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54 CNS > MDD > Flashcards

MDD Flashcards

1
Q

Suicide risk assessment

A
  1. Identifying & managing underlying disorders
  2. Identifying risk factors
  3. Identifying protective factors (or lack thereof)
  4. Removing means
  5. Activating support system
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2
Q

Suicide risk factors

A

a. Prior attempt
b. Past/current psychiatric disorder
c. Key symptoms: anhedonia, hopelessness, anxiety, impulsivity, aggression,
delusions
d. Family history (suicide, child maltreatment)
e. Stressors (humiliating events)
f. Access to medicine (overdose), firearms, pesticides, other lethal means

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3
Q

Columbia-Suicide Severity Rating Scale (C-SSRS) Q1

A

Have you wished you were dead or wished you could go to sleep and not wake up?

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4
Q

Columbia-Suicide Severity Rating Scale (C-SSRS) Q2

A

Have you had any actual thoughts of killing yourself?

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5
Q

Columbia-Suicide Severity Rating Scale (C-SSRS) Q3

A

Have you been thinking about (how) you might do this?

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6
Q

Columbia-Suicide Severity Rating Scale (C-SSRS) Q4

A

Have you had these thoughts and had some intention of acting on them?

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7
Q

Columbia-Suicide Severity Rating Scale (C-SSRS) Q5

A

Have you started to work out or have worked out the details of how to kill yourself?

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8
Q

Columbia-Suicide Severity Rating Scale (C-SSRS) Q6a

A

Have you done anything, or start to do anything, or prepared to do anything to end your life?

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9
Q

Columbia-Suicide Severity Rating Scale (C-SSRS) Q6b

A

If yes (to 6a), was this within the past 3 months?

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10
Q

Pathophysiology of MDD

A
  1. Hormonal influences: increase secretion of cortisol (major stress hormone)
  2. Monoamine hypothesis: decrease neurotransmitters in the brain (norepinephrine, serotonin, dopamine)
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11
Q

What was an important early evidence of monoamine theory?

A

Reserpine, which inhibits NE and 5-HT, depressed mood

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12
Q

Secondary causes for MDD

A
  1. Medical disorders
  2. Psychiatric disorder
  3. Drug-induced
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13
Q

What medical disorders can cause depression? (1)

A

Endocrine disorder: hypothyroidism, Cushing syndrome, T2DM (bidirectional association in women)

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14
Q

What medical disorders can cause depression? (2)

A

Deficiency states: anaemia, Werncikle’s encephalopathy

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15
Q

What medical disorders can cause depression? (3)

A

Infections: CNS infections, STD/HIV, TB

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16
Q

What medical disorders can cause depression? (4)

A

Metabolic disorders: electrolyte imbalance (decreased K+, Na+), hepatic encephalopathy

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17
Q

What medical disorders can cause depression? (5)

A

CV: CAD, CHF, MI

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18
Q

What medical disorders can cause depression? (6)

A

Neurological: AD, epilepsy, pain, PD, post-stroke

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19
Q

What medical disorders can cause depression? (7)

A

Malignancy

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20
Q

What psychiatric disorders can cause depression?

A

Alcoholism
Anxiety disorders
Eating disorders
Schizophrenia

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21
Q

Drug-induced depression

A

Lipid-soluble beta blockers
Psychotropics: CNS depressants (benzodiazepines, opioids, barbiturates), anticonvulsants, tetrabenazine
**Withdrawal from alcohol, stimulants
Corticosteroids, systemic
Isotretinoin
Interferon- ß-1a

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22
Q

DSM-5 for MDD (A)

A

At least 5 symptoms have been present during the same 2 week period and represent change from previous functioning
One of the symptoms must be depressed mood or loss of interest

