Psychopharm of antidepressants/anxiolytics

Question 1

Monoamine hypothesis

Answer 1

Monoamines are depleted in depression and that ADs work by boosting levels of these NTs

Question 2

Downstream effects of ADs

Answer 2

Induce neuronal adaptations
Down-regulate/normalize receptors
Promote growth regulation factors

Question 3

4 general mechanisms of primary AD action

Answer 3

Block reuptake of NTs
Antagonize receptors controlling NT release
Stimulate receptor activity
Interfere with NT breakdown

Question 4

First line antidepressants

Answer 4

SSRIs: fluoxetine, citalopram, escitalopram, sertraline, paroxetine, fluvoxamine
SNRIs: venlafaxine, duloxetine, desvenlafaxine
Others: buproprion, mirtazapine, vortioxetine

Question 5

Second line antidepressants

Answer 5

SNRIs: levomilnacipran
TCAs
Others

Question 6

SSRIs

Answer 6

Selective serotonin reuptake inhibitors
Blocks SERT (the reuptake pump)

Question 7

Side effects of SSRIs

Answer 7

CNS: initial agitation/worsening of anxiety, tremors, insomnia, sedation, serotonin syndrome
GI: diarrhea, constipation
GU: sexual dysfunction
Cardiac: QTc prolongation
Endocrine: hyponatremia
Heme: bleeding

Question 8

Problems with paroxetine

Answer 8

Most problematic for medication interactions, worse discontinuation effects, highest risk of weight gain

Question 9

What drug causes the most pronounced GI effects

Answer 9

Sertraline

Especially nausea and diarrhea

Question 10

What drug is the easiest to taper? Why?

Answer 10

Fluoxetine

Has the longest half life

Question 11

SSRI Discontinuation Syndrome

Answer 11

Symptoms may include flu-like symptoms, GI disturbance, headaches, dizziness, paraesthesias, sleep disturbance, fatigue, sweating
Taper medications slowly makes this syndrome less likely

Question 12

Serotonin Syndrome

Answer 12

Syndrome of excess serotonin
Most often occurs within hours of medication change/addition
Often resolves within 24 hours following cessation of implicated agents
More likely in cases of polypharmacy
May occur with med combos with than ADs
Can use a 5HT2a (ciproheptadin) to treat

Question 13

Clinical presentation of serotonin syndrome

Answer 13

Triad:
Autonomic (sweating, tachycardia, etc)
Cognitive (delirium, etc)
Neuromuscular (clonus, hyperreflexia, etc)

Question 14

SNRIs

Answer 14

Serotonin and Norepinephrine Reuptake Inhibitors

Blocks both SERT and NET

Question 15

Side effects of SNRIs

Answer 15

Same as SSRIs

Plus peripheral noradrenergic effects (sweating, increased BP and HR, urinary retention)

Question 16

NDRI (what does it stand for, example, how does it work, side effects)

Answer 16

Norepinephrine Dopamine Reuptake Inhibitor
Ex: Buproprion
Blocks NET and DAT
Side effects: nausea, vomiting, decreased appetite, agitation, headache, seizure, rash)

Question 17

SNS (what does it stand for, example, how does it work, side effects, pearl)

Answer 17

Serotonin modulator and stimulator
Ex: Vortioxetine
Some direct actions: blocks SERT and 5HT 3 and 7, stimulates 5HT-1A/B
Side effects: same as SSRIs but nausea may be more significant. Dizziness and pruritis common
Possible benefit for cognitive symptoms

Question 18

NaSSA (what does it stand for, example, how does it work, side effects, pearl)

Answer 18

Noradrenergic Serotonin Specific Antidepressant
Ex: Mirtazapine
Action: Blocks a2 receptors (increases release of 5-HT and NE), and blocks other serotonin receptors and histamine
Side effects: similar to SSRIs and SNRIs plus sedation, dizziness, constipation, increased appetite, weight gain
Sedation is greater at lower doses

Question 19

SARI (what does it stand for, example, how does it work, side effects, pearl)

Answer 19

Serotonin antagonist and reuptake inhibitor
Ex: trazodone
Action: SSRI, 5HT-2, alpha adrenergic and histamine blockade
Side effects: sedation, dizziness, orthostatic hypotension and priapism
Primarily used off label as a sedative

Question 20

SPARI (what does it stand for, example, how does it work, side effects, pearl)

Answer 20

Serotonin partial agonist and reuptake inhibitor
Ex: vilazodone
Action: partial agonist of 5HT1A, blocks SERT
Side effects: nausea, diarrhea, insomnia
Basically a combo of SSRI and buspirone
May have less weight gain and sexual side effects vs SSRIs/SNRIs

Question 21

TCAs (what does it stand for, example, how does it work, side effects)

Answer 21

Tricyclic ADs
Ex: amitriptyline (SNRI), desipramine (NRI) and clomipramine (SSRI)
Action depends on agent
Side effects: constipation, sedation, dizziness, orthostatic hypotension, tachy, seizures, coma, blurry vision, arrthymias, urinary retention
Can be potentially deadly in overdose, so they are second line

Question 22

4 NTs of key interest in anxiety

Answer 22

Serotonin
NE
GABA
Glutamate

Question 23

Buspirone (action, side effects)

Answer 23

For anxiety
Action: partial 5-HT1A agonist
Side effects: dizziness, nausea, drowsiness, initial nervousness, fatigue
No abuse/depedence potential, no sedation or cognitive effects

Question 24

Gabapentin/pregabalin (action, side effects)

Answer 24

For anxiety
Action: blocks the a2 delta subunit of calcium channels –> decreases Ca flow and the presynaptic release of glutamate
Side effects: sedation, tremors, dizziness, diplopia, dry mouth, peripheral edema

Question 25

Benzodiazepines (examples, action, effects)

Answer 25

Ex: -pam
Action: binds to post synaptic GABA-A receptor and increased GABAergic transmission
Sedative/hypnotic, muscle relaxant, anticonvulsant, amnestic and anxiolytic

Question 26

Side effects of benzos

Answer 26

Dependence, tolerance and addiction
Cognitive/neuromuscular function may be impaired
Disinhibition
Paradoxical reactions
Abrupt discontinuation after chronic use can cause seizures

Question 27

Why are TCAs second line?

Answer 27

Can be potentially deadly in overdose