Anti-depressants Flashcards
Neurotrophic hypothesis
Depression is associated with loss of neurotrophic support
Monoamine hypothesis
Depression is related to a deficiency in the amount or function of cortical and limbic serotonin (5-HT), norepinephrine (NE), and dopamine (DA)
Main classes of antidepressants and prototype
SSRI: Fluoxetine SNRI: Venlafaxine, Duloxetine TCA: Imipramine 5-HT2 Antagonist (-zodone): Trazodone MAOI: Selegiline, tranylcypromine
MOA of SSRI
Inhibition of SERT (serotonin transporter)
Examples of SSRI
Citalopram Es-citalopram FLuoxetine (Prozac) Sertraline (Zoloft) Paroxetine Fluvoxamine
MOA of SNRI
Inhibit SERT and NET (NE transporter)
Example of SNRI
DDV:
Desvenlafaxine
Duloxetine
Venlafaxine
MOA of TCA
Inhibit SERT, NET and other monoamines
Indication of TCA
Used in depression unresponsive to SSRIs and SNRIs
Compare imipramine and desipramine
Imipramine – highly anticholinergic, relatively
strong serotonin and NE reuptake inhibitor
Desipramine– less anticholinergic, more potent,
more selective NE reuptake inhibitor
Examples of 5-HT2 Antagonist
-zodone
Trazodone
Nefazodone
Fluoxetine + MAOI leads to
serotonin syndrome
(fluoxetine Has to be discontinued 4 weeks or more before MAOI can
administered to prevent serotonin syndrome)
Fluoxetine is an enzyme inhibitor or inducer?
Enzyme inhibitor (inhibits CYP2D6)
Lowest protein binding of all antidepressants
Venlafaxine
(appears in the blood stream faster
compared to other antidepressants)
It is has unicyclic aminoketone structure; resembles
amphetamine, has CNS activating properties
Bupropion
Examples of MAOI
Tranylcypromine
Selegiline
TCAs have many side-effects because of its
Antimuscarinic receptor affinity – dry mouth, constipation
H1 receptor affinity – used as hypnotic (sedative) and
antipruritic
Alpha adrenoceptor blockade – orthostatic hypotension
Compare MAO A vs MAO B
MAO-A
- Present in both dopamine and NE neurons
- Found in brain, gut, placenta, liver
- Primary substrates: NE, epinephrine, serotonin
MAO-B
- Found in serotonergic and histaminergic neurons
- Brain, liver, platelets
- Acts on tyramine, phenylethylamine, benzylamine
irreversible, nonselective
MAOIs
Phenelzine, tranylcypromine
reversible selective inhibitor of MAO-A
Moclobemide
irreversible MAO-B inhibitor
Selegiline
AE of SSRI
serotonin syndrome
“discontinuation syndrome” – dizziness, paresthesias after
stopping the drug
AE of TCAs
Anticholinergic effects: dry mouth, constipation, urinary
retention, blurred vision, confusion
v Alpha blockade: orthostatic hypotension
v H1 blockade: weight gain, sedation
v Interference with cardiac rhythm (class 1A)
v Sexual effects (clomipramine)
AE of SNRIs
Serotonergic effects as previously mentioned
v Noradrenergic effects: increased BP (venlafaxine), HR
v Cardiac toxicity: venlafaxine overdose (rare)
v Hepatic toxicity: duloxetine
v CNS activation: insomnia, anxiety, agitation
Can cause priapism
trazodone
Hepatotoxic
nefazodone
SNRI that causes cardiac toxicity
venlafaxine
SNRI that causes hepatotoxicity
duloxetine
5-HT2 antagonist that causes hepatotoxicity
nefazodone
Can cause parkinsonian syndrome
amoxapine
MAOI interacts with cheese because it contains
tyramine
Serotonin Syndrome
Serious drug interaction associated with MAOIs + serotonergic
agents
A 55-year-old teacher began to experience changes in
mood. He was losing interest in his work and lacked
the desire to play his daily tennis match. He was
preoccupied with feelings of guilt, worthlessness, and
hopelessness. In addition to the psychiatric symptoms,
the patient complained of muscle aches throughout his
body. Physical and laboratory tests were unremarkable.
After 6 weeks of therapy with fluoxetine, his symptoms
resolved. However, the patient complains of sexual
dysfunction. Which of the following drugs might be
useful in this patient?
A. Fluvoxamine.
B. Sertraline.
C. Citalopram.
D. Mirtazapine.
E. Lithium.
Correct answer = D. Mirtazapine is largely free from sexual
side effects. However, sexual dysfunction commonly occurs
with SSRIs (fluvoxamine, sertraline, and citalopram), as
well as with TCAs, and SNRIs. Lithium is used for the treatment
of mania and bipolar disorder.
A 25-year-old woman has a long history of depressive
symptoms accompanied by body aches and pain
secondary to a car accident 2 years earlier. Physical
and laboratory tests are unremarkable. Which of the
following drugs might be useful in this patient?
