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depression Flashcards

1
Q

What are the symptoms exhibited by a patient suffering from major depressive disorder as defined in DSM-5

A

In.SAD.CAGES. At least 5 symptoms present during the same 2 weeks period. One of the symptoms must be depressed mood or loss of interest

Symptoms causes significant distress and impairment in important areas of functioning

Symptoms NOT causes by underlying medical condition or substance abuse

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2
Q

What are the symptoms of In.SAD.CAGES

A

1) Loss of interest/ Decreased interest
2) Sleep: Poor sleep or excessive sleep
3) Appetite: Loss of appetite, weight loss
4) Depressed: Depressed mood in adults (Irritable mood in children)
5) Concentration: Impaired concentration and decision making
6) Activity: Pyschomotor retardation or agitation
7) Guilt: Feelings of guilt or worthlessness
8) Energy: Decreased energy or fatigue
9) Suicidal thoughts or attempts

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3
Q

What are the risk factor for suicide in the general population?

A

1) Previous attempts
2) Isolation
3) Poor health (Physical/mental comorbidities)
4) Poor wealth status
5) Male
6) Elderly

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4
Q

What are the neurotransmitters involved in depression?

A

1) Norepinephrine
2) Serotonin
3) Dopamine

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5
Q

What are the hormonal influences that can cause depression?

A

Increased secretion of cortisol (major stress hormone)

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6
Q

What are the secondary (Medical) causes for depression?

A

1) Endocrine disorder: Hypothyroidism
2) Cardiovascular: CAD, CHF, MI, ACS
3) Infections
4) Deficiency states
5) Neurological: Alzheimer’s, Epilepsy, Parkinson’s
6) Malignancy

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7
Q

What are the drug induced causes for depression?

A

1) Lipid-soluble beta blockers
2) Psychotropics: CNS depressants
3) Withdrawal from alcohol, stimulants
4) Systemic corticosteroids
5) Isotretinoin
6) Interferon-beta-1a

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8
Q

What are the relevant pt’s history to take prior to diagnosis and treatment?

A

1) Psychiatric hx
2) Substance use hx
3) Complete med and medications hx
4) Family, social, occupational, developmental hx
5) Hx of present illness

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9
Q

What must be assessed prior to diagnosis and treatment?

A

Assess suicidal/ Homicidal ideations and risks during mental state exam (MSE)

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10
Q

What is the “gold-standard” for clinician-rated psychiatric rating scales?

A

Hamilton rating scale for depression (HAM-D)

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11
Q

What is the remission criteria for HAM-D?

A

HAM-D score smaller or equal to 7.

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12
Q

How does PHQ-9 categorised severity of depression?

A 
Score:
1-4 : Minimal symptoms
5-9: Mild depression
10-14: Moderate
15-19: Moderately-severe
More than or equal to 20: Severe
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13
Q

At which PHQ-9 score is antidepressant recommended

A

For score 10 and above

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14
Q

What are the non-pharmacological managements for depression?

A

1) Sleep hygiene
2) Psychotherapy
3) Neurostimulation: Electroconvulsive treatment/ Repetitive transcranial magnetic stimulation

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15
Q

What are the first line medications for depression?

A

1) SSRI
2) SNRI
3) Mirtazapine or Bupropion

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16
Q

How many phases are there in the treatment of depression?

A

1) Acute phase

2) Continuation phase

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17
Q

Describe the acute phase treatment

A

1) Adequate trial = Adequate dose + duration
2) 4 - 8 weeks, maximum 12 weeks
3) Physical symptoms may improve in 1-2 weeks, mood symptoms may take 4-6 weeks to improve

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18
Q

Describe the continuation phase treatment

A

For the 1st episode of MDD, continue at least 4-9 months after acute-phase treatment

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19
Q

How long will depression treatment take?

A

Initiation + Acute phase + Continuation phase = 6-12 months

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20
Q

What are the different antidepressant classes?

A

1) Selective Serotonin Reuptake Inhibitor (SSRI)
2) Serotonin-Norepinephrine reuptake inhibitor (SNRI)
3) Tricyclic antidepressant (TCA)
4) Reversible MAOI
5) Noradrenergic and specific serotonergic antidepressant (NaSSA)
6) Others (Melatonin receptor agonist, Serotonin antagonist and reuptake inhibitor, Norepinephrine-Dopamine reuptake inhibitor)
7) Serotonin Modulators and Stimulators (SMS)

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21
Q

Why does mood symptoms take longer to improve?

