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PR3136 PT IV > Depression NBT > Flashcards

Depression NBT Flashcards

1
Q

What is the 1st-line treatment for mild depression?

A

Psychosocial treatment (social support)

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2
Q

What is the treatment for moderate and severe depression?

A

Pharmacological & psychological treatments

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3
Q

What is the lifetime prevalence of Major Depressive Disorder?

A

5.8%

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4
Q

What is the lifetime prevalence of OCD and GAD?

A

ocd: 3%
gad: 0.9%

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5
Q

Among persons with a chronic physical illness, what is the % who also had a mental illness?

A

14.3%

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6
Q

Among persons with a mental illness, what is the % who also had a chronic physical illness?

A

50.6%

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7
Q

Do most people with serious mental health problems seek professional help?

A

No

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8
Q

What are the general risk factors for suicide in the general population?

A

A POOR, ELDERLY, LONELY, MAN with physical/mental COMORBIDITIES and previous ATTEMPTS

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9
Q

What is the etiology and pathophysiology (biological) of depression? (hypothesis)

A
  • hormonal influences: inc secretion of cortisol (major stress hormone)
  • IMPT: MONOAMINE hypothesis: dec neurotransmitters in brain (NE, 5-HT, DA)
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10
Q

What are some secondary causes for depression?

A
  1. Medical disorders

2. Pharmacological: drug-induced

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11
Q

What constitutes in medical disorders (secondary cause of depression)?

  • means it is RED in colour
A
  • endocrine disorders: hypothyroidism, cushing syndrome; bidirectional assoc btw depression and T2DM in women
  • Deficiency states: anaemia, wernicke’s encephalopathy
  • Infections: CNS infection, std/hiv, TB
  • Metabolic disorders: electrolyte imbalance (dec K+, Na+), hepatic encephalopathy
  • Cardiovascular: CAD, CHF, MI; depression as a risk factor for poor diagnosis among pts with ACS
  • Neurological: Alzheimer’s, Epilepsy, Pain, Parkinsons;, post-stroke
  • Malignancy, e.g. cancer
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12
Q

What constitutes in drug-induced (secondary cause of depression)?

A
  • withdrawal from alcohol, stimulants
  • lipid soluble b-blockers
  • psychotropics (cns depressants: bzd, opioids, barbiturates)
  • corticosteroids, systemic
  • isotretinoin
  • interferon beta-1a
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13
Q

How do we clinically diagnose Major Depressive Disorder?

A

Using the DSM-5 Diagnostic Criteria for Major Depressive Disorder

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14
Q

How to read/interpret DSM-5 Diagnostic Criteria for Major Depressive Disorder?

  • means RED in colour
A
  • At least 5 smx present during the same 2 week period and represent a change from previous functioning; ONE of the smx MUST be DEPRESSED MOOD or LOSS OF INTEREST

In.SAD.CAGES

  • 1) Decreased (In)terest*
    2) (S)leep: insomnia/hypersomnia
    3) Decreased (A)ppetite, weight loss
  • 4) (D)epressed mood; may be irritable mood in children*
    5) Impaired (C)oncentration and decision making
    6) (A)ctivity: psychomotor retardation or agitation
    7) Feelings of (G)uilt or worthlessness
    8) Decreased (E)nergy or fatigue
    9) (S)uicidal thoughts or attempts
  • Smx cause significant distress or impairment in social, occupational, or other impt areas of functioning
  • Smx are not caused by an underlying medical condition or substance
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15
Q

Which Depressive disorder are we focusing on?

A

Major Depressive Disorder (MDD)

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16
Q

What is the differential diagnosis for MDD? (may not be impt to revise)

A
  • adjustment disorder (w depressed mood): smx within 3 months of onset of a stressor; but once stressor gone, smx dont persist for additional 6 months
  • seasonal affective disorder
  • substance-induced mood disorder
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17
Q

What are the general assessments/evaluation prior to diagnosis and treatment of MDD?

