Antidepressant notes Flashcards
T: Drugs used to treat mood disorders, OCD/eating disorders, chronic pain
antidepressants
4 things anti treat
Drugs used to treat mood disorders, OCD/eating disorders, chronic pain
2 ways antidepressants differ from stimulants
- Target brain, not parasympathetic system
2. Mechanism of action
antidepressants affect …. not … like stimulants
mood, arousal
what is the mechanism of action in antidepressants
second messenger/ mRNA factors
T: illness1 that affects how you feel, think and behave2 causing persistent feelings of sadness and loss of interest in previously enjoyed activities3.
major depressive disorder
illness1 that affects how you feel, think and behave2 causing persistent feelings of sadness and loss of interest in previously enjoyed activities3. explain what 1 implies
Biological origins
what are the biological origins of depression, what are the areas anatomically that we see differences in people with depression
anatomical differences have emerged in mesolimbic and frontal areas
antidepressants are only used to treat depression
f treat mood, OCD, eating and chronic pain disorders
what is the problem with the biological origins
correlation
antidepressants influence arousal
f do not change heart rate act, changes mood
do antidepressants target brain or body
brain(cognitive components)
illness1 that affects how you feel, think and behave2 causing persistent feelings of sadness and loss of interest in previously enjoyed activities3 explain 2
Holistic (not selective)
illness1 that affects how you feel, think and behave2 causing persistent feelings of sadness and loss of interest in previously enjoyed activities3 explain 3
not situational and comparative
comparing to times without depression e.g. if your pessimistic thats different
what is the common denominator of MDD
monamines
does stim influence the body or brain
body= working on NS= sympathomimetic
what monamines are influenced in MDD
seretonin
dopamine
nonep
seretonin influences what aspects of MDD
anxiety and obsession
nonep influences what aspects of MDD
alertness, attention, enjoyment
dopamine influences what aspects of MDD
motivation and reward
why and how does depression onset arise
permissive hypothesis
how was antidepressants found
TB treatment made people feel way better even though they still had symptoms
where did the permissive hypothesis come from
TB pills were seretonergics = improved mood
supposed that bcs of low serotonin in body system transforms dopamine into serotonin (body can do this easily) but as a result of compensation find stuff less rewarding and motivation that is naturally rewarding
T: low serotonin causes low norepinephrine/dopamine
permissive hypothesis
the permissive hypothesis says Dopamine compensates by providing more …
precursor
someone with OCD would have what monoamine imbalance
seretonin
what are the problems with permissive hypothesis 2
- Intake is immediate, behavioural change is delayed
* general monoamine depletion doesn’t result in depression
it takes 2-4 weeks for antidepressants to work, why the delay
?
you can see depression from birth
f different onset than most other disorders
how can we best understand onset of depression
diathesis stress model (bio psyho social)
Diathesis stress support: emergence of depression in typical cohort who have experienced ….,
very stressful life events (kicks off depression)
Diathesis stress support: Family studies demonstrate … of depression
heritability
since dep is kicked off by stressful life event does that mean no genetic component
f just didn’t know what it meant
what is the heritability of depression
30-40%
why are heterability findings scewed 2
men vs female depression diagnosis
depressed mother deprives enviro
when does the cognitive aspect of MDD emerge
precede depression (thought processes before change in mood)
when do schemas (cognitive component) go away?
dissipate during remission of depression in response to stress
Organic stress, such as withdrawal, lack of sunlight (SADs), postpartum hormone, or drug abuse (DSM-5)* is known to induce depression
f depression like symptoms (comorbidity different from having disorder as result of)
what are the 3 types of antidepressants
first, second, third generation
what ae the 2 types of first generation
MAOIs and Trycylics
Inhibit enzyme which breaks down monoamines at synapse
MAOIs
what antidepressants inhibiting an inhibitor
MAOIs
what antidepressants causes the cheese reaction
MAOIs
the diagnosing of MDD requires a stressful life event
t
depression can happen to people with no family history
true
depression can happen to people with no family history
true
what’s the assumption of what caused depression in MAO time
too much of the MAO monoamine around which break apart and transform NT
what did they think MAOs
block off enzyme, so it won’t be breaking apart dopamine to create serotonin = enough serotonin in system
what were the problems with MAOIs
“cheese reaction”
what wasn’t being broken down that caused cheese reaction
tyramine
what does an increase in tyramine do to body
tyramine elevates blood pressure and results in stroke
T: Block reuptake of serotonin and norepinephrine at synapse
tricyclics
is the MAOI cheese reaction reversible?