A

This is due to time needed to downregulate the presynaptic monoamine autoreceptors

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22
Q

What is Duloxetine indicated for?

A

Depression and GAD

Diabetic neuropathy, stress urinary incontinence, fibromyalgia and Chronic musculoskeletal pain

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23
Q

Which drugs are in the TCA class?

A

1) Amitriptyline –> Nortriptyline
2) Imipramine –> Desipramine
3) Dothiepin
4) Clomipramine

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24
Q

MOA of TCA?

A

They block the reuptake of NE and 5-HT in the synapses

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25
Q

What are the SE of TCAs?

A

1) Sexual dysfunction
2) Anticholinergic (Constipation, dry mouth, blurred vision, urinary retention)
3) Orthostatic hypotension
4) Sedation, weight gain
5) Arrhythmias
6) Seizure
7) Fatal on OD

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26
Q

What is Clomipramine indicated for apart from depression?

A

1) OCD

2) Cateplexy associated with narcolepsy

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27
Q

Which TCAs have lesser anticholinergic, sedation and cardiotoxic SEs?

A

Secondary amines such as Nortriptyline and Desipramine

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28
Q

Starting doses for Amitriptyline?

A

50 - 100mg/day

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29
Q

Usual dose/ day for amitriptyline and Clomipramine?

A

Ami: 30 -300mg/day

Clomi: 25-250mg/day

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30
Q

Max dose for Amitriptyline and Clomipramine?

A

300mg for both

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31
Q

Starting dose for Clomipramine?

A

25mg /day

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32
Q

Which drugs are in the SSRI class?

A

1) Fluoxetine
2) Fluvoxamine
3) Escitalopram
4) Citalopram
5) Paroxetine
6) Sertraline

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33
Q

Which SSRI has the long half-life?

A

Fluoxetine (4-6 days)

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34
Q

What is the MOA of SSRI?

A

Selective Serotonin reuptake inhibitor

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35
Q

SEs of SSRI?

A

1) Sexual dysfunction
2) GI side effects (N/V, diarrhoea)
3) Increased bleeding risk
4) EPSE
5) Insomnia (Fluoxetine specific)
6) Hyponatremia via SIADH
7) Headache and transient nervousness at initiation
8) QTc prolongation (arrhythmia) in elderly at high dose (Escitalopram/ Citalopram)
9) Sedation/ Anti-cholinergic (Paroxetine)

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36
Q

Special administration instruction for Sertraline?

A

Take with food

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37
Q

Which SSRI has the most SE?

A

Paroxetine. Most sedating, most anti-cholinergic, causes weight gain and risk of withdrawal due to short half life

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38
Q

Which SSRIs are indicated for OCD?

A

1) Fluoxetine
2) Fluvoxamine
3) Sertraline

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39
Q

Which SSRIs are indicated for anxiety disorder?

A

1) Escitalopram

2) Paroxetine

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40
Q

Which SSRIs are indicated for panic disorder?

A

1) Citalopram

2) Sertraline

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41
Q

Which SSRI is indicated for Bulimia nervosa?

A

Fluoxetine

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42
Q

Starting dose of Fluoxetine?

A

20 mg OM

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43
Q

Usual dose and max dose for Fluoxetine?

A

20-60mg/day

Max: 80mg

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44
Q

Which drugs are in SNRI class?

A

1) Venlafaxine
2) Desvenlafaxine
3) Duloxetine
4) Levomilnacipran (??)

45
Q

Which SNRIs are used in GAD?

A

1) Venlafaxine

2) Duloxetine

46
Q

MOA of SNRI?

A

Dual action. Serotonin and Norepinephrine reuptake inhibitor

47
Q

SE of SNRI?

A

1) Increased BP
2) Urinary retention (Duloxetine)
3) GI side effects
4) Sexual dysfunction
5) Headache
6) Transient headache @ initiation
7) Bleeding risk
8) EPSE

48
Q

Starting dose of Duloxetine?

A

60mg/day

49
Q

Usual /Max dose of Duloxetine?

A

30 - 60 mg/day

120 mg/day

50
Q

Starting dose of Desvenlafaxine?

A

50mg /day

51
Q

Usual/Max dose of Desvenlafaxine?