A. Fluoxetine.
B. Sertraline.
C. Phenelzine.
D. Mirtazapine.
E. Duloxetine.
Correct answer = E. Duloxetine is a SNRI that can be used
for depression accompanied by symptoms of pain. SSRIs
(fluoxetine and sertraline), MAOIs (phenelzine), and atypical
antidepressants (mirtazapine) have little activity against
pain syndromes.
A 51-year-old woman with symptoms of major
depression also has angle-closure glaucoma. Which of
the following antidepressants should be avoided in this
patient?
A. Amitriptyline.
B. Sertraline.
C. Bupropion.
D. Mirtazapine.
E. Fluvoxamine.
Correct answer = A. Because of its potent antimuscarinic
activity, amitriptyline should not be given to patients with
glaucoma because of the risk of acute increases in intraocular
pressure. The other antidepressants all lack antagonist
activity at the muscarinic receptor.
A 36-year-old man presents with symptoms of
compulsive behavior. If anything is out of order, he
feels that “work will not be accomplished effectively or
efficiently.” He realizes that his behavior is interfering
with his ability to accomplish his daily tasks but cannot
seem to stop himself. Which of the following drugs
would be most helpful to this patient?
A. Imipramine.
B. Fluvoxamine.
C. Amitriptyline.
D. Tranylcypromine.
E. Lithium.
Correct answer = B. SSRIs are particularly effective in treating
obsessive–compulsive disorder, and fluvoxamine is
approved for this condition. The other drugs are less effective
in the treatment of obsessive–compulsive disorder
Which antidepressant has, as its two proposed
principle mechanisms of action, 5-HT1a receptor
partial agonism and 5-HT reuptake inhibition?
A. Fluoxetine.
B. Aripiprazole.
C. Maprotiline.
D. Vilazodone.
E. Mirtazapine.
Correct answer = D. In addition to inhibition of serotonin
reuptake, the antidepressant activity of vilazodone may be
related to its 5-HT1a receptor agonism. Though aripiprazole
is also proposed to have 5-HT1a partial agonism, it is not a
serotonin reuptake inhibitor.
Which antidepressant is the most sedating? A. Fluoxetine. B. Duloxetine. C. Nortriptyline. D. Citalopram. E. Venlafaxine.
Correct answer = C. Nortriptyline is the most sedating of the
list due to its histamine-blocking activity.
Which mood stabilizer is completely renally eliminated and may be beneficial for patients with hepatic impairment? A. Valproic acid. B. Carbamazepine. C. Lithium. D. Risperidone. E. Aripiprazole.
Correct answer = C. Lithium is the only agent for bipolar
disorder that does not require hepatic metabolism and,
thus, may be dosed without issue in a hepatically impaired
patient. However, if the patient had renal impairment, the
lithium dosage would have to be adjusted.
Which antidepressant has, as its two principle mechanisms of action, 5-HT2A receptor antagonism and α2 receptor antagonism? A. Fluoxetine. B. Doxepin. C. Maprotiline. D. Mirtazapine. E. Selegiline.
Correct answer = D. Mirtazapine is the only antidepressant
with this combination of mechanisms of action that are
believed to contribute to its therapeutic effects. The other
agents listed are reuptake inhibitors of either serotonin
(fluoxetine) or norepinephrine (maprotiline), or both (doxepin),
or act as a MAOI (selegiline).
Which agent is best known to have the side effect of decreasing the thyroid function of the patient being chronically treated with this agent? A. Carbamazepine. B. Lithium. C. Valproic acid. D. Chlorpromazine. E. Lurasidone.
Correct answer = B. Lithium is best known for causing a
drug-induced hypothyroidism in patients after long-term
use. Though it is possible with other mood stabilizers, lithium
has the most reported cases, and thus, thyroid function
tests should be performed at baseline and during followup
to monitor for this possible effect. Also, since hypothyroidism
may present with symptoms of depression, it is
important to differentiate a patient’s observed depressive
symptoms from the psychopathology of the bipolar disorder
or depression versus symptoms of hypothyroidism.
Which agent would be a poor choice in a 70-yearold
elderly female with depressive symptoms due to
the drug having significant α1 receptor antagonism
and thus a higher risk for falls due to orthostatic
hypotension?
A. Lithium.
B. Bupropion.
C. Escitalopram.
D. Imipramine.
E. Sertraline.
Correct answer = D. Lithium should not be used for depression
in an elderly patient without first trying first-line antidepressants,
and even then, it is used as an adjunct.
Bupropion, sertraline, and escitalopram have very little
effect on blood pressure (no α1 receptor antagonism) and
are considered acceptable choices for the treatment of
depression in the elderly. Imipramine is associated with a
high risk for orthostasis in the elderly and should be avoided
due to its adverse effect profile and risk for falls.