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23
Q

What are the symptoms of MDD in DSM-5? (1)
In.SAD.CAGES

A

Interest: decreased interest and pleasure in normal activities

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24
Q

What are the symptoms of MDD in DSM-5? (2)
In.SAD.CAGES

A

Sleep: insomnia or hypersomnia

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25
Q

What are the symptoms of MDD in DSM-5? (3)
In.SAD.CAGES

A

Appetite: decreased appetite, weight loss

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26
Q

What are the symptoms of MDD in DSM-5? (4)
In.SAD.CAGES

A

Depressed: depressed mood

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27
Q

What are the symptoms of MDD in DSM-5? (5)
In.SAD.CAGES

A

Concentration: impaired concentration & decision making

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28
Q

What are the symptoms of MDD in DSM-5? (6)
In.SAD.CAGES

A

Activity: psychomotor retardation or agitation

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29
Q

What are the symptoms of MDD in DSM-5? (7)
In.SAD.CAGES

A

Guilt: feelings of guilt or worthlessness

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30
Q

What are the symptoms of MDD in DSM-5? (8)
In.SAD.CAGES

A

Energy: decreased energy or fatigue

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31
Q

What are the symptoms of MDD in DSM-5? (9)
In.SAD.CAGES

A

Suicidal thoughts or attempts

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32
Q

DSM-5 for MDD (B)

A

Symptoms cause significant distress or impairment in social, occupational, or other
important areas of functioning.

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33
Q

DSM-5 for MDD (C)

A

Symptoms are not caused by an underlying medical condition or substance.

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34
Q

Differential diagnosis (1)

A

Adjustment Disorder (with Anxiety and/or Depressed Mood)
Symptoms occur within 3 months of onset of a stressor; but once the stressor is terminated, symptoms do not persist for additional 6 months

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35
Q

Differential diagnosis (2)

A

Acute Stress Disorder
Symptoms occur within1 month of a traumatic event, and lasts 3 days – 1 month.
Symptoms include intense fear, helplessness, horror, with dissociation, re-experiencing, avoidance, increased arousal.

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36
Q

General assessment (1)

A

History of present illness

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37
Q

General assessment (2)

A

Psychiatric history
Any history of manic/ hypomanic episodes? (starting an antidepressant may cause “manic switch” in patients with underlying bipolar disorder)

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38
Q

General assessment (3)

A

Substance use history: Cigarettes/ETOH/substances

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39
Q

General assessment (4)

A

Complete medical & medication history

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40
Q

General assessment (5)

A

Family, social, forensics, developmental & occupational history

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41
Q

General assessment (6)

A

Physical & neurological exam

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42
Q

General assessment (7)

A

MSE for accurate diagnosis
- Assess suicidal/homicidal ideations and risks
- Reassess MSE on every interview to evaluate efficacy & tolerability

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43
Q

General assessment (8)

A

Labs
Vital signs, weight & BMI, FBC, U/E/Cr, LFTs, TFTs, ECG, FBG, lipid panel, urine toxicology

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44
Q

General assessment (9)

A

To exclude general medical conditions or substance-induced/withdrawal symptoms, e.g.
delirium/ psychosis/ depression/ mania/ anxiety/ insomnia/ thyroid disfunction/ diabetes

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45
Q

Gold standard rating scale

A

Hamilton Rating Scale for Depression
- By clinician
- Remission = HAM-D score ≤7 (therapy goal: symptom free)

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46
Q

Non-pharmacological

A
  1. Sleep hygiene
  2. Psychotherapy
  3. Neurostimulation (ECT, rTMS)
  4. Light therapy (for seasonal affective disorder)
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47
Q

1st line (antidepressant monotherapy)

A

Mirtazapine
SSRI
SNRI
Bupropion

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48
Q

Antidepressant indicated for ______ depression, not routinely indicated for _____ depression.

A

Moderate-severe
Mild

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49
Q

Antidepressants ± adjunctive meds selection is based on?

A

Target symptoms
Comorbidities
DDI
Prior response
Preference

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50
Q

Phases of treatment

A

i) acute phase
ii) continuation phase

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51
Q

What is considered adequate trial during acute phase treatment?

A

Adequate dose + duration (4-8 weeks)

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52
Q

What could cause delayed onset of effectiveness?

A

Gradual down-regulation of pre-synaptic auto receptors in synapse, which facilitates neurotransmitter release.

