PSYCH 643 Study Guide Module 5: Depression
Familiarize yourself with theories of bipolar spectrum disorder and their criticism (Article:
Bipolar Spectrum: A Critical Perspective) with consideration of the following:
1. Patient presentation rarely fits neatly into unipolar depression, bipolar I and bipolar II
diagnostic criteria.
2. Treatment decisions can be guided by the bipolar spectrum classification.
What are the 3 neurotransmitters most implicated in mood disorders?
Serotonin, Dopamine, Norepinephrine
Describe the synthesis of norepinephrine.
Tyrosine Hydroxylase convert amino acid Tyrosine into DOPA, DOPA
decarboxylase convert DOPA to DA, Dopamine b hydroxylase converts DA into
NE
How is norepinephrine metabolized?
Monoamine oxidase (MAO) A or B, Catechol-o-methyl-transferase (COMT)
What is the significance of presynaptic alpha-2 receptors?
Presynaptic alpha 2 receptors are located in both the axon terminal and soma. Only a2
receptors can act as presynaptic autoreceptors, presynaptic alpha 2 receptors regulate
norepinephrine release
Describe how norepinephrine regulates serotonin.
NE regulates 5HT neuros via alpha 1 and alpha 2 receptors, a1 accelerate and a2 brake
Compare the monoamine hypothesis of depression to the monoamine receptor
hypothesis and the proposed validity of each. (This information is also covered in
Chapter 7.)
Monoamine hypothesis conclude that depression is due to a deficiency of monoamine
neurotransmitters and mania is due to an excess of monoamine neurotransmitters.
Monoamine receptor hypothesis posits that abnormality in the receptors for monoamine
neurotransmitters leads to depression.
Describe the role of stress, BDNF and brain atrophy in depression. What is the
relationship between monoamines and BDNF?
Under stress brain-derived neurotrophic factor (BDNF) is repressed. Stress lower 5HT
levels and can acutely increase, then chronically deplete both NE and DA. These
,monoamine neurotransmitters changes together with deficient amounts of BDNF may lead
to atrophy of neurons in the hippocampus and other brain areas like the prefrontal cortex.
What is stress sensitization and its presumed role in depression?
Certain types of stress such as child abuse can sensitize brain circuits and render them
vulnerable to future stressors. Patients with vulnerable brain circuits who become
exposed ti multiple life stressors can result in development of depression.
What is the significance of neural circuits in depression?
Inefficient information processing in neural circuits leads to depression
Stahl Chapter 7 + Supplemental Materials
Define treatment response, remission, relapse and recovery in depression.
According to the Star D study, which symptoms are most likely to respond to
antidepressant treatment?
Depressed mood, suicidal ideation and psychomotor retardation
Describe the mechanism of action of SSRIs.
For the following SSRIS, how do their secondary mechanisms of action differ? What is
the clinical significance of these differences? Are their particular patient profiles that are
best matched to these medications?
Describe the unique mechanism of action of vilazodone.
Vilazodone SERT inhibition + 5HT1a partial agonisim
Describe the mechanism of action of trazodone. How does treatment effect differ for
dose strengths?
What are the clinical findings for the 4 newest antidepressants, vilazodone,
Describe the mechanism of action of MAO-inhibitors?
Describe the mechanism of action of hypertensive crisis in MAOIs.
Describe symptoms associated with hypertensive crisis and describe its treatment.
Identify foods that are contraindicated while taking MAO-I.
What are the roles of folate, SAMe and thyroid in depression?
(Brain stimulation will be covered in the next module.)
How does symptom presentation guide antidepressant selection?
Know, understand and apply the implications of all warnings and safety risks associated
with antidepressants including:
,Suicide risk
Mania Switch
Serotonin Syndrome Discontinuation Syndrome
What clinical symptoms differentiate serotonin syndrome from hypertensive crisis?
Identify unique clinical features/uses of individual antidepressants. Use quizlet
flashcards to support your learning.
· Review sexual side effects of antidepressant medications
· Review augmentation agents used to treat depression
Buspirone +SSRI
Quetipine +SSRI
Aripiprazole +SSRI
· Review antidepressant augmentation with atypical antipsychotics
· Review length of time treatment is continued in the remission of
depression
· Review side effects that may improve in regards to dose timing or
formulation change
· Review mechanism of action for selective serotonin reuptake
inhibitors
· Review hyponatremia regarding antidepressants
· Review antidepressant least likely to cause sexual side effects
Vilazodone due to lesser degrees of SERT inhibition then SSRI
· Review unique clinical profile for select SSRI’s (matching)
1.Fluoxetine (Prozac)- also have 5HT2c antagonist, improve pt
energy/concentration and attention. In combination with olanzapine approve for
treatment-resistant unipolar depression and for bipolar depression. Approve for
treatment of eating disorder (bulimia)
2. Fluvoxamine (Luvox)- SSRI with sigma 1 receptor binding- use for obsessive-
compulsive disorder and social anxiety disorder
3.Sertraline (Zoloft)-an SSRI with dopamine transported
inhibition and sigma 1 binding. Improving symptoms of
hypersomnia, low energy and mood reactivity.
