depression Flashcards
What are the symptoms exhibited by a patient suffering from major depressive disorder as defined in DSM-5
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
What are the symptoms of In.SAD.CAGES
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
What are the risk factor for suicide in the general population?
1) Previous attempts
2) Isolation
3) Poor health (Physical/mental comorbidities)
4) Poor wealth status
5) Male
6) Elderly
What are the neurotransmitters involved in depression?
1) Norepinephrine
2) Serotonin
3) Dopamine
What are the hormonal influences that can cause depression?
Increased secretion of cortisol (major stress hormone)
What are the secondary (Medical) causes for depression?
1) Endocrine disorder: Hypothyroidism
2) Cardiovascular: CAD, CHF, MI, ACS
3) Infections
4) Deficiency states
5) Neurological: Alzheimer’s, Epilepsy, Parkinson’s
6) Malignancy
What are the drug induced causes for depression?
1) Lipid-soluble beta blockers
2) Psychotropics: CNS depressants
3) Withdrawal from alcohol, stimulants
4) Systemic corticosteroids
5) Isotretinoin
6) Interferon-beta-1a
What are the relevant pt’s history to take prior to diagnosis and treatment?
1) Psychiatric hx
2) Substance use hx
3) Complete med and medications hx
4) Family, social, occupational, developmental hx
5) Hx of present illness
What must be assessed prior to diagnosis and treatment?
Assess suicidal/ Homicidal ideations and risks during mental state exam (MSE)
What is the “gold-standard” for clinician-rated psychiatric rating scales?
Hamilton rating scale for depression (HAM-D)
What is the remission criteria for HAM-D?
HAM-D score smaller or equal to 7.
How does PHQ-9 categorised severity of depression?
Score: 1-4 : Minimal symptoms 5-9: Mild depression 10-14: Moderate 15-19: Moderately-severe More than or equal to 20: Severe
At which PHQ-9 score is antidepressant recommended
For score 10 and above
What are the non-pharmacological managements for depression?
1) Sleep hygiene
2) Psychotherapy
3) Neurostimulation: Electroconvulsive treatment/ Repetitive transcranial magnetic stimulation
What are the first line medications for depression?
1) SSRI
2) SNRI
3) Mirtazapine or Bupropion
How many phases are there in the treatment of depression?
1) Acute phase
2) Continuation phase
Describe the acute phase treatment
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
Describe the continuation phase treatment
For the 1st episode of MDD, continue at least 4-9 months after acute-phase treatment
How long will depression treatment take?
Initiation + Acute phase + Continuation phase = 6-12 months
What are the different antidepressant classes?
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)
Why does mood symptoms take longer to improve?
This is due to time needed to downregulate the presynaptic monoamine autoreceptors
What is Duloxetine indicated for?
Depression and GAD
Diabetic neuropathy, stress urinary incontinence, fibromyalgia and Chronic musculoskeletal pain
Which drugs are in the TCA class?
1) Amitriptyline –> Nortriptyline
2) Imipramine –> Desipramine
3) Dothiepin
4) Clomipramine
MOA of TCA?
They block the reuptake of NE and 5-HT in the synapses
What are the SE of TCAs?
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
What is Clomipramine indicated for apart from depression?
1) OCD
2) Cateplexy associated with narcolepsy
Which TCAs have lesser anticholinergic, sedation and cardiotoxic SEs?
Secondary amines such as Nortriptyline and Desipramine
Starting doses for Amitriptyline?
50 - 100mg/day
Usual dose/ day for amitriptyline and Clomipramine?
Ami: 30 -300mg/day
Clomi: 25-250mg/day
Max dose for Amitriptyline and Clomipramine?
300mg for both
Starting dose for Clomipramine?
25mg /day
Which drugs are in the SSRI class?
1) Fluoxetine
2) Fluvoxamine
3) Escitalopram
4) Citalopram
5) Paroxetine
6) Sertraline
Which SSRI has the long half-life?
Fluoxetine (4-6 days)
What is the MOA of SSRI?
Selective Serotonin reuptake inhibitor
SEs of SSRI?
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)
Special administration instruction for Sertraline?