A
  1. Hx of present illness
    - Psychiatric Hx: any Hx of maniac/hypomanic episode (antidepressants may cause ‘maniac switch’ in pts w underlying bipolar disorder)
  • Substance Use Hx (use of cig/EtOH/subs?)
  • Complete Medical Hx and Medication Hx (drug allergy, Hx of med response -effectiveness and tolerability; other meds/supplements; compliance; reassessing adherence to medications on every visit)
  • Family (any 1st-degree family hx of illness, tx and response), social, forensic, development, and occupational Hx; REVIEW pt’s psychosocial circumstances (isolation, lack of social support) on every visit
  • Physical and Neurological Exam
  • Mental State Exam (MSE); assess for suicidal/homicidal ideations and risks + reassess MSE on every interview to evaluate efficacy and tolerability
  • Labs and other investigations: vital signs; to exclude general medical conditions or substance-induced smx e.g. psychosis/depression/mania/anxiety/insomnia
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18
Q

What are some psychiatric rating scales that can be used to assess MDD?

A

Clinician-rated

  • Hamilton Rating Scale for Depression (HAM-D) “gold standard”; Remission: HAM-D =< 7 (therapy goal: smx-free)
  • others: CGI-S, MADRS

Self-rated:

  • screening tool: Patient Health Questionnaire (PHQ-2)
  • assessment tool (PHQ-9)
  • others: IDS-SR, BDI
  • Geriatric depression scale (GDS): 15-item short form; 30-item long form
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19
Q

What are the non-pharmacological management for MDD?

A
  • Sleep hygiene; improve sleep habits
  • Psychotherapy (not suitable for moderate-severe depression); usually combi with antidepressants
  • Neurostimulation: Electroconvulsive treatment (ECT); Repetitive Transcranial Magnetic Stimulation (rTMS)
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20
Q

What are the pharmacological management for MDD?

A

Antidepressants +/- Adjunctive meds: select based on target smx, comorbid conditions, drug interactions, prior response, preference

  • note that may not be used routinely in mild depression
  • CHOICE OF ANTIDEPRESSANTS:
  • 1ST LINE MONOTHERAPY: SSRI/ SNRI / Mirtazapine or Bupropion*
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21
Q

What is the duration/ phases of treatment for MDD?

A

1) Acute Phase Treatment: Adequate Trial = adequate dose + duration (4-8 weeks; Max 12 weeks); Delayed onset due to down-regulation of pre-synpatic autoreceptors
Time couse of treatment response:
- physical smx: improve in ~1-2 weeks (Sleep, appetite)
- mood smx may take longer time to improv ~ 4-6 weeks (reduce guilt and suicidal thoughts)

2) Continuation Phase
1st episode of MDD: continue at least 4-9 months after acute-phase treatment

  • Inititation + Acute Phase + Continuation = TOTAL AT LEAST 6-12 MONTHS*
  • longer-term maintenance therapy: if consider high risks, >= 2 episodes MDD and geriatric MDD (longer for elderly)
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22
Q

What is the total duration of treatment for MDD? IMPT

A

Initiation + Acute Phase + Continuation = TOTAL AT LEAST 6-12 MONTHS

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23
Q

What are the antidepressant classes?

A
  1. TCA: Amitriptyline, Clomipramine (not 1st line)
    2. SSRI: Fluoxetine, Fluvoxamine, Escitalopram
  2. SNRI: Venlafaxine, Duloxetine
  3. SMS: Serotonin modulators and stimulators (Vortioxetine)
  4. NaSSA: Mirtazapine
  5. RIMA: Reversible inhibitor of monoamine oxidase A (Moclobemide)
    Others: NDRI - Bupropion, Agomelatine, SARI - serotonin antagonist and reuptake inhibitor (Trazodone)
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24
Q

What are the steps of chemical transmission? (how it works)

A
  • transmitters are released into the synaptic cleft, where they either interact with presynaptic autoreceptors to regulate synthesis and release
  • interact with postsynaptic receptors to induce the events of the downstream signal transduction cascade
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25
Q