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53
Q

Time course of treatment response

A

Physical symptoms: 1-2 weeks to improve
Mood symptoms: 3-8 weeks (longer time)

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54
Q

Continuation phase duration

A

For 1st episode uncomplicated MDD: continue for at least another 4-9 months after acute phase treatment (total 6-12 months at least)

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55
Q

Examples of tricyclic antidepressants

A

Amitriptyline
Imipramine
Nortriptyline
Desipramine
Clomipramine

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56
Q

MOA of TCAs

A

Inhibits reuptake of serotonin and norepinephrine in presynaptic terminal, increasing concentration of these neurotransmitter in the synaptic cleft.

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57
Q

Which TCAs are non selective for 5-HT & NE neurotransmitters?

A

Imipramine, Amitriptyline, Nortriptyline

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58
Q

Which TCAs are selective for NE neurotransmitters?

A

Desipramine

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59
Q

Which is a 2nd generation TCA?

A

Secondary amines:
Nortriptyline
Desipramine

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60
Q

What receptors do TCAs have affinity to, causing AEs?

A

H1 histamine receptor antagonism
a1-adrenoceptor sympathetic block
Muscarinic receptor antagonism

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61
Q

AEs of TCAs

A

H1: sedation (can develop in 1-2 weeks)
a1: postural hypotension (dose related)
M1: dry mouth, blurred vision, constipation

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62
Q

Cautions in TCAs

A

Patients with history of MI: QTc prolongation, tdp
CV: cardiac conduction delays, heart block, arrhythmias

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63
Q

Which TCA can be used for OCD (other than depression)?

A

Clomipramine

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64
Q

Examples of SSRI

A

Fluoxetine
Fluvoxamine
Escitalopram
Citalopram
Paroxetine
Sertraline

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65
Q

Which is the least favourite SSRI?

A

Sertraline

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66
Q

Why do SSRIs have fewer AEs than TCAs?

A

Have a low affinity for other receptors including alpha1-adrenergic (α1), histaminic (H1), and muscarinic (M1) receptors

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67
Q

Fluoxetine approximately ___ folds selectivity for 5HT

A

50

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68
Q

Citalopram approximately ___ folds selectivity for 5HT

A

1000

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69
Q

What tolerability issues of TCA can affect its adherence?

A

Weight gain, sexual dysfunction

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70
Q

TCA is ______ on overdose.

A

Fatal

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71
Q

Most common dose-dependent tolerability issue of SSRI

A

Limited to 1-2 weeks after initiation or dose increase: GI symptoms
Somnolence, insomnia

72
Q

Which SSRIs have long t1/2?

A

Fluoxetine: 4-6 days
Norfluoxetine: 4-16 days

73
Q

Administration for Sertraline

A

Take with food to increase absorption

74
Q

Which SSRI has more anticholinergic and antihistaminergic activity linked with increased sedation and weight gain?

A

Paroxetine
Citalopram

75
Q

Which SSRI has short t1/2?

A

Paroxetine - withdrawal symptoms

76
Q

Which SSRI can cause QTc prolongation if high dose in elderly?

A

Escitalopram/Citalopram

77
Q

What tolerability issues of SSRIs can affect its adherence?

A

GI, sexual dysfunction

78
Q

Examples of SNRIs

A

Venlafaxine (Desvenlafaxine - metabolite of Venlafaxine)
Duloxetine

79
Q

MOA of SNRIs

A

Inhibits reuptake of serotonin and norepinephrine in presynaptic terminal, increasing concentration of these neurotransmitter in the synaptic cleft.

80
Q

Venlafaxine and its primary active metabolite, desvenlafaxine, inhibit ____ reuptake at low doses, and ___ reuptake at higher doses.

A

5-HT, NE

81
Q

Advantages of SNRIs

A

Claimed to work slightly faster than other anti-depressants and better in treatment-resistant patients

82
Q

AEs of SNRIs

A

Same as SSRIs

83
Q

Which SNRI increases BP?

