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Therapeutics IV > Mngt Depression - Concepts > Flashcards

Mngt Depression - Concepts Flashcards

1
Q

Most prevalent type of depression

A

MDD (Major Depressive Disorder), 5.8% lifetime prevalence

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2
Q

A single sentence that sums up 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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3
Q

Main concept explaining the pathophysiology of Depression

A

Monoamine Hypothesis:

  • Decreased Neurotransmitters (NT) in brain
  • NTs are: NE, 5HT, DA
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4
Q

Name the three broad secondary causes for depression

A
  1. Medical disorders
  2. Psychiatric Disorders
  3. Drug-induced
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5
Q

Name some examples of medical disorders that could be a secondary cause for depression

A
  1. Endocrine disoders (E.g. hypothyroidism)
  2. CVD like CAD, CHF, MI
  3. Others:
    - Deficiency states (anemia)
    - infecitons (esp CNS)
    - Metabolic disorders (like electrolyte imbalance)
    - Neurological like alzheimers, epilepsy
    - Malignancy
    (M-MIND)
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6
Q

Some examples of psychiatric disorders that are possible seccondary causes for depression

A
  1. Alcoholism
  2. Anxiety disorders
  3. Eating disorders
  4. Schizo
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7
Q

Name the most important drug-induced secondary cause for depression

A

Withdrawal from alcohol and stimulants

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8
Q

Acronym for the Clinical presentation of depression. What do each letter stand for?

A

IN SAD CAGES

  • Interest: decreased
  • Sleep: Insomnia/hypersomnia
  • Appetite: decreased + weight loss
  • Depressed mood (may be irritable in children)
  • Concentration decreased, impaired decision
  • Activity: Psychomotor retardation/agitation
  • Guilt: feeling of worthlessness
  • Energy: Decreased (fatigue)
  • Suicidal thoughts or attempts
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9
Q

Consequence of sx in depression

A

Significant distress or impairment in social/occupational/other important areas of functioning

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10
Q

When dx depression, what is to be ruled out that is MOST important

A

Sx NOT caused by:

  • Underlying medical condition
  • Substance abuse
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11
Q

What is the DSM-5 diagnostic criteria to dx MDD?

A
  1. ≥5 sx present in the SAME 2-week period and represent a change from previous functioning
  2. ONE sx must be either “depressed mood” or “loss of interest”
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12
Q

What is considered one most important thing to asses for BEFORE starting ADs

A

Hx of mania/hypomania

  • Usually ask “time of past where you never felt need to sleep (less than 3h still can function)
  • To rule out bipolar depression, in which antidepressant will worsen the situation
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13
Q

Gold Standard scale for Psychiatric disorders. What is the score for the scale that represents remission, and that represents response?

A

Hamilton Rating Scale for Depression (HAM-D)

  • Remission: HAM-D ≤ 7
  • Response: 50% improvement
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14
Q

Tx goal of depression

A
  • Sx-free

- HAM-D: 100% improvement in the very last two months of tx

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15
Q

List some examples of Non-Pco tx for Depression. How effective are they in the different severity of depression?

A
  1. Sleep Hygiene: For all types
  2. Psychotherapy:
    - Mild: Can be monotherapy
    - Mod-Severe: Must be used with ADs
  3. Neurostimulation like ECT and rTMS: For severe only

(rTMS = repetitive transcranial magnetic stimulation)

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16
Q

What are the two most important things to assess for patients presenting with depression?

A
  1. Psychiatric hx: Any history of mania/hypomania?
    - ADs will not be effective and may cause “manic switch”
  2. Mental State Exam (MSE): Suicidal/homicidal ideations and risks
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17
Q

What are other general assessments of depression aside from Psychiatric and MSE?

A
  1. Hx of illness
  2. Substance use Hx
  3. Complete Medical and Medication Hx
  4. Fam/social/ developmental/occuaptional Hx
  5. Physical and Neurological exam to assess pain
  6. Labs

Main Point: Exclude general medical conditions, or substance-induced sx

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18
Q

First line AD Options for depression as monotherapy

A

SSRI, SNRI, Mirtazapine

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19
Q

What is an “Adequate Trial” of ACUTE phase tx of depression?

