Anti-depressants Flashcards by Jo Poblete

Neurotrophic hypothesis

Depression is associated with loss of neurotrophic support

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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)

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Main classes of antidepressants and prototype

SSRI: Fluoxetine
SNRI: Venlafaxine, Duloxetine
TCA: Imipramine
5-HT2 Antagonist (-zodone): Trazodone
MAOI: Selegiline, tranylcypromine

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MOA of SSRI

Inhibition of SERT (serotonin transporter)

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Examples of SSRI

Citalopram
Es-citalopram
FLuoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine
Fluvoxamine

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MOA of SNRI

Inhibit SERT and NET (NE transporter)

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Example of SNRI

DDV:
Desvenlafaxine
Duloxetine
Venlafaxine

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MOA of TCA

Inhibit SERT, NET and other monoamines

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Indication of TCA

Used in depression unresponsive to SSRIs and SNRIs

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Compare imipramine and desipramine

Imipramine – highly anticholinergic, relatively
strong serotonin and NE reuptake inhibitor

Desipramine– less anticholinergic, more potent,
more selective NE reuptake inhibitor

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Examples of 5-HT2 Antagonist

-zodone
Trazodone
Nefazodone

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Fluoxetine + MAOI leads to

serotonin syndrome
(fluoxetine Has to be discontinued 4 weeks or more before MAOI can
administered to prevent serotonin syndrome)

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Fluoxetine is an enzyme inhibitor or inducer?

Enzyme inhibitor (inhibits CYP2D6)

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Lowest protein binding of all antidepressants

Venlafaxine

(appears in the blood stream faster
compared to other antidepressants)

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It is has unicyclic aminoketone structure; resembles

amphetamine, has CNS activating properties

Bupropion

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Examples of MAOI

Tranylcypromine

Selegiline

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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.