What are the common indicators for antidepressants? Pg 29

A

ALL TCA, SSRI, SNRI, SMS, NaSSA, RIMA, and others are indicated for DEPRESSION

+
For OCD, GAD, PD and SAD, look for drugs in anxiety lecture
-OCD: TCA clomipramine, SSRI fluoxetine, fluvoxamine and sertraline
- GAD: SNRI Venlafaxine and Duloxetine
- Anxiety disorders: SSRI Paroxetine, escitalopram
- Panic disorder: SSRI Citalopram and Sertraline
- Social anxiety disorder: RIMA Moclobemide

Off-label insomnia: Trazodone

Bulimia nervosa: fluoxetine

smoking cessation: bupropion

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26
Q

Which drugs have medical indications? (not really impt i guess)

A
  • TCA Amitriptyline: neuropathic pain; Migraine prophylaxis
  • TCA Clomipramine: Cataplexy associated with narcolepsy
  • TCA Imipramine: Nocturnal enuresis in children
  • TCA nortriptyline: Neuropathic pain
  • SNRI Duloxetine: diabetic neuropathy; stress urinary incontinence; Fibromyalgia; Chronic muscoloskeletal pain
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27
Q

Which drug class has more anticholinergic effects, sedation, orthostatic hypotension, seizures and conductance abnormalities?

A

TCA

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28
Q

Which drug class should we be less worried of antidepressant withdrawal smx? (its elimination half-life)

A
  • SSRI esp Fluoxetine is 4-6 days of elimination half-life

- SMS Vortioxetine 66 hours of elimination half life

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29
Q

What are the drug names of TCA?

A
  • Amitriptyline –> Nortriptyline
  • Imipramine –> Desipramine (desi selective for NET)
  • Dothiepin (Dosulepin)
  • Clomipramine
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30
Q

What is the MOA of TCA?

A

blocks reuptake of NE and 5-HT

  • Anticholinergic
  • H1 and a-adrenergic antagonism
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31
Q

What are the SE of TCA?

  • means words are in red
A

GI and sexual dysfn
Anticholinergic
Sedation, weight gain
Orthostatic dec BP, Arrhythmias
Seizure
Fatal on overdoses

TDM is possible

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32
Q

Which TCAs have lower anticholinergic, sedation and cardiotoxic SE?

A

2nd gen Nortriptyline, Desipramine

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33
Q

Which TCA is indicated for OCD?

A

Clomipramine

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34
Q

What are the drug names for SSRI?

  • means words are in red
A
    • Fluoxetine –> Norfluoxetine*
    • Fluvoxamine*
  • Escitalopram/ Citalopram
  • Sertraline
  • Paroxetine
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35
Q

What is the MOA of SSRI?

A

blocks reuptake of 5-HT selectively

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36
Q

What are the SE of SSRI?

A

GI and sexual dysfn

HA, transient nervousness during initiation

Insomnia: Fluoxetine

Hyponatremia (SIADH)

Bleeding risk, EPSE (Extrapyramidal movement disorder)

(‘serotonin syndrome’: tremor, hyperthermia, CV collapse)

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37
Q

What are some points to take note of for the half-life fluoxetine and norfluoxetine? SSRI

A

t1/2 of fluoxetine: 4-6d

norfluoxetine: 4-16d

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38
Q

What are some points to take note of for paroxetine? SSRI

A

Most anticholinergic, sedating, inc weight, t1/2 is short (withdrawal)
- does it mean high withdrawal syndrome?

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39
Q

What are some points to take note of for escitalopram/Citalopram? SSRI

A

QTc prolongation if high dose in elderly

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40
Q

What are some drug names of SNRI?

A
    • Venlafaxine –> Desvenlafaxine

- Duloxetine*

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41
Q

What is the MOA of SNRI?

A

Blocks reuptake of NE and 5-HT

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42
Q

What are some SE of SNRI?

