Lecture 9 Depression & Antidepressants Flashcards
Name 4 depressive disorders
Major Depressive Disorder
Disruptive mood dysregulation disorder
Persistent Depressive Disorder
Premenstrual Dysphoric Disorder
What is MDD?
Major Depressive Disorder
Name 9 symptoms of MDD
Depressed Mood Apathy Weight appetite changes Sleep disturbances Psychomotor Fatigue Worthlessness Executive Dysfunction Suicidal Ideation
What were the first antidepressants?
MAOIs (originally anti-tuberculosis agents)
isoniazid & iproniazid
What is a TCA and name one
Tricyclic antidepressant
Imipramine
SSRI
Selective Serotonin Reuptake inhibitors
Allows excess activation of serotonin
SNRI
Serotonin-norepinephrine reuptake inhibitor
SDRI
Serotonin Dopamine Reuptake inhibitor
NDRI
Norepinephrine dopamine reuptake inhibitors
What is the monoamine hypothesis of depression?
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.
MAOI
Monoamine oxidase inhibitors inhibit the breakdown of monoamines by monoamine oxidase, thereby elevating extracellular monoamine levels (DA, NE, 5HT)
What has been shown to alter functional connectivity and what does that mean.
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
What do antidepressants do to receptors?
Causes down regulation of receptors which can occur within hours
In the depressed state describe the neuronal landscape of receptors.
In the depressed state, low 5-HT levels cause an upregulation of postsynaptic and somatodendritic 5-HT1A autoreceptors
Describe how SSRIs work.
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
What is Buspar and what does it do?
Buspar is a 5-HT1a receptor partial agonists that facilitates 5-HT1A downregulation and is often prescribed as augmentation therapy to speed the effects.
What are the likely therapeutic changes caused by SSRIs?
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
Growth factor theory of antidepressants
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
What are the most commonly prescribed SSRIs?
Citalopram, Dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
What are common side effects of SSRIs?
Weight gain, insomnia, tremors, altered EKG, dizziness, constipation, dry mouth, nausea, sexual dysfunction
Most common SNRIs
Duloxetine, venlafaxine, desvenlafaxine, milnacipran, levmilnacipran
Most common NDRIs
Buproprion, methylphenidate, dexmethylphenidate
NRI
Selective norepinephrine uptake inhibitors
Most common NRI
Reboxetine, atomoxetine, viloxazine
What are some factors that influence responses to antidepressants?
Age, gender, genetic makeup, metabolism, ethnicity, expectancies, endocrine systems, use of other approaches (exercise, psychotherapy)
Name three non-pharmacological approaches to treatment resistant depression.
And how may it work?
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.
What is the active ingredient of St. Johns Wort?
And what can it treat?
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.
What is ketamine and what are some of its effects?
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.
Name a ketamine-like antidepressant and what are the advantages
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.
Disruptive Mood Dysregulation Disorder
Chronic, severe, persistent irritability
Persistent Depressive Disorder (Dysthmia)
Depressed mood that occurs for most of the day for more days than not, for at least 2 years
