ic12 bipolar disorder

Question 1

what is defined as a bipolar disorder and what is the duration of illness

Answer 1

severe mood swings; cyclical mood disorder with recurrent fluctuations in mood, energy and behavior

lifelong (medications cannot prevent mood swings but can reduce severity and frequency

illness duration largely predominated by depressive episodes (80%)

Question 2

what is the prevalence of bipolar disorder in SG and when is the peak onset of bipolar disorder

Answer 2

1.6%

peak onset 15-19yo

Question 3

compare the differences in the first episode presentation between males and females

Answer 3

males: manic
females: depressive

Question 4

how long do mood episodes last if it is untreated

Answer 4

mood episodes can last for weeks to months if untreated

Question 5

how does progression of bipolar disorder relate to the cycle freq of mood swings

Answer 5

the cycle freq accelerates as the disease progresses

Question 6

what effect do ASM have for bipolar disorder

Answer 6

ASM has anti-kindling effect for bipolar disorder (helps to avoid successive relapses)

Question 7

how much more likely are bipolar individuals to suffer from suicides

Answer 7

they are 15x more likely to commit suicide

Question 8

describe the evolution of bipolar disorder (relate to age and types of episodes at each juncture)

Answer 8

15-20yo: mild bipolar mood swings (with possibly first major depression)

21-30yo: experiences first manic episode with post manic depression (starts with the cycles of manic and depression episodes that are of higher severity than that experienced in 15-20yo)

31yo onwards: rapid cycling can occur aka very freq mood swings

Question 9

what are the risk factors for bipolar disorder

Answer 9

1. genetics (80-90% of those with bipolar has a relative with mood disorder)
2. induced by treatment
   i) antidepressants can result in a manic episode due to incr in NE or DA transmission (accounts for 20-40%)
   ii) ECT can cause 1 in 4 to switch from depressive episode into hypomanic or manic episode (bc subjecting the brain to an electric current thus at a certain voltage it would stimulate epileptic activity in the brain aka initial release of NT f/b recovery and the initial release of NT can precipitate mania)
3. induced by general medical conditions (consider those for mania episode and depressive episode)
4. hx of trauma (perinatal, head, physical abuse)
5. physical stressors
6. seasonal changes

Question 10

what are the secondary causes for mania

Answer 10

1. medical conditions that induce mania
   i) CNS disorders (brain tumor, head injuries, strokes, multiple sclerosis, subdural hematoma, systemic lupus erythematosus, temporal lobe seizures, huntington’s disease)
   ii) CNS infections (encephalitis, neurosyphilis, sepsis, HIV)
   iii) endocrine/ hormonal dysregulation (hypo/hyperthyroidism, menstrual or pregnancy or perimenopausal related mood disorders, cushing’s disease)
   *note that hypo causes depression while hyperthyroidism causes mania
   iv) electrolyte or metabolic abnormalities (Ca/ Na fluctuations, hyper or hypoglycemia)
   v) vitamin and nutritional deficiency
2. medications or drugs that induce mania
   i) drugs of abuse (alcohol, hallucinogens, marijuana)
   ii) drug withdrawal states (alcohol, alpha2 agonist antidepressants, benzodiazepines, opiates)
   iv) antidepressants
   v) DA-augmenting agents (CNS stimulants, DA agonist/ reuptake inhib/ releasers)
   vi) NE-augmenting agents (alpha2 antag, beta agonist, NE reuptake inhib)
   vii) thyroid preparations (T3/T4)
   viii) xanthine
   ix) OTC weightloss or decongestants (pseudoephedrine)
   x) herbal products (st john’s wort)

Question 11

what are the secondary causes for depression (same as for MDD)

Answer 11

1. medical conditions that induce depression
   i) endocrine (hypothyroidism, T2DM in females)
   ii) CVD (CAD, CHF, MI)
   iii) infection (CNS, HIV/STD, TB)
   iv) malignancy
   v) neurologic (PD, AD, epilepsy, post stroke, pain)
   vi) deficiency state (anemia, wernicke’s)
   vii) metabolic (electrolyte imbalances, hepatic encephalopathy)
   viii) psychiatric conditions (anxiety, alcoholism, eating disorders, schizo)
2. medications or drugs that induce depression
   i) lipid soluble BB
   ii) psychotropic: CNS depressants, anticonvulsants
   iii) withdrawal from alcohol or stimulants
   iv) corticosteroids
   v) isotretinoin
   vi) interferon beta 1a

Question 12

what is the clinical presentation of bipolar disorder (what is the key feature)