A

As for SSRI.
inc BP
urinary hesitation for duloxetine)

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43
Q

What is duloxetine indicated for? SNRI

A

Indicated for Diabetic Peripheral Neuropathy, Fibromyalgia, Chronic musculoskeletal pain

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44
Q

What is the MOA of Vortioxetine? SMS

A

same as SSRI: blocks reuptake of 5-HT selectively

recall: Vortioxetine: 5HT1A agonist
5HT1B partial agonist
5HT1D, 5HT7, 5HT3 antagonist

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45
Q

What are the SE of vortioxetine? SMS

A

same as SSRI

GI and sexual dysfn

HA

transient nervousness during initiation

Hyponatremia (SIADH -Syndrome of inappropriate antidiuretic hormone secretion)

Bleeding risk

EPSE

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46
Q

What is the MOA of Mirtazapine? NaSSA

A

a2-adrenoceptor antagonist
inc 5-HT and NE
5-HT2 and 5-HT3, H1 antagonism

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47
Q

What are the SE of Mirtazapine?

A

Somnolence, inc appetite, weight gain (H1 antagonism)

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48
Q

How does Mirtazapine helps SSRI/SNRI?

A

*Reverse GI and sexual SE of SSRI/SNRI
*
(not cyroheptadine?)

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49
Q

What is the MOA of Bupropion? NDRI

A

Blocks reuptake of NE and Dopamine

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50
Q

What are the SE of Bupropion?

A

Seizure, psychosis (due to dopamine), insomnia (due to NE)

NOT suitable for eating disorders, h/o of seizures and psychosis

51
Q

How does Bupropion helps SSRI/SNRI?

A
  • decrease sexual SE of SSRI/SNRI
52
Q

Which drug is used for smoking cessation aid?

A

Bupropion

53
Q

What is the MOA of Moclobedmide? MAOI

A

Reversible MAOI-A (RIMA) - flushes out within 24 hours

most safest out of all MAOIs

54
Q

What is the SE of moclobemide?

A

hypertensive crisis

55
Q

What is the MOA of Trazodone?

A

Blocks reuptake of 5-HT;

Antagonises 5-HT2A, H1 and a1-adrenoceptor

56
Q

What is the SE of Trazodone?

A

As for SSRI:

  • Sedation
  • Orthostatic hypotension

Rare SE: Priapism
- Priapism is a prolonged erection of the penis

57
Q

Which drug is used more for insomnia than depression?

A

Trazodone

why not agomelatine?

58
Q

What is the MOA of agomelatine?

A

MT-1, MT-2 agonist;
5-HT2C antagonist

(used for sleep disorders?)

59
Q

What are some SE and contraindications for agomelatine

A

GI, inc LFTs; check LFTs at baselines and week 3,6,12,24

contraindicated: fluvoxamine, Ciprofloxacin

60
Q

What are some adjunctive medications for MDD?

A
  • hypnotics: benzodiazepines; Z-Hypnotics; Antihistamine
  • Melatonin prolonged-release (Circadin)
  • Others: Second-gen antipsychotics; Esketamine
61
Q

What are the MOA and SE of Benzodiazepines?

A

MOA: Potentiates GABA

SE: Sedation, drowsiness, amnesia, muscle weakness, ataxia. Less commonly, slurred speech, vertigo, HA, confusion

62
Q

What are the doses and t1/2 of lorazepam (ativan) and diazepam (valium)?

A

Lorazepam:
t1/2 - 12 (8-25) hr
adult dose: po 0.5-2mg HS PRN

Diazepam:
t1/2 - 20-54 hr
adult dose: po 2-15mg HS PRN

Minimise risk for dependence by limiting to 2-weeks PRN short-course therapy, at lowest effective dose

63
Q

What are the MOA and SE of Z-Hypnotics (Zolpidem and Zopiclone)?

A

MOA: preferentially binds to benzodiazepine-binding sites with gamma and alpha1 subunits (causes sedation)

SE: taste disturbance for Zopiclone; less commonly N/V, dizziness, drowsiness, dry mouth, HA; rarely amnesia, confusion, hallucination, nightmares, complex sleep behaviours (sleep-walking)

zolpidem (hypnotic), good for insomnia, not effective anxiolytics

64
Q

What are the doses and t1/2 of Zolpidem and Zopiclone?