A

Venlafaxine

84
Q

Which SNRI causes urinary hesitation?

A

Duloxetine

85
Q

What SNRI is indicated for diabetic peripheral neuropathy, fibromyalgia and chronic musculoskeletal pain?

A

Duloxetine

86
Q

What to use for treatment resistant depression (TRD)?

A

Symbyax: Olanzapine 6mg + Fluoxetine 25mg

87
Q

MOA of serotonin modulator and simulator (SMS)

A

Agonist activity at the 5-HT1A receptor
Partial agonist activity at the 5-HT1B receptor
Antagonism at the 5-HT1D, 5-HT7, and 5-HT3 receptors

88
Q

Example of SMS

A

Vortioxetine

89
Q

AEs of SSRI

A

GI & sexual dysfunction.
Headache, transient nervousness during initiation
Hyponatremia (SIADH)
Bleeding risk; EPSE

90
Q

NaSSA

A

Norepinephrine and specific serotonin antidepressant

91
Q

What drug class is Mirtazapine?

A

NaSSA

92
Q

MOA of Mirtazapine

A

a. Enhances central noradrenergic and serotonergic activity through the antagonism of central presynaptic α2-adrenergic autoreceptors and heteroreceptors.
b. Antagonizes postsynaptic 5-HT2, 5-HT3, and H1 receptors resulting in anxiolytic, anti-nausea, and sedative effects, respectively.

93
Q

Side effects of Mirtazapine

A

Somnolence
Increase appetite
Weight gain

94
Q

Advantages of Mirtazapine

A

Reverse GI & sexual dysfunction

95
Q

What drug class is Bupropion?

A

Norepinephrine-dopamine reuptake inhibitor (NDRI)

96
Q

MOA of NDRI

A

No appreciable effect on the 5-HT reuptake
Inhibits both the NE and DA reuptake

97
Q

When is NDRI useful?

A

Older adult patient - decreased motivation, low energy, fatigue

98
Q

Side effects of NDRI

A

Seizure
Insomnia
Psychosis

99
Q

When is NDRI unsuitable?

A

Eating disorder (imbalance of electrolytes can cause seizures)

100
Q

Function of monoamine oxidase (MAO)

A

Breaks down monoamines (NE, 5-HT, DA)

101
Q

Where are MAO found?

A

Nearly in all tissue
Intracellularly, mostly on mitochondrial surface

102
Q

What is 5-HT broken down by?

A

Mainly MAO-A

103
Q

What is NE broken down by?

A

Both MAO-A & B

104
Q

What is DA broken down by?

A

Both MAO-A & B

105
Q

Non-selective irreversible inhibitors of MAO-A & B

A

Isocarboxazid
Phenelzine
Tranylcypromine

106
Q

AEs of Isocarboxazid, Phenelzine, Tranylcypromine

A

Hypertensive crisis

107
Q

Why is tyramine restriction necessary?

A

Tyramine is usually metabolized by MAO-A in the gut and not absorbed into systemic circulation where it acts as a potent vasoconstrictor. Oral MAOIs block gut MAO-A resulting in absorption of tyramine.

108
Q

Selegiline transdermal patch

A

Irreversible MAO-B inhibition

109
Q

Which is the safest MAOi?

A

Moclobemide

110
Q

Moclobemide

A

Reversible MAO-A inhibition

111
Q

AEs of MAOi (1)

A

Postural hypotension
Due to sympathetic block produced by
accumulation of dopamine in the cervical (neck)
ganglia, where is acts as an inhibitory transmitter

112
Q

AEs of MAOi (2)

A

Restlessness & insomnia
Due to CNS stimulation

113
Q

MOA of tyramine

A

Taken up into adrenergic terminal, competes with norepinephrine for vesicular compartment, increase release of norepinephrine into synapses

114
Q

Any antidepressant that increases serotonergic neurotransmission can be associated with _____.

