MDD Flashcards
(177 cards)
1
Q
Suicide risk assessment
A
- Identifying & managing underlying disorders
- Identifying risk factors
- Identifying protective factors (or lack thereof)
- Removing means
- Activating support system
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
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?
4
Q
Columbia-Suicide Severity Rating Scale (C-SSRS) Q2
A
Have you had any actual thoughts of killing yourself?
5
Q
Columbia-Suicide Severity Rating Scale (C-SSRS) Q3
A
Have you been thinking about (how) you might do this?
6
Q
Columbia-Suicide Severity Rating Scale (C-SSRS) Q4
A
Have you had these thoughts and had some intention of acting on them?
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?
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?
9
Q
Columbia-Suicide Severity Rating Scale (C-SSRS) Q6b
A
If yes (to 6a), was this within the past 3 months?
10
Q
Pathophysiology of MDD
A
- Hormonal influences: increase secretion of cortisol (major stress hormone)
- Monoamine hypothesis: decrease neurotransmitters in the brain (norepinephrine, serotonin, dopamine)
11
Q
What was an important early evidence of monoamine theory?
A
Reserpine, which inhibits NE and 5-HT, depressed mood
12
Q
Secondary causes for MDD
A
- Medical disorders
- Psychiatric disorder
- Drug-induced
13
Q
What medical disorders can cause depression? (1)
A
Endocrine disorder: hypothyroidism, Cushing syndrome, T2DM (bidirectional association in women)
14
Q
What medical disorders can cause depression? (2)
A
Deficiency states: anaemia, Werncikle’s encephalopathy
15
Q
What medical disorders can cause depression? (3)
A
Infections: CNS infections, STD/HIV, TB
16
Q
What medical disorders can cause depression? (4)
A
Metabolic disorders: electrolyte imbalance (decreased K+, Na+), hepatic encephalopathy
17
Q
What medical disorders can cause depression? (5)
A
CV: CAD, CHF, MI
18
Q
What medical disorders can cause depression? (6)
A
Neurological: AD, epilepsy, pain, PD, post-stroke
19
Q
What medical disorders can cause depression? (7)
A
Malignancy
20
Q
What psychiatric disorders can cause depression?
A
Alcoholism
Anxiety disorders
Eating disorders
Schizophrenia
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
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
23
Q
What are the symptoms of MDD in DSM-5? (1)
In.SAD.CAGES
A
Interest: decreased interest and pleasure in normal activities
24
Q
What are the symptoms of MDD in DSM-5? (2)
In.SAD.CAGES
A
Sleep: insomnia or hypersomnia
25
What are the symptoms of MDD in DSM-5? (3)
In.SAD.CAGES
Appetite: decreased appetite, weight loss
26
What are the symptoms of MDD in DSM-5? (4)
In.SAD.CAGES
Depressed: depressed mood
27
What are the symptoms of MDD in DSM-5? (5)
In.SAD.CAGES
Concentration: impaired concentration & decision making
28
What are the symptoms of MDD in DSM-5? (6)
In.SAD.CAGES
Activity: psychomotor retardation or agitation
29
What are the symptoms of MDD in DSM-5? (7)
In.SAD.CAGES
Guilt: feelings of guilt or worthlessness
30
What are the symptoms of MDD in DSM-5? (8)
In.SAD.CAGES
Energy: decreased energy or fatigue
31
What are the symptoms of MDD in DSM-5? (9)
In.SAD.CAGES
Suicidal thoughts or attempts
32
DSM-5 for MDD (B)
Symptoms cause significant distress or impairment in social, occupational, or other
important areas of functioning.
33
DSM-5 for MDD (C)
Symptoms are not caused by an underlying medical condition or substance.
34
Differential diagnosis (1)
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
35
Differential diagnosis (2)
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.
36
General assessment (1)
History of present illness
37
General assessment (2)
Psychiatric history
Any history of manic/ hypomanic episodes? (starting an antidepressant may cause “manic switch” in patients with underlying bipolar disorder)
38
General assessment (3)
Substance use history: Cigarettes/ETOH/substances
39
General assessment (4)
Complete medical & medication history
40
General assessment (5)
Family, social, forensics, developmental & occupational history
41
General assessment (6)
Physical & neurological exam
42
General assessment (7)
MSE for accurate diagnosis
- Assess suicidal/homicidal ideations and risks
- Reassess MSE on every interview to evaluate efficacy & tolerability
43
General assessment (8)
Labs
Vital signs, weight & BMI, FBC, U/E/Cr, LFTs, TFTs, ECG, FBG, lipid panel, urine toxicology
44
General assessment (9)
To exclude general medical conditions or substance-induced/withdrawal symptoms, e.g.
delirium/ psychosis/ depression/ mania/ anxiety/ insomnia/ thyroid disfunction/ diabetes
45
Gold standard rating scale
Hamilton Rating Scale for Depression
- By clinician
- Remission = HAM-D score ≤7 (therapy goal: symptom free)
46
Non-pharmacological
1. Sleep hygiene
2. Psychotherapy
3. Neurostimulation (ECT, rTMS)
4. Light therapy (for seasonal affective disorder)
47
1st line (antidepressant monotherapy)
Mirtazapine
SSRI
SNRI
Bupropion
48
Antidepressant indicated for ______ depression, not routinely indicated for _____ depression.
