Case 8 - Bipolar

Question 1

what is bipolar 1 disorder

Answer 1

manic episodes typically alternate with depressive episodes during the course of illness

there is a recurrent mania subtype which is rare

Question 2

what is bipolar II disorder

Answer 2

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

Question 3

what is a manic episode

Answer 3

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

Question 4

what is hypomania

Answer 4

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

Question 5

how is food fortified

Answer 5

add micronutrients

Question 6

what is first onset age of first moof episode in bipolar I

Answer 6

18

Question 7

when is first mode episode of bipolar II

Answer 7

mid 20’s

Question 8

what is the average life expectancy reduced by

Answer 8

9-20 years

Question 9

what is the lifetime suicide risk of bipolar

Answer 9

at least 15 times of the gen pop

Question 10

which kind of environment makes you more prone to getting bipolar

Answer 10

more common in high income counties
adverse childhood experiences
stress and loss
seasonal effets
medical disorders

Question 11

what medications make you more prone to developing bipolar

Answer 11

corticosteroids, Ldopa, thyroid hormones, antidepressants

Question 12

what are the genetic risk loci now identified for bipolar

Answer 12

voltage gated Ca2+ and Na+ channels
GluN2 subunit of NMDA receptors
synaptic components
regulation of Insulin secretion
endocannabinoid signalling

Question 13

what is BPI strongly correlated with

Answer 13

SCHZ

Question 14

what Is BPII strongly correlated with

Answer 14

MDD

Question 15

what is the genetic overlap with schizophrenia

Answer 15

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

Question 16

how many people will develop psychosis during their lifetime with bipolar

Answer 16

50%, predominantly in the manic phase and some in severe depressive episodes.

Question 17

what do manic episodes in bipolar disorder respond to

Answer 17

antipsychotic drugs - D2 receptor antagonists

Question 18

is dopamine synthesis altered in bipolar disorder without psychosis

Answer 18

no

Question 19

which parts of the brain have elevated DA synthesis in bipolar

Answer 19

all striatum divisions

Question 20

what dopamine dysfunction is associated with psychosis

Answer 20

presynaptic dopamine dysfunction

Question 21

what are the three phases of bipolar

Answer 21

acute manic
acute major depressive
maintenance phase

Question 22

what drug are given during the acute manic episodes

Answer 22

antipsychotics - D2 antagonists
lithium - mood stabiliser
valproate - an anti epileptic
carbamazepine - an antiepileptic

Question 23

what medicine I given in acute depressive episodes

Answer 23

quetiapine in relatively low doses
lamotrigine - an anti epileptic
lithium

Question 24

why are antidepressants not used

Answer 24

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

Question 25

what are combinations of anti manic and anti depressive drugs q

Answer 25

fluoxetine and olazapine SSRI and Li combination

Question 26

what is maintenance treatment directed towards

Answer 26

prophylaxis against future acute episodes

Question 27

what is the gold standard maintenance treatment

Answer 27

lithium efficacy in reducing the risk of suicide

Question 28

what other drugs are used prophylacticly

Answer 28

quetiapine - better against depression valproate - against mania

Question 29

features of lithium

Answer 29

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

Question 30

what kind of salt is lithium administered as

Answer 30

carbonate or citrate

Question 31

why is there caution around lithium

Answer 31

renal impairment

Question 32

what is the therapeutic window

Answer 32

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

Question 33

what test is done regularity with lithium

Answer 33

regular blood tests for Li level

Question 34

what is first line treatment for all phases of bipolar disorder

Answer 34

lithium

Question 35

what are the mechanisms of action of lithium

Answer 35

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

Question 36

what are protective factors of lithium

Answer 36

BDNF and the anti-apoptotic factor B cell lymphoma-2

Question 37

side effects of lithium

Answer 37

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/

Question 38

signs of toxicity

Answer 38

increasing anorexia, nausea, diarrhoea Muscle weakness, drowsiness, ataxia, course tremor, muscle twitching At 2.0 mmol/L increased disorientation, seizures coma and death

Question 39

what is valproate a general term to describe

Answer 39

valproic acid Sodium valproate Valproate semisodium (a coordination complex of valproic acid and sodium valproate in a 1:1 molar relationship. AKA depakote

Question 40

what are the indications for valproate in bipolar disorder

Answer 40

- actue manic episodes (third line in resistant mania and added to lithium when lithium and antipsychotics have not been adequately effective -

Question 41

when would valproate be used as maintenance in bipolar

Answer 41

indicated when lithium has not been effective or is poorly tolerated moderate protection against manic relapse less protective against depressive release

Question 42

what is the mechanism of action of valproate

Answer 42

wide range of immediate and long term biochemical and genomic effects

Question 43

what are the acute effects of valrpoate

Answer 43

increased GAB decreased neuronal excitability via the blockade of voltage gated Na+ channels

Question 44

what are the long term effects of valproate in changes in systems in the body

Answer 44

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

Question 45

what are the other long term effects of valproate

Answer 45

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

Question 46

what are the other long term effects of valproate

Answer 46

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

Question 47

what are the side effects in pregnancy

Answer 47

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

Question 48

what is the pregnancy prevention programme

Answer 48

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