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Pharm III - Exam 4 > Antidepressants > Flashcards

Antidepressants Flashcards

1
Q

What do the symptoms of MDD reflect changes in?

A

Norepi
Serotonin (5HT)
Dopamine

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2
Q

Hospitalization of MDD patients is based on:

A
  • Suicide risk
  • Physical state of health
  • Support system
  • Presence of psychotic features
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3
Q

Treatment phases of MDD

A
  1. Acute: lasts 6-8 wks, goal is remission of symptoms
  2. Continuation: lasts 4-9 mos, eliminate residual symptoms and prevent relapse
  3. Maintenance: lasts 12-36 mos, goal is to prevent recurrence
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4
Q

Response to antidepressants

A
  • 65-70% of pts improve
  • Well documented placebo effect
  • ADEs may occur immediately
  • Resolution of symptoms may take 2-4 wks or longer
  • Adherence is essential to success
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5
Q

Black box warning of antidepressants

A

ALL carry warning of increased suicidality risk in 18-24 yo during initial stages of treatment

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6
Q

How do TCAs work?

A
  • Potentiate activity of NE and 5HT via reuptake blockade

- Block M1, a1, H1 receptors

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7
Q

What can TCAs be used to treat besides depression?

A
  • Enuresis
  • Migraines
  • Nausea w/chemo
  • Neuralgia
  • Urticaria
  • OCD
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8
Q

Which TCAs block 5HT reuptake more than NE reuptake?

A

Amitriptyline

Clomipramine

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9
Q

Which TCAs block NE reuptake more than 5HT reuptake?

A

Desipramine

Nortriptyline

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10
Q

TCA metabolism?

A

Hepatic - CYP1A2, 3A4, 2D6

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11
Q

TCA ADEs

A
  • Tachy
  • Orthostatic hypotension
  • Cardiac rhythm changes
  • Wt gain
  • Sedation
  • Lowers seizure threshold
  • Sexual dysfunction
  • Narrow therapeutic index
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12
Q

How do tertiary amine TCAs compare to secondary amine TCAs?

A
  • More pronounced anticholinergic, antihistaminergic, hypotensive effects
  • Avoid in elderly due to postural hypotension, risk of fall, and other CV effects
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13
Q

TCA contraindications

A
  • BPH
  • Closed angle glaucoma
  • Cardiac disease
  • Hepatic impairment
  • Elderly
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14
Q

TCA drug interactions

A
  • Avoid other CYP450 drugs
  • May increase vasopressor response to direct acting sympathomimetics
  • Additive adverse effects w/other agents w/serotonergic, anti-ACh, sedative or hypotensive properties
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15
Q

Examples of MAOIs

A

Phenelzine
Tranylcypromine
Selegiline transdermal patch

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16
Q

How do MAOIs work?

A

Block metabolism of NE, 5HT, DA via inhibition of MAO enzyme

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17
Q

Common ADEs of MAOIs

A
  • Orthostatic hypotension
  • Dizzy
  • Mydriasis
  • Edema
  • Piloerection
  • Tremor
  • Wt gain
  • Insomnia
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18
Q

Rare ADEs of MAOIs

A

Allergic reactions
Hepatic dysfunction
Blood dyscrasias

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19
Q

Describe hypertensive crisis caused by MAOIs

A
  • Occurs after ingestion of tyramine containing foods/drugs
  • Tyramine is metabolized in gut by MAO enzymes (causes release of NE from presynaptic sites)
  • Medical emergency
  • HTN, occipital HA, neck stiffness, diaphoresis
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20
Q

What MAOI does not require as much dietary restriction?

A

Selegiline transdermal patch at 6 mg/24 hrs

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21
Q

MAOI drug interactions

A
  • Drugs that can precipitate HTN crisis (ephedrine, pseudoephedrine, phenylephrine)
  • Serotonin syndrome w/other antidepressants, narcotics
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22
Q

When is a washout period of 14 days required?

A

Switching from one MAOI to another antidepressant

Switching from other antidepressant to an MAOI

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23
Q

When is a 5 wk washout period required?

