bipolar Flashcards
bipolar disorder definition
Severe mood swings
Lifelong, cyclical mood disorder with variable course
* Recurrent fluctuations in mood, energy, behaviour
* Duration dominated by depressive episodes
bipolar sx presentation WHEN?
- 1st ep in teens
- first major dep (F), mania (M) peaks 15-19 yo
* lasts from wks - mnths if untx - rapid cycling (freq epi of mania –> dep) as illness progress
rapid cycling
=/> 4 ep in 12mnths
- mania, hypomania, or depressive episodes
causes of bipolar
1) genetics (relatives with mood d/o) (chromosone 18, 11p15, 21)
2) induced by tx
3) induced by general medical conditions
4) hx of trauma
5) physical stressors
6) seasonal changes
induced by tx
- Antidep
- Induce manic in few days ~ 2wks
- Incr NE, DA transmissions
- MANIC SWITCH
- ECT
- Depressed –> hypomanic/ manic mood
- Use in refractory MDD
- Voltage stimulate electro-activity, large/ fast release of neurotransmitters
secondary causes of mania
- CNS disorders (tumor, stroke, head injury, subdural hematoma, multiple sclerosis, SLE, temporal lobe seizure, Huntington’s)
- CNS infections
- Encephalitis, neurosyphilis, sepsis, HIV
- Electrolyte or metabolic abnormalities
- Ca, Na fluctuation,
- Hyper/hypo BGL
- Endocrine or hormonal dysregulation
- Addison, Cushing’s
- hypothyroidism (dep)
- Hyperthyroidism (mania)
- Menstrual related/ preg related/ perimenopausal mood
- Vitamins, nutritional deficiencies
- Essential aa, FA, vit B
2nd causes (medications/ drugs) that induce
- Drugs of abuse:
- alcohol intoxication, hallucinogens, marijuana (psychosis, paranoia, ANX, restlessness)
- Drug withdrawal state
- Alcohol, a2 agonist, antidep, barbiturates, benzodiazepines, opioids
- Antidep
- MAOi, TCA, 5HT/ NE/ DA reuptake inhibitors
- 5HT antagonists
- DA-augmenting agents
- CNS stimulants, amphetamines, cocaine, sympathomimetics, DA agonist/releasers/ reuptake inhibitors)
- NE augmenting agents
- A2 antagonists, b-agonists, NE reuptake inhibitors
- Steroids — confusion
- Anabolic, CS, adrenocorticotropic
- Thyroid preps
- T3 > T4 (potency)
- Xanthines
- Caffeine, theophyllines (asthma)
- OTC weight loss agents, decongestants
- pseudoephedrine
- Herbal pdts (st John’s wort)
low mood sx
DIGES. CAPS
- depressed mood
- interest diminished, anhedonia
- guilt, low self esteem
- energy
- sleep incr/ decr
- conc poor
- appetite incr/ decr
- psychomotor agitation/ retardation
- suicide ideation
high moods
DIGFAST
- distractibility (fraustrated)
- irresponsible behaviour
- grandiosity
- flight of ideas (racing thoughts)
- activity incr
- sleep decr
- talkativeness
DSM-5 dx of bipolar
—> Based on duration, n.o. of sx, degree of functional impairment
- Major depressive: sx > 2wks (functional impairment) dep/ loss interest + 3 other sx
- Manic: sx =/> 1wk (functional impairment) Elevated mood + 3 sx // 4 sx (if mood irritable)
- Hypomanic: sx =/> 4 d (no functional impairment, no psychosis)
mood disorders
- Depressive disorders
○ MDD = unipolar + somatic & cognitive sx
○ Dysthymic disorder = depressed mood (not MDD), > 2yrs - Bipolar disorder
○ Bipolar I = mania +/- depressive ep
○ may have anxious or atypical features
○ Bipolar II = hypomania + depressive ep
bipolar II –> I eventually
tx general assessments similar to other psych but
- preg test (SV, Li, CBP)
- toxicology (sub-induced/ withdrawal sx)
- med conditions (delirium, Psychosis, Depression, ANX, Insomnia, Thyroid dysfunction, DM)
- MSE (high risk of suicidality - impulse)
- pgx: if start CBP, HLAB*1502
- PGx: CYP2D6 poor metaboliser (risperidone, aripiprazole)
psych rating scales
- usually used in research
- mood (YMRS, young mania rating scale)
- general/ functioning (CGI, clinical global impression)
- health-related QOL assessment (psychological general well being)
tx goals
- Reduce freq, severity, duration of mood episodes
