ic11 depression Flashcards

1
Q

what is the risk factors for depression

A

“poor, elderly, lonely, man with physical or mental comorbs and prev attempts”

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2
Q

how is suicide risk assessed

A

through thorough risk assessment which involves

  1. build rapport, active listening, empathy, direct qns
  2. collateral info (with pt’s consent)
  3. conduct suicide inquiry (ideation, suicide plan, intent, explore ambivalence of reasons to die vs reasons to live)
  4. consultation w specialist whenever in doubt
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3
Q

how is suicide risk managed

A
  1. identifying and managing underlying disorders if any (tx w adherence, referrals)
  2. identifying risk factors (prior attempts, past or current psychiatric disorder, key sx incl anhedonia, hopelessness, anxiety, impulsivity, aggression, delusions, family hx of suicide or child maltreatment, stressors like triggering events, access to meds/ firearms/ pesticides/ other lethal means)
  3. identifying protective factors (or lack thereof) (family/ community support, problem solving skills)
  4. removing the means
  5. activating support system
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4
Q

what kind of questions might be asked in assessing suicide risk

A
  1. have you wished you were dead or wished you could go to sleep and not wake up
  2. have you had any actual thoughts of killing yourself
  3. have you been thinking about (how) you might do this
  4. have you had these thoughts and had some intention of acting on them
  5. have you started to work out or worked out the details of how to kill yourself
  6. have you done anything, started to do anything, or prepared to do anything to end your life?
  7. if yes, ask was this within the past 3m
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5
Q

what kind of helplines or referrals are available

A

for mental well being: IMH mental helpline 6389 2222, samaritans of SG 1800-221-4444, tinkle friend www.tinklefriend.sg, community health assessment team www.chat.mentalhealth.sg

for counseling: TOUCHline, TOUCH Care Line, online (mindline.sg, thinkle friend, community health assessment team)

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6
Q

what is the etiology and pathophysiology of MDD (general classification)

A
  1. biological (hormonal influences incl incr secretion of cortisol which is a major stress hormone, monoamine theory of reduction in NT - dopamine, 5HT, NE, glutamate)
  2. psychological (loss, negative self-evaluation)
  3. psychosocial (isolation, lack of social support)
  4. genetics (first degree relative, second degree relative, monozygotic twin, dizygotic twin, polymorphism in 5HTT gene)
  5. secondary to medical disorders
  6. pharmacological aka drug-induced
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7
Q

explain the impact on risk of depression depending on the polymorphism of a gene

A

polymorphism in 5HTT gene

individuals with S allele of the promoter region of SERT gene are more vulnerable to the depressive effects of early life stress

S/S genotype most vulnerable to depression while L/L genotype more immune to depressive effects of early life trauma (protective effect)

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8
Q

what are the secondary causes of depression

A
  1. medical disorders: [endocrine] hypothyroidism, T2DM in women [deficiency] anemia, wenicke’s encephalopathy [infections] CNS, STD/HIV, TB [metabolic] electrolyte imbalance (K, Na), hepatic encephalopathy [CV] CAD, CHF, MI [neurological] alzheimer’s, epilepsy, pain, parkinson’s, post-stroke [malignancy]
  2. psychiatric disorders: alcoholism, anxiety disorders, eating disorders, schizophrenia
  3. drug induced: lipid soluble BB, psychotropics (CNS depressants like benzodiazepines, opioids, barbiturates), anticonvulsants, withdrawal from alcohol and stimulants, corticosteroids, isotretinoin, interferon beta-1-a for HepA
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9
Q

what is the clinical presentation and diagnostic criteria for MDD

A

(A) at least 5 sx present during the same 2w period and represent a change from prev func

relate to acronym In SAD CAGES

Interest: decr interest and pleasure in normal activities
Sleep: insomnia or hypersomnia
Appetite: decr appetite, weight loss
Depressed: depressed mood or irritable mood (in children)
Concentration: impaired conc and decision making
Activity: psychomotor retardation or agitation
Guilt: feelings of guilt or worthlessness
Energy: decr energy or fatigue
Suicidal: thoughts or attempts

(B) sx cause significant distress or impairment in social, occupational, or impt areas of func

(C) sx are not caused by underlying medical condition or substance

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10
Q

what are the types of depressive disorders (classification based on DSM-5)

