6 - Antidepressants, Antiaxiolytics

Question 1

What are the different classes of anti-depressants?

Answer 1

a. SSRI
b. SNRI
c. Tricyclics
d. MAO-I
e. Atypicals

Question 2

a. SSRI
b. SNRI
c. Tricyclics
d. MAO-I
e. Atypicals

All of these medications have a mechanism of action that is consistent with the biogenic amine theory of depression. What does that theory propose?

Answer 2

There is a deficiency of norepinephrine and /or serotonin at key locations in the brain

Question 3

BY is a 28 year old man suffering from major depression. He reports that he feels depressed every day and wishes he could “just fade away”. He denies having a suicidal plan and states even if he did, he doesn’t have the energy to do it. He reports feeling worthless and can’t remember the last time he did something fun. He is currently taking no medications and denies recreational drug use. He will occasionally drink a beer.

You decide to start BY on Fluoxetine (Prozac). Which class of medications does fluoxetine belong to? How does this drug (and the others in its class) work?

Answer 3

SSRI, blocks uptake of serotonin to increase amount available in the synaptic cleft

Question 4

What are the approved indications for the SSRI class of medicines? What is the one indication that is only approved for fluoxetine?

Answer 4

Depression, OCD, Panic disorder, Anxiety d/o, PTSD, premenstrual dysphoric disorder. Fluoxetine only: bulemia

Question 5

How are the pharmacokinetics of fluoxetine different from the other SSRIs?

Answer 5

Half life is much longer

Question 6

What side effects would you discuss with BY when initiating this therapy?

Answer 6

Sexual side effects (decreased libido), sleep disturbances, motor restlessness, black box warning about increased suicidality in teens and young adults.

Question 7

BY is a 28 year old man suffering from major depression. He reports that he feels depressed every day and wishes he could “just fade away”. He denies having a suicidal plan and states even if he did, he doesn’t have the energy to do it. He reports feeling worthless and can’t remember the last time he did something fun. He is currently taking no medications and denies recreational drug use. He will occasionally drink a beer.

What is the black box warning associated with SSRI’s? How would this affect your prescribing of this medicine for BY?

Answer 7

black box warning about increased suicidality in teens and young adults. Would make me keep in close contact with pt during initiation of therapy.

Question 8

In the event that BY took an overdose of his fluoxetine, what symptoms might you expect to see?

Answer 8

Hyperthermia, muscle rigidity, sweating, myoclonus, mental status changes

Question 9

BY is a 28 year old man suffering from major depression. He reports that he feels depressed every day and wishes he could “just fade away”. He denies having a suicidal plan and states even if he did, he doesn’t have the energy to do it. He reports feeling worthless and can’t remember the last time he did something fun. He is currently taking no medications and denies recreational drug use. He will occasionally drink a beer.

You see BY back in 3 months and you ask about his mood. He reports that he has been attending therapy and taking his meds, but doesn’t really see a difference.

At this point would you increase his dose? Change to a different SSRI medicine? Change to a different class of anti-depressant?

Answer 9

Change to a different SSRI OR change to a different class (SNRI)

Question 10

BY is a 28 year old man suffering from major depression. He reports that he feels depressed every day and wishes he could “just fade away”. He denies having a suicidal plan and states even if he did, he doesn’t have the energy to do it. He reports feeling worthless and can’t remember the last time he did something fun. He is currently taking no medications and denies recreational drug use. He will occasionally drink a beer.

You see BY back in 3 months and you ask about his mood. He reports that he has been attending therapy and taking his meds, but doesn’t really see a difference.

What are the recommendations from the APA about starting therapy with anti-depressants?

Answer 10

a. Pts w/ some improvement in initial weeks - continue taking med for total of at least 4–8 wks
b. Moderate improvement NOT observed w/ max doses after 4–8 weeks - reappraisal & adjustment
c. If NO improvement in initial weeks, need earlier adjustment. Consider changing antidepressant rather than increasing the dose of the medication.

Question 11

How are the SNRI’s different from the SSRIs?

Answer 11

Blocks norepinephrine uptake as well as serotnonin.

Question 12

BY is a 28 year old man suffering from major depression. He reports that he feels depressed every day and wishes he could “just fade away”. He denies having a suicidal plan and states even if he did, he doesn’t have the energy to do it. He reports feeling worthless and can’t remember the last time he did something fun. He is currently taking no medications and denies recreational drug use. He will occasionally drink a beer.

You see BY back in 3 months and you ask about his mood. He reports that he has been attending therapy and taking his meds, but doesn’t really see a difference.

You also consider using a tricyclic antidepressant like imipramine? What important side effect and pharmacologic property might deter you from using this medication if you thought overdose was a concern?

Answer 12

Cardiac dysrhythmias, narrow therapeutic index

Question 13

What are some of the other common adverse effects related to TCAs?

Answer 13

Anti-cholinergic effects, orthostatic hypotension, dizziness, reflex tachycardia, sexual side effects, psychiatric SEs.

