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PR3136 > Treatment of Depression > Flashcards

Treatment of Depression Flashcards

1
Q

Etiology & Pathophysiology of Depression

A
  • Biological
  • -> Hormonal influences: Increase cortisol
  • -> Monoamine hypothesis: Decrease in neurotransmitters in brain (NE, 5-HT, DA)
  • Psychological
  • Psychosocial
  • Genetics
  • Medical disorders
  • -> Endocrine disorders: Hypothyroidism, Bidirectional association between depression & T2DM in women
  • -> Neurological & Malignancy: -ve impact on mood
  • -> Deficiency states
  • -> Infections
  • -> Metabolic disorders
  • -> CVS (Depression as rf for poor diagnosis among pts with ACS)
  • Psychiatric disorders
  • -> Alcoholism (CNS Depressant: will eventually cause depression)
  • -> Anxiety disorders
  • -> Eating disorders
  • -> Schizophrenia
  • Drug-induced
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2
Q

DSM-5 Diagnostic Criteria for major depressive disorder

A

Criteria: At least 5 symptoms during same 2-week period
- One of the symptom has to be depressed mood/ lost of interest

“In.SAD.CAGES”
I: Decreased interest*
S(leep): Insomnia
A(petite): Decreased appetite/weight loss
D: Depressed mood*
C(oncentration): Impaired conc & decision making
A(ctivity): Psychomotor retardation/agitation
G: Guilt/ unworthiness
E(nergy): Decreased energy/fatigue
S: Suicidal thoughts or attempts

  • Symptoms cause significant depression/impairment
  • Not caused by underlying medical condition/substance
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3
Q

General Assessments of Depression

A
  • Hx of present illness, Psychiatric hx, Substance use hx, Complete medical & medication hx, family social forensic developmental & occupational hx
  • Phy & neurological exam
  • Labs & other investigation (To exclude general medical conditions or substance-induce symptoms)
  • Mental state exam (MSE)
  • -> Assess for suicidal/homicidal ideation & risks
  • -> Reassess MSE on every interview

Psychiatric rating scales
Clinician-rated: Hamilton rating scale for depression
(HAM-D) “Gold standard”
Self-rated: Screening -> PHQ-2
Assessment tool -> PHQ-9
(Proceed if pt ans ‘yes’ to either qn in PHQ-2)
Geriatric depression scale: 15-item short form
30-item long form

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4
Q

Non-pharmacological treatment of Depression

A
  • Sleep hygiene
  • Psychotherapy
  • Neurostimulation:
    Electroconvulsive treatment (ECT) - for severe refractory
    cases
    Repetitive Transcranial magnetic stimulation (rTMS)
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5
Q

Pharmacological treatment of Depression

A

Mod-severe depression, certain anxiety disorders & dysthmia:

Antidepressants +/- Adjunctive meds
- Choice based on target symptoms, comorb conditions, DDI, prior response, preference

1st line: SSRI/SNRI/Mirtazapine (subsidised)
Buproprion

SSRI, SNRI, NaSSA, Buproprion > Agomelatine > Vortioxetine > TCA > MAOIs

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6
Q

Phases of Depression Treatment

A

Acute phase:

  • Adequate trial = adequate dose + duration (4-8wks)
  • Delayed onset due to down-regulation of pre-synaptic autoreceptors*
  • Phy symptoms may improve in ~1-2wks
  • Mood symptoms in ~4-6wks

Continuation phase:
- Continue for at least 4-9 mths after acute phase treatment

=> Total = 6-12mths

Longer-term Maintenance Therapy:
- Consider if high risks, >= 2 episodes MDD & geriatric MDD

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7
Q

Why are TCAs not favoured & the exception when it is still used?

A
  • Toxicity in overdose, strong anticholinergic, sedative, orthostatic hypotension effects, conductance abnormalities….

Exception:
Clomipramine for OCD (when SSRIs fail)

Note:
Amitriptyline & Clomipramine - Max: 300mg

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8
Q

Which antidepressants have long t1/2 so there’s < worry of antidepressant withdrawal syndrome?

A

Fluoxetine (SSRI): 4-6days
Vortioxetine (SMS): 66hrs
Buproprion

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9
Q

SSRIs

[Compare between options, SE & Additional notes]

A

Options:
- Fluoxetine (20mg OM, Max: 80mg): long t 1/2
- Fluvoxamine: > sedative
- Esticalopram/Citaprolam: More $ & Qtc prolongation
(high doses, elderly women) but less DDI
- Sertraline: Much safer
- Paroxetine: Most anticholinergic, sedating, increase wt,
short t1/s (withdrawal)

Side Effects:
GI (5-HT3) & Sexual dysfunction (5-HT2)
Initial jitters!!!
Insomnia (fluoxetine)
Hyponatremia (SIADH) - Cramps, muscle twitching
Bleeding risk; EPSE

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10
Q

SNRIs

[Compare between options, SE & Additional notes]

A

Options:

  • Venlafaxine: Has box warning for uncontrolled BP
  • Desvenlafaxine (50mg/day)
  • Duloxetine: Also indicated for Diabetic peripheral neuropathy, fibromyalgia, chronic muscoskeletal pain

Side Effects (As for SSRIs):

  • Increase BP
  • Urinary hesitation (Dulox)
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11
Q

NaSSA: Mirtazapine

[MOA, SE & Additional notes]

A

MOA:
Aims straight for the presynaptic membrane, alpha2-adrenoreceptor antagonist, increases 5-HT & NE, 5HT2,3 & H1 antagonism

Side Effects:

  • Somnolence
  • Increases appetite -> Weight gain

Note:
- Reverses sexual dysfunction of SSRI & SNRI

Dose: 15-45mg

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12
Q

NDRI: Buproprion

[MOA, SE & Additional notes]

A

MOA:
Blocks re-uptake of DA & NE

Side effects:
*Seizures
*Not suitable for eating d/o/seizures/psychosis
Insomnia
Psychosis

Note:

  • Decreases sexual dysfunction of SSRI & SNRI
  • Smoking cessation aid
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13
Q

Use of Moclobemide

A

Reversible MAOI-A

Use (Rare, 2nd/3rd line):

  • Atypical depression
  • Social phobia
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14
Q

Pointers to note for Agomelatine

A

Increases LFT

- Check at baseline & at week 3, 6, 12, 24

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15
Q

Pointers to note for Trazodone

A
  • Very sedating

- Rare SE: Priapism (painful penile erection)

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16
Q

Adjunctive medications for Depression

A

1) Benzodiazepines (eg. Lorazepam, Diazepam)
- SE: Sedation, drowsiness, amnesia, muscle weakness
- Note: Limit to 2 weeks PRN, lowest effective dose

2) Z-Hypnotics (eg. Zolpidem, Zopiclone)
- Causes sedation
- SE: Taste disorders (zopiclone), complex sleep disorders eg. sleep walking
- Note: Half dose of Zolpidem for females (6.25mg alt day)

3) Antihistamine (eg. Promethazine/Hydroxyzine)
- SE: Sedation, anticholinergic (dry mouth, constipation)

17
Q

Therapeutic lifestyle/behavioural changes for Depression

A
  • Sleep hygiene
  • Exercise
  • Relaxation techniques
  • Others, as appropriate
18
Q

DDI with antidepressants

A

1) St john’s wort
- Significant DDI, not to be used concomitantly

2) 2x Serotonergic Agents -> Serotonin syndrome
- SSRIs increase risks of bleeding (Higher risk in elderly on NSAIDs, Warfarin, Steroids -> Consider to + PPI/ Stop 2 weeks b/f surgery if high bleeding risks)
- Increases CNS depressants effects with Alcohol/other antidepressants
- “Do not take med at the same time as alcohol, separate them 4-6hrs apart”

3) Benzodiazepines + Opioids = Increased mortality
- CNS depression, avoid if possible

19
Q

Special populations & other considerations to consider in Depression

A

1) Pregnancy
- Nortripyline in late pregnancy

2) Breastfeeding
- Sertraline/ Mirtazapine

3) Elderly
- Avoid TCAs, anticholinergic, CNS, hypotensive or other cardiac SE
- SIADH (mostly for SSRIs, lesser risk for Agomelatine, Mirtazapine, Buproprion)
- -> Monitor serum Na+ at baseline, 2nd, 4th week thn 3mthly

4) Children & Young Adult
- Association to suicidality in pts <= 24yo, require counselling to patients

20
Q

Which antidepressants have fewer CYP interactions?

A
  • Mirtazapine
  • Esticalopram
  • Venlafaxine
  • Desvenlafaxine
  • Vortioxetine
21
Q

Managing partial/no response

A

Switching

  • When ineffective/intolerable to adequate dose in 1-4wks
  • Gradual tampering when switching from serotonergic -> non-serotoninergic agent
  • Wash-out period is necessary for MAOIs

Augmentation
- Combine by adding a 2nd antidepressant: Mirtazapine, Quetiapine XR, Aripriprazole, Brexipiprazole

Treatment-Resistant Depression

  • Neurostimulation: ECT, rTMS
  • Symbyax oral capsule
  • Spravato nasal spray as adjunct to SSRI/SNRI treatment
22
Q

Antidepressant Discontinuation Syndrome

A
  • Worse with abrupt discontinuation syndrome
  • -> Esp with short t1/2 antidepressants: Paroxetine, Venlafaxine

Symptoms: FINISH

  • Flu-like symptoms (fatigue, MA, HA)
  • Insomnia
  • Nausea
  • Imbalance (dizziness)
  • Sensory (‘electric shock’ sensations)
  • Hyperarousal (anxiety, agitation)
23
Q

Patient Counselling for Depression

A
  • May take a couple of weeks to help with symptoms of low mood/poor sleep/appetite, at least a couple of mths to help with anxiety
  • Do not take same time as alcohol (4-6h apart)
  • To contact Dr asap if you feel your condition worsening/ feeling suicidal/ agitated/ bothersome & persistent side effects

Possible Side Effects:

  • Drowsy
  • Insomnia
  • Dizzy/light-headedness
  • Stomach upset
  • Changes in sexual dysfunction (can be reversed & treated if it occurs)
24
Q

How to discontinue antidepressants?

A

Taper over 4 weeks

PR3136 (14 decks)

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