A 
Zolpidem (Stilnox):
t1/2 - 1.5-4hrs
adult dose: >18yo; po 10mg HS PRN, CR 6.25-12.5mg HS PRN
Females: half dose
elderly: 5mg HS PRN

Zopiclone (Imovane):
t1/2 - 6hrs
adult dose: >18yo po 7.5mg HS PRN
elderly: po 3.75mg HS PRN (inc if necessary)

65
Q

What are the MOA, SE and doses for antihistamine - promethazine or hydroxyzine?

A

MOA: H1 antagonism
SE: Sedation, anticholinergic (Dry mouth, constipation)

Promethazine or Hydroxyzine: po 25-50mg ON PRN

hydroxyzine helps w itching, anxiolytic

66
Q

What are the MOA and SE of second-generation antipsychotics (SGA)?

A

MOA: 5-HT2A antagonism, 5-HT1A partial agonism

SE:
Aripiprazole/ Brexipiprazole: EPSE
Quetiapine, Olanzapine: Metabolic SE

67
Q

What are the Adjuncts to antidepressants and which drug is used for Treatment-resistant depression (TRD)?

A

Adjuncts to antidepressants for MDD: Aripiprazole, Brexipiprazole, Quetiapine XR (no dose stated)

for Treatment-resistant depression (TRD): Symbyax (Olanzapine 6mg + Fluoxetine 25mg capsule)

68
Q

What is the MOA, SE and dose for Esketamine (Spravato Nasal Spray)

A

MOA: NMDA receptor antagonist (ketamine)

SE: Dissociation (anaesthesia), dizziness, nausea, sedation, anxiety, inc BP, (euphoria?)

Adjunct to SSRI/SNRI (for Treatment-resistant depression (TRD)):
1 session = 56mg or 84mg (if elderly, lower dose)
W1-4: 2 sessions per week (1st session with 1 dose)
W5-8: 1 session per week
W9 onwards: 1 session q1-2w, x6mo at least

69
Q

What is the dose for amitriptyline and clomipramine (TCA)?

A

amitriptyline:
usual adult starting dose: 50-100 mg/day
usual adult dose range (per day): 30-300mg
max adult recommended dose (per day): 300mg

clomipramine:
usual adult starting dose: 25 mg/day
usual adult dose range (per day): 25-250mg
max adult recommended dose (per day): 300mg

70
Q

What is the dose for fluoxetine? SSRI

A

usual adult starting dose: 20mg om

usual adult dose range (per day): 20-60mg

max adult recommended dose (per day): 80mg

71
Q

What is the dose for desvenlafaxine XR? SNRI

A

usual adult starting dose: 50mg/day

usual adult dose range (per day): 50mg/day

max adult recommended dose (per day): 100mg

72
Q

What is the dose of mirtazapine?

A

usual adult starting dose: 15mg/day

usual adult dose range (per day): 15-45mg/day

max adult recommended dose (per day): 45mg

73
Q

What are the complementary and alternative medicines for MDD?

A
  1. Therapeutic lifestyle/ Behavioural changes: sleep hygiene, exercise, relaxation techniques, others, as appropriate
  2. Nutritional: Vit B12, L-methylfolate, Vit D, S-adenosylmethionine (SAMe), Omega-3 FA, 5-hydroxytryptophan (5-HTP)
  3. Herbal: St John’s Wort: significant DDI with antidepressant; DO NOT USE concomitantly with antidepressants
    - serotonin syndrome with antidep
74
Q

When to switch the antidepressants to manage partial/ no response?

A
  • Switch to alternative antidepressant when ineffective or intolerable to adequate dose in 1-4weeks (e.g. SSRI switched to SNRI, Mirtazapine, Bupropion, Agomelatine, or Vortioxetine)
75
Q

What to look out for when doing cross-titration of antidepressants?

A

watch for serotonin syndrome if combining serotonergic agents (e.g. dec Fluoxetine + inc Mirtazapine)

76
Q

What is a direct switch of serotonergic agents?

A

one SSRI can be stopped totally and the next serotonergic agent initiated

77
Q

How to switch serotonergic agent to non-serotonergic agent?

