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PHRM 845 Module #1 > Lecture 69 - Pharmacotherapy of Depression > Flashcards

Lecture 69 - Pharmacotherapy of Depression Flashcards

1
Q

Risk of Recurrence for Depression

A

Risk of Recurrence:
1 episode: 50-60%
2 episodes: 70%
3 episodes: 90%

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2
Q

Recurrence

A

Risk becomes lower over time as duration of remission increases
Persistent mild symptoms during remission is a predictor of recurrence
Function deteriorates during the episode and goes back to baseline upon remission

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3
Q

DSM-5 Diagnostic Criteria

A

At least one of the symptoms must be depressed mood or loss of interest or pleasure in doing things

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4
Q

DSM-5 Diagnostic Criteria Mnemonic

A

SIGE CAPS
Sleep (insomnia/hypersomnia)
Interest decreased (anhedonia)
Guilt/worthlessness
Energy loss/fatigue
Concentration difficulties
Appetite change (increase or decrease)
Psychomotor agitation/retardation
Suicidal ideation

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5
Q

Self-administered rating scales

A

patient health questionnaire (PHQ-9): developed for primary care setting, used repeatedly to determine efficacy and treatment
mood disorder questionnaire (MDQ): can be used to rule out bipolar disorder

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6
Q

Goals of Treatment

A
  1. reduce or eliminate s/s of depression
  2. restore occupational and psychosocial functioning to baseline
  3. reduce the risk of relapse and recurrence
  4. reduce the risk of harmful consequences (suicidal ideation)
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7
Q

Phases of treatment

A

Acute: 6-12 weeks or remission of sx; goal is to induce remission
Continuation: 4-9 additional months, recommended for all pts; goal is to prevent relapse
Maintenance: patient-specific duration; often indefinite treatment if >/= 3 major depressive episodes; goal is to prevent recurrence

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8
Q

Risk of Suicidality

A

Boxed warning for suicidality in ALL antidepressant medications (for patients aged < 24 years of age)
*Decreased risk in ≥ 65 years old

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9
Q

SSRIs

A

citalopram
fluoxetine
fluvoxamine
paroxetine
sertraline

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10
Q

Citalopram

A
  • Dose-dependent QTc prolongation
  • Substrate of 2C19 and 3A4
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11
Q

Fluoxetine

A
  • Long half-life (96-144 hours)
  • Activating potential
  • 2D6 inhibitor, 3A4 inhibitor (norfluoxetine)
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12
Q

Fluvoxamine

A
  • Inhibitor 1A2, 2C19
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13
Q

Paroxetine/Paroxetine CR

A
  • MUST taper due to anticholinergic effects
  • Weight gain, sedation
  • Septal wall defect risk to the fetus
  • Inhibitor 2D6, 2B6
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14
Q

Sertraline

A
  • More GI upset than other antidepressants
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15
Q

SSRIs – Adverse Effects/Key Points

A

Weight gain (paroxetine)
Weight loss (fluoxetine)
Increased bleeding risk (platelet inhibition)
Hyponatremia (especially in elderly)
Sexual dysfunction

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16
Q

SNRIs

A

desvenlafaxine
duloxetine
levomilnacipran
venlafaxine

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17
Q

Desvenlafaxine

A
  • Active metabolite of venlafaxine
  • Dose-limiting side effect: nausea
  • No major CYP interactions
18
Q

Duloxetine

A
  • Slow titration or divided dosing help with nausea
  • FDA warning for hepatotoxicity
  • Inhibitor 2D6
19
Q

Levomilnacipran

A
  • MUST adjust in renal impairment or strong 3A4
  • Substrate 3A4
20
Q

Venlafaxine

A
  • Must be >150 mg/day to have NE effects
  • 2D6 inhibitor at higher doses
21
Q

SNRIs – Adverse Effects/Key Points

A

Useful in pain syndrome, musculoskeletal pain, fibromyalgia, and neuropathic pain
Duloxetine: Obtain LFTs at baseline and when symptomatic or every 6 months
Blood pressure elevation
Nausea

22
Q

TCAs

A

Amitriptyline (Elavil): Tertiary amine
* Used to lower doses for neuropathic pain

