Drugs for Depression & Anxiety Flashcards
_____ & ______ are essential emotions for survival - much of the neuron circuitry regulating these emotions is subcortical (subconcious)
fear, anxiety
state the part of the brain that is our thinking mind
cortex
________ is a powerful motivator of behaviour
emotion
define fear
an emotional state aroused by specific external stimuli that gives rise to defensive and escape behaviours
define anxiety
a generalized response to an unknown threat or internal conflict - Concern about a future event that might be threatening - when we don’t have a feeling of control
define anxiety disorders
psychiatric conditions characterized by overactivity (dysregulation) of the autonomic nervous system (fight or flight), expectation of an impending threat, and continuous vigilance for danger (not caused by drug intoxication or drug withdrawal)
define panic disorder
characterized by episodic periods of intense fear and ANS over activation
what are the signs of panic disorder/ANS overactivation
- fast heartbeat
- short breath
- patients sincerely believe they are dying
define generalized anxiety disorder
persistent state of excessive worry and anxiety serious enough to cause a disruption in normal activities
define anticipatory anxiety
a fear of having a panic attack; may lead to the development of agoraphobia
define agoraphobia
a fear of being away from home or other protected place
define social anxiety disorder
excessive fear of being exposed to the scrutiny of other people that leads to avoidance of social situations
define post traumatic stress disorder
a reaction to a terrifying event that occurs to or is witnessed by the patient
Everyone experienced a traumatic event but only a portion has a persistent debilitating syndrome from it
what are the signs of ptsd
- flashbacks
- nightmares
- anxiety
- compulsive thoughts about the event/rumination
what is the lifetime prevalence of anxiety disorders
at least 20% (high!)
what may anxiety disorders be comorbid with
depression
females are ______ as likely as males to develop an anxiety disorder - emphasizes biological nature but gender may also play a role
twice
what is the heritability to anxiety disorders
0.3 (based on family and twin studies, quite low)
bdnf (gene) and val66met allele may play a role for what disorder (and what does val66met do)
ptsd, val66met may impair the ability to forget a fear memory in humans and mice
why might ptsd be easier to understand
bc they can see the genetic differences in people who can move on and those who cannot
chronic psychological stress persistently increases _______ and effects _________ _________ numbers
cortisol, neuron synapse
what happens in the brain during periods of stress
there is increased connectivity = you learn about what the stress is. But enduring consistent stress leads to persistent increase in cortisol and effects the connections in the synaptic connections = possible loss in volume of the cortex (decreases synapse number in hippocampus and cortex) = fear not working properly
stress affects hypothalamus –> anterior pituitary –> adrenal gland –> cortisol (long term has much dire affects)
what devices provides the best evidence for the neurobiology of anxiety disorders
fMRI - functional magnetic resonance imaging
DTI - diffusion tensor imaging
what can you see in the fMRI regarding anxiety disorders
Sees blood flow - when neurons fire it has blood sent to the area and the iron in the blood gets picked up
brain regions that are activated have increased blood flow
name the part of the brain that patients w anxiety disorders have an overactivation of
the amygdala
what does the amygdala do
regions for fear, anger, negative emotions
describe what the DTI studies
white matter tracts and connectivity
anxiety disorders reduce connectivity between _____ ____ and the _________
frontal cortex and amygdala
which is easier to treat, anxiety disorders or depression
anxiety disorders
for anxiety disorders, __________ has similar efficacy to pharmacotherapy
psychotherapy
describe the first line therapy for anxiety disorders
SSRIs (selective serotonin reuptake inhibitors) and antidepressants that are actually more effective for anxiety than they are for depression - the effect of increasing serotonin is particularly effective in anxiety disorders
what might be used as alternate treatment for GAD (generalized anxiety disorder) and PD
benzodiazepines
why might benzodiazepines be limited in treating GAD and PD
- tolerance
- withdrawal
- rebound effect: If you stop taking it then you get a return on the anxiety and it may be worse
- abuse liability: Need more and more and more to control the anxiety
list the characteristics of major depressive disorder (MDD) (9)
- depressed mood most of the day
- diminished interest or pleasure in all or most activities
- significant unintentional weight loss or gain
- insomnia or sleeping too much
- agitation or psychomotor retardation noticed by others
- fatigue or loss of energy
- feelings of worthlessness or excessive guilt
- diminished ability to think or concentrate, or indecisiveness
- recurrent thoughts of death
state the most common brain disorder, based on WHO
depression, over 350 million people of all ages globally
what is the leading cause of disability world wide, based on WHO
depression
based on WHO, how is disability measured
DALYs - disability adjusted life years: how many years of healthy life are lost to the disease
DALY=YLL+YLD
which sex is more affected by depression
women
how many people globally die from suicide, based on WHO
1 million
what may prevent people from accessing therapies for depression
cultural stigmas
state the heritability of depression
30%-40%
what are some risks/what are some factors that determines prevalence
- environmental risk, psychological stress
- age; early adulthood onset mostly but can occur anything
- gender; more females than males
- marital status; divorced, widowed, single, married
- education
- socioeconomic status
describe how stress reduces synapses
- chronic stress induces depression
- production of cortisol causes a decrease in brain derived neurotrophic factor (protein)
- decrease in bdnf causes a decrease in new neurons and retraction of dendrites
- can be reversed w antidepressant treatment
- the synpases have significantly less dendritic sprouts
t/f can the process of stress induced synapse reduction be reversed
yes, by antidepressants
how can antidepressants reverse the synapse reduction due to chronic stress
New connections forming and an increase in new born neurons (stem cells waiting to be differentiated into a neuron - not common but there is a low level of neurogenesis) - when you take antidepressants, you see an increase in neurogenesis
state the psychotherapy treatment for depression
cognitive behavioural therapy
list the 5 pharmacotherapies as treatments for depression
- tricyclic antidepressants (tcas)
- monoamine oxidase inhibitors (MAOi’s)
- selective serotonin reuptake inhibitors (SSRIs)
- serotonin/norepinephrine reuptake inhibitors (SNRIs)
- hallucinogens (ket (most researched), psilocybin, MDMA) - work much quicker than 1-4
other than psychotherapy and pharmacotherapