Tx of Depression

Question 1

Monoamine theory of depression

Answer 1

Raising NE and serotonin= elevation of mood.
Decreasing NE and serotonin= depression

Newer studies reveal that neurotrophic and endocrine factors play a larger role. Neurotrophic hypothesis.

Question 2

3 forms of depression

Answer 2

Reactive- normal. No functional problem in brain. Will resolve.

Endogenous- arises without any precipitating event or remains in individuals with reactive depression. Tx with meds.

Drug induced

Question 3

First choice drug to treat endogenous depression

Answer 3

SSRI, SNRI

If pt doesn’t respond to these, use MAOIs and tricyclics

Question 4

Life cycle of NE

Answer 4

Synthesized in axon terminal.
Tyrosine imported from extracellular space, converted to L dopa, converted to dopamine, dopamine is put into storage vesicles and then converted into NE.

Removed from gap by reuptake into axon terminal. Repackaged and metabolized by MAO. Diffuses into surrounding tissues.

Question 5

Life cycle of serotonin

Answer 5

Synthesized in axon terminal.
Tryptophan imported from extracellular space. Converted to 5HTP and then to serotonin. Then put into storage vesicles.

Removed from the synaptic gap by reuptake into axon terminal. Repackaged and metabolized by MAO.

Question 6

Noradrenergic and serotonergic neurons have their cell bodies in the ___ and axons project to ____ and ___.

Answer 6

Cell bodies in midbrain

Project to all areas of brain, but neocortex and limbic are most important. Critical to thought process and emotion.

Question 7

Are NE and 5HT excitatory or inhib

Answer 7

Excitatory. Except at a2 receptors- these are inhib and will decrease NE transmission.

Question 8

Activation of NE and 5HT receptors can be increased by which 2 ways.

How can the receptors by decreased?

Answer 8

Increased by increasing release of stored NE and 5HT
or by decreasing the reuptake.

Can decrease receptors by reducing amount of stored NT.

Question 9

Clinical efficacy vs chemical efficacy time line

Answer 9

Clinical efficacy of anti depressants is delayed a few weeks.

Chemical effect seen right away.

Question 10

MAO breaks down which NT

Answer 10

NE, 5HT and dopamine.

Question 11

Why must you wait a min of 2 weeks when switching from MAOI to another therapy?

Answer 11

MAO regeneration takes several weeks after medication is stopped.
If you don’t wait, you may end up with way too much NT, causing more side effects.

Question 12

MAOI metabolites

Answer 12

Amphetamine-like. CNS stimulating effects.

Question 13

MAOI adverse effects

Answer 13

Pts taking have extensive rules they must follow to prevent fatal serotonin syndrome.

Orthostatic hypotension.
Serotonin syndrome- hypertension, cardiac arrhythemia/angina, sleep disturbances, weight gain, blurred vision, dry mouth. Made worse by agents that cause release of NE such as other antidepressants, foods that contain tyramine, amphetamines, and OTC cold meds.

Question 14

Serotonin syndrome is only seen in drugs that increase

Answer 14

5HT levels. Made worse by agents that cause release of NE such as other antidepressants, foods that contain tyramine, amphetamines, and OTC cold meds.

Question 15

What MAOI side effect will affect eyes

Answer 15

Blurry vision if pt has serotonin syndrome.

Question 16

MAO of tricyclic antidepressants

Answer 16

Blocks reuptake of 5HT and NE by inhibiting the transporter protein.

Also blocks some other receptors, causing some adverse effects.

Question 17

Metabolism of MAOI and tricyclic

Answer 17

MAOI: amphetamine like metabolites
Tricyclic: many drug drug interactions due to CYP450 system.

Question 18

Tricyclic adverse side effects

Answer 18

Antagonize muscarinic, histamine, and adrenergic receptors. Get a mix of sympathetic and parasympathetic side effects.

Dry mouth 
Confusion
Weight gain 
Increased IOP
Blurred vision 
Sedation

Question 19

Tricyclic side effects that effect eyes

Answer 19

Blurred vision and increased IOP

Question 20

Which SSRI undergoes significant first pass metabolism

Answer 20

Sertaline.

Question 21

SSRI half life in general. Which one has the longest?

Answer 21

Long. 24 hour or more.

Fluoxetine is 50 hour. Can be dosed once weekly. Metabolite is as potent as a parent molecule.

Question 22

SSRI discontinuation syndrome

Answer 22

1/3 of patients will experience when they come off the short half life SSRIs. (rare with fluoxetine)
Dizzy, vertigo, nausea, fatigue and HA.

Question 23

Side effects of SSRIs

Answer 23

Discontinuation syndrome: 1/3 of patients will experience when they come off the short half life SSRIs. (rare with fluoxetine)
Dizzy, vertigo, nausea, fatigue and HA.

Dry mouth
GI
Insomnia
Sexual dysfunction

Question 24

What group of drugs may be more effective if pain is experienced along with depression?

Answer 24

SNRI

Question 25

Burproprion MOA and contra

Answer 25

Weak dopamine and NE reuptake inhib.
Short half life.
Assists in decreasing the craving and attenuating the withdrawal symptoms of nicotine.

CONTRAindicated in patients with seizures.

Question 26

Mirtazapine

Answer 26

Enhances serotonin and NE transmission.
a2 antagonist.
potent antihistamine activity. Sedative. may be an advantage if patient has difficulty sleeping.

Question 27

Trazadone and Nefazodone

Answer 27

Weak inhib of serotonin reuptake.
Potent antihistamine activity.

Adverse effects
Hepatotoxicity
Orthostatic hypotension.
Dizzy

Question 28

All drugs that treat ____ have capacity to induce suicide

Answer 28

Depression.

Bc medication is slow to act.

Question 29

Antidepressant to help w smoking cessation

Answer 29

Buproprion

Question 30

Uses of antidepressants

Answer 30

Chronic anxiety
Pain disordrs
Smoking cessation- bupropion
Tx bulimia (NOT anorexia)