are observable by others
E. the episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalisation. If there are psychotic features preset, the episode is, by definition, manic
F. not attributable to the physiological effects of a substance or medical condition
how is food fortified
add micronutrients
what is first onset age of first moof episode in bipolar I
18
when is first mode episode of bipolar II
mid 20’s
what is the average life expectancy reduced by
9-20 years
what is the lifetime suicide risk of bipolar
at least 15 times of the gen pop
which kind of environment makes you more prone to getting bipolar
more common in high income counties
adverse childhood experiences
stress and loss
seasonal effets
medical disorders
what medications make you more prone to developing bipolar
corticosteroids, Ldopa, thyroid hormones, antidepressants
what are the genetic risk loci now identified for bipolar
voltage gated Ca2+ and Na+ channels
GluN2 subunit of NMDA receptors
synaptic components
regulation of Insulin secretion
endocannabinoid signalling
what is BPI strongly correlated with
SCHZ
what Is BPII strongly correlated with
MDD
what is the genetic overlap with schizophrenia
27% of the 30 risk loci associated with schizophrenia
a detailed family history will often find familial co aggregation of bipolar disorder and schizophrenia in the same family tree
how many people will develop psychosis during their lifetime with bipolar
50%, predominantly in the manic phase and some in severe depressive episodes.
what do manic episodes in bipolar disorder respond to
antipsychotic drugs - D2 receptor antagonists
is dopamine synthesis altered in bipolar disorder without psychosis
no
which parts of the brain have elevated DA synthesis in bipolar
all striatum divisions
what dopamine dysfunction is associated with psychosis
presynaptic dopamine dysfunction
what are the three phases of bipolar
acute manic
acute major depressive
maintenance phase
what drug are given during the acute manic episodes
antipsychotics - D2 antagonists
lithium - mood stabiliser
valproate - an anti epileptic
carbamazepine - an antiepileptic
what medicine I given in acute depressive episodes
quetiapine in relatively low doses
lamotrigine - an anti epileptic
lithium
why are antidepressants not used
increased risk of switch to mania or rapid cyclone
may sometimes be helpful but used as 2nd or 3rd line and must be used with an effective anti manic drug
what are combinations of anti manic and anti depressive drugs q
fluoxetine and olazapine
SSRI and Li combination
what is maintenance treatment directed towards
prophylaxis against future acute episodes
what is the gold standard maintenance treatment
lithium
efficacy in reducing the risk of suicide
what other drugs are used prophylacticly
quetiapine - better against depression
valproate - against mania
features of lithium
an alkali metal usually administered as a salt
not bound to plasma proteins, is not metabolised and is excreted unchanged almost soloed by the kidney
what kind of salt is lithium administered as
carbonate or citrate
why is there caution around lithium
renal impairment
what is the therapeutic window
0.6-0.8mmol/L (12 hours post dose)
Below 0.6 - decreased or absent effectiveness
Above 0.8 - decreased tolerability
Above 1.2 - high risk of toxicity
what test is done regularity with lithium
regular blood tests for Li level
what is first line treatment for all phases of bipolar disorder
lithium
what are the mechanisms of action of lithium
increase 5HT and GABA (inhibitory) neurotransmission
decreased glutamate and DA neurotransmission
possibly via effects on adenylate cyclase, inositol metabolism an protein kinase C activity
decreased oxidative stress
increased trophic and protectivee factors
what are protective factors of lithium
BDNF and the anti-apoptotic factor B cell lymphoma-2
side effects of lithium
fine tremor
Mild GI upset
Clinically evident nephrogenic diabetes insipidus (NDI) (reversible)
Increased thirst, polyuria, and reduced urinary concentrating ability
Renal tubule mechanism: Li probably inhibits a G-protein coupled pathway that is activated by ADH to increase aquaporin channels in the collecting ducts
mild cognitive effects
Metallic taste
Ankle oedema
Weight gain
Increased risk of hypothyroidism and hyperparathyroidism
Very small risk of decreased renal function with chronic use particularly which levels >0.8mmol/
signs of toxicity
increasing anorexia, nausea, diarrhoea
Muscle weakness, drowsiness, ataxia, course tremor, muscle twitching
At 2.0 mmol/L increased disorientation, seizures coma and death
what is valproate a general term to describe
valproic acid
Sodium valproate
Valproate semisodium (a coordination complex of valproic acid and sodium valproate in a 1:1 molar relationship. AKA depakote
what are the indications for valproate in bipolar disorder
- actue manic episodes (third line in resistant mania and added to lithium when lithium and antipsychotics have not been adequately effective
-
when would valproate be used as maintenance in bipolar
indicated when lithium has not been effective or is poorly tolerated
moderate protection against manic relapse
less protective against depressive release
what is the mechanism of action of valproate
wide range of immediate and long term biochemical and genomic effects
what are the acute effects of valrpoate
increased GAB
decreased neuronal excitability via the blockade of voltage gated Na+ channels
what are the long term effects of valproate in changes in systems in the body
changes in:
- glucocorticoid, 5HT, and DA neurotransmitter systems
- inositol metabolism and protein kinase C activity
- Want/beta-catenin cell signalling pathway
- brain lipids and their metabolism
what are the other long term effects of valproate
increased trophic and protective factors e.g BDNF and the anti-apoptotic factor B cell lymphoma 2
class I histone deacetylases (HDAC) inhibition leads to altered gene expression
what are the other long term effects of valproate
increased trophic and protective factors e.g BDNF and the anti-apoptotic factor B cell lymphoma 2
class I histone deacetylases (HDAC) inhibition leads to altered gene expression
what are the side effects in pregnancy
teratogenic and developmental effect in a range of foetal organ systems
rates of major malformations around 7-14%
exposure in first trimester leads to increase risk of SB, atrial septal defect and cleft palate
postnatal neurodevelopment problems in up to 30-40% of exposed children
risk of autism increased3-5 times
what is the pregnancy prevention programme
an assessment of their potential for becoming pregnant
Pregnancy tests before starting and during treatment
Counselling about the risks of valproate and the need for effective contraception throughout treatment
A review of ongoing treatment by a specialist at least annually
A new risk acknowledgement form that patients and prescribers will go through every year
valproate packing also now carries a visual warning, patients are given a warning card with every prescription, and pharmacists are required to discuss the risks every time they dispense valproate to women of childbearing potential