Answer 12

key feature is hx of mania or hypomania not caused by substances or other conditions

sx of depression: In SAD CAGES (considered a depressive episode if at least 5x for 2w with depressed mood or loss of interest)
Interest
Sleep
Appetite
Depressed mood
Concentration
Activity
Guilt
Energy
Suicidal

sx of mania: DIGFAST (considered a manic episode if at least 3sx for 1w with elevated/ expansive mood; or at least 4sx if only mood is irritable)
Distractibility and easily frustrated
Irresponsibility and erratic uninhibited behaviour
Grandiosity (inflated self esteem)
Flight of ideas (racing of thoughts)
Activity incr (incr goal directed activities or psychomotor agitation)
Sleep (decr sleep)
Talkativeness

Question 13

what does it mean to have a manic episode

Answer 13

abnormal and persistently elevated/ expansive/ irritable mood

sx of mania (considered a manic episode if at least 3sx for 1w or 4sx if the only mood is irritable):
DIGFAST
Distractibility and easily frustrated
Irresponsibility and erratic uninhibited behavior
Grandiosity
Flight of ideas
Activity level incr
Sleep need decr
Talkativeness

Question 14

what is the criteria regarding depressive sx, mania sx in order to classify it as a depressive episode or manic episode or hypomanic

Answer 14

depressive episode if sx lasts more than 2w; pt has functional impairment (MDD if persist for more than 2yr)

manic episode if sx lasts for 1w or more; pt has functional impairment

hypomanic episode if sx lasts 4d or more; pt has no func impairment and no psychosis

Question 15

differentiate the types of bipolar disorder

Answer 15

bipolar I = mania w/wo depressive episodes

bipolar II = hypomania w depressive episodes

Question 16

how is bipolar disorder (bipolar I) coded

Answer 16

bipolar I disorder (f/b type of current or most recent episode) (f/b severity/ psychotic/ remission specifiers) (f/b specifiers)

specifiers eg. incl:
w anxious features, w atypical features, w mixed features, w rapid-cycling, w catatonia, w melancholic features, w mood congruent psychotic features, w mood incongruent psychotic features, w peripartum onset, w seasonal pattern

Question 17

what are the types of assessments required for diagnosis of bipolar disorder

Answer 17

1. hx of presenting illness
2. psychiatric hx (esp whether they have had a hx of manic/ hypomanic episode)
3. substance use hx
4. complete medical hx and medication hx
5. family, social, occupation, forensic, developmental hx
6. physical and neurological exam
7. mental state exam (MSE)
8. labs and other investigations incl PREGNANCY TEST, vital signs, weight and BMI, RFTs using U/Cr/E, LFTs, TFTs, lipid panel, fasting blood glucose, ECG, urine toxicology, FBC
   *to exclude causative factors relating to general medical conditions, mediation/ substance induced/ withdrawal sx
9. PGx HLAB1502 genotype test mandated prior to starting CBZ

Question 18

when is PGx genotyping necessary and for which allele

Answer 18

PGx testing mandatory for HLAB1502 prior to initiating CBZ

Question 19

what are the psychiatric rating scales used for bipolar disorder (which is the gold standard)

Answer 19

1. mood
   i) young mania rating scale (YMRS) *gold standard
   ii) depression and mania scale (SDMS-D&M)
   iii) brief bipolar disorder sx scale
   iv) brief psychiatric rating scale (BPRS)
   v) hamilton depression scale (HAM-D)
   vi) montgomery-asberg depression rating scale (MADRS)
   vii) schedule for affective disorder and schizophrenia (SADS)
2. general/ functioning
   i) clinical global impression severity scale (CGI-S)
   ii) global assessment of functioning (GAF)
   iii) global assessment scale (GAS)
3. health related QoL assessment
   i) short form (SF)-36
   ii) psychological general well being scale

Question 20

what are the goals of tx for bipolar disorder

Answer 20

1. reduce freq, severity and duration of mood episode ***
2. prevent suicide ***
3. maximise adherence
4. minimise s/e
5. for an acute tx phase: eliminate mood episode w remission of sx
6. for maintenance/ continuation tx phase: to reduce freq, severity and duration of recurring mood episodes, reduce suicidal ideation and attempts, regain psychosocial func, avoidance of stressors or substances that can precipitate an acute mood episode

Question 21

what are the non pharmacotx for bipolar disorder

Answer 21

1. psychoeducation about disorder, tx and monitoring for pt and caregiver
   i) recognise early s/sx of mania and depression
   ii) charting mood changes
   iii) importance of compliance
   iv) about psychosocial, physical stressors, susbtances or drugs that can precipitate an episode
   v) stress reduction techniques
   vi) develop a crisis intervention plan
2. psychotherapy (interpersonal, CBT/iCBT, behavioural couples therapy)
3. stress reduction techniques
4. sleep hygiene
   i) regular sleep and wake schedule
   ii) avoid alcohol and caffeine intake right before bed
5. nutrition
   i) intake of protein rich food and essential fatty acids
   ii) supplements for vitamins and minerals
6. exercise
   i) regular aerobic and weight training exercises at least 3x/w