23
Q

TCAs – Adverse Effects/Key Points

A

Side effects often limit higher doses:
* CNS: sedation, reduced seizure threshold, confusion
* Anticholinergic: blurred vision, urinary retention, constipation
* Cardiovascular: orthostatic hypotension, tachycardia
* Other: weight gain, sexual dysfunction
Narrow therapeutic index:
* Fatal in overdose as low as 1000 mg (~4-10 tablets) due to cardiac arrhythmias or seizures

24
Q

MAO Inhibitors drugs

A

isocarboxazid
phenelzine
selegiline
tranylcypromaine

25
Q

MAO Inhibitors Clinical Pearls

A
  • Must have 2 week washout period before switching antidepressants (5 week washout period if switching from fluoxetine)
  • All require tyramine diet except selegiline 6 mg/24 hour patch
  • Caution due to hypertensive crisis and serotonin syndrome
26
Q

Selegiline patch

A

Tyramine diet NOT required with the 6 mg patch

27
Q

MAOis – Hypertensive Crisis

A
  1. Tyramine diet is required with MAOis:
    * Tyramine is degraded by monoamine oxidase → MAOis inhibit monoamine oxidase → Increase in tyramine increases blood pressure
  2. What is included in a tyramine diet?
    * Smoked, aged, pickled meats or fish; sauerkraut; aged cheeses; yeast extracts; flava beans; beer; wine
  3. What about in small amounts?
    * Beer, wine, avocados, meat extracts, caffeine, chocolate
28
Q

Bupropion (Wellbutrin)

A

Mechanism:
* Dopamine and norepinephrine reuptake inhibitor
* Stimulating – insomnia and appetite suppression
Pearls:
* 2D6 Inhibitor
* Contraindicated in active seizure disorder and eating disorders
* Can be used in combination with SSRI/SNRIs
Dosing:
SR/XL dosing

29
Q

Mirtazapine (Remeron)

A

Dosing: Sedation and increased appetite occur with doses ≤ 15 mg/day
Pearls: Warnings: agranulocytosis, increased cholesterol; Can be used in combination with SSRI/SNRIs

30
Q

Trazodone (Desyrel)

A

Mechanism: Selectively inhibits neuronal reuptake of serotonin and acts as an antagonist at 5HT1, 5HT2, H1 and α1
Dosing: Higher doses needed for depression
Side effects: Orthostatic hypotension; Risk of priapism – medical emergency

31
Q

Vilazodone (Viibryd)

A

Mechanism:
* Primarily SSRI, may have some 5HT1a agonism which may provide anxiolytic effects
* Do not use in combination with SSRI/SNRIs
Pearls:
* Take with food - Significant nausea; Bioavailability increases with food
* Substrate 3A4

32
Q

Vortioxetine (Trintellix)

A

Mechanism:
* SSRI + 5HT1A agonist + 5HT3 antagonist
* Do not use in combination with SSRI/SNRIs
Pearls:
* Possibly less sexual dysfunction
* Substrate 2D6
* Nausea

33
Q

Serotonin Syndrome

A

Medical emergency due to excessive amounts of serotonin in the CNS

34
Q

Serotonin Syndrome - Treatment

A

Stop the offending agent + supportive care
Potentially could use serotonin blockers
Cyproheptadine → variable efficacy
70% of patients recover within 24 hours

35
Q

Antidepressant Withdrawal Syndrome

A

Common with ALL antidepressants EXCEPT fluoxetine
Antidepressants with anticholinergic activity should be tapered no matter what

36
Q

Augmentation – Atypical Antipsychotics

A

FDA-approved augmentation agents:
* Aripiprazole (Abilify)
* Brexpiprazole (Rexulti)
* Cariprazine (Vraylar)
* Quetiapine

37
Q

Antidepressants for Specific Purposes

A

post-partum depression
treatment-resistant depression

38
Q

Post-partum depression

A

allosteric modulator of alloprenanolone
* Brexanolone
* Zuranolone

39
Q

Treatment-resistant depression

A

Esketamine Nasal Spray – NMDA receptor antagonist

40
Q

Overall Key Counseling Points

A

Abrupt discontinuation can lead to antidepressant withdrawal syndrome
Possible increase in suicidal thinking during the first few weeks of therapy

PHRM 845 Module #1 (50 decks)

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