Question 14

What are some conditions other than depression for which you might prescribe a TCA?

Answer 14

Nocturnal enuresis, migraine, abdominal migraine, chronic pain, insomnia

Question 15

You see BY back in 3 months and you ask about his mood. He reports that he has been attending therapy and taking his meds, but doesn’t really see a difference.

At this point would you increase his dose? Change to a different SSRI medicine? Change to a different class of anti-depressant?

Answer 15

Change to a different SSRI OR change to a different class (SNRI)

Question 16

In lecture, we discussed the class of drugs called MAO-Is. What is the reason that these drugs are not generally used as a first line therapy?

Answer 16

Dietary restrictions required (cannot eat anything containing tyramine)

Question 17

What life threatening complication can occur if someone on an MAOI eats a meal rich in tyramine?

Answer 17

Hypertensive crisis

Question 18

According to the APA and the STAR*D trial, what it thought about the comparative efficacy of anti-depressants? Does failure in one medicine in a class indicate success of other medications in the class?

Answer 18

All of the anti-depressants are equally effectve. (50-75% efficacy)

** Know that failure to respond to one medication within a class does NOT predict failure of all drugs in that class. It is reasonable to change within or between classes

Question 19

What is the potential role of pharmacogenetics/ pharmacogenomics testing in the prescription of medications where there is not clear evidence about which drug might be best?

Answer 19

These tests may be helpful to guide dosing of medications based on predicted genetic differences in the metabolism of them. (or other drug-gene interactions)

Question 20

What is the potential role of pharmacogenetics/ pharmacogenomics testing in the prescription of medications where there is not clear evidence about which drug might be best?

Answer 20

These tests may be helpful to guide dosing of medications based on predicted genetic differences in the metabolism of them. (or other drug-gene interactions)

Question 21

AK is a 57 year old woman who is about to undergo a mastectomy for breast cancer. She is currently admitted pre-operatively and she is visibly anxious. She admits that she is concerned that she might panic when the anesthesiologist comes to speak to her. You decide that a short term anxiolytic might be in order.

Many of the anxiolytic medications act on the GABA receptor. What is the role of GABA/ the GABA receptor in the CNS in general? ** know that there are different binding sites for different agonist on the GABA receptor and that they can potentiate one another!

Answer 21

! GABA is the primary inhibitory neurotransmitter in the CNS

Question 22

AK is a 57 year old woman who is about to undergo a mastectomy for breast cancer. She is currently admitted pre-operatively and she is visibly anxious. She admits that she is concerned that she might panic when the anesthesiologist comes to speak to her. You decide that a short term anxiolytic might be in order.

You decide to administer lorazepam to AK. What class of medications does this drug belong to?

Answer 22

Benzodiazepine

Question 23

AK is a 57 year old woman who is about to undergo a mastectomy for breast cancer. She is currently admitted pre-operatively and she is visibly anxious. She admits that she is concerned that she might panic when the anesthesiologist comes to speak to her. You decide that a short term anxiolytic might be in order.

What unique benefits do benzodiazepines offer – particularly in the case of someone who is about to undergo a procedure?

Answer 23

Antegrade amnesia

Question 24

What unique benefits do benzodiazepines offer – particularly in the case of someone who is about to undergo a procedure?

Answer 24

Antegrade amnesia

Question 25

How do benzodiazepines act as a muscle relaxant?

Answer 25

Acting on the GABA receptors in the spinal cord

Question 26

Benzodiazepines are occasionally used chronically and patients may become physically and psychologically dependent on them. What symptoms might you expect with the abrupt discontinuation of benzodiazepines in someone who has been on them for several months?

Answer 26

Agitation, anxiety, insomnia,

Question 27

Is there a reversal agent that can be used in the case of a benzodiazepine overdose? What clinical concern would you have when giving a reversal agent?

Answer 27

Flumazenil – risk of seizures

Question 28

What are the advantages of Buspirone?

Answer 28

Serotonin activity – better for chronic anxiety

Question 29

How do barbiturates work? Why would a barbiturate be a reasonable option for MRI sedation?

Answer 29

Activation of the GABA receptor (at a site distinct from the site of action of benzodiazepines). Barbiturates provide sedation without analgesia ( MRI shouldn’t be a painful procedure)

Question 30

If excessive doses of a barbiturate are given, what clinical effects are possible?

Answer 30

Coma, death – respiratory depression, decreased cardiac output, neurologic depression

Question 31

If AK was having long term problems with sleep, zolpidem might be a better option. What is the primary indication for zolpidem? What are its advantages? What are the concerns about this drug?

Answer 31

Advantages are: Insomnia. Doesn’t alter sleep architecture

Concerns are: Black box warning for complex sleep behaviors

Question 32

How do melatonin and its receptor agonists help with sleep?

Answer 32

Mimic physiologic release of melatonin when it becomes dark and one should become sleepy.