Moderate-severe
Mild
49
Antidepressants ± adjunctive meds selection is based on?
Target symptoms
Comorbidities
DDI
Prior response
Preference
50
Phases of treatment
i) acute phase
ii) continuation phase
51
What is considered adequate trial during acute phase treatment?
Adequate dose + duration (4-8 weeks)
52
What could cause delayed onset of effectiveness?
Gradual down-regulation of pre-synaptic auto receptors in synapse, which facilitates neurotransmitter release.
53
Time course of treatment response
Physical symptoms: 1-2 weeks to improve
Mood symptoms: 3-8 weeks (longer time)
54
Continuation phase duration
For 1st episode uncomplicated MDD: continue for at least another 4-9 months after acute phase treatment (total 6-12 months at least)
55
Examples of tricyclic antidepressants
Amitriptyline
Imipramine
Nortriptyline
Desipramine
Clomipramine
56
MOA of TCAs
Inhibits reuptake of serotonin and norepinephrine in presynaptic terminal, increasing concentration of these neurotransmitter in the synaptic cleft.
57
Which TCAs are non selective for 5-HT & NE neurotransmitters?
Imipramine, Amitriptyline, Nortriptyline
58
Which TCAs are selective for NE neurotransmitters?
Desipramine
59
Which is a 2nd generation TCA?
Secondary amines:
Nortriptyline
Desipramine
60
What receptors do TCAs have affinity to, causing AEs?
H1 histamine receptor antagonism
a1-adrenoceptor sympathetic block
Muscarinic receptor antagonism
61
AEs of TCAs
H1: sedation (can develop in 1-2 weeks)
a1: postural hypotension (dose related)
M1: dry mouth, blurred vision, constipation
62
Cautions in TCAs
Patients with history of MI: QTc prolongation, tdp
CV: cardiac conduction delays, heart block, arrhythmias
63
Which TCA can be used for OCD (other than depression)?
Clomipramine
64
Examples of SSRI
Fluoxetine
Fluvoxamine
Escitalopram
Citalopram
Paroxetine
Sertraline
65
Which is the least favourite SSRI?
Sertraline
66
Why do SSRIs have fewer AEs than TCAs?
Have a low affinity for other receptors including alpha1-adrenergic (α1), histaminic (H1), and muscarinic (M1) receptors
67
Fluoxetine approximately ___ folds selectivity for 5HT
50
68
Citalopram approximately ___ folds selectivity for 5HT
1000
69
What tolerability issues of TCA can affect its adherence?
Weight gain, sexual dysfunction
70
TCA is ______ on overdose.
Fatal
71
Most common dose-dependent tolerability issue of SSRI
Limited to 1-2 weeks after initiation or dose increase: GI symptoms
Somnolence, insomnia
72
Which SSRIs have long t1/2?
Fluoxetine: 4-6 days
Norfluoxetine: 4-16 days
73
Administration for Sertraline
Take with food to increase absorption
74
Which SSRI has more anticholinergic and antihistaminergic activity linked with increased sedation and weight gain?
Paroxetine
Citalopram
75
Which SSRI has short t1/2?
Paroxetine - withdrawal symptoms
76
Which SSRI can cause QTc prolongation if high dose in elderly?
Escitalopram/Citalopram
77
What tolerability issues of SSRIs can affect its adherence?
GI, sexual dysfunction
78
Examples of SNRIs
Venlafaxine (Desvenlafaxine - metabolite of Venlafaxine)
Duloxetine
79
MOA of SNRIs
Inhibits reuptake of serotonin and norepinephrine in presynaptic terminal, increasing concentration of these neurotransmitter in the synaptic cleft.
80
Venlafaxine and its primary active metabolite, desvenlafaxine, inhibit ____ reuptake at low doses, and ___ reuptake at higher doses.
5-HT, NE
81
Advantages of SNRIs
Claimed to work slightly faster than other anti-depressants and better in treatment-resistant patients
82
AEs of SNRIs
Same as SSRIs
83
Which SNRI increases BP?
