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Pharmacotherapeutics > Antidepressants CA2 > Flashcards

Antidepressants CA2 Flashcards

1
Q

Physical illness and mental illness are not related. T/F?

A

False. More than half of those with mental illness also have a chronic physical illness.

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2
Q

Etiology and pathophysiology of depression.

A

Primary cause:
Monoamine hypothesis: reduced number of neurotransmitters in brain (e.g. norepinephrine (NE), serotonin (5-HT), dopamine (DA)).

Secondary causes:
Endocrine disorders: hypothyroidism, T2DM in women
Cardioavascular: CAD, CHF, MI

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3
Q

Clinical presentation for MDD (In. SAD. CAGES)

A

o At least 5 symptoms have been present during the same 2-week period
o One of the symptoms must be depressed mood or lost of interest
 Interest: decreased interest
 Sleep: insomnia
 Appetite: decreased appetite
 Depressed: depressed mood
 Concentration: impaired concentration and decision making
 Activity: psychomotor retardation or agitation
 Guilt: feelings of guilt or worthlessness
 Energy: decreased energy or fatigue
 Suicidal thoughts or attempts
o Symptoms cause significant distress or impairment in social, occupational or other important areas of functioning.
o Symptoms are not caused by an underlying medical condition or substance.

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4
Q

Assessments for depression

A

Clinician-rated

  • Hamilton Rating Scale for Depression (HAM-D): “gold standard”
  • Remission = HAM-D score ≤ 7 (Therapy goal: symptom-free)

Self-rated:
- Screening tool: Patient Health Questionnaire (PHQ-2)
- Assessment tool: PHQ-9
Score above 5 to be considered depressed

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5
Q

Treatment principle

A

Combination of non-pharmacological and pharmacological treatment method

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6
Q

Non-pharmacological therapy for depression

A
  • Sleep hygiene

- Psychotherapy

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7
Q

Pharmacological therapies (in general)

A
  • Antidepressants ± adjunctive medicines

- First-line (antidepressant monotherapy): SSRI, SNRI, Mirtazapine or Bupropion

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8
Q

Types of TCAs

A

Amitriptyline, clomipramine, dothiepin, imipramine, nortriptyline

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9
Q

Types of SSRIs

A

Escitalopram, fluvoxamine, fluoxetine, paroxetine, sertraline, citalopram

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10
Q

Types of SNRIs

A

Venlafaxine, duloxetine

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11
Q

Type of SMS

A

Vortioxetine

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12
Q

Type of NaSSA

A

Mirtazapine

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13
Q

RIMA

A

Moclobemide

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14
Q

Others

A

Bupropion, trazodone, agomelatine

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15
Q

Other psychiatric indication in addition to depression

A
  1. OCD
    - Clomipramine, fluoxetine, fluvoxamine, sertraline
  2. Anxiety disorders
    - Escitalopram, paroxetine
  3. Panic disorder
    - Citalopram, sertraline
  4. Generalized Anxiety Disorder
    - Venlafaxine, duloxetine
  5. Social Anxiety Disorder
    - Moclobemide
  6. Off-label for insomnia
    - Trazodone
  7. Smoking cessation
    - Bupropion
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16
Q

TCAs:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A 
Types: 
Amitriptyline -> Nortriptyline 
Imipramine ->  Desipramine 
Dothiepin 
Clomipramine

MOA:
Blocks reuptake of 5HT and NA

Side effects:

  • GI and sexual dysfunction
  • Anticholinergic, sedation, orthostatic hypotension, seizures, weight gain, arrhythmia.
  • Fatal on overdoses

Notes:
- 2° amines (nortriptyline, desipramine) have lower anticholinergic, sedation and cardiotoxic side effects

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17
Q

Phases of treatment

A
  1. Acute Phase Treatment
    - Adequate trial = adequate dose + duration
    - Delayed onset due to down-regulation of pre-synaptic autoreceptors.
    - Time course of treatment response
    » Physical symptoms may improve in 1-2 weeks (e.g. sleep, appetite)
    » Mood symptoms take longer time to improve (e.g. 4-6 weeks)
  2. Continuation Phase
    - Initiation + Acute Phase + Continuation = total at least 6-12 months
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18
Q

SSRIs:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A 
Types: 
Fluoxetine -> norfluoxetine 
Fluvoxamine 
Escitalopram 
Citalopram 
Paroxetine 
Sertraline

MOA:
Selective 5-HT antagonism

Side effects:

  • GI and sexual dysfunction
  • Headache, transient nervousness during initiation.
  • Insomnia (fluoxetine)
  • Hyponatremia
  • Bleeding risk, EPSE

Notes:

  • Long half-life for fluoxetine (4-6 days)
  • Norfluoxetine has the longest t1/2.
  • Paroxetine: most anticholinergic, sedating, weight gain, short half-life. Can go into withdrawal syndrome.
  • Escitalopram/citalopram: QTc prolongation of high dose in elderly.
19
Q

SNRIs:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A

Types:
Venlafaxine -> desvenlafaxine
Duloxetine

MOA:
5 HT, NA antagonism

Side effects:
- Same as SSRI. Increased BP. Urinary incontinence (duloxetine)

  • Venlafaxine: low chance of causing seizures. Very low: anticholinergic side effects, sedation. None: orthostatic hypotension
  • Duloxetine (safer option): very low chance of anticholinergic side effects and orthostatic hypotension. None for the rest.
20
Q

SMS:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A

Type:
- Vortioxetine

MOA:

  • Same as SSRI.
  • 5HT1A antagonist

Side effects:

  • Same as SSRI
  • May worsen hypertension
21
Q

NaSSA:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A

Type:
- Mirtazapine

MOA:

  • α2-adrenoreceptor antagonist
  • 5HT and NA antagonism.
  • 5HT2&3, H1 antagonism

Side effects:
- Somnolence, increased appetite, weight gain

Notes:
- Reverse GI and sexual side effects of SSRI/SNRI.

22
Q

NDRI:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A

Type:
Bupropion

MOA:
- blocks uptake of NE and DA

Side effect:
- Seizure, not suitable for those with psychosis or eating disorders

Notes:
- Reduce sexual side effects of SSRI/SNRI.

23
Q

MAOI:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A

Type: Moclobemide
- Reversible MAOi-A

Notes:
- Safest amongst MAOIs

24
Q

Trazadone

  • MOA
  • Side effects
  • Notes
A

MOA:

  • Blocks reuptake of 5HT
  • Antagonises 5HT2A, H1 and α1-adrenoreceptor.

Side effects:
- Same as SSRI, sedation, orthostatic hypotension

Notes:
- Used for insomnia and depression

25
Q

Adjunctive hypnotics:

  • Type of antidepressants
  • MOA
  • Side effects
  • Notes
A 
A. Benzodiazepines 
- MOA: potentiates GABA 
- Side effects: sedation, drowsiness, amnesia 
- Dosings: 
>> Lorazepam: PO 0.5-2mg HS PRN 
>> Diazepam: PO 2-5mg HS PRN 
Limit to 2-week PRN course

B. Z-Hypnotics
- MOA: causes sedation
- Side effects: taste disturbance (Zopiclone), complex sleep behaviors (sleep-walking)
- Dosings:
» Zolpidem: females, half-dose (5mg HS PRN)
» Zopiclone: 7.5mg HS PO PRN for adults, 3.75mg HS PO PRN for elderly.

C. Second generation antipsychotics
- Aripiprazole, Braxiprazole, Quetiapine

26
Q

Types of complementary and alternative medicines

A
  • Therapeutic Lifestyle/Behavioural Changes
    » Sleep hygiene
  • Herbal
    » St John’s Wort
    • Significant drug interactions and cannot be used concomitantly with antidepressant
27
Q

If an antibiotic has partial to no reponse:

A
  • can switch medications, but washout period is necessary for MAOIs
28
Q

Depression: Special Populations and Other Considerations

A
  • Elderly: Avoid TCAs and anticholinergic, CNS, hypotensive or other cardiac side effects.
  • Hyponatremia: common in elderly, mostly reported for SSRIs.
  • Association to suicidality in patients ≤ 24 years old, require counselling.
29
Q

Clinically significant drug-drug interactions

A
  • Serotonergic agent + serotonergic agent = serotonin syndrome
  • SSRIs: increase risks of bleeding
    » Higher risks In elderly on NSAIDs, warfarin, steroids.
    » Consider adding PPI.
  • Increased CNS depressant effects with alcohol and other CNS depressants.
    » Do not take medication at the same time as alcohol, separate them 4-6 hours apart.
    » Benzodiazepines + Opioids = Increased mortality
30
Q

Drug-Drug interactions for CYP1A2

A

Substrates:
Theophylline, amiodarone, warfarin-R, Agomelatine

Inhibitors:
Fluvoxamine

31
Q

Drug-drug interactions for CYP2C19

A

Substrate: Warfarin-R

Inhibitor: fluvoxamine

32
Q

Drug-drug interactions for CYP2D6

A

Substrates: Metoprolol, Codeine, Tramadol

Inhibitors: Fluoxetine, Paroxetine, Bupropion

33
Q

Drug-drug interactions for CYP3A4

A

Substrates: Simvastatin, lovastatin, nifedipine, amlodipine, diltazem

Inhibitors: grapefruit juice

Inducers:
Rifampicin, carbamazepine, phenytoin, St. John’s Wort

34
Q

Drugs with the fewest CYP interactions

A

Mirtazapine, escitalopram

35
Q

Symptoms of antidepressant discontinuation syndrome

A 
Flu-like symptoms 
Insomnia 
Nausea 
Imbalance 
Sensory 
Hyperarousal
36
Q

Which drugs are likely to have discontinuation withdrawal syndrome?

A

Drugs with short half-life: paroxetine, venlafaxine

37
Q

How should we discontinue the medications

A

gradual tapering over time, around 4 weeks

38
Q

Goals of major depressive disorder therapy?

A

remission of symptoms, treatment adherence and prevention

39
Q

Drug choice of antidepressants

A
  • SSRI, SNRI, NaSSA, Bupropion > Agomelatine, Vortioxetine > TCA > MAOIs
  • Selection based on target symptoms, interactions
40
Q

Amitriptyline dose

A

300mg max per day

41
Q

fluoxetine dose

A

20mg om, 80mg max per day

42
Q

mirtazapine dose

A

15-45mg per day

43
Q

clomipramine dose

A

300mg per day

Pharmacotherapeutics (28 decks)

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