16: Antidepressants Flashcards
With regards to depression, list three sex differences.
10-25% of women versus 5-12% of men will become clinically depressed during their lifetime.
Women affected almost twice as often, probably due to hormonal changes.
Men are 4x more likely to commit suicide.
What is the monoamine theory for depression?
Deficit of monoamines: NA, 5-HT, and DA in brain. Decreases concentration in the synaptic cleft, reduces neurotransmission in brain.
What is the cortisol theory for depression?
Depressed patients have raised baseline cortisol concentration.
Aside from medication, what are two methods for treating depression?
Electroconvulsive therapy - success rate of 78%, effective for severe depression and in cases where alternate methods do not provide relief.
Psychotherapy - learning about disorder, improving quality of life.
Describe monoamine oxidase inhibitors (MAOIs). What were they initially developed for?
Phenelzine, tranylcypromine. Initially developed for tuberculosis.
Describe tricyclic antidepressants (TCAs). What were they initially developed for?
Imipramine, amitriptyline; second-generation amoxapine, maprotiline. Initially developed as antipsychotics.
MAOIs and TCAs are considered to be what generation of antidepressants? Why are they not commonly used?
First generation. Not commonly used due to drug/food interactions and side effect profile.
What comprises selective 5-HT reuptake inhibitors (SSRIs)?
Fluoxetine, citalopram.
What comprises selective NA reuptake inhibitors (SNRIs, NARIs)?
Reboxetine.
What comprises mixed mechanism antidepressants (SSNRIs)? What neurotransmitters are targeted?
Venlafaxine (5-HT, NA, DA), bupropion (DA, NA).
SSRIs, SNRIs, NARIs, and SSNRIs are considered to be what generation of antidepressants? Why are they more commonly used?
Second generation. Commonly used due to reduced side effects.
Describe the three atypical antidepressants and their benefits.
Mianserine: presynaptic α2 blocker. Sedative, anxiolytic.
Tianepine: 5-HT reuptake. Few adverse drug effects.
Viloxazine: NE reuptake. Not cardiotoxic or cholinolytic.
Describe the general pharmacology of antidepressants.
Similar absorption (SSRIs are slower), high protein binding (95%), extensive first-pass metabolism (inhibited by EtOH).
What are the half-lives of MAOIs, TCAs, SSRIs?
MAOIs: 2-4h
TCAs: 24h
SSRIs: 15-20h
How are fluoxetine and active metabolites distinct regarding their half-lives? What percent of the population are slow fluoxetine metabolizers?
Fluoxetine has half life of 6d, active metabolites 16d.
7% of the population are slow metabolizers.
What is the main mechanism for all antidepressants?
All enhance monoamine levels in synapse (most block reuptake).
What is the therapeutic antagonism for amitriptyline, nefazadone/terazodone. Agonist for buspirone?
Amitriptyline: 5-HT2 and NE alpha-2 antagonist.
Nefazadone/terazodone: 5-HT2A antagonist.
Buspirone: 5-HT1 agonist.
TCAs produce what non-therapeutic antagonism? What are the side effects?
ACh muscarinic antagonism.
Side effects: dry mouth, blurred vision.
What is the effect of SSRIs on SERT expression in the brain?
Single dose of 10 mg Citalopram significantly blocks SERT activity by 75%, reduced by 84% after 3 weeks of treatment.
A study examining SSRI and TCA time lag in animals via novelty suppressed feeding found what?
After 5 days of oral administration, no effect on feeding latency. Effect shown only after 28 days.
What are two explanations for the paradox in which antidepressants’ effect on monoamines is immediate, but the therapeutic effect takes 2-3 weeks?
Postsynaptic receptor downregulation and 5-HT autoreceptor downregulation.
What effect do SSRIs have on 5-HT KO mice?
SSRIs don’t work.
What effect does depression have on the hippocampus? What reduces antidepressant effect?
Hippocampus decreases in volume. Preventing hippocampal neurogenesis reduces antidepressant effect.
In a brain imaging study on depressed patients, 5-HT1A receptors are reduced by how much in where?
42% in the raphe, 33% in the limbic structures, and 27% in the cortex.