- Prevent suicide
- Maximise adherence with therapy
- Minimise ADR (employ meds with most acceptable tolerability, fewest drug interactions)
- Acute tx phase = Eliminate mood ep with remission of sx
- Maintenance/ continuation tx phase
- reduce mood ep
- reduce suicide ideation/ attempts
- regain psychosocial functioning)
- Avoid stressors or substances that may ppt an acute mood ep
non pharm
- Psychoeducation (disorder, tx, monitoring for pt and caregiver)
○ Recognise early s&sx of mania and depression
○ Chart mood changes
○ Importance of compliance with therapy
○ Psychosocial, physical stressors and sub that ppt mania ep - Psychotherpy
○ Indiv, grp, family
○ Interpersonal cognitive behavioural therapy (CBT) - Stress reduction techniques, relaxation therapy
- Sleep hygiene
○ Regular sleep, wake schedule
○ Avoid alcohol, caffeine intake ON - Nutrition
○ Protein rich foods, drinks, essential FA, supplemental vit and minerals - Exercise (aerobic, weight TDS)
pharm tx course
- Short course of benzodiazepines (adjunct)
○ Help pt relax and sleep
○ Onset in hrs
○ Taper off when condition improved, mood stabilier optimised - Start mood stabilisers (mania or dep)
○ onset for stabilising mood: 3-5d
○ Counsel pts: mood stabilising, cause drowsiness (ON)
mood stabiliser select by
○ Response (change in sx)
○ Tolerability of SE
○ Serum drug lvl when applicable
○ Avoid drug interactions
○ Type and trend of mood ep
○ Suicide risk: Li best to reduce suicide
○ Onset to stabilise mood in 3-5d, but hrs to relieve agitation
maniac control
qora
- APS
* SGA: olan, quet, (titrate) risp (severe mania), aripip (LAI), haloperidol - Li (TDM)
- SV (least preferrred, X child bearing)
(combi from any 2 grp: except SV + LAMO)
bipolar depression control
- Li
* 1st line for maintenace, suicide prevention - APS (quet, cariprazine)
* + SSRI: fluoxetin (olan)
* FGA: lurasidone - Lamotrigine
* not anti-maniac, only antidep
* +/- APS (mania)
* just no VA (SJS, TEN)
Li - mixed features
MOA
- Normalise/ inhibit 2nd messenger system
- Reduce PKC
- Alter cation transport across cell mem in nerve and muscle cells
- reduce reuptake of serotonin and/or norepinephrine
- inhibit second messenger systems
- Reduce PKC
- Decr 5HT uptake
- Decr DA release
Li dose
400-800mg/day
Max 1.8g/d
Li TDM
Narrow TI: TDM
therapeutic range: (0.6 - 1 mmol/L) – lower in elderly
Target: SS (12hrs after dose)
Acute mania = 0.8-1 mEq/L
Maintain = 0.6-1 mEq/L
5-7d (after initiate) –> q3mnths (1st yr) –> q3-6mnthly thereafter (stable)
SE of Li common at
- > 0.8mEq/L
- Acute tremors, polyuria
- hypoTHY, ECG change
- Weight gain, N, fatigue, cognitive impair, DM
- Li toxicity
Li toxicity
1.5- 2 (mild): NVD, lethargy, confusion, hand tremors, drowsy
2-2.5 (mod): severe NVD, slurred speech, confusion, ataxia (coord), blurred vision, lethargy, tinnitus, apathy
> 3 (severe): severe NVD, imparired consciousness, deep tendon reflexes, stupor, coma, seizure, death
DDI with Li
- Li toxicity (incr Li lvl) : STAND
- Neurotoxicity: CBP, dilitiazem, losartan, methyldopa, metronidazole, phenytoin, verapamil
- (decr Li conc) Enhance renal elimination: caffeine, theophylline
STAND
- Low Na
○ (body try to accumulate Na back into blood, Na, Li similar monocation + small size) - Thiazide (incr Li reab)
- ACEi, ARB (decr GFR, Li reab)
- NSAID (reab Li PGE2)
- dehydrate (Na,Li reab)
monitor for Li
TFT, electrolytes (Ca, Na)
RENAL
metabolic (BGL, lipid, BMI)
FBC
ECG
(baseline + 6-12mnthly)
* physical exam (preg) at base only
SV – mixed (more mania ) MOA
- Incr GABA
- Decr DA turnover
- May decr PKC
- Normalise Na, Ca channel inhibitors
- Antikindling properties
* Prevent sx from getting more severe
dose of SV
Initial: 400-750mg/day
LD 20mg/kg/day (max 60mg/kg/day)
Max 2.5g . Use divided doses
food delays absorption
SE of SV
- Hepatotoxic