A

Serotonin syndrome (especially increase release or duration of serotonin activity)

115
Q

Serotonin syndrome symptoms

A

Mental status changes, autonomic instability, and neuromuscular abnormalities (eg, hyperreflexia, myoclonus)

116
Q

MOA of Trazodone

A

Blocks reuptake of 5-HT;
Antagonizes 5-HT2A,H1 and a1 adrenoceptor

117
Q

MOA of Trazodone

A

Blocks reuptake of presynaptic 5-HT;
Antagonizes postsynaptic 5-HT2A, H1 and a1 adrenoceptor

118
Q

When is Trazodone more likely used for rather than depression?

A

Insomnia

119
Q

SE of Trazodone

A

Priapism

120
Q

MOA of Agomelatine

A

MT-1, MT-2 agonist
5-HT-2C antagonist
Increases DA and NE

121
Q

What monitoring is required for Agomelatine?

A

LFTs

122
Q

Contraindications of Agomelatine

A

Fluvoxamine
Ciprofloxacin
Both are strong inhibitors of the enzyme, increasing [agomelatine]

123
Q

Adjunctive treatment for MDD

A
  • SGA (Aripiprazole, Brexpiprazole, Quetiapine XR)
  • Esketamine (NMDA receptor antagonist)
  • PRN hypnotics
124
Q

Esketamine dosing

A

1 session: 56mg or 84mg (lower in elderly)

125
Q

Esketamine frequency

A

W1-4: 2 sessions/week
W5-8: 1 session/week
>W9: 1 session every 1-2 week, for at least 6 months

126
Q

Benzodiazepines

A

Lorazepam
Potentiates GABA
Has dependence

127
Q

Z-hypnotics

A

Zopiclone
Zolpidem CR
Preferentially binds to benzodiazepine-binding sites with Y and a1 subunits (causes sedation).

128
Q

SEs of Z-hypnotics

A

Drowsiness
Taste disturbance (Zopiclone)
Complex sleep behaviors (sleep-walking)
Dependence

129
Q

Maximum dose of Amitriptyline

A

300mg/day

130
Q

Maximum dose of Clomipramine

A

300mg/day

131
Q

Starting dose of Fluoxetine

A

20mg OM

132
Q

Maximum dose of Fluoxetine

A

80mg/day

133
Q

Usual dose of Mirtazapine

A

15-45mg/day

134
Q

Therapeutic Lifestyle/Behavioral Changes

A
  1. Sleep Hygiene
  2. Exercise
  3. Relaxation techniques
135
Q

Nutritional

A
  • Vit. B12
    – L-methylfolate
    – Vit. D
    – S-adenosylmethionine (SAMe)
    – Omega-3 fatty acids
    – 5-hydroxytryptophan (5-HTP)
136
Q

Herbal

A

St John’s Wort
- Significant drug interactions with antidepressant
- Do not use concomitantly

137
Q

Approaches to manage partial/no response (A)

A

Switch when completely ineffective or intolerable to adequate dose in 2-4w
(e.g. SSRI switched to SNRI, Mirtazapine, Bupropion, Agomelatine, or Vortioxetine)

138
Q

Precautions during cross-titration

A

Watch for serotonin syndrome if combining serotonergic agents

139
Q

Precautions when switching from serotoninergic antidepressant to non-serotoninergic antidepressant

A

Antidepressant Discontinuation Syndrome
- Gradual cross tapering over several weeks

140
Q

What is needed when switch involves MAOi?

A

Wash-out period

141
Q

Switch from Moclobemide to another antidepressant

A

24 hours wash out

142
Q

Switch from another antidepressant to Moclobemide

A

Wash out at least 1 week
Wash out at leas 5 weeks if stopping Fluoxetine

143
Q

Approaches to manage partial/no response (B)

A

Augmentation

144
Q

How to augment?