Week DAT inhibitory actions of sertraline contributes to its
clinical portfolio
4.Escitalopram (Lexapro)- the quintessential SSRI- contains only
Pure S enantiomer-Pure SERT inhibition which makes it the
, best tolerated SSRI with fewest CYP-mediated drug
interactions
5. Paroxetine (Paxil)- an SSRI with Muscarinic anticholinergic and
norepinephrine transporter (NET) inhibitory action- tends to be
more calming and sedating in early treatment. Paroxetine
inhibits the enzyme nitric oxide synthetase which contributes
to sexual dysfunction especially in men. Associated with
withdrawal upon sudden discontinuation
6. Citalopram (Celexa)- Two enantiomers R and S(aka racemic
citalopram)- R enantiomers is bad, QTc prolongation with dose
increase.
· Review dry mouth as a symptoms with antidepressant use
· Review food and monoamine oxidase inhibitors
Ingesting food containing tyramine like aged cheese, wine and
beers ( Hypertensive crisis/blood pressure elevation).
Selegiline transdermal patch does not have any dietary
restriction/it bypass the gut.
· Review the best treatment for sexual side effects caused by
antidepressants
Combining either a stimulant or sildenafil with an SNRI
· Review which drug class serotonin/norepinephrine/dopamine are
key targets for
· Review medication profile for tricyclic antidepressants
· Review medication profile for Trazodone
Block 5HT2a and 5HT2c as well as serotonin. Also know as
serotonin antagonist/reuptake inhibitor (SARI).
At lower dose Trazodone is effective a treating insomnia.
At higher dose it treat depression by recruiting SERT inhibition
and raise serotonin levels
· Review briefly the findings of the STAR D study
Only one third of patients remit on their first antidepressant
treatment, and even after a year of treatment with a sequence
of 4 different antidepressants given for 12 weeks, only about 2
thirds of depressed patients achieve remission of their
symptoms.
· Review what medication may cause increase bleeding with
antidepressant use.
· Review comparison of desvenlafaxine to venlafaxine
Familiarize yourself with theories of bipolar spectrum disorder and their criticism (Article:
Bipolar Spectrum: A Critical Perspective) with consideration of the following:
1. Patient presentation rarely fits neatly into unipolar depression, bipolar I and bipolar II
diagnostic criteria.
2. Treatment decisions can be guided by the bipolar spectrum classification.
What are the 3 neurotransmitters most implicated in mood disorders?
Serotonin, Dopamine, Norepinephrine
Describe the synthesis of norepinephrine.
Tyrosine Hydroxylase convert amino acid Tyrosine into DOPA, DOPA
decarboxylase convert DOPA to DA, Dopamine b hydroxylase converts DA into
NE
How is norepinephrine metabolized?
Monoamine oxidase (MAO) A or B, Catechol-o-methyl-transferase (COMT)
What is the significance of presynaptic alpha-2 receptors?
Presynaptic alpha 2 receptors are located in both the axon terminal and soma. Only a2
receptors can act as presynaptic autoreceptors, presynaptic alpha 2 receptors regulate
norepinephrine release
Describe how norepinephrine regulates serotonin.
NE regulates 5HT neuros via alpha 1 and alpha 2 receptors, a1 accelerate and a2 brake
Compare the monoamine hypothesis of depression to the monoamine receptor
hypothesis and the proposed validity of each. (This information is also covered in
Chapter 7.)
Monoamine hypothesis conclude that depression is due to a deficiency of monoamine
neurotransmitters and mania is due to an excess of monoamine neurotransmitters.
Monoamine receptor hypothesis posits that abnormality in the receptors for monoamine
neurotransmitters leads to depression.
Describe the role of stress, BDNF and brain atrophy in depression. What is the
relationship between monoamines and BDNF?
Under stress brain-derived neurotrophic factor (BDNF) is repressed. Stress lower 5HT
levels and can acutely increase, then chronically deplete both NE and DA. These
,monoamine neurotransmitters changes together with deficient amounts of BDNF may lead
to atrophy of neurons in the hippocampus and other brain areas like the prefrontal cortex.
What is stress sensitization and its presumed role in depression?
Certain types of stress such as child abuse can sensitize brain circuits and render them
vulnerable to future stressors. Patients with vulnerable brain circuits who become
exposed ti multiple life stressors can result in development of depression.
What is the significance of neural circuits in depression?