A

If switching from a serotonergic antidepressant used daily for the past 2 months to a non-serotonergic agent (E.g. switching from SSRI/SNRI to Bupropion), gradual cross-tapering over several weeks can reduce risk of Antidepressant Discontinuation Syndrome

78
Q

Why is the wash-out period for MAOIs necessary?

A

To prevent serotonin syndrome

e. g. switching from moclobemide to another antidepressant –> 24hr washout
e. g. if switching another antidepressant to moclobemide: wash-out at least 1 wk (or 5 wks if stopping fluoxetine)

79
Q

How to augment the antidepressant response?

A

Combine a 2nd antidepressant (with a different MOA) to the existing antidepressant with a partial response

e.g. add: Mirtazapine, Bupropion-SR, T3 (Liothyronine), Lithium, Adjunctive SGAs (quetiapine XR, Aripiprazole, Brexipiprazole)

80
Q

What is Treatment-resistant depression (TDR)?

A

No response to 2 adequate trials of antidepressants

81
Q

What are the treatment options for Treatment-resistant depression (TDR)?

A
  • neurostimulation: electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation
  • Symbyax PO capsule (Olanzapine 6mg + Fluoxetine 25mg capsule)
  • Spravato Nasal Spray (Esketamine 28mg per vial); as adjunct to SSRI/SNRI treatment
82
Q

Which special populations should we be cautioned when prescribing antidepressants?

A
  1. pregnancy: may consider NORTRIPTYLINE in late preg
  2. Breast-feeding: may consider SERTRALINE or MIRTAZAPINE
  3. postpartum depression - Brexanolone (positive allosteric modulator of GABA(a))
  4. Bipolar depression - lithium, lamotrigine, lurasidone, quetiapine, etc.
  5. Renal impairment - may consider VORTIOXETINE
  6. Hepatic impairment: AVOID agomelatine; Mild-moderate: consider VORTIOXETINE
  7. Post-MI depression: may consider SERTRALINE
  8. Elderly: AVOID TCAs, and anticholinergics, CNS, hypotensive or other cardiac SE
  9. Hyponatremia
  10. Suicidality
83
Q

what are the signs of experiencing hyponatremia and how to we monitor sodium levels?

A

Hyponatremia (drowsiness, confusion, or convulsions)

SIADH, usually in elderly
(Syndrome of inappropriate antidiuretic hormone secretion)

Associated with all antidepressants; mostly reported for SSRIs; possibly lower risk with agomelatine, mirtazapine or bupropion

Monitor serum sodium at baseline, 2nd week, 4th week, then 3-monthly

84
Q

Which population is highly associated with suicidality when taking antidepressants and how do we monitor/review/counsel affected patients?

A

suicidality and antidepressants in children and young adults

Association to suicidality in patients =< 24yo; require counselling to patients and caregivers for close monitoring, regular review

medication guide must be provided with dispensing, counselling should be documented in medical/medication records

85
Q

What are the symptoms of serotonin syndrome?

A

serotonergic agent + serotonergic agent –> serotonin syndrome

Mild: insomnia, anxiety, nausea, diarrhoea, HTN, tachycardia, hyper-reflexia

Moderate: agitation, myoclonus, tremor, mydriasis, flushing, diaphoresis, low fever (<38.5oC)

Severe: severe hyperthermia, confusion, rigidity, respiratory failure, coma, death

86
Q

What is the onset for serotonin syndrome and what causes (DDI) serotonin syndrome?

A

onset: acute (within 6-8hrs)

Causes: concomitant Rx of high-dose serotonergic meds, e.g.

  • triptans
  • sibutramine
  • opioids (tramadol, fentanyl, pethidine), dextromethorphan
  • linezolid, ritonavir
87
Q

What is the risk to look out for SSRI?

A

Inc risk of bleeding by at least 1-2 folds
- higher risks in elderly on NSAIDs, warfarin, steroids; consider adding PPI

  • consider stopping serotonergic antidepressant 2 weeks before surgery if high bleeding risks
  • agomelatine is the safest
88
Q

What should not be taken with CNS depressants and to be spaced 4-6 hours apart?

A

Do not take medication at the same time as alcohol, separate them 4-6 hours apart

89
Q

What should not be taken with benzodiazepines?