A

Combine 2nd antidepressant with different MOA (must have partial response)
+ Mirtazapine, Bupropion-SR, T3 (Liothyronine), Lithium
Adjuctive SGAs: Quetiapine XR, Aripiprazole, Brexpiprazole

145
Q

TRD (no response to ≥ 2 adequate trials of antidepressants)

A
  1. Neurostimulation: Electroconvulsive Therapy, repetitive Transcranial Magnetic Stimulation
  2. Symbyax® Oral Capsule (Olanzapine 6mg + Fluoxetine 25mg per Cap)
  3. Spravato® Nasal Spray (Esketamine 28mg per vial), as adjunct to SSRI/SNRI treatment.
146
Q

Pregnancy

A

Consider Nortriptyline in late pregnancy (>28 weeks)

147
Q

Breast feeding

A

Sertraline
Mirtazapine

148
Q

PP depression

A

Brexanolone

149
Q

Renal impairment

A

Vortioxetine

150
Q

Hepatic impairment

A

Avoid Agomelatine
Mild-moderate: Vortioxetine

151
Q

Post-MI depression

A

Sertraline

152
Q

Elderly

A

Avoid TCAs

153
Q

Hyponatremia

A

SIADH (usually in elderly)
ALL antidepressant, mostly SSRIs
Possibly lower risk with Agomelatine, Mirtazapine or Bupropion.

154
Q

What to monitor for hyponatremia?

A

Serum Na at baseline, 2nd week, 4th week, then 3-monthly.

155
Q

Common serotonergic agents (other than antidepressants)

A

Triptans
Sibutramine
Opioids (Tramadol, Fentanyl, Pethidine)
Dextromethorphan
Linezolid, Ritonavir (e.g. in Paxlovid®)
MAOI

156
Q

SSRIs increases risk of _____________?

A

Bleeding.
Higher risks in elderly on NSAIDs, warfarin, steroids -> consider adding PPI

157
Q

If patient has a scheduled surgery, which antidepressants require cautions?

A

Consider stopping serotonergic antidepressant 2 weeks before surgery if high bleeding risks

158
Q

Which antidepressant is safest for patients with high bleeding risks?

A

Agomelatine

159
Q

Drugs with fewer CYP interactions

A

Mirtazapine, Escitalopram, Venlafaxine, Desvenlafaxine, Vortioxetine

160
Q

Which drugs has more apparent antidepressants discontinuation syndrome?

A

Paroxetine
Venlafaxine

161
Q

What drug class is Paroxetine?

A

SSRI

162
Q

What drug class is Venlafaxine?

A

SNRI

163
Q

When does antidepressants discontinuation syndrome happens?

A

Abruptly stopping a regular treatment

164
Q

Symptoms of ADS (Finish)

A

Flu-like symptoms (lethargy, fatigue, headache, achiness, sweating)

164
Q

Symptoms of ADS (fInish)

A

Insomnia (with vivid dreams or nightmares)

165
Q

Symptoms of ADS (fiNish)

A

Nausea (sometimes vomiting)

166
Q

Symptoms of ADS (finIsh)

A

Imbalance (dizziness, vertigo, light-headedness)

167
Q

Symptoms of ADS (finiSh)

A

Sensory disturbances (“burning,” “tingling,” “electric-like” sensations)

168
Q

Symptoms of ADS (finisH)

A

Hyperarousal (anxiety, irritability, agitation, aggression, mania, jerkiness)

169
Q

Onset of ADS

A

36-72 hours

170
Q

Duration of ADS

A

3 - 7 days, typically resolve over 1-2 weeks without treatment

171
Q

How to avoid ADS?

A

Gradually tapering

172
Q

Which drugs do not require gradual tapering?

A

Fluoxetine
Bupropion
Due to long t1/2.

173
Q

Patient counselling (1)

A

Antidepressants may take at least a couple of weeks to help with symptoms of low mood, poor sleep and appetite, may need at least a couple of months to help with anxiety

174
Q

Patient counselling (2)

A

Do not take at same time as alcohol (space 4-6 hours part)

175
Q

Patient counselling (3)

A

Tell your Drs & nurses what other medicines you are using

176
Q

Patient counselling (4)

A

If your condition is worsening, or if you feel suicidal or bothered by side effects, contact Dr
(Suicide risk highest for children & adolescents ≤ 24 years old, hence need to monitor closely)

54 CNS (13 decks)

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