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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
Describe the mechanism that leads to the downregulation of pre-synaptic autoreceptors, using SSRI as an example
- 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
The COMPELLING indications for Duloxetine in Depression (and GAD)
1. Diabetic neuropathy 2. Stress Urinary incontinence (SUI) 3. Fibromyalgia (widespread muscle pain) 4. Chronic musculoskeletal pain
27
Drug class of Vortioxetine
Serotonin Modulators and Stimulators (similar to SSRI)
28
Concern with Escitalopram/Citalopram
In Elderly: QTc Prolongation
29
Significant DDI with SSRIs. Describe possible ways to avoid such DDI
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
Caution of AD use in Children and Young Adults
Association to suicidality in ≤24yo, must COUNSEL
31
SE of SSRIs
1. NIDS (Nausea, Insomnia/Drowsy, Sex Dysfunc) 2. SIADH: Caution for ELDERLY 3. Bleeding Risk 4. Weight gain due to increased appetite
32
Disadvantages of Paroxetine
1. Most Sedating, anti-M, Weight gain | 2 Shortest half-life hence most withdrawal sx
33
SE of SNRI
1. All of SSRI 2. Increased BP (due to more NE) 3. Urinary Hesitation
34
Advantage of fluoxetine
Very long half life | - Less withdrawal even in missed dose
35
Main SE of Mirtazapine
Increased appetite causing weight gain
36
Advantage of Mirtazapine
- Reverse GI and sexual SE of SSRI/SNRI | due to H1 antagonism and 5HT2 antagonism
37
MoA of Bupropion. What is its most important SE
MoA: NARI + DARI (dopamine) SE: May cause Seizure
38
Main AE of MAOI (hint: DFI)
Hypertensive crisis (due to tyramine effect)
39
Before initiating Agomelatine, what must be assessed, and how frequently?
Baseline LFTs | frequent checks at 3,6,12,24 weeks (aka 3x2x2x2)
40
Main SE and concerns for TCAs
1. GI and sexual dysfunction 2. Anti-M effect 3. Fatal on overdose
41
List the classes of Medication used as adjunctive medications in Depression. State their purpose.
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
List the BZDs used as adjunct in MDD. State its dosage regimen
1. Lorazepam PO 0.5-2mg HS PRN | 2. Diazepam PO 2-15mg HS PRN
43
Recommended duration of use of BZD. Why is it so?
2 weeks PRN, to reduce risk for dependence
44
SE of BZDs
1. Sedation, Drowsiness | 2. Amnesia
45
List the Z-Hypnotics used in depression as adjunct. State its dosage regimen
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
SE of Z-Hypnotics
1. Zopiclone: Taste Disturbance 2. Both: Sleep-walking (complex sleep behaviours) - Use in caution with hx of sleep-walking
47
Herb to avoid in MDD therapy
St. John's Wort due to DDI with many ADs
48
Methods of switching between ADs, and from what to what?
1. Cross-titrate: For Serotonergic AD to non-serotonergic agent, watch out for SS 2. Direct switch: Stop one, initiate the other
49
For no response, when to switch and how to switch?
- Switch when ineffective/intolerable to adequate dose in 1-4wks - Change class (E.g. SSRI to SNRI)
50
When switching between ADs, when is wash-out period necessary?
When switching out of MAOI
51
What is considered tx-resistant depression (TRD)?
When two ADEQUATE TRIALS of ADs have failed
52
For Elderly with SIADH, what must be done before and during AD therapy, and what are the drug of choice?
1. Monitor serum Na at basline (then 2,4 week, then 3 monthly) 2. Use lower risk drugs like Agomelatine, Mirtazapine, Bupropion
53
Drug with fewer CYP interactions hence less DDI?
1. Mirtazapine | 2. Others: Escitalopram, Venlafaxine, Desvelafaxine, Vortioxetine
54
ADs that are 2D6 inhibitors
1. Fluoxetine 2. Paroxetine 3. Bupropion
55
AD that is 1A2 inhibitor?
Fluvoxamine
56
Food to avoid with AD therapy
- Grapefruit Juice (3A4 Inhibitor) | - SJW (3A4 Inducer)
57
Antihistamine used as adjunct in depression for insomnia. State its regimen
Promethazine or Hydroxyzine PO 25-50mg ON PRN
58
Sx of AD discontinuation syndrome and its cause
``` - 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
ADs most prone to cause AD discontinuation syndrome and least to cause AD discontinuation (hence no need tapering)
Most likely: 1. Paroxetine 2. Venlafaxine Least likely (due to long half-life): 1. Bupropion 2. Fluoxetine
60
How to avoid AD discontinuation syndrome?
Taper over ≥4 weeks, usually 25% per 1-2weeks
61
Problem with sudden withdrawal of BZDs
1. Seizure | 2. Hallucination
62
How to avoid BZD discontinuation symptoms
Gradual discontinuation | 25% weekly till 50% of dose, then 1/8 every 4-7d

Therapeutics IV (9 decks)

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