A

Benzodiazepines + Opioids = increased mortality (CNS depression)
avoid combi if possible or limit doses and duration

90
Q

Anticholinergic agents can cause what type of effects?

A

Excessive anticholinergic effects

delirium effect in elderly

91
Q

What are the substrates and inhibitors of CYP1A2?

  • means red in colour
A

Substrates: Theophylline, Amiodarone, Warfarin-R, Agomelatine
others: Clozapine, Phenothiazines

Inhibitors: Fluvoxamine, Ciprofloxacin - both inc AUC >= 5-folds or dec CL >80%

92
Q

What are the substrate of CYP2B6?

A

Efavirenz

93
Q

What are the substrates and inhibitor of CYP2C8?

A

Substrates: Repaglinide, Rosiglitazone, Paclitaxel

Inhibitor: Gemfibrozil (inc AUC >= 5-folds or dec CL >80%)

94
Q

What are the substrates and inhibitors of CYP2C19?

  • means red in colour
A

Substrates: Warfarin-R
others: Lanso/Pranto/Esomeprazole, SFUs: Tolbutamide

Inhibitors: Fluvoxamine, Omeprazole/Esomeprazole, Ticlopidine (all inc AUC >= 5-folds or dec CL >80%)

95
Q

What are the substrates and inhibitors of CYP2D6?

  • means red in colour
A

Substrates: metoprolol, codeine, hydrocodone, oxycodone, tramadol
others: desipramine, atomoxetine, risperidone, aripiprazole, olanzapine, thioridazine

Inhibitors: fluoxetine, paroxetine, bupropion (all inc AUC >= 5-folds or dec CL >80%)

96
Q

IMPT What are the substrates, inhibitors and inducers of CYP3A4?

  • means red in colour
A

Substrates: simvastatin, lovastatin, nifedipine, amlodipine, diltiazem
others: cyclosporine, sirolimus/ tacrolimus, ergotamine, fentanyl/ alfentanil, midazolam, risperidone, aripiprazole, quetiapine, ziprasidone, phenobarbitone

Inhibitors: grapefruit juice
clarithromycine, Telitromycin; EES
PI (indinavir, Ritonavir), Itra-/Keto-/Vori-conazole

Inducers: rifampicin, carbamazepine, phenytoin, St John’s Wort

all inhibitors and inducers inc AUC >= 5-folds or dec CL >80%)

97
Q

Which drugs have fewer CYP interactions?

  • means red in colour
A

Mirtazapine, Escitalopram, Venlafaxine, Desvenlafaxine, Vortioxetine

98
Q

What is antidepressant discontinuation syndrome?

A
  • worse with abrupt discontinuation of long-term regular therapy
    ~ especially with short T1/2 antidepressants such as Paroxetine and Venlafaxine
    ~Onset: 36-72hrs, Duration 3-7days but typically resolves over 1-2 weeks without treatment
99
Q

What are the smx of antidepressant discontinuation syndrome?

A 
FINISH
Flu-like smx: fatigue, muscle aches, HA
Insomnia
Nausea
Imbalance - dizziness
Sensory - 'electric shock' sensations, paresthesia
Hyperarousal -anxiety, agitation
100
Q

How to taper drugs to prevent antidepressant discontinuation syndrome?

A

If need to stop a long-term antidepressant therapy (after daily treatment >= 8 weeks), recommended to gradually taper over at least 4 weeks

Fluoxetine, Bupropion: generally unnecessary because of their very long T1/2 (Fluoxetine is 4-6 days of elimination half-life)

For the rest, taper by 25% every 1-2 weeks, or as gradually as clinically indicated

101
Q

How to discontinue benzodiazepines?

A
  • gradual discontinuation of long-term, high-dose use
  • e.g. dec dose by 25% weekly until reaching 50% of dose, then reduce one-eighth every 4-7 days, or as gradually as clinically indicated
102
Q

What are some patient counselling points for patients taking antidepressants?