Take with food
Which SSRI has the most SE?
Paroxetine. Most sedating, most anti-cholinergic, causes weight gain and risk of withdrawal due to short half life
Which SSRIs are indicated for OCD?
1) Fluoxetine
2) Fluvoxamine
3) Sertraline
Which SSRIs are indicated for anxiety disorder?
1) Escitalopram
2) Paroxetine
Which SSRIs are indicated for panic disorder?
1) Citalopram
2) Sertraline
Which SSRI is indicated for Bulimia nervosa?
Fluoxetine
Starting dose of Fluoxetine?
20 mg OM
Usual dose and max dose for Fluoxetine?
20-60mg/day
Max: 80mg
Which drugs are in SNRI class?
1) Venlafaxine
2) Desvenlafaxine
3) Duloxetine
4) Levomilnacipran (??)
Which SNRIs are used in GAD?
1) Venlafaxine
2) Duloxetine
MOA of SNRI?
Dual action. Serotonin and Norepinephrine reuptake inhibitor
SE of SNRI?
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
Starting dose of Duloxetine?
60mg/day
Usual /Max dose of Duloxetine?
30 - 60 mg/day
120 mg/day
Starting dose of Desvenlafaxine?
50mg /day
Usual/Max dose of Desvenlafaxine?
50mg/day
100mg/day
Starting dose of Venlafaxine?
75mg/day
Usual/Max dose of Venlafaxine?
75 - 225mg/day
375mg/day
MOA of Mirtazapine?
Noradrenergic/ Specific Serotonergic antidepressant
alpha-2-adrenoceptor antagonist, 5-HT(2/3) antagonist
Starting dose of Mirtazapine?
15mg/day
Usual/Max dose of Mirtazapine?
15-45mg/day
45mg/day
SE of Mirtazapine
1) Increase appetite
2) Weight gain
3) Drowsiness
What are the benefits of Mirtazapine over SSRIs/SNRI?
Reverse sexual and GI side effect of SSRI/SNRI
How does Mirtazapine reverse sexual and GI side effect of SSRI/SNRI
By antagonising 5-HT2 (Sexual dysfunction) and 5-HT3 (GI side effect)
MOA of Bupropion?
It is a norepinephrine/ dopamine reuptake inhibitor.
SEs of Bupropion?
1) Seizure
2) Insomnia
3) Psychosis
Starting dose of Bupropion?
150mg OM x 4d, then BD
Usual/Max dose of Bupropion?
150mg BD
300MG (2 divided doses)
What is bupropion indicated for?
Depression
Smoking cessation
What drugs are in SMS class?
1) Vortioxetine
2) Vilazodone
What is the MOA of SMSs?
Similar to SSRI, vortioxetine is also 5-HT1A agonist, while vilazodone is a 5-HT1A partial agonist
SEs of SMSs?
1) Similar to SSRI
What is the drug in reversible MAOI class?
Moclobemide
What is Moclobemide useful for?
Atypical depression
SEs of MAOI?
1) Hypertensive crisis
2) Anxiety
3) Arrhythmias
4) CVA
5) Weight gain
6) Sexual dysfunction
How long is the washout period for Moclobemide?
If switching from Moclobemide: 24hrs
If switching to Moclobemide: 1 week (5 weeks for Fluoxetine)
Starting dose of Moclobemide?
300mg/day in divided doses
Usual/Max dose of Moclobemide?
150-600mg/day
600mg
MOA of MAOIs?
Increase availability of monoamines by inhibiting monoamine oxidase, which breaks down monoamine
What class is Trazodone in?
Serotonin antagonist and reuptake inhibitor
MOA of Trazodone?
Blocks reuptake of 5-HT, antagonizes 5-HT2A receptors
SE of Trazodone?
1) Similar to SSRI
2) Sedation (H1 antagonism)
3) Orthostatic hypotension (a1-adrenoceptor antagonism)
4) Priapism (Rare SE)
Indication of Trazodone?
Depression, off-label for insomnia. Trazodone is used more for insomnia than depression
MOA of Agomelatine?