A
  1. MDD (at least 5 sx for 2w incl depressed mood or loss of interest)
  2. persistent depressive disorder (dysthymia) (depressed mood with 2 or more sx for two years but do not fulfil MDD criteria)
  3. disruptive mood dysregulation disorder (for children up to age 18yo)
  4. premenstrual dysphoric disorder
  5. substance/ medication induced depressive disorder
  6. depressive disorder due to another medical condition
  7. other specified depressive disorder
  8. unspecified depressive disorder
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11
Q

what does it mean by MDD “with mixed features”

A

co existence within a major depressive episode of at least 3 manic sx (but unable to satisfy criteria for a manic or hypomanic episode)

manic sx incl

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12
Q

what are the differential diagnoses for depression

A
  1. adjustment disorder (w anxiety and/or depressed mood) - sx occur within 3m from onset of stressor but once stressor removed, the sx do not persist for additional 6m
  2. acute stress disorder - sx occur within 1m from a traumatic event lasting 3d-1m; sx incl horror, fear, helplessness, dissociations, re-experiencing, avoidance, incr arousal
  3. seasonal affective disorder
  4. substance induced mood disorder
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13
Q

what are the general assessments to help with diagnosing depression

A
  1. hx of presenting illness
  2. psychiatric hx
  3. substance use hx
  4. complete medical hx and medication hx
  5. family, forensic, developmental, social, occupational hx
  6. physical and neurological exam
  7. mental state exam
  8. labs and other investigations
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14
Q

how to differentiate between depression, delirium, dementia, withdrawal/ intoxication

A

differentiate using comparators onset, consciousness, memory

depression: cyclical onset, generally unimpaired consciousness, intact memory

delirium: acute onset, impaired consciousness, poor memory

dementia: insidious/ step wise change onset, consciousness remains clear until later stages, poor short and long term memory

withdrawal/ intoxication: acute onset, continuum of unimpaired to impaired consciousness, intact memory

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15
Q

what are the psychiatric rating scales used for assessment (clinician used and self rated)

A

clinician used rating scales incl:
1. hamilton rating scale for depression (HAM-D) - remission if score 7 or less (therapy goal is to be sx free)
2. clinical global impression - severity scale (CGI-S)
3. montgomery-asberg depression rating scale (MADRS)

self rated scales incl:
1. screening tool use patient health questionnaire (PHQ-2)
2. assessment tool use PHQ-9 - score 1-4 indicates minimal sx (in remission), 5-9 indicates mild depression, 10-14 indicates moderate depression, 15-19 indicates moderately-severe depression, 20 and above indicates severe depression
3. quick inventory for depressive sx (IDS) -SR
4. beck depression inventory (BDI)
5. geriatric depression scale (GDS) - 15-item short form, 30-item long form

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16
Q

based on the PHQ9 assessment tool, which score is indicated for tx with antidepressants

A

score 1-4: minimal sx (in remission)
score 5-9: mild depression
score 10-14: moderate depression
score 15-19: moderately-severe depression
score 20 and above: severe depression

classification of moderate depression or worse means indicated for tx

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17
Q

what are the qns asked in screening tool PHQ-2 and when would PHQ-9 be administered to a pt

A

PHQ-2 qns: over the past 2 weeks how often have you been bothered by any of the following problems? (i) little interest or pleasure in doing things (ii) feeling down, depressed or hopeless
-> if pt has a positive resp to either qn, consider administering PHQ-9
-> if pt has a negative resp to both qns, it is a neg result for depression screening

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18
Q

outline the types of non pharmacotx for depression

A
  1. sleep hygiene - to improve sleep habits
  2. psychotherapy - not suitable for monotx in moderate to severe depression, typically adjunct with antidepressants
  3. neurostimulation - electroconvulsive therapy (ECT) for severe refractory cases, repetitive transcranial magnetic stimulation (rTMS)
  4. light therapy - for seasonal affective disorder
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19
Q

outline the types of pharmacotx for depression (when is pharmacotx indicated and what are the considerations before deciding on agent and what is first line)