- rash, SJS/TEN
- High dose: GI, pancreatitis, N, dizzy, somnolence, hyperNH3, ataxia, tremor, incr weight
DDI of SV
Risk of SJS w/ LAMO (incr conc)
acts as a CYP Inhibitor (2C9, 2D6, 3A4/3) not 450
monitor SV
baseline + 6-12mn: FBC (thrombocytopenia), LFT, metabolic (BGL, lipid, bmi), TDM
base: physical exam (rash, reg, alopecia, SJS/TEN)
SV TDM
therapeutic range: 50-125 mg/L
trough sample, before 1st dose of day
NOT ROUTINE (unless poor adherence/ effectivness/ toxicity)
* 2-3d after initiation/ change dose
CBP - mixed (more mania) MOA
- Incr glutamate transport
- Block voltage Na+ channels
CBP dose
2nd line after Li, SV
Initial: 200-1800mg/day (2-4 divided dose)
* due to autoinduction to active metabolite, start at lower dose
Max 1.6g
CBP SE
- GI, CNS toxicity
- Decr Na, WNC, blood dyscrasis
- Rash, SJS/TEN
CBP DDI
Induce CYP1A2, 2C9/10, 3A3/4
autoinduction – 3A4, 2C9 (incr active metabolite)
Agranulocytosis w/ clozapine
CBP monitor
pgx: HLA-B*1502 allele genotype (sjs/ ten)
- BASE + 6-12mn: FB (thrombocytopenia), renal (Na), LFT, TDM
- base: physical exam (preg, rash, SJS/TEN, gx)/ metabolic (BGL, lipid, BMI)
CBP TDM
- > 7mg/L bipolar (epilepsy at 4-12)
- TROUGH (morning before st dose of day)
- monitor: initiate (2-4 wk reach ss) –> q6M (1st yr) –> annuals
lamotrigine – dep only
MOA
Block voltage activated Ca2+ and Na+ channels
LMT dose
Initial: 25mg/day
Adjust 2wkly
50-200mg day in divided dose
LMT SE & DDI
Rash (esp with VA which incr LMT dose)
Less sedation & weight gain than others
monitor LMT
base + 6-12mn: LFT
base: physical, FBC, preg, renal
BZP as adjunct
MOA and dose
- potentiates GABA
- short term
(short) Lorazepam 0.5mg TDS, max 10mg/day
(long) Clonazepam 0.25mg BD, max 4mg/day
since onset 3-5d for mood stabilising effect to
BZP SE
CNS depression
Sedation
Cognitive, motor impair
Dependence, withdrawal
manage poor resp
- switch/ augment
- ECT
- antidep
- bipolar d/o with rapid cycling
switch/ augement by
- If non-responsive/ intolerant to ADR of 1st line drugs should be switched
- Mania not responded in 2-4wks with 1st line
○ Augment with another 1st line
○ Switch to SGA (olanzapine)
○ Reserve CBP if fail above
ECT
- Severe/ tx resistant manic/ depressive sx, preg
○ Can worsen mania
○ Alt days 9-12sessions - Omit Li, anticonvulsants ASM, BZP =/> 12hrs before
○ Except when lorazepam/ clonazepam used for catatonia
add antidep
- Recurrent depressive ep require LT Li, quetiapine, olan+fluoxetine, lamo, lurasidone, cariprazine
- Counsel on risk of SUICIDE
rapid cycling manage
- Avoid antidep/ stimulants in rapid cycling or if hx antidep-induced mania
- Antidep-induced rapid cycling
○ Avoid or taper off antidep and other agents that incr NE/ DA activity
○ CNS stimulants, sympathomimetics, caffeine - Tx hypoTHY, hormonal imbalance, sub abuse
- Optimise mood stabiliser: SV, Li, LAMO
preg
- should be planned, weigh risk-benefit
* taper off meds before med
* avoid meds 1st trimester
* throughout preg (teratogenic risk in 1st trimester) - AVOID
SV (neural tube defect, spina bifida)
Li (fetal thyroid goiter)
CBP (teratogenic)
– safer: FGA > SGA (quet, olan, ris – gestational DM)
– ECT (severe mania)
– LAMO
breastfeeding
- risks-benefits
- all are secreted in breast milk
- maybe (olan, quet / cloz but not BF)
CVS
consider VA
monitor: BP, HR, peripheral oedema
APS: QTc prolong
Li: cardiac arrhythmia
liver impairment
Li
renal impairment
not Li
consider SV (monitor serum lvl)
child/ adol
consider Li, SV
(SV not preferred in women with childbearing potential)
elderly
all psychotropics incr risk of SE
* avoid renal excreted Li
* avoid CBP (DDI, SE)
LAMO not sig influenced by age (still need mania control + APS)
suicidal behaviour
Li first line (optimise dose, level TDM)
aggressive behaviour
BZP (short term)/ add on APS
optimise dose, lvl of existing (Li, SV)