Venlafaxine
84
Which SNRI causes urinary hesitation?
Duloxetine
85
What SNRI is indicated for diabetic peripheral neuropathy, fibromyalgia and chronic musculoskeletal pain?
Duloxetine
86
What to use for treatment resistant depression (TRD)?
Symbyax: Olanzapine 6mg + Fluoxetine 25mg
87
MOA of serotonin modulator and simulator (SMS)
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
Example of SMS
Vortioxetine
89
AEs of SSRI
GI & sexual dysfunction.
Headache, transient nervousness during initiation
Hyponatremia (SIADH)
Bleeding risk; EPSE
90
NaSSA
Norepinephrine and specific serotonin antidepressant
91
What drug class is Mirtazapine?
NaSSA
92
MOA of Mirtazapine
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
Side effects of Mirtazapine
Somnolence
Increase appetite
Weight gain
94
Advantages of Mirtazapine
Reverse GI & sexual dysfunction
95
What drug class is Bupropion?
Norepinephrine-dopamine reuptake inhibitor (NDRI)
96
MOA of NDRI
No appreciable effect on the 5-HT reuptake
Inhibits both the NE and DA reuptake
97
When is NDRI useful?
Older adult patient - decreased motivation, low energy, fatigue
98
Side effects of NDRI
Seizure
Insomnia
Psychosis
99
When is NDRI unsuitable?
Eating disorder (imbalance of electrolytes can cause seizures)
100
Function of monoamine oxidase (MAO)
Breaks down monoamines (NE, 5-HT, DA)
101
Where are MAO found?
Nearly in all tissue
Intracellularly, mostly on mitochondrial surface
102
What is 5-HT broken down by?
Mainly MAO-A
103
What is NE broken down by?
Both MAO-A & B
104
What is DA broken down by?
Both MAO-A & B
105
Non-selective irreversible inhibitors of MAO-A & B
Isocarboxazid
Phenelzine
Tranylcypromine
106
AEs of Isocarboxazid, Phenelzine, Tranylcypromine
Hypertensive crisis
107
Why is tyramine restriction necessary?
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
Selegiline transdermal patch
Irreversible MAO-B inhibition
109
Which is the safest MAOi?
Moclobemide
110
Moclobemide
Reversible MAO-A inhibition
111
AEs of MAOi (1)
Postural hypotension
Due to sympathetic block produced by
accumulation of dopamine in the cervical (neck)
ganglia, where is acts as an inhibitory transmitter
112
AEs of MAOi (2)
Restlessness & insomnia
Due to CNS stimulation
113
MOA of tyramine
Taken up into adrenergic terminal, competes with norepinephrine for vesicular compartment, increase release of norepinephrine into synapses
114
Any antidepressant that increases serotonergic neurotransmission can be associated with _____.
Serotonin syndrome (especially increase release or duration of serotonin activity)
115
Serotonin syndrome symptoms
Mental status changes, autonomic instability, and neuromuscular abnormalities (eg, hyperreflexia, myoclonus)
116
MOA of Trazodone
Blocks reuptake of 5-HT;
Antagonizes 5-HT2A,H1 and a1 adrenoceptor
117
MOA of Trazodone
Blocks reuptake of presynaptic 5-HT;
Antagonizes postsynaptic 5-HT2A, H1 and a1 adrenoceptor
118
When is Trazodone more likely used for rather than depression?
Insomnia
119
SE of Trazodone
Priapism
120
MOA of Agomelatine
MT-1, MT-2 agonist
5-HT-2C antagonist
Increases DA and NE
121
What monitoring is required for Agomelatine?
LFTs
122
Contraindications of Agomelatine
Fluvoxamine
Ciprofloxacin
Both are strong inhibitors of the enzyme, increasing [agomelatine]
123
Adjunctive treatment for MDD
- SGA (Aripiprazole, Brexpiprazole, Quetiapine XR)
- Esketamine (NMDA receptor antagonist)
- PRN hypnotics
124
Esketamine dosing
1 session: 56mg or 84mg (lower in elderly)
125
Esketamine frequency
W1-4: 2 sessions/week
W5-8: 1 session/week
>W9: 1 session every 1-2 week, for at least 6 months
126
Benzodiazepines
Lorazepam
Potentiates GABA
Has dependence
127
Z-hypnotics
Zopiclone
Zolpidem CR
Preferentially binds to benzodiazepine-binding sites with Y and a1 subunits (causes sedation).