A

Adequate Trial = Adequate dose + Duration

  • Duration: 4-8wks, max 12wks
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20
Q

Estimated time to improve the different sx of depression. Account for the duration of onset

A
  • Physical Sx: 1-2 wks
  • Mood Sx: 4-6 wks

Reason: Time to down-regulation of pre-synaptic autoreceptors is quite long

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21
Q

Describe the Continuation Phase of Depression tx

A

For continuation phase of 1st episode of MDD:

  • Full titrated dose at least 4-9 months AFTER acute-phase tx
  • Continued even after sx resolve
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22
Q

Total duration of tx for depression

A

Total duration = Initiation + Acute Phase + Continuation

At least 6-12 months

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23
Q

MoA of Mirtazapine

A

NaSSA

NE and specific 5-HT AD

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24
Q

When are the situations to consider longer-term maintenance therapy for depression?

A
  • ≥ 2 episodes MDD (recurrent)

- Geriatric MDD

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25
Q

Describe the mechanism that leads to the downregulation of pre-synaptic autoreceptors, using SSRI as an example

A
  • Give SSRI = Inhibit 5HT pump
  • 5HT in synapse signals to autoreceptor to inhibit further release of 5HT (hence there is still lack of 5HT)
  • After weeks-months, synapse adapts by downregulating pre-synaptic autoreceptors
  • Thus, decreased negative feedback = more 5HT released = AD mood improvement
26
Q

The COMPELLING indications for Duloxetine in Depression (and GAD)

A
  1. Diabetic neuropathy
  2. Stress Urinary incontinence (SUI)
  3. Fibromyalgia (widespread muscle pain)
  4. Chronic musculoskeletal pain
27
Q

Drug class of Vortioxetine

A

Serotonin Modulators and Stimulators (similar to SSRI)

28
Q

Concern with Escitalopram/Citalopram

A

In Elderly: QTc Prolongation

29
Q

Significant DDI with SSRIs. Describe possible ways to avoid such DDI

A
  1. Serotonin Syndrome with another serotonergic agent
  2. Risk BLEEDING in ELDERLY with NSAIDs, Warfarin, Steroids
    - Consider PPI
    - Stop AD 2 weeks bef surgery
    - Use Agomelatine if needed
  3. Increased CNS depressant effect with other CNS depressant:
    - Avoid BZD, Opioids, Alc
  4. Excessive anti-M with other anti-M agents (since SSRI got anti-M SE)
30
Q

Caution of AD use in Children and Young Adults

A

Association to suicidality in ≤24yo, must COUNSEL

31
Q

SE of SSRIs

A
  1. NIDS (Nausea, Insomnia/Drowsy, Sex Dysfunc)
  2. SIADH: Caution for ELDERLY
  3. Bleeding Risk
  4. Weight gain due to increased appetite
32
Q

Disadvantages of Paroxetine

A
  1. Most Sedating, anti-M, Weight gain

2 Shortest half-life hence most withdrawal sx

33
Q

SE of SNRI

A
  1. All of SSRI
  2. Increased BP (due to more NE)
  3. Urinary Hesitation
34
Q

Advantage of fluoxetine

A

Very long half life

- Less withdrawal even in missed dose

35
Q

Main SE of Mirtazapine

A

Increased appetite causing weight gain

36
Q

Advantage of Mirtazapine

A
  • Reverse GI and sexual SE of SSRI/SNRI

due to H1 antagonism and 5HT2 antagonism

37
Q

MoA of Bupropion. What is its most important SE

A

MoA: NARI + DARI (dopamine)

SE: May cause Seizure

38
Q

Main AE of MAOI (hint: DFI)

A

Hypertensive crisis (due to tyramine effect)

39
Q

Before initiating Agomelatine, what must be assessed, and how frequently?

A

Baseline LFTs

frequent checks at 3,6,12,24 weeks
(aka 3x2x2x2)

40
Q

Main SE and concerns for TCAs

A
  1. GI and sexual dysfunction
  2. Anti-M effect
  3. Fatal on overdose
41
Q

List the classes of Medication used as adjunctive medications in Depression. State their purpose.