  • means red in colour
A
  1. Antidepressants may take at least a couple of weeks to help with smx of low mood, poor sleep, and appetie, may need at least a couple of months to help iwith anxiety
  2. Dont take same time as alochhol (space 4-6hrs apart)
  3. tell your Dr, nurses and pharmacists the medicines you are using
  4. If you feel your condition is worsening, or feeling suicidal, agitated, or experiencing bothersome and persistent SE, contact DR asap
  5. Possible SE: Drowsy, Insomnia, Dizzy/Light-headedness/ Stomach upset/ Changes in sexual function

Sexual dysfn - SE less likely with Mirtazapine, Bupropion, Agomelatine

PIL to search for medication in HealthHub

103
Q

SUMMARY

How to diagnose MDD?

A
  • At least 5 out of 9 smx In.SAD.CAGES (INCL depressed mood D or loss of interest In), over the most of the same 2-week period, causing significant distress or functional impairment.
104
Q

SUMMARY

Are MDD smx are caused by drugs/ another medical condition?

A

No.

Smx are not drug-induced and not caused by another medical condition

105
Q

SUMMARY

What is the goal of therapy?

A

Remission of smx, treatment adherence, Suicide prevention

106
Q

SUMMARY

What are the non-pharmacological therapies for MDD?

A

Sleep hygiene, Psychotherapy; severe MDD may require neurostimulation (ECT)

107
Q

SUMMARY

Which is the first-line antidepressants? and order the drugs from the 1st line to last line

A

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

Selection based on target smx, interactions (with other drugs, comorbidities or food), prior response, patient preference

108
Q

SUMMARY

How long is the acute phase treatment?

A

4-8 weeks on adequate dose

1-2 months

109
Q

SUMMARY

How long does it take to improve physical smx after acute phase treatment is initiated?

A

Physical smx (e.g. poor sleep or appetite) may improve in 1-2 weeks

110
Q

SUMMARY

How long does it take to improve mood smx after acute phase treatment is initiated?

A

Mood smx may take longer to improve, e.g. > 6 weeks

111
Q

SUMMARY

How long is the continuous phase treatment?

A

additional 4-9 months

112
Q

SUMMARY

What is the total duration for acute and continuous phase?

A

at least 6-12 months

1-2 months + 4-9 months

113
Q

SUMMARY

when should adjunctive medication be given and how long is the duration?

A

only if needed, short course of PRN hypnotics/anxiolytics

114
Q

SUMMARY

How efficacious are antidepressants?

A
  • all antidepressants are similar in efficacy for uncomplicated 1st episode MDD
115
Q

SUMMARY

What is duloxetine indicated for?

A
  • Duloxetine also indicated for diabetic peripheral neuropathy, fibromyalgia and chronic musculoskeletal pain
116
Q

SUMMARY

What are the side effects of all serotonergic agents (SSRI, SNRI, SMS, TCA)?

A

GI side effects, sexual dysfunction

117
Q

SUMMARY

What is the SE of venlafaxine?

A

cause/worsen HTN

118
Q

SUMMARY

What is the SE of Mirtazapine?

A

Cause sedation and weight gain (may be beneficial for insomnia and poor appetite);
may reverse sexual SE of serotonergic agents

119
Q

SUMMARY

What is the SE of Bupropion?

A

no serotonergic effects (hence no sexual SE), BUT not suitable for hx of seizures, psychosis or eating disorders

120
Q

SUMMARY

What are the SE of TCAs?

A

Poor tolerability (Sedation, anticholinergic, orthostatic hypotension, arrhythmias, seizures, fatal on overdose)

121
Q

SUMMARY

Which age group is associated with Suicidality?

A

association in patients =< 24yo need to counsel patients and caregivers

122
Q

SUMMARY

Which drugs have minimal CYP interactions?

A

Mirtazapine, Escitalopram, Venlafaxine, Desvenlafaxine, Vortioxetine

123
Q

SUMMARY

What are the significant Pharmacodynamic interactions?

A
  • CNS depression*

* Serotonin syndrome*

124
Q

SUMMARY

How to discontinue antidepressants?

A

Taper over 4 weeks (after long-term use), to minimise antidepressant discontinuation syndrome

PR3136 PT IV (17 decks)

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