no MAO inhibited for life
what was new about the new MAOIs
selectively block MAO A not MAO B = reversible MAOI after 20 y
what do the tycyclics selectively block
non. ep
dopamine and sert
problem with TCAs
produce irregular or elevated heart-rate
why were TCAs better than MAOIs
only change cognitive not physiological system
what about the TCAs produce irregular or elevated heart-rate
levo nonep has effects in body
T: Selective Serotonin Reuptake inhibitors
second generation
T: Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
third generation
what were second gen antidepressants trying to avoid
attaching to nonep = heart problems
what was the benefit of SSRIs
Reduced the cardiologic side-effects
prozac is what kind of antidepressants
second gen
was prozac discovered or designed
designed
why did you not see heart problems in SNRIs even though the block nonep
targeted dex not levo nonep
blocking reuptake of nonep might be dangerous as it resembles…
amphet= amphet psychosis
what do third gen block
Block reuptake of both serotonin and norepinephrine in brain
Are antidepressants effective?
no
what was ineffective about 2nd and 3rd gen
did not understand secondary effects
2nd /3rd gen. medication actively altered for depression use
t
1st gen. anti-depressants “discovered” when treating other disorders what’s the problem with this
secondary effects, can’t understand what’s actually happening with disorder (mechanism)
what happened when patent ran out
found out antisepsis were 50% effective
how did placebo compare to second generation
??
T: negative results found 50% of the time, however never promoted beyond FDA
Publication bias
what NT represents mood and motivation in the system
mood= seretonin motivation= dopamine
why are people newly on antidepressants on suicide watch
increase in motivation takes on first before change in mood = serotonin. will to do stuff increases
what protects people from suicdie in depression
no motivation= can’t leave bed
when prozac was released to public there was a spike in suisides
t
teenagers were just as likely to commit suicide on or off meds
t = no better option
T: suicide warnings introduced in 2003 caused
a decrease in prescription to children/teens
black box
what is primary effect of antidepressants
seretonin
what is primary effect of antidepressants
seretonin
3 other drugs that can treat depression
sympathomimetic stimulants
oxytocin
heterocyclic
T: Amphetamine-like substances
Sympathomimetic Stimulants
T: Hormone that rewards inter-personal behaviour
oxytoxin (give hormone that facilitates social bonding
what’s the problem with treating depression with sympathomimetic stimulants
euphoria is an emotion whereas mood is a long term change = effects don’t last
T: serious negative secondary/side effects: last resort
heterocyclic
when you hug someone you get what NT
oxytocin
do oxytocin medications work
in short term then gain tolerance
different between tricyclics and heterocyclcis
?
what systems do heterocyclic target
norep seretonin dopamine
how do heterocyclic influence monamines
blocking reuptake and adding second kick of addictive effect
3 mechanisms of action of Heterocyclics
Block reuptake of Norepinephrine and Serotonin
– Block dopamine transporter protein (reuptake mechanism) (?) – Stimulate release of Norepinephrine (?)
what is the problem with heterocyclic
Block post-synaptic histamine, and acetylcholine receptors (hitting all quadrants makes everything more bioavalible)
side effects (in body) of heterocyclic? 2
1) Sever cardiovascular irregularities
2) downregulation of Norepinephrine receptors
any drug that plays with … system and you’ll have circulatory changes that effect the heart
norepinephrine changes
the 2) downregulation of Norepinephrine receptors results in what kind of behaviour
resemble tolerance and withdrawal of amphetamines= reemergence of depressive symptoms
how do heterocyclic result in reemergence of depressive symptoms
could be from tolerance form homeostatic or from rebound
which antidepressants produces withdrawal symptoms
heterocyclic (mild)
do you have drug seeking behaviour on antidepressants
f only heterocyclic
what is the problem with withdrawal on heterocyclic
are behavioural or physiological?