A
  1. BZDs: Insomnia
  2. Z-Hypnotics: Insomnia
  3. Antihistamine: Insomnia
  4. Second Gen Antipsychotics:
    - Adjunct OR for Tx-resistant depression
  5. Esketamine Nasal Spray: Adjunct
42
Q

List the BZDs used as adjunct in MDD. State its dosage regimen

A
  1. Lorazepam PO 0.5-2mg HS PRN

2. Diazepam PO 2-15mg HS PRN

43
Q

Recommended duration of use of BZD. Why is it so?

A

2 weeks PRN, to reduce risk for dependence

44
Q

SE of BZDs

A
  1. Sedation, Drowsiness

2. Amnesia

45
Q

List the Z-Hypnotics used in depression as adjunct. State its dosage regimen

A
  1. Zolpidem
    - PO 10mg HS PRN
    - PO 5mg HS PRN (Elderly)
    - CR PO 6.25-12.5mg HS PRN
  2. Zopiclone
    - PO 7.5mg HS PRN
    - PO 3.75mg HS PRN (Elderly)
46
Q

SE of Z-Hypnotics

A
  1. Zopiclone: Taste Disturbance
  2. Both: Sleep-walking (complex sleep behaviours)
    - Use in caution with hx of sleep-walking
47
Q

Herb to avoid in MDD therapy

A

St. John’s Wort due to DDI with many ADs

48
Q

Methods of switching between ADs, and from what to what?

A
  1. Cross-titrate: For Serotonergic AD to non-serotonergic agent, watch out for SS
  2. Direct switch: Stop one, initiate the other
49
Q

For no response, when to switch and how to switch?

A
  • Switch when ineffective/intolerable to adequate dose in 1-4wks
  • Change class (E.g. SSRI to SNRI)
50
Q

When switching between ADs, when is wash-out period necessary?

A

When switching out of MAOI

51
Q

What is considered tx-resistant depression (TRD)?

A

When two ADEQUATE TRIALS of ADs have failed

52
Q

For Elderly with SIADH, what must be done before and during AD therapy, and what are the drug of choice?

A
  1. Monitor serum Na at basline (then 2,4 week, then 3 monthly)
  2. Use lower risk drugs like Agomelatine, Mirtazapine, Bupropion
53
Q

Drug with fewer CYP interactions hence less DDI?

A
  1. Mirtazapine

2. Others: Escitalopram, Venlafaxine, Desvelafaxine, Vortioxetine

54
Q

ADs that are 2D6 inhibitors

A
  1. Fluoxetine
  2. Paroxetine
  3. Bupropion
55
Q

AD that is 1A2 inhibitor?

A

Fluvoxamine

56
Q

Food to avoid with AD therapy

A
  • Grapefruit Juice (3A4 Inhibitor)

- SJW (3A4 Inducer)

57
Q

Antihistamine used as adjunct in depression for insomnia. State its regimen

A

Promethazine or Hydroxyzine PO 25-50mg ON PRN

58
Q

Sx of AD discontinuation syndrome and its cause

A 
- Sx: FINISH:
Flu-like sx
Insomnia
Nausea
Imbalance - Dizziness
Sensory - "electric shock" sensations
Hyperarousal

Cause: Abrupt AD discontinuation of long-term regular therapy, onset in 36-72h

59
Q

ADs most prone to cause AD discontinuation syndrome and least to cause AD discontinuation (hence no need tapering)

A

Most likely:

  1. Paroxetine
  2. Venlafaxine

Least likely (due to long half-life):

  1. Bupropion
  2. Fluoxetine
60
Q

How to avoid AD discontinuation syndrome?

A

Taper over ≥4 weeks, usually 25% per 1-2weeks

61
Q

Problem with sudden withdrawal of BZDs

A
  1. Seizure

2. Hallucination

62
Q

How to avoid BZD discontinuation symptoms

A

Gradual discontinuation

25% weekly till 50% of dose, then 1/8 every 4-7d

Therapeutics IV (9 decks)

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