Lecture 9 Depression & Antidepressants

Question 1

Name 4 depressive disorders

Answer 1

Major Depressive Disorder
Disruptive mood dysregulation disorder
Persistent Depressive Disorder
Premenstrual Dysphoric Disorder

Question 2

What is MDD?

Answer 2

Major Depressive Disorder

Question 3

Name 9 symptoms of MDD

Answer 3

Depressed Mood
Apathy
Weight appetite changes
Sleep disturbances
Psychomotor
Fatigue
Worthlessness
Executive Dysfunction
Suicidal Ideation

Question 4

What were the first antidepressants?

Answer 4

MAOIs (originally anti-tuberculosis agents)

isoniazid & iproniazid

Question 5

What is a TCA and name one

Answer 5

Tricyclic antidepressant

Imipramine

Question 6

SSRI

Answer 6

Selective Serotonin Reuptake inhibitors

Allows excess activation of serotonin

Question 7

SNRI

Answer 7

Serotonin-norepinephrine reuptake inhibitor

Question 8

SDRI

Answer 8

Serotonin Dopamine Reuptake inhibitor

Question 9

NDRI

Answer 9

Norepinephrine dopamine reuptake inhibitors

Question 10

What is the monoamine hypothesis of depression?

Answer 10

Depression results from reduced monoamine levels (DA, NE, 5-HT) in the frontal cortex.

This reduced monoamine levels result in up-regulation of monoamine receptors.

Question 11

MAOI

Answer 11

Monoamine oxidase inhibitors inhibit the breakdown of monoamines by monoamine oxidase, thereby elevating extracellular monoamine levels (DA, NE, 5HT)

Question 12

What has been shown to alter functional connectivity and what does that mean.

Answer 12

A single dose of the SSRI lexapro reduces the functional connectivity in the brain.

Similar patterns of activation in different brain regions regardless of their physical connections

Question 13

What do antidepressants do to receptors?

Answer 13

Causes down regulation of receptors which can occur within hours

Question 14

In the depressed state describe the neuronal landscape of receptors.

Answer 14

In the depressed state, low 5-HT levels cause an upregulation of postsynaptic and somatodendritic 5-HT1A autoreceptors

Question 15

Describe how SSRIs work.

Answer 15

SSRIs block both presynaptic and somatodendritic 5-HT transporters (SERT) resulting in increased 5-HT in the synaptic cleft and near the cell body/dendrites.

Increased 5-HT causes 5-HT1A autoreceptors to desensitize and down regulate.

Down regulation of activity regulating somatodendritic 5-HT1A autoreceptors causes neurons to increase activity and release more 5-HT.

Increased 5-HT release causes postsynaptic 5-HT receptors to down regulate and cause therapeutic changes in postsynaptic neurons

Question 16

What is Buspar and what does it do?

Answer 16

Buspar is a 5-HT1a receptor partial agonists that facilitates 5-HT1A downregulation and is often prescribed as augmentation therapy to speed the effects.

Question 17

What are the likely therapeutic changes caused by SSRIs?

Answer 17

Increased production of growth factors such as brain derived growth factor which increases synaptic plasticity.

Increased synthesis of various other proteins i.e. receptors enzymes

These changes take weeks to occur

Question 18

Growth factor theory of antidepressants

Answer 18

Chronic stress causes stress hormones and other neurotransmitters to inhibit transcription factors that activate BDNF synthesis.

As a result lowered BDNF causes dendritic atrophy and perhaps cell death while antidepressant induced BDNF production causes dendritic arborization and increased connectivity

Question 19

What are the most commonly prescribed SSRIs?

Answer 19

Citalopram, Dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

Question 20

What are common side effects of SSRIs?

Answer 20

Weight gain, insomnia, tremors, altered EKG, dizziness, constipation, dry mouth, nausea, sexual dysfunction

Question 21

Most common SNRIs

Answer 21

Duloxetine, venlafaxine, desvenlafaxine, milnacipran, levmilnacipran

Question 22

Most common NDRIs

Answer 22

Buproprion, methylphenidate, dexmethylphenidate

Question 23

NRI

Answer 23

Selective norepinephrine uptake inhibitors

Question 24

Most common NRI

Answer 24

Reboxetine, atomoxetine, viloxazine

Question 25

What are some factors that influence responses to antidepressants?

Answer 25

Age, gender, genetic makeup, metabolism, ethnicity, expectancies, endocrine systems, use of other approaches (exercise, psychotherapy)

Question 26

Name three non-pharmacological approaches to treatment resistant depression.

And how may it work?

Answer 26

Vagus Nerve Stimulation
Transcranial Magnetic Stimulation
Deep Brain Stimulation

As a trimonoamine booster. A stimulus is utilized to activate the prefrontal cortex and works backwards to activate the nuclei that release monoamines.

Question 27

What is the active ingredient of St. Johns Wort?

And what can it treat?

Answer 27

The active component is hyperforin, a non-selective inhibitor of DA, NE, 5-HT and GABA reuptake.

Efficacious in relieving mild depression and anxiety. It can aggravate psychosis in schizophrenia and alters cytochrome P450 liver enzymes.

Question 28

What is ketamine and what are some of its effects?

Answer 28

Ketamine is an NMDA-type glutamate receptor antagonist that has dissociative and analgesic effects. The antidepressant mechanisms are unknown but seem to last 2-3 days and effects occur very rapidly.

Question 29

Name a ketamine-like antidepressant and what are the advantages

Answer 29

Lanicemine has a reduced risk of dissociate effects.

Lanicemine is a low trapping NMDA channel blocker that produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects.

Question 30

Disruptive Mood Dysregulation Disorder

Answer 30

Chronic, severe, persistent irritability

Question 31

Persistent Depressive Disorder (Dysthmia)

Answer 31

Depressed mood that occurs for most of the day for more days than not, for at least 2 years