TCAs: - Type of antidepressants - MOA - Side effects - Notes

``` 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

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

SSRIs: - Type of antidepressants - MOA - Side effects - Notes

``` 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.

Antidepressants CA2 Flashcards by Faith Wong

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

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

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Etiology and pathophysiology of depression.

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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Clinical presentation for MDD (In. SAD. CAGES)

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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Assessments for depression

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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Treatment principle

Combination of non-pharmacological and pharmacological treatment method

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Non-pharmacological therapy for depression

Sleep hygiene

- Psychotherapy

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Pharmacological therapies (in general)

Antidepressants ± adjunctive medicines

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

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Types of TCAs

Amitriptyline, clomipramine, dothiepin, imipramine, nortriptyline

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Types of SSRIs

Escitalopram, fluvoxamine, fluoxetine, paroxetine, sertraline, citalopram

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Types of SNRIs

Venlafaxine, duloxetine

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Type of SMS

Vortioxetine

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Type of NaSSA

Mirtazapine

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RIMA

Moclobemide

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Others

Bupropion, trazodone, agomelatine

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Other psychiatric indication in addition to depression

OCD
- Clomipramine, fluoxetine, fluvoxamine, sertraline
Anxiety disorders
- Escitalopram, paroxetine
Panic disorder
- Citalopram, sertraline
Generalized Anxiety Disorder
- Venlafaxine, duloxetine
Social Anxiety Disorder
- Moclobemide
Off-label for insomnia
- Trazodone
Smoking cessation
- Bupropion

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TCAs:

Type of antidepressants
MOA
Side effects
Notes

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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Phases of treatment

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)
Continuation Phase
- Initiation + Acute Phase + Continuation = total at least 6-12 months

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SSRIs:

Type of antidepressants
MOA
Side effects
Notes

Study These Flashcards

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.

SNRIs:

Type of antidepressants
MOA
Side effects
Notes

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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.

SMS:

Type of antidepressants
MOA
Side effects
Notes

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Type:
- Vortioxetine

MOA:

Same as SSRI.
5HT1A antagonist

Side effects:

Same as SSRI
May worsen hypertension

NaSSA:

Type of antidepressants
MOA
Side effects
Notes

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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.

NDRI:

Type of antidepressants
MOA
Side effects
Notes

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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.

MAOI:

Type of antidepressants
MOA
Side effects
Notes

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Type: Moclobemide
- Reversible MAOi-A

Notes:
- Safest amongst MAOIs

Trazadone

MOA
Side effects
Notes

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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

Adjunctive hypnotics: - Type of antidepressants - MOA - Side effects - Notes

``` 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

Types of complementary and alternative medicines

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

If an antibiotic has partial to no reponse:

- can switch medications, but washout period is necessary for MAOIs

Depression: Special Populations and Other Considerations

- 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.

Clinically significant drug-drug interactions

- 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

Drug-Drug interactions for CYP1A2

Substrates: Theophylline, amiodarone, warfarin-R, Agomelatine Inhibitors: Fluvoxamine

Drug-drug interactions for CYP2C19

Substrate: Warfarin-R Inhibitor: fluvoxamine

Drug-drug interactions for CYP2D6

Substrates: Metoprolol, Codeine, Tramadol Inhibitors: Fluoxetine, Paroxetine, Bupropion

Drug-drug interactions for CYP3A4

Substrates: Simvastatin, lovastatin, nifedipine, amlodipine, diltazem Inhibitors: grapefruit juice Inducers: Rifampicin, carbamazepine, phenytoin, St. John's Wort

Drugs with the fewest CYP interactions

Mirtazapine, escitalopram

Symptoms of antidepressant discontinuation syndrome

``` Flu-like symptoms Insomnia Nausea Imbalance Sensory Hyperarousal ```

Which drugs are likely to have discontinuation withdrawal syndrome?

Drugs with short half-life: paroxetine, venlafaxine

How should we discontinue the medications

gradual tapering over time, around 4 weeks

Goals of major depressive disorder therapy?

remission of symptoms, treatment adherence and prevention

Drug choice of antidepressants

- SSRI, SNRI, NaSSA, Bupropion > Agomelatine, Vortioxetine > TCA > MAOIs - Selection based on target symptoms, interactions

Amitriptyline dose

300mg max per day

fluoxetine dose

20mg om, 80mg max per day

mirtazapine dose

15-45mg per day

clomipramine dose

300mg per day

Antidepressants CA2 Flashcards

(43 cards)