A

50mg/day

100mg/day

52
Q

Starting dose of Venlafaxine?

A

75mg/day

53
Q

Usual/Max dose of Venlafaxine?

A

75 - 225mg/day

375mg/day

54
Q

MOA of Mirtazapine?

A

Noradrenergic/ Specific Serotonergic antidepressant

alpha-2-adrenoceptor antagonist, 5-HT(2/3) antagonist

55
Q

Starting dose of Mirtazapine?

A

15mg/day

56
Q

Usual/Max dose of Mirtazapine?

A

15-45mg/day

45mg/day

57
Q

SE of Mirtazapine

A

1) Increase appetite
2) Weight gain
3) Drowsiness

58
Q

What are the benefits of Mirtazapine over SSRIs/SNRI?

A

Reverse sexual and GI side effect of SSRI/SNRI

59
Q

How does Mirtazapine reverse sexual and GI side effect of SSRI/SNRI

A

By antagonising 5-HT2 (Sexual dysfunction) and 5-HT3 (GI side effect)

60
Q

MOA of Bupropion?

A

It is a norepinephrine/ dopamine reuptake inhibitor.

61
Q

SEs of Bupropion?

A

1) Seizure
2) Insomnia
3) Psychosis

62
Q

Starting dose of Bupropion?

A

150mg OM x 4d, then BD

63
Q

Usual/Max dose of Bupropion?

A

150mg BD

300MG (2 divided doses)

64
Q

What is bupropion indicated for?

A

Depression

Smoking cessation

65
Q

What drugs are in SMS class?

A

1) Vortioxetine

2) Vilazodone

66
Q

What is the MOA of SMSs?

A

Similar to SSRI, vortioxetine is also 5-HT1A agonist, while vilazodone is a 5-HT1A partial agonist

67
Q

SEs of SMSs?

A

1) Similar to SSRI

68
Q

What is the drug in reversible MAOI class?

A

Moclobemide

69
Q

What is Moclobemide useful for?

A

Atypical depression

70
Q

SEs of MAOI?

A

1) Hypertensive crisis
2) Anxiety
3) Arrhythmias
4) CVA
5) Weight gain
6) Sexual dysfunction

71
Q

How long is the washout period for Moclobemide?

A

If switching from Moclobemide: 24hrs

If switching to Moclobemide: 1 week (5 weeks for Fluoxetine)

72
Q

Starting dose of Moclobemide?

A

300mg/day in divided doses

73
Q

Usual/Max dose of Moclobemide?

A

150-600mg/day

600mg

74
Q

MOA of MAOIs?

A

Increase availability of monoamines by inhibiting monoamine oxidase, which breaks down monoamine

75
Q

What class is Trazodone in?

A

Serotonin antagonist and reuptake inhibitor

76
Q

MOA of Trazodone?

A

Blocks reuptake of 5-HT, antagonizes 5-HT2A receptors

77
Q

SE of Trazodone?

A

1) Similar to SSRI
2) Sedation (H1 antagonism)
3) Orthostatic hypotension (a1-adrenoceptor antagonism)
4) Priapism (Rare SE)

78
Q

Indication of Trazodone?

A

Depression, off-label for insomnia. Trazodone is used more for insomnia than depression

79
Q

MOA of Agomelatine?

A

Melatonin receptor (MT-1, MT-2) agonist

5-HT2C antagonist

80
Q

SE of Agomelatine?

A

1) GI side effects

2) Increased LFTs, check LFT at baseline and at week 3,6,12,24

81
Q

Which drugs are contraindicated with concurrent use of Agomelatine?

A

1) Fluvoxamine

2) Ciprofloxacin

82
Q

What are the classes of adjunctive medications use in treatment of depression?

A

1) Benzodiazepines
2) Z-hypnotics
3) Antihistamines
4) Melatonin receptor agonist
5) Second generation antipsychotics
6) Esketamine

83
Q

Which benzodiazepines are used as adjunct? State dose

A

1) Lorazepam PO 0.5-2mg at bedtime PRN

2) Diazepam PO 2-15mg at bedtime PRN

84
Q

How long should the course of benzodiazepines be?

A

2 weeks PRN

85
Q

Which Z-hypnotics is used as adjunct? State dose

A

1) Zolpidem PO 10mg or 6.25-12.5mg at bedtime PRN (Adult)

Female: Half dose

Elderly: PO 5mg at bedtime PRN

2) Zopiclone PO 7.5mg at bedtime PRN

Elderly: PO 3.75mg at bedtime PRN (increase if necessary)

86
Q

Side effect of Zopiclone?