128
SEs of Z-hypnotics
Drowsiness
Taste disturbance (Zopiclone)
Complex sleep behaviors (sleep-walking)
Dependence
129
Maximum dose of Amitriptyline
300mg/day
130
Maximum dose of Clomipramine
300mg/day
131
Starting dose of Fluoxetine
20mg OM
132
Maximum dose of Fluoxetine
80mg/day
133
Usual dose of Mirtazapine
15-45mg/day
134
Therapeutic Lifestyle/Behavioral Changes
1. Sleep Hygiene
2. Exercise
3. Relaxation techniques
135
Nutritional
- Vit. B12
– L-methylfolate
– Vit. D
– S-adenosylmethionine (SAMe)
– Omega-3 fatty acids
– 5-hydroxytryptophan (5-HTP)
136
Herbal
St John's Wort
- Significant drug interactions with antidepressant
- Do not use concomitantly
137
Approaches to manage partial/no response (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
Precautions during cross-titration
Watch for serotonin syndrome if combining serotonergic agents
139
Precautions when switching from serotoninergic antidepressant to non-serotoninergic antidepressant
Antidepressant Discontinuation Syndrome
- Gradual cross tapering over several weeks
140
What is needed when switch involves MAOi?
Wash-out period
141
Switch from Moclobemide to another antidepressant
24 hours wash out
142
Switch from another antidepressant to Moclobemide
Wash out at least 1 week
Wash out at leas 5 weeks if stopping Fluoxetine
143
Approaches to manage partial/no response (B)
Augmentation
144
How to augment?
Combine 2nd antidepressant with different MOA (must have partial response)
+ Mirtazapine, Bupropion-SR, T3 (Liothyronine), Lithium
Adjuctive SGAs: Quetiapine XR, Aripiprazole, Brexpiprazole
145
TRD (no response to ≥ 2 adequate trials of antidepressants)
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
Pregnancy
Consider Nortriptyline in late pregnancy (>28 weeks)
147
Breast feeding
Sertraline
Mirtazapine
148
PP depression
Brexanolone
149
Renal impairment
Vortioxetine
150
Hepatic impairment
Avoid Agomelatine
Mild-moderate: Vortioxetine
151
Post-MI depression
Sertraline
152
Elderly
Avoid TCAs
153
Hyponatremia
SIADH (usually in elderly)
ALL antidepressant, mostly SSRIs
Possibly lower risk with Agomelatine, Mirtazapine or Bupropion.
154
What to monitor for hyponatremia?
Serum Na at baseline, 2nd week, 4th week, then 3-monthly.
155
Common serotonergic agents (other than antidepressants)
Triptans
Sibutramine
Opioids (Tramadol, Fentanyl, Pethidine)
Dextromethorphan
Linezolid, Ritonavir (e.g. in Paxlovid®)
MAOI
156
SSRIs increases risk of _____________?
Bleeding.
Higher risks in elderly on NSAIDs, warfarin, steroids -> consider adding PPI
157
If patient has a scheduled surgery, which antidepressants require cautions?
Consider stopping serotonergic antidepressant 2 weeks before surgery if high bleeding risks
158
Which antidepressant is safest for patients with high bleeding risks?
Agomelatine
159
Drugs with fewer CYP interactions
Mirtazapine, Escitalopram, Venlafaxine, Desvenlafaxine, Vortioxetine
160
Which drugs has more apparent antidepressants discontinuation syndrome?
Paroxetine
Venlafaxine
161
What drug class is Paroxetine?
SSRI
162
What drug class is Venlafaxine?
SNRI
163
When does antidepressants discontinuation syndrome happens?
Abruptly stopping a regular treatment
164
Symptoms of ADS (Finish)
Flu-like symptoms (lethargy, fatigue, headache, achiness, sweating)
164
Symptoms of ADS (fInish)
Insomnia (with vivid dreams or nightmares)
165
Symptoms of ADS (fiNish)
Nausea (sometimes vomiting)
166
Symptoms of ADS (finIsh)
Imbalance (dizziness, vertigo, light-headedness)
167
Symptoms of ADS (finiSh)
Sensory disturbances (“burning,” “tingling,” “electric-like” sensations)
168
Symptoms of ADS (finisH)
Hyperarousal (anxiety, irritability, agitation, aggression, mania, jerkiness)
169
Onset of ADS
36-72 hours
170
Duration of ADS
3 - 7 days, typically resolve over 1-2 weeks without treatment
171
How to avoid ADS?
Gradually tapering
172
Which drugs do not require gradual tapering?
Fluoxetine
Bupropion
Due to long t1/2.
173
Patient counselling (1)
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
Patient counselling (2)
Do not take at same time as alcohol (space 4-6 hours part)
175
Patient counselling (3)
Tell your Drs & nurses what other medicines you are using
176
Patient counselling (4)
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)