A

pharmacotx indicated for moderate to severe depression

antidepressants w/wo adjunctive meds

consider target sx (eg. bupropion for if pt has low energy, mirtazapine for if pt has loss of appetite and insomnia), comorbids, ddi, prior response, preferences

first line is mirtazapine, SSRI, SNRI or bupropion

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20
Q

what are the tx phases for tx of depression

A
  1. acute phase: adequate trial = 4-8w at adequate dose
  2. continuation phase: continue for at least another 4m after acute phase (at least 6-12m total)
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21
Q

in the acute phase, how long does it take for physical sx and mood sx improve, why and what does it imply if pt does not show such improvements within that time frame

A

physical sx take 1-2w (sleep, appetite) -> if pt does not show response at 2w then they unlikely to improve in 4w/6w thus consider changing
mood sx take 4-8w

mood sx delayed improvement bc gradual down regulation of presynaptic autoreceptors in the synapse which in turns facilitate NT release

22
Q

in what ways does a signal transmission terminate

A
  1. enzyme breakdown of NT
  2. reuptake of NT into presynapse for breakdown or recycling
  3. presynaptic autoreceptor which acts as a negative feedback loop to regulate synthesis and release
23
Q

what are the classes of antidepressants and list the drugs in each class

A
  1. MAOi (monoamine oxidase inhibitor; irreversible and non selective): phenalzine
  2. TCAs (tricyclic antidepressants): [non selective for SERT/NET] amitriptyline, imipramine, clomipramine [selective for NET] desipramine
  3. SSRIs (selective 5HT reuptake inhibitor): fluoxetine, fluvoxamine, escitalopram, citalopram, paroxetine, sertraline
  4. SNRIs (selective NE reuptake inhibitor): venlafaxine, desvenlafaxine, duloxetine
  5. NaSSA (Noradrenergic and specific serotonergic antidepressant): mirtazapine
  6. RIMA (reversible inhibitor of monoamine oxidase): meclobemide
  7. NDRI (NE-domapine reuptake inhibitor): bupropion
  8. melatonin receptor agonist: agomelatin
  9. SARI (5HT antagonist and reuptake inhibitor): trazodone
  10. SMS (serotonin modulators and stimulators): vortioxetine
24
Q

identify the drug (drug class) and its additional indications if any (psychiatric related)

A

clomipramine (TCAs) for OCD

fluoxetine (SSRIs) for OCD

fluvoxamine (SSRIs) for OCD

escitalopram (SSRIs) for anxiety

paroxetine (SSRIs) for anxiety

citalopram (SSRIs) for panic

sertraline (SSRIs) for OCD, panic

venlafaxine (SNRIs) for GAD

duloxetine (SNRIs) for GAD

bupropion (NDRI) for smoking cessation

trazodone (SARI) for off label use in insomnia

meclobemide (RIMA) for social anxiety

25
Q

identify the drug (drug class) and its additional indications if any (non psychiatric related)

A

amitriptyline (TCAs): neuropathic pain, migraine prophylaxis

nortriptyline (TCAs): neuropathic pain

duloxetine (SNRIs): chronic MSK pain, diabetic neuropathy

26
Q

identify which TCA has secondary amine and which TCA has tertiary amine (and compare the s/e profile between secondary amine TCA vs tertiary amine TCAs)

A

amitriptyline is tertiary

imipramine is tertiary

clomipramine is tertiary

desipramine is secondary

nortriptyline is secondary

secondary amine TCAs have lower s/e profile

27
Q

how many metabolites does bupropion get metabolised into and identify the metabolites and relate this to its formulation

A

bupropion has three metabolites which are hydroxybupropion, threohydrobupropion, erythrohydrobupropion

bupropion dosed in daytime and space first and second dose 8h apart

bupropion has sustained release formulations

28
Q

which antidepressants (drug class) has long half life

A

fluoxetine (SSRIs) with half life of 4-6d; its active metabolite norfluoxetine has even longer half life of 40-60d

vortioxetine (SMS) with half life of 66h

29
Q

state the moa and s/e profile of TCAs

A

moa: inhibit reuptake of 5HT and NE, anticholinergic, H1 and alpha adrenergic antagonism

s/e: GI, sexual dysfunc, anticholinergic, sedation, weight gain, postural hypotension, arrhythmias, seizures

*fatal on overdose

note that secondary amine TCAs have lower s/e profile

30
Q

state the moa and s/e profile of SSRIs

A

moa: selectively inhibit reuptake of 5HT

s/e: GI s/e, sexual dysfunc, HA, transient nervousness during initiation, insomnia for fluoxetine, hypoNa, bleeding risk, EPSE

note that paroxetine is the most anticholinergic, sedating and incr weight and has short half life

note that escitalopram and citalopram has potential for QTc prolongation in elderly