A

Taste disturbances

87
Q

Which antihistamine are used as adjunct? State dose

A

1) Hydroxyzine
2) Promethazine

PO 25-50mg ON PRN for both

88
Q

Which antipsychotic are used as adjunct for MDD?

A

1) Aripiprazole,
2) Brexpiprazole
3) Quetiapine XR

89
Q

Which antipsychotic are used as adjunct for treatment resistant depression (TRD)? State dose

A

Symbyax (Olanzapine 6mg + Fluoxetine 25mg)

90
Q

What is Esketamine indicated for?

A

Adjunct to SSRI/SNRI for TRD

91
Q

Which herb should not be used concomitantly with antidepressants?

A

St John’s wort

92
Q

What are the treatment options for Treatment resistant depression?

A

1) Neurostimulation (Electroconvulsive therapy, repetitive transcranial magnetic stimulation)
2) Symbyax
3) Spravato (Esketamine 28mg nasal spray) as adjunct to SSRI/SNRI

93
Q

What can be combined to the existing antidepressant with a partial response?

A

1) Mirtazapine
2) Bupropion-SR
3) T3 (Liothyronine)
4) Lithium
5) SGA: Brexpiprazole, Quetiapine, Aripiprazole

94
Q

Which antidepressants/SE should be avoided in elderly?

A

1) TCA
2) Anticholinergic
3) CNS
4) Hypotensive
5) Cardiac SE

95
Q

What are the symptoms of hyponatremia?

A

1) Drowsiness
2) Confusion
3) Convulsion

96
Q

Which drug leads to higher risk of hyponatremia? Which drug has a lower risk?

A

Higher risk: SSRI

Lower risk: Bupropion, Mirtazapine, Agomelatine

BUT hyponatremia is associated with all antidepressants

97
Q

Suicidality is associated with?

A

Patient ≤ 24 years old, must counsel patients

98
Q

What causes serotonin syndrome?

A

Concomitant rx of high-dose serotonergic meds

99
Q

Serotonergic agent + Serotonergic agent = ?

A

Serotonin syndrome

100
Q

What increases risk of bleeding with SSRIs?

A

Elderly on NSAIDs, warfarin, steroids. Consider adding PPI

101
Q

What are the significant DDI with antidepressant

A

1) Alcohol and other CNS depressant (Benzo)
2) NSAIDs, Warfarin, Steroid
3) Serotonergic agents
4) Anticholinergic agents
5) Hepatic enzyme (specifically 2D6/3A4) inhibitors/ inducers

102
Q

Which antidepressants are potent CYP inhibitors

A

1) Fluvoxamine (CYP1A2, 2C19)
2) Fluoxetine (CYP2D6)
3) Paroxetine (CYP2D6)
4) Bupropion (CYP2D6)

103
Q

Which antidepressants have lesser CYP interactions?

A

1) Mirtazapine
2) Escitalopram
3) Venlafaxine
4) Desvenlafaxine
5) Vortioxetine
6) Levomilnacipran

104
Q

What are the symptoms of antidepressant discontinuation syndrome

A

F.I.N.I.S.H

1) Flu-like symptoms
2) Insomnia
3) Nausea
4) Imbalance (Dizziness)
5) Sensory (“electric shock” sensations, paresthesia)
6) Hyperarousal (Anxiety, agitation)

105
Q

How to prevent antidepressant discontinuation syndrome?

A

If patient is on long-term treatment (daily tx ≥ 8 weeks), gradually taper over 4 weeks. Taper by 25% every 1-2 week.

106
Q

Which antidepressants do not need gradual tapering upon discontinuation? Why?

A

1) Fluoxetine
2) Bupropion

Due to their long half-life

107
Q

Goals of depression treatment?

A

1) Remission of symptoms
2) Treatment adherence
3) Suicide prevention

108
Q

Rank the antidepressant class according to relevance in clinical practice

A

1) SSRI, SNRI, NaSSA
2) Bupropion
3) Agomelatine, Vortioxetine
4) TCA
5) MAOIs

109
Q

Patients with history of ____ should avoid using Bupropion

A

1) Eating disorder
2) Psychosis
3) Seizures

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