Antidepressants Flashcards

1
Q

How effective are antidepressant at treating MDD?

A

50% will recover fully; however, 20-35% will not improve substantially (an there is great inter-patient variability).

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2
Q

What are the four classes of antidepressants?

A

(1) SSRIs (most common); (2) SNRIs (also used in neuropathic pain; (3) TCAs; and (4) MAOIs (largely replaced by safer options; there is also a group of newer antidepressants that work through a variety of mechanisms.

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3
Q

Describe the mechanism of action for SSRIs:

A

They block the reuptake of serotonin within hours of administration; however it takes 3-6 weeks to achieve a therapeutic effect, implying a secondary mechanism.

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4
Q

What is the postulated second MOA of SSRIs?

A

A serotonergic feedback mechanism which allows serotonin to accumulate in the synaptic cleft; there is also evidence of secondary messenger cascades and alterations in gene expression.

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5
Q

How long does SSRI therapy typically last?

A

6-8 weeks in total; truncated therapy results in relapse 80% of the time.

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6
Q

What are the most common ADRs with SSRIs?

A

Reduced appetite, weight loss, excessive sweating, headache, insomnia, jitteriness, sedation, dizziness, and sexual dysfunction.

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7
Q

Describe the sexual dysfunction that occurs with SSRIs:

A

Decreased libido, and impotence occurs in 50% of patients; it generally does not go away and is a common reason for discontinuation.

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8
Q

Why is half-life important with SSRIs?

A

Half-life varies significantly between SSRIs; short half-life drugs have a high incidence of withdrawal effects, those with a longer half-life are more likely to “self-taper”.

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9
Q

Describe the withdrawal effects of SSRIs:

A

They often mirror a heart attack or flu-like symptoms – tachycardia, anxiety, dizziness, and nausea.

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10
Q

Which SSRIs have a short half-life?

A

Luvox (fluvoxamine); and Paxil (paroxetine).

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11
Q

Which SSRIs have a longer half-life?

A

Zoloft (sertraline); Celexa (citalopram); Lexapro (escitlopram); and Prozac (fluoxetine).

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12
Q

Which drug interactions can occur with SSRIs?

A

They should not be taken with MAOIs,, and they are 2D6 and 3A4 inhibitors.

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13
Q

Which SSRIs have the greatest potential for kinetic interactions?

A

Fluoxetine and paroxetine – must be especially careful with 2D6 substrates (metoprolol).

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14
Q

How do SNRIs work?

A

They block the reuptake of both serotonin and norepinephrine.

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15
Q

Describe the MOA for Effexor (venlafaxine):

A

It is more selective for serotonin reuptake inhibition, at larger doses it will also inhibit norepinephrine reuptake; it behaves similarly to SSRIs.

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16
Q

What are the ADRs for venlafaxine?

A

Nausea, insomnia, sedation, dizziness; increased diastolic BP.

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17
Q

Describe the kinetics of venlafaxine:

A

It has a very short half-life, and thus potential for causing serotonin withdrawal syndrome; however it has minimal CYP interactions.

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18
Q

How does Cymbalta (duloxetine) work?

A

It inhibits the reuptake of both serotonin and norepinephrine with high-affinity; it is used similarly to other SRIs, but with minimal effects on BP or weight.

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19
Q

Describe the considered secondary amine TCA?TCAs:

A

They inhibit the reuptake of both serotonin and norepinephrine; they are older drugs, equal in efficacy to SSRIs but with a problematic side-effect profile, and they are lethal in overdose.

20
Q

What are the other indications for SSRIs?

A

Migraine prophylaxis and neuropathic pain.

21
Q

Which drugs are considered tertiary amine TCAs?

A

Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.

22
Q

Which drugs are considered secondary amine TCAs?

A

Desipramine, nortriptyline,mamoxapine, and protriptyline.

23
Q

Which drug is considered tetracyclic?

A

maprotiline.

24
Q

What other receptors do TCAs have an affinity for blocking?

A

Muscarinic receptors, H1 histamine-receptors, and alpha-1 receptors; this activity creates many ADRs.

25
Q

What are the anticholinergic ADRs of TCAs?

A

Dry mouth, blurred vision, constipation, urinary hesitancy, tachycardia and ejaculatory difficulty; these are less common in secondary and tertiary amine TCAs.

26
Q

What are the anti-histaminergic ADRs that occur with TCAs?

A

Sedation, carbohydrate craving, and weight gain.

27
Q

What ADR is caused by alpha-1 blockade in TCAs?

A

Orthostatic hypotension.

28
Q

When are the cardiac effects of TCAs most concerning?

A

These are dose-related effects that occur primarily in susceptible individuals and in cases of overdose.

29
Q

What pre-existing conditions are TCAs contraindicated in?

A

Heart block, bundle branch block, and prolonged QT interval (TCAs can slow conduction through the AV node).

30
Q

What are the other cardiac concerns with TCAs?

A

Use great caution with other antiarrhythmics; they can block the antihypertensive effects of some drugs; they can cause significant orthostatic hypotension in those with congestive heart failure.

31
Q

Why are TCAs contraindicated in suicidal patients?

A

They have a low toxicity threshold; a 1-week supply is lethal in overdose.

32
Q

How do the MAOIs work?

A

They inhibit an enzyme on the outer membrane of the mitochondria responsible for catabolizing monoamines (such as dopamine). These drugs work on both MAO-A and MAO-B subtypes.

33
Q

What are the two MAOIs?

A

Nardil (phenylzine) and Parnate (tranylcyromine).

34
Q

When are MAOIs most effective?

A

They are effective at treating atypical depression (hypersomnia, hyperphagia, extreme fatigue, etc.)

35
Q

What is ENSAM (selegiline)?

A

An MAOI available as a 24 hour patch.

36
Q

How does Wellbutrin (bupropion) work?

A

It blocks the reuptake of norepinephrine and dopamine.

37
Q

What are the ADRs of bupropion?

A

Agitation, insomnia, weight loss, dry mouth, headache, constipation, and tremor; IR formulation may induce seizure.

38
Q

What are the benefits of bupropion over other antidepressants?

A

They are safe in cardiac disease; they do not cause sexual dysfunction; and they can also be used for smoking cessation.

39
Q

What are the downsides to bupropion?

A

They are NOT an anti-anxiety drug; they should not be used with MAOIs.

40
Q

What is Remeron (mirtazapine)?

A

An alpha-2 antagonist (increases release of serotonin and norepinephrine); H1-antagonist; and serotonin receptor antagonist.

41
Q

What are the ADRs of mirtazapine?

A

Somnolence, weight GAIN, dizziness, dry mouth, constipation, orthostatic hypotension, VERY sedating.

42
Q

What is mirtazapine most useful for?

A

Depression caused by cancer chemotherapy (increases appetite and anti amnetic).

43
Q

What is trazodone?

A

An older drug that inhibits serotonin uptake, blocks serotonin receptors, and blocks alpha-1 receptors.

44
Q

What are the ADRs of trazodone?

A

Sedation, orthostatic hypotension, headache, priapism (rare); arrhythmia.

45
Q

What is trazodone primarily used for today?

A

It is primarily used as a sleeping aid.