Inefficient information processing in neural circuits leads to depression
Stahl Chapter 7 + Supplemental Materials
Define treatment response, remission, relapse and recovery in depression.
According to the Star D study, which symptoms are most likely to respond to
antidepressant treatment?
Depressed mood, suicidal ideation and psychomotor retardation
Describe the mechanism of action of SSRIs.
For the following SSRIS, how do their secondary mechanisms of action differ? What is
the clinical significance of these differences? Are their particular patient profiles that are
best matched to these medications?
Describe the unique mechanism of action of vilazodone.
Vilazodone SERT inhibition + 5HT1a partial agonisim
Describe the mechanism of action of trazodone. How does treatment effect differ for
dose strengths?
What are the clinical findings for the 4 newest antidepressants, vilazodone,
Describe the mechanism of action of MAO-inhibitors?
Describe the mechanism of action of hypertensive crisis in MAOIs.
Describe symptoms associated with hypertensive crisis and describe its treatment.
Identify foods that are contraindicated while taking MAO-I.
What are the roles of folate, SAMe and thyroid in depression?
(Brain stimulation will be covered in the next module.)
How does symptom presentation guide antidepressant selection?
Know, understand and apply the implications of all warnings and safety risks associated
with antidepressants including:
,Suicide risk
Mania Switch
Serotonin Syndrome Discontinuation Syndrome
What clinical symptoms differentiate serotonin syndrome from hypertensive crisis?
Identify unique clinical features/uses of individual antidepressants. Use quizlet
flashcards to support your learning.
· Review sexual side effects of antidepressant medications
· Review augmentation agents used to treat depression
Buspirone +SSRI
Quetipine +SSRI
Aripiprazole +SSRI
· Review antidepressant augmentation with atypical antipsychotics
· Review length of time treatment is continued in the remission of
depression
· Review side effects that may improve in regards to dose timing or
formulation change
· Review mechanism of action for selective serotonin reuptake
inhibitors
· Review hyponatremia regarding antidepressants
· Review antidepressant least likely to cause sexual side effects
Vilazodone due to lesser degrees of SERT inhibition then SSRI
· Review unique clinical profile for select SSRI’s (matching)
1.Fluoxetine (Prozac)- also have 5HT2c antagonist, improve pt
energy/concentration and attention. In combination with olanzapine approve for
treatment-resistant unipolar depression and for bipolar depression. Approve for
treatment of eating disorder (bulimia)
2. Fluvoxamine (Luvox)- SSRI with sigma 1 receptor binding- use for obsessive-
compulsive disorder and social anxiety disorder
3.Sertraline (Zoloft)-an SSRI with dopamine transported
inhibition and sigma 1 binding. Improving symptoms of
hypersomnia, low energy and mood reactivity.
Week DAT inhibitory actions of sertraline contributes to its
clinical portfolio
4.Escitalopram (Lexapro)- the quintessential SSRI- contains only
Pure S enantiomer-Pure SERT inhibition which makes it the
, best tolerated SSRI with fewest CYP-mediated drug
interactions
5. Paroxetine (Paxil)- an SSRI with Muscarinic anticholinergic and
norepinephrine transporter (NET) inhibitory action- tends to be
more calming and sedating in early treatment. Paroxetine
inhibits the enzyme nitric oxide synthetase which contributes
to sexual dysfunction especially in men. Associated with
withdrawal upon sudden discontinuation
6. Citalopram (Celexa)- Two enantiomers R and S(aka racemic
citalopram)- R enantiomers is bad, QTc prolongation with dose
increase.
· Review dry mouth as a symptoms with antidepressant use
· Review food and monoamine oxidase inhibitors
Ingesting food containing tyramine like aged cheese, wine and
beers ( Hypertensive crisis/blood pressure elevation).
Selegiline transdermal patch does not have any dietary
restriction/it bypass the gut.
· Review the best treatment for sexual side effects caused by
antidepressants
Combining either a stimulant or sildenafil with an SNRI
· Review which drug class serotonin/norepinephrine/dopamine are
key targets for
· Review medication profile for tricyclic antidepressants
· Review medication profile for Trazodone
Block 5HT2a and 5HT2c as well as serotonin. Also know as
serotonin antagonist/reuptake inhibitor (SARI).
At lower dose Trazodone is effective a treating insomnia.
At higher dose it treat depression by recruiting SERT inhibition
and raise serotonin levels
· Review briefly the findings of the STAR D study
Only one third of patients remit on their first antidepressant
treatment, and even after a year of treatment with a sequence
of 4 different antidepressants given for 12 weeks, only about 2
thirds of depressed patients achieve remission of their
symptoms.
· Review what medication may cause increase bleeding with
antidepressant use.
· Review comparison of desvenlafaxine to venlafaxine