Question 22

what is the pharmacotx for bipolar disorder (general)

Answer 22

1. short course of PRN benzodiazepines
2. mood stabilisers
   i) for mania: antipsychotics (SGA incl olan, quet, risp, ari/ FGA incl halo), lithium, VPA (but VPA least preferred)
   ii) for bipolar depression: lithium, SGA (quet, olan w fluoxetine, lurasidone), LTG

*note LTG does not have anti-manic properties
*note VPA should not be given to females of childbearing potential

Question 23

what are the considerations when choosing which mood stabiliser to start for tx bipolar disorder and what is the typical onset of mood stabilisers

Answer 23

i) response
ii) tolerability
iii) serum drug levels when applicable
iv) avoidance of ddi
v) type and trend of mood disorder
vi) suicide risk (lithium has the strongest evidence to reduce suicides)

onset about 3-5d

Question 24

what is the purpose of giving benzodiazepine, what is the onset of effectiveness and how long would pt be on it for

Answer 24

to help pt relax and sleep
onset within hrs
taper off when condition improved and mood stabiliser is optimised

(short course PRN benzodiazepine)

Question 25

which mood stabiliser has the best evidence for reducing suicide

Answer 25

lithium

Question 26

what are the pt counselling points regarding use of mood stabilisers

Answer 26

this is a mood stabilising medication to give you better control of your mood, will not get carried away or impulsive or agitated, can also help with depressive episodes

may cause drowsiness and may cause weight gain, best taken at night or bed time

see dr immediately if experience any severe and bothersome s/e incl rashes, tremors, N, fever or sore throat or if feeling suicidal or unwell

mood episodes may come back but this medication can help to reduce the severity, duration and freq of these mood swings and give you greater control over your life

educate about non pharmacotx also (psychoeducation, psychotherapy, stress reduction techniques, sleep hygiene, nutrition, exercise)

Question 27

what is the moa, dose, labs, ss target, s/e, ddi and monitoring freq for lithium

Answer 27

moa: inhibit secondary messenger system, may reduce protein kinase C, decr 5HT reuptake and decr DA release

dose: 400-800mg/d

labs: TFTs, electrolytes, RFTs, FBC, ECG, urinalysis, pregnancy, serum drug level for TDM, FBG, lipids, BMI

target for ss in 5d: 0.8-1.0 for acute mania, 0.6-1.0 for maintenance

s/e: tremor, polyuria, hypothyroidism, ECG changes, acne, N, weight gain, fatigue, cognitive impairment, diabetes insipidus

ddi: lithium toxicity with decr Na, thiazides, ACEi/ARBs, NSAIDs, dehydration

monitor freq: q3m in first 6m then q6-12m

Question 28

which protein and NT is involved in mania for bipolar disorder

Answer 28

incr signalling from protein kinase C and incr levels of DA and NE can cause mania

Question 29

what is the moa, dose, labs, ss target, s/e, ddi and monitoring freq for VPA

Answer 29

moa: incr GABA levels, decr DA turnover, may decr PKC, normalises Na+ and Ca2+ channels, anti-kindling properties
*note GABA is an inhibitory NT

dose: 400-750mg/d

labs: LFTs, pregnancy test, FBC, FBG, lipid, BMI, serum drug level for TDM

target for ss in 3-5d: 50-125mg/L

s/e: hepatotoxicity in child, rash (SJS/TEN), high dose can have GI s/e, pancreatitis, decr PLT (thrombocytopenia), incr weight, N, dizziness, somnolence, ataxia, tremor, hyperammonemia

ddi: incr risk of SJS w LTG

monitoring freq: first month, q6m then q12m

Question 30

what is the moa, dose, labs, ss target, s/e and ddi for CBZ

Answer 30

moa: block Na channel, incr glutamate transport

dose: 200-1800mg/d

labs: LFTs, FBC, electrolytes, HLAB1502 allele genotyping prior to initiating, serum drug level for TDM

target ss: in 4w, 4-12mg/L for epilepsy (>7mg/L for bipolar)

s/e: GI and CNS toxicity, decr Na (can cause seizure), decr WBC, blood dyscrasias, rash (SJS/TEN)

ddi: agranulocytosis w clozapine, autoinduction, also induces metab of other drugs bc it is inducer of 1A2, 2C9/10, 3A3/4

