Antidepressants

Question 1

List three categories of antidepressant drugs

Answer 1

uptake inhibitors
monoamine oxidase inhibitors
atypical agents

Question 2

It is important to screen for _____ before initiating an antidepressant

Answer 2

mania or hypomania

Question 3

List two early TCAs

Answer 3

imipramine and amitriptyline

Question 4

List two later TCAs

Answer 4

Desipramine (metabolite of imipramine) and nortryptyline (metabolite of amitriptyline)

Question 5

Describe the mechanism of action of TCAs

Answer 5

Mixed serotonin and norepinephrine uptake inhibition

Question 6

List common adverse effects of TCAs (5)

Answer 6

Anticholinergic activity → variety of autonomic effects
Moderate a adrenergic blockade → orthostatic hypotension
Moderate antihistamine activity → sedation
Class IA antiarrhythmic-like activity: blockade of cardiac Na+ channels; extremely dangerous in high doses
Potential serotonin syndrome

Question 7

Describe the mechanism of action of imipramine

Answer 7

Inhibits 5-HT uptake more than NE uptake

Significant anticholinergic effects: blocks ACh receptors (also used to treat enuresis)

Question 8

List precautions for imipramine and nortriptyline

Answer 8

Cardiac disease: acute MI, AV block, bundle-branch block, QT prolongation
Ileus
MAO inhibitor therapy
Avoid serotonergic agents e.g. triptans, St. John’s Wort, buspirone
Blood dyscrasias
Hepatic disease- check LFTs
TCAs may sensitize skin to sunburn

Question 9

Nortriptyline inhibits ____ uptake more than ___ uptake

Answer 9

Norepinephrine more than serotonin

Question 10

List some adverse reactions of nortriptyline

Answer 10

xerostomia, constipation, lethargy, sedation, orthostatic hypotension, cycloplegia (blocks accommodation at muscarinic receptors)

Question 11

List five SSRIs

Answer 11

citalopram
escitalopram
fluoxetine
paroxetine
sertraline

Question 12

List two SNRIs

Answer 12

duloxetine

venlafaxine

Question 13

List one NRI

Answer 13

reboxetine

Question 14

List some advantages of SSRIs/SNRIs/NRIs over TCAs

Answer 14

little or no anticholinergic activity, a adrenergic blockade, antihistamine activity

Question 15

Sertraline is a _____ drug and has no significant affinity for adrenergic, cholinergic, GABA, dopaminergic, histaminergic, or serotonergic receptors

Answer 15

SSRI

Question 16

List precautions for sertraline and venlafaxine

Answer 16

MAO inhibitor therapy
Avoid serotonergic agents e.g. triptans, St. John’s Wort, lorcaserin, buspirone
Avoid sudden DC, taper dosage gradually
Hepatic disease

Question 17

Venlafixine is a ____ drug that inhibits serotonin uptake more than norepinephrine uptake

Answer 17

SNRI

Question 18

Iproniazid is a ____ drug that is an isomer of isoniazid (used to treat TB)

Answer 18

MAOI

Question 19

Describe the mechanism of action of MAOIs

Answer 19

Increase monoamine neurotransmitter activity by inhibiting MAO metabolism of 5-HT, DA, NE

Question 20

Tranylcypromine is a ____ drug that is second line tx for depression.

Answer 20

MAOI

Question 21

Describe the mechanism of action of tranylcypromine

Answer 21

Nonselective, irreversible inhibitor of both MAO-A and MAO-B

Question 22

List adverse reactions seen with tranylcypromien

Answer 22

Sympathomimetic effects: hypertension, agitation, insomnia, tachycardia, mydriasis, diaphoresis, tremor, aggressiveness, urinary retention

Question 23

List precautions for tranylcypromine

Answer 23

CV: acute MI, angina arrhythmias, heart failure, cerebrovascular disease, hypertension
Hepatic disease, jaundice
Pheochromocytoma
Radiographic contrast administration (MAOIs can precipitate seizures)
Renal disease
Sympathomimetics e.g. local anesthetics containing epinephrine, OTC cold remedies
Diabetes

Question 24

Selegiline is a ____ drug used in treatment of Parkinsons and off label to treat depression

Answer 24

MAOI

Question 25

Describe the mechanism of action of selegiline

Answer 25

Noncompetitive, irreversible antagonist of MAO-B, which metabolizes dopamine (decreases dopamine metabolism)

Question 26

List precautions for use of selegiline

Answer 26

Monoamine uptake inhibitors
Dementia, severe psychosis, tardive dyskinesia, or excessive tremor
Peptic ulcers
Sympathomimetic drugs

Question 27

____ is an atypical antidepressant; it and its metabolites inhibit 5-HT, NE, and DA uptake and metabolites are amphetamine-like

Answer 27

Bupropion

Question 28

List precautions for bupropion treatment

Answer 28

MAO inhibitor therapy
Seizure disorder
Bulimia, anorexia nervosa
Sympathomimetic drugs
Hepatic disease

Question 29

Describe the mechanism of action for the atypical antidepressants trazodone and nefazodone

Answer 29

Antagonism at 5-HT2A receptors and a1 receptors, inhibition of 5-HT uptake

Question 30

Describe the mechanism of action of the atypical antidepressant mirtazapine

Answer 30

Potent antagonist at 5-HT2A, 5-HT2C, 5-HT3, and H1 receptors, also antagonizes presynaptic a2 receptors (↑ NE release), and is a weak antagonist at 5-HT1 receptors

Question 31

List some other indications for use of antidepressants

Answer 31

Anxiety disorders (SSRIs, TCAs, MAOIs)
Pain disorders (SNRIs, TCAs)
PMDD (SSRIs)
Smoking cessation (bupropion, nortriptyline)
Eating disorders (SSRIs)
Enuresis (TCAs)

Question 32

Describe how ketamine acts as an antidepressant

Answer 32

activates the mTOR pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses