Antidepressants Flashcards
(45 cards)
How effective are antidepressant at treating MDD?
50% will recover fully; however, 20-35% will not improve substantially (an there is great inter-patient variability).
What are the four classes of antidepressants?
(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.
Describe the mechanism of action for SSRIs:
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.
What is the postulated second MOA of SSRIs?
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.
How long does SSRI therapy typically last?
6-8 weeks in total; truncated therapy results in relapse 80% of the time.
What are the most common ADRs with SSRIs?
Reduced appetite, weight loss, excessive sweating, headache, insomnia, jitteriness, sedation, dizziness, and sexual dysfunction.
Describe the sexual dysfunction that occurs with SSRIs:
Decreased libido, and impotence occurs in 50% of patients; it generally does not go away and is a common reason for discontinuation.
Why is half-life important with SSRIs?
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”.
Describe the withdrawal effects of SSRIs:
They often mirror a heart attack or flu-like symptoms – tachycardia, anxiety, dizziness, and nausea.
Which SSRIs have a short half-life?
Luvox (fluvoxamine); and Paxil (paroxetine).
Which SSRIs have a longer half-life?
Zoloft (sertraline); Celexa (citalopram); Lexapro (escitlopram); and Prozac (fluoxetine).
Which drug interactions can occur with SSRIs?
They should not be taken with MAOIs,, and they are 2D6 and 3A4 inhibitors.
Which SSRIs have the greatest potential for kinetic interactions?
Fluoxetine and paroxetine – must be especially careful with 2D6 substrates (metoprolol).
How do SNRIs work?
They block the reuptake of both serotonin and norepinephrine.
Describe the MOA for Effexor (venlafaxine):
It is more selective for serotonin reuptake inhibition, at larger doses it will also inhibit norepinephrine reuptake; it behaves similarly to SSRIs.
What are the ADRs for venlafaxine?
Nausea, insomnia, sedation, dizziness; increased diastolic BP.
Describe the kinetics of venlafaxine:
It has a very short half-life, and thus potential for causing serotonin withdrawal syndrome; however it has minimal CYP interactions.
How does Cymbalta (duloxetine) work?
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.
Describe the considered secondary amine TCA?TCAs:
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.
What are the other indications for SSRIs?
Migraine prophylaxis and neuropathic pain.
Which drugs are considered tertiary amine TCAs?
Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.
Which drugs are considered secondary amine TCAs?
Desipramine, nortriptyline,mamoxapine, and protriptyline.
Which drug is considered tetracyclic?
maprotiline.
What other receptors do TCAs have an affinity for blocking?
Muscarinic receptors, H1 histamine-receptors, and alpha-1 receptors; this activity creates many ADRs.