heterocyclic are More … than other antidepressants
toxic
T: Delirium, seizures, light sensitivity, raised pulse rate, lowered core body temp, respiratory arrest, cardiovascular collapse, impaction (elderly)
toxic effects of other antidepressants
4 problems of heterocyclic
- severe cardiovascular irregularities
- down regulation of nonep. receptors
- more toxic than other antidepressants
- more severe side effects
the withdrawal symptoms of heterocyclic are the product of what problem with them
down regulation of nonep
what are the side effects of heterocyclic
Anorexia, insomnia, anxiety, mania, psychotic episodes (amphet psychosis)
T: the tendency for patients to suddenly (willingly) stop taking medication after four weeks, resulting in re- emergence of symptoms
discontinuation syndrome
problems with discontinuation syndrome
unclear how discontinuation and symptoms interact don’t know why they go off them distance between how they feel and think
how do patients describe the side effects of antidepressants (why they went off them)
side effects described as “brain shivers” or “brain numbing”
when do patients report brain shivers
not when on meds only after
is there consistency with which side-effects reported
f
2 speculation of what may cause discontinuation syndrome
– patients feel better -> stop taking meds
– delayed/slow effects -> think it’s not working
is discontinuation syndrome related to withdrawal
no rebound (can’t be because they would be wanting more of the drug)
are the symptoms in patients who go off their antidepressants caused by tolerance
no
do those who discontinue their meds move on to harder drugs = gateway?
no Patients do not exhibit drug-seeking behaviour just don’t want it anymore
was the antidepressants causing compulsive, out of control, or negative
consequences?
no none
why did patients go off meds then?
delayed response
what sparked the debate of the mechanisms behind antidepressants?
late temporal onset to reward = feeling better
is depression caused by serotonin imbalance
yes partly but brain cell growth and connections also play a role
what area of the brain is smaller in depressed people
hippocampus and others
what does the hippocampus control
memory and emotion (cells deteriorate)
what happens when hippocampus neutrons are regenerated
mood improves
why does serotonin improve mood then?
indirectly effect on cell growth (promote release of other chemicals that promote neurogenesis )
what is the genetic component in depression
short or long serotonin gene (and others= different kinds of depression)
what 2 systems os the hippocampus related to
limbic and cortical systems
the hippocampus is very close to the …. which is in charge of +. and - emotions
amygdala
does depression have a structural component
yes! synaptogenosis decrease (without this you’re in a rut)
T: Both theories state that stress induces release of cortisol (hormone) that atrophies the hippocampus, resulting in MDD.
glucocorticoid or BDNF theory
what does BDNF stand for
brain derived neurotropic factor
T: chemical that facilitates growth
BDNF
T: stage in cortisol development in which chemicals effect brain in a specific way
glucocorticoid
which NT involved in fight or flight
nonep immediate system
cortisol longer term stress system
T:induces cortisol release
Glucocorticoid
problem with having too much Glucocorticoid in the system
shuts down aspects of system worried with anything other than worry
what could be the treatment of too much glucocorticoid hormone
antagonizing glucocorticoid receptors
T: facilitates neurogenesis (of the hippocampus)
BDNF
problem with BDNF
too little of this chemical is produced
treatment of too little of BDNF chemical produced
increase BDNF
in response to same life stressors some people get depression some don’t why
BDNF allows bounce back (easier learning of coping strategies)
which depression theory Best account for environmental influence on the emergence of depression
BDNF and gluco
what would happen if increased BDNF
could have hyperconnectivity = disorder (need synaptic pruning
what would happen if decreased glucocorticoid
don’t have natural stress response
2 things “Glucocorticoid” or “BDNF” theory can account for that serotonin couldn’t
❑Best account for environmental influence on the emergence of depression
o May also help account for polyphony of depressions