Melatonin receptor (MT-1, MT-2) agonist
5-HT2C antagonist
SE of Agomelatine?
1) GI side effects
2) Increased LFTs, check LFT at baseline and at week 3,6,12,24
Which drugs are contraindicated with concurrent use of Agomelatine?
1) Fluvoxamine
2) Ciprofloxacin
What are the classes of adjunctive medications use in treatment of depression?
1) Benzodiazepines
2) Z-hypnotics
3) Antihistamines
4) Melatonin receptor agonist
5) Second generation antipsychotics
6) Esketamine
Which benzodiazepines are used as adjunct? State dose
1) Lorazepam PO 0.5-2mg at bedtime PRN
2) Diazepam PO 2-15mg at bedtime PRN
How long should the course of benzodiazepines be?
2 weeks PRN
Which Z-hypnotics is used as adjunct? State dose
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)
Side effect of Zopiclone?
Taste disturbances
Which antihistamine are used as adjunct? State dose
1) Hydroxyzine
2) Promethazine
PO 25-50mg ON PRN for both
Which antipsychotic are used as adjunct for MDD?
1) Aripiprazole,
2) Brexpiprazole
3) Quetiapine XR
Which antipsychotic are used as adjunct for treatment resistant depression (TRD)? State dose
Symbyax (Olanzapine 6mg + Fluoxetine 25mg)
What is Esketamine indicated for?
Adjunct to SSRI/SNRI for TRD
Which herb should not be used concomitantly with antidepressants?
St John’s wort
What are the treatment options for Treatment resistant depression?
1) Neurostimulation (Electroconvulsive therapy, repetitive transcranial magnetic stimulation)
2) Symbyax
3) Spravato (Esketamine 28mg nasal spray) as adjunct to SSRI/SNRI
What can be combined to the existing antidepressant with a partial response?
1) Mirtazapine
2) Bupropion-SR
3) T3 (Liothyronine)
4) Lithium
5) SGA: Brexpiprazole, Quetiapine, Aripiprazole
Which antidepressants/SE should be avoided in elderly?
1) TCA
2) Anticholinergic
3) CNS
4) Hypotensive
5) Cardiac SE
What are the symptoms of hyponatremia?
1) Drowsiness
2) Confusion
3) Convulsion
Which drug leads to higher risk of hyponatremia? Which drug has a lower risk?
Higher risk: SSRI
Lower risk: Bupropion, Mirtazapine, Agomelatine
BUT hyponatremia is associated with all antidepressants
Suicidality is associated with?
Patient ≤ 24 years old, must counsel patients
What causes serotonin syndrome?
Concomitant rx of high-dose serotonergic meds
Serotonergic agent + Serotonergic agent = ?
Serotonin syndrome
What increases risk of bleeding with SSRIs?
Elderly on NSAIDs, warfarin, steroids. Consider adding PPI
What are the significant DDI with antidepressant
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
Which antidepressants are potent CYP inhibitors
1) Fluvoxamine (CYP1A2, 2C19)
2) Fluoxetine (CYP2D6)
3) Paroxetine (CYP2D6)
4) Bupropion (CYP2D6)
Which antidepressants have lesser CYP interactions?
1) Mirtazapine
2) Escitalopram
3) Venlafaxine
4) Desvenlafaxine
5) Vortioxetine
6) Levomilnacipran
What are the symptoms of antidepressant discontinuation syndrome
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)
How to prevent antidepressant discontinuation syndrome?
If patient is on long-term treatment (daily tx ≥ 8 weeks), gradually taper over 4 weeks. Taper by 25% every 1-2 week.
Which antidepressants do not need gradual tapering upon discontinuation? Why?
1) Fluoxetine
2) Bupropion
Due to their long half-life
Goals of depression treatment?
1) Remission of symptoms
2) Treatment adherence
3) Suicide prevention
Rank the antidepressant class according to relevance in clinical practice
1) SSRI, SNRI, NaSSA
2) Bupropion
3) Agomelatine, Vortioxetine
4) TCA
5) MAOIs
Patients with history of ____ should avoid using Bupropion
1) Eating disorder
2) Psychosis
3) Seizures