A

Switching from fluoxetine to an MAOI

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24
Q

Switching from MAOI to another antidepressant requires a ___ washout period

A

14 days

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25
Q

Switching from fluoxetine to an MAOI requires a ____ washout period

A

5 week

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26
Q

SSRI agents:

A
  • Fluoxetine
  • Sertraline
  • Paroxetine
  • Citalopram
  • Fluvoxamine
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27
Q

What is Fluvoxamine and what is it FDA approved for?

A

SSRI

FDA approved ONLY for OCD

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28
Q

Which SSRI is only approved for OCD use?

A

Fluvoxamine

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29
Q

What is 1st line pharm treatment of MDD?

A

SSRI

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30
Q

What can SSRIs be used for besides MDD?

A
  • Anxiety disorders (OCD, PTSD, GAD, etc.)
  • Bulemia
  • Premenstrual Dysphoric Disorder
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31
Q

Common ADEs of SSRIs

A
  • Nausea
  • HA
  • Sleep disturbances
  • Agitation/anxiety
  • Sexual dysfunction
  • Tremor
32
Q

Why are SSRIs more favorable than TCAs or MAOIs?

A

Less sedating and cause less weight gain

33
Q

Overdose of SSRIs?

A

Not lethal

34
Q

What is discontinuation syndrome of SSRIs?

A
  • Potential for withdrawal w/abrupt d/c of short acting SSRIs
  • Vivid dreams/nightmares, tremor, dizzy, crying spells, nausea, poor concentration
  • Occurs as early as 1-4 days or up to 25 days after d/c
  • Taper dose slowly over 7-10 days
35
Q

How should SSRIs be d/c?

A

Taper dose slowly over 7-10 days to avoid discontinuation syndrome

36
Q

How should most SSRIs be administered?

A

Recommended morning dosing d/t “energizing” effect

37
Q

Which SSRI can be dosed in morning or evening?

A

Paroxetine (depending on pt response)

38
Q

Fluoxetine drug interactions

A
  • 5 wk washout before starting MAOI (2 wk for all other SSRIs)
  • Potent inhibitor of CYP2D6
  • Weak inhibitor of CYP3A4 and 2C9 (phenytoin, warfarin)
39
Q

Sertraline drug interactions

A

Weak inhibitor of CYP2D6 at low doses (becomes more potent at higher doses, but still weaker than fluoxetine and paroxetine)

40
Q

Paroxetine drug interactions

A

Potent inhibitor of CYP2D6

41
Q

Citalopram and escitalopram drug interactions

A

Possible dose dependent inhibition of CYP2D6

42
Q

Fluvoxamine drug interactions

A
  • Potent inhibitor of CYP1A2

- Weak inhibitor of CYP2C9

43
Q

What are mixed 5HT/NE reuptake inhibitors?

A

Venlafaxine
Duloxetine
Desvenlafaxine

44
Q

How does Venlafaxine work?

A
  • Potent 5HT/NE reuptake inhibitor
  • At lower doses, much higher 5HT reuptake inhibition
  • Weak DA reuptake inhibitor
45
Q

Describe Venlafaxine

A
  • Mixed 5HT/NE reuptake inhibitor for MDD

- XR formulation is considered 1st line agent for MDD

46
Q

Metabolism of Venlafaxine

A

Substantial 1st pass via CYP2D6

47
Q

ADEs of Venlafaxine

A

Similar SE profile to SSRIs

48
Q

Venlafaxine drug interactions

A
  • Weak inhibitor of CYP2D6

- Serotonin syndrome

49
Q

How does Duloxetine work? What is it indicated for?

A
  • Balanced reuptake inhibitor of 5HT and NE

- FDA approved for MDD, diabetic neuropathy, fibromyalgia

50
Q

Which antidepressant is FDA approved for MDD, diabetic neuropathy and fibromyalgia?

A

Duloxetine

51
Q

What is Bupropion (Wellbutrin)?

A
  • Potent DA reuptake inhibition

- Very low reuptake inhibition of NE

52
Q

Indications for Bupropion (Wellbutrin)?