Question 31

what is the moa, dose, labs, s/e and ddi of LTG

Answer 31

moa: block Na and Ca channel

dose: 25mg/d f/b 50-200mg/d

labs: no TDM

s/e: rash (SJS/TEN)
*note less weight gain and drowsiness
*note safer in pregnancy than other ASMs

ddi: incr risk of SJS w VPA

Question 32

what is the moa and dosing for benzodiazepines used

Answer 32

moa: adjunctive tx, potentiates GABA

dose: lorazepam 05mg TDS (max 10mg/d), clonazepam 0.25mg BD (max 4mg/d)
*these are high potency benzodiazepines

Question 33

list all s/e of lithium and categorise the s/e seen with respect to serum level of lithium (toxicity)

Answer 33

s/e of Li more common at >0.8mEq/L
s/e of Li: fine to coarse tremors, hypothyroidism, cardiac effects (ECG changes), polyuria, N, weight gain, fatigue, cognitive impairment, diabetes insipidus

mild toxicity (1.5-2.0): [GI] N/V, loose stools [CNS] lethargy, confusion, coarse hand tremors, drowsiness, lightheadedness

moderate toxicity (2.0-2.5): [GI] severe N/V/D [CNS] slurred speech, worsening confusion, ataxia, blurred vision, profound lethargy, tinnitus, apathy

severe toxicity (>3.0): [GI] severe N/V/D [CNS] seriously impaired consciousness, incr deep tendon reflexes, stupor, coma, seizures, death

*note that progression between all three levels of toxicity can be very fast (approx within 1hr)

Question 34

why might Na levels affect Li and can cause Li toxicity

Answer 34

Na and Li are small monovalent cations and at level of kidney, if there is hypoNa, the kidney has to reabsorb back Na but it cannot differentiate between Li and Na thus it might also absorb Li

Question 35

what is the ddi with lithium that causes Li toxicity (also by how much incr in levels)

Answer 35

STAND up acronym

Sodium depletion
Thiazide (incr by 50%)
Ace inhibitor/ ARBs (incr by 200-300%)
Nsaids (incr by 50%)
Dehydration

Question 36

compare the hepatic metabolism between lithium, VPA, LTG and CBZ

Answer 36

lithium is not hepatically metabolised bc it is a small cation, but is fully renally cleared (thus relate to how do not need to monitor LFTs but need to monitor RFTs -> good for liver impairment)

VPA is hepatically metabolised

LTG is hepatically metabolised

CBZ is hepatically metabolised and induces the metabolism of itself and of other drugs

Question 37

how does VPA affect half life of LTG

Answer 37

half life of LTG incr if with VPA (also remember will have incr risk of SJS)

Question 38

which mood stabilisers require TDM (list the therapeutic range, sampling time and monitoring freq)

Answer 38

1. lithium: range is 0.6-1.0mmol/L, 5-7d after initiation or changes, take trough level 12h after administration, monitor q3-6m when stable
2. VPA: range is 50-125mg/L, 3-5d after initiation or changes, take trough level in the morning before first dose of the day, routine monitoring not req
3. CBZ: range is 4-12mg/L for epilepsy (>7mg/L for bipolar), 2-4w after initiation, take trough level in the morning before first dose of the day, monitor q6m for first yr then q12m after

Question 39

what are the strategies if there is poor response

Answer 39

1. switching or augmentation: if no response within 2-4w then augment with another first line or switch to SGA
2. ECT: for severe or tx resistent (omit lithium, ASM, benzodiazepines for at least 12h before ECT)
3. role of antidepressants: for recurrent depressive episodes, will need long term lithium, quet, or olan+fluox, LTG, lurasione (counsel risk of suicidaility)
4. if it is bipolar disorder with rapid cycling (aka four or more mood episodes per yr): avoid antidepressants or stimulants, evaluate and treat underlying hypothyroidism, hormonal imbalance, substance abuse and optimise mood stabilisers (VPA, lithium, LTG)

Question 40

what are the special populations to consider for tx of bipolar disorder

Answer 40

1. pregnancy: planned, weigh risk and benefit, VPA avoided (also avoid CBZ and Li), SGA relatively safer but monitor for s/e like gestational DM, FGA low risk of teratogenicity, consider ECT for severe
2. breastfeeding: weigh risk and benefit, all in breastmilk
3. CVD: VPA and monitor for incr in BP, HR and peripheral edema
4. liver impairment: Lithium
5. renal impairment: VPA
6. elderly: avoid CBZ bc alot of ddi, avoid renally cleared drugs, all have incr risk of s/e, LTG not significantly influenced by age
7. children: lithium, VPA
8. suicidal behavior: hospitalise - lithium first line for suicidal prevention
9. aggression/ violence: hospitalise - lithium or VPA and consider adding antipsychotic