31
Q

state the moa and s/e profile of SNRIs

A

moa: block reuptake of NE and 5HT

s/e: as per SSRI

note that venlafaxine can incr BP

note that duloxetine can cause urinary hesitation

32
Q

state the moa and s/e profile of SMS

A

a drug under SMS class is vortioxetine

moa: as for SSRI

s/e: as for SSRI

33
Q

state the moa and s/e profile of NaSSA

A

a drug under NaSSA class is mirtazapine

moa: causes incr in 5HT and NE, block alpha, 5HT2, 5HT3, H

s/e: (reverses GI s/e and sexual dysfunc) somnolence, incr appetite, weight gain

34
Q

state the moa and s/e profile of NDRI

A

a drug that is under NDRI class is bupropion

moa: block reuptake of NE and DA

s/e: (since no effect on 5HT, no GI s/e and no sexual dysfunc) seizure, insomnia, psychosis

note that bupropion not suitable for eating disorders

35
Q

state the moa and s/e profile of RIMA

A

a drug under RIMA class is meclobemide

moa: reversible inhibitor of monoamine oxidase

note that it is safest among MAOis

36
Q

state the moa and s/e profile of SARI

A

a drug under SARI class is trazodone

moa: block reuptake of 5HT, antag 5HT2A, H1, alpha1

s/e: as per SSRI, sedation, postural hypotension; rare s/e is priapism

note that it is more often used for insomnia than for depression

37
Q

state the moa and s/e profile of melatonin receptor agonist

A

a drug eg. would be agomelatin

moa: MT1 and MT2 agonist, antag of 5HT2C thus incr DA, NE

s/e: GI, incr LFTs

38
Q

what are the adjunctive tx with antidepressants

A
  1. SGA (ari, quet, brexipiprazole)
  2. PRN hypnotics (benzodiazepines, z-hypnotics, antihistamines)
39
Q

relate the type of 5HT receptor to the type of s/e

A

agonist of 5HT2 receptor causes s/e relating to sexual dysfunc

agonist of 5HT3 receptor relates to GI s/e (gastritis, N/V/D, stomach upset)

40
Q

what are the s/e of SSRIs

A

GI s/e (N/V/D, abdominal pain, gastritis), sexual dysfunc, bleeding risk, EPSE, hypoNa (SIADH), insomnia for fluoxetine, HA, transient nervousness during initiation

41
Q

what is the dosing for amitriptyline, clomipramine, fluoxetine, desvenlafaxine XR, mirtazapine (starting, dose range, max)

A

amitriptyline: 50-100mg/d; 30-300mg/d; 300mg/d

clomipramine: 25mg/d; 25-250mg/d; 300mg/d

fluoxetine: 20mg OM; 20-60mg/d; 80mg/d

desvenlafaxine XR: 50mg/d; 50mg/d; 100mg/d

mirtazapine: 15mg/d; 15-45mg/d; 45mg/d

42
Q

what are the various approaches to partial or no response

A
  1. switching
    i) switch to another antidepressant if ineffective or untolarable s/e in 2-4w; SNRI/ mirtazapine/ bupropion/ agomelatine/ vortioxetine
    *note if cross titrate, monitor for serotonin syndrome
    *note if direct switching, can stop current and start new
    *note washout period must have for MAOIs
    (a) if current is meclobemide, wash out for at least 24h
    (b) if switching to meclobemide, wash out for at least 1w (5w if switching to meclobemide from fluoxetine)
  2. augmenting
    i) add a second antidepressant with a diff moa (mirtazapine, bupropion SR)
    ii) adjunctive SGA (quet, ari, brexpiprazole)
  3. tx resistant: if at least 2 trials (adequate dose for 4-8w)
    i) neurostimulation through ECT/ rTMS
    ii) symbyax PO capsule which is a combi of olanzapine with fluoxetine
    iii) spravato nasal spray which is esketamine adjunctive to SSRI/SNRI
43
Q

what are the considerations for the various special populations (pregnant, breastfeeding, elderly, renal impairment, hepatic impairment, child/ young adults, postpartum depression, bipolar depression, post MI depression)