A

Depression

Smoking cessation

53
Q

Which antidepressant is indicated for smoking cessation?

A

Bupropion (Wellbutrin)

54
Q

Bupropion drug interactions

A
  • Use caution w/drugs known to lower seizure threshold
  • Use w/MAOI is CONTRAINDICATED
  • Very low inhibition of CYP2D6
55
Q

What is Nefazodone?

A
  • 5HT2 blocker AND reuptake inhibitor

- NOT a 1st line agent for depression

56
Q

Nefazodone ADEs

A
  • Black box warning: cases of life threatening hepatic failure
  • Potent CYP3A4 inhibitor
57
Q

Describe Trazodone

A
  • 5HT2 blocker AND reuptake inhibitor
  • Uncommonly used in depression (d/t ADEs)
  • Commonly used as sedative
  • Rare cases of priapism, QTc prolongation
58
Q

What is Mirtazapine?

A

Selective, presynaptic a2 receptor antagonist (enhancement of NE transmission)

59
Q

Mirtazapine ADEs

A
  • Sedation
  • Dry mouth
  • Constipation
  • Increased appetite, weight gain
60
Q

Mirtazapine drug interactions

A
  • Other sedating agents

- MAOIs

61
Q

Rare ADE of Vilazodone

A

May cause new or worsening cataracts with long term use

62
Q

Describe Levomilnacipran

A
  • SNRI (higher selectivity for NE than 5HT)
  • Primarily excreted by kidneys
  • Role in treatment of depression is unknown (only studied vs. placebo)
63
Q

Describe Vortioxetine

A
  • 5HT reuptake inhibitor and agonist
  • Role in depression treatment is unknown
  • MC ADEs: NV, constipation
64
Q

St. John’s wort in the treatment of depression?

A
  • Found to be safe and effective for mild-mod depression
  • NOT FDA regulated though
  • Significant drug interactions (potent CYP3A4 inducer)
65
Q

How does ECT work?

A
  • Small current used to induce a seizure
  • 30-60 secs in duration
  • Pts are given sedative and paralytic
  • 6 to 12 treatments (2-3 times per week)
66
Q

Indications for ECT?

A
  • High suicide risk
  • Rapid physical decline
  • Drug non-response or intolerability
  • History of prior response to ECT
67
Q

Contraindications to ECT?

A

NO absolute contraindications

68
Q

Limitations/ADEs of ECT

A
  • High relapse rate
  • Impairments in memory and neurocognitive function
  • Treatment-emergent mania
  • HA, nausea, muscle aches
69
Q

Describe depression in the elderly

A
  • Often mistaken for another disorder (e.g. dementia)
  • Depressed mood may be less prominent than other symptoms
  • Increased suicide attempts
  • Start LOW and go SLOW
70
Q

Depression treatment in pregnant/lactating patients

A
  • New evidence for potential resp distress and withdrawal syndrome in neonates whose mothers took SSRIs during pregnancy
  • ECT can be used safely during pregnancy
  • Sertraline and paroxetine appear in low concentrations in breast milk
71
Q

How is response to antidepressants measured?

A
  1. Non-response: less than 25% decrease in baseline symptoms
  2. Partial: 26-49% decrease
  3. Partial remission: over 50% decrease
  4. Remission: return to baseline functioning
72
Q

What is considered an adequate trial of antidepressants?

A

6-8 weeks at a maximum dosage

up to 12 wks in elderly

73
Q

How to prevent relapse with antidepressant treatment?

A

Continue at full therapeutic dose for 4-9 months after symptom remission (aka continuation therapy)

74
Q

When is lifelong maintenance therapy recommended in depression?

A

Patients with high risk of recurrence (2 or more previous episodes)

75
Q

Define treatment resistant depression

A

Remission not achieved after 2 optimal antidepressant trials (6-8 wks)

76
Q

Approaches to treatment resistant depression

A
  1. Switch to another SSRI or antidepressant w/different MOA

2. Augment w/another antidepressant, Li, T3, atypical antipsychotic, ECT, psychotherapy

Pharm III - Exam 4 (5 decks)

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