A

pregnant: nortriptyline (in late pregnancy)

breastfeeding: mirtazapine, setraline

elderly: avoid TCAs and minimise all s/e; SIADH (hypoNa sx incl confusion, drowsiness, convulsions) high risk in elderly and is assoc for all antidepressants but esp SSRIs and is lower risk for mirtazapine, bupropion, agomelatine *monitor serum Na at baseline, second week, forth week, q3m after

renal/ hepatic impairment: vortioxetine

child/ young adults: suicidaility assoc in 24yo and younger so req to counsel

postpartum depression: brexanolone

bipolar depression: lithium, LTG, lurasidone, quetiapine

post MI depression: sertraline

44
Q

list the antidepressant to be used or avoided when there are various medical comorbs present (underweight, neuropathic pain)

A

if underweight, use mirtazapine (incr appetite s/e)

if neuropathic pain, use TCAs or SNRIs (duloxetine licensed for diabetic neuropathy and chronic MSK pain)

45
Q

what are the c/i for bupropion

A

hx of seizures, psychosis, eating disorders

46
Q

what are the clinically significant ddi specifically for antidepressants (and what kind of ddi are they)

A

the ddi for antidepressants are PD related

  1. serotonin syndrome
  2. SSRIs incr risk of bleed (esp for elderly on NSAIDs, warfarin, steroids; consider adding PPI or switch to agomelatine bc safest)
  3. incr CNS depressants effects w alcohol and other CNS depressants
  4. anticholinergic agents can incr anticholinergic s/e
  5. st john’s wort (might be PK related ddi bc st john’s wort is a 3A4 inducer)
47
Q

what are the sx of serotonin syndrome (categorise into mild, moderate and severe)

A

mild: insomnia, N/D, anxiety, HTN, tachycardia, hyper-reflexia

moderate: tremor, myoclonus, agitation, flushing, diaphoresis, fever (<38.5)

severe: severe hyperthermia, respiratory failure, confusion, rigidity, coma, death

48
Q

what is the onset of serotonin syndrome and what are the drugs that can cause serotonin syndrome

A

6-8h

high dose serotonergic drugs eg.
i) triptans
ii) opioids (tramadol, fentanyl, pethidine), dextromethorphan
iii) linezolid, ritonavir
iv) MAOIs + serotonergic antidepressant (thus washout period necessary)

49
Q

which class of antidepressants incr risk of bleeding and which special population is most at risk and how to manage this risk

A

SSRIs

elderly on NSAIDs, warfarin, steroids

consider adding PPI, consider stopping serotonergic antidepressant 2w before surgery if high risk, consider switching to agomelatine which is the safest

50
Q

what are the pt counselling points for antidepressants

A
  1. antidepressants may take a couple of weeks to help with sx of low mood, poor appetite and sleep, may need couple of months to help with anxiety
  2. do not take with alcohol (space 4-6h)
  3. inform about other medications
  4. if condition is worsening or feel suicidal or bothered by s/e, contact doctor (suicide risk highest for children and young adults below age 24)
  5. possible s/e incl
    i) drowsiness (take at bedtime)
    ii) insomnia (take in the morning)
    iii) dizzy/ lightheadedness (stand up slowly)
    iv) stomach upset (take after food)
    v) changes in sexual func (less likely for mirtazapine, bupropion, agomelatine)
51
Q

what is the risk of discontinuing antidepressants abruptly and which antidepressants are more likely to cause this

A

can result in antidepressant discontinuation syndrome (not withdrawal)

esp paroxetine, venlafaxine

52
Q

what are the onset, duration and sx of antidepressant discontinuation syndrome, and how can it be prevented

A

onset: 36-72h
duration: 3-7d; typically resolve in 1-2w w/o tx

sx (mnemonic finish):
i) flu like sx (lethargy, fatigue, HA, achiness, sweating)
ii) insomnia (w vivid dreams or nightmares)
iii) N (sometimes V)
iv) imbalance (dizziness, vertigo, lightheadedness)
v) sensory disturbances (electric like sensations, tingling, burning)
vi) hyperarousal (anxiety, aggression, irritability, agitation, mania, jerkiness)

pt feel discomfort but not life threatening

taper gradually by half table lowest strength q1-2w if pt on regular dosing for more than 6-8w
*note that gradual tapering of fluoxetine and bupropion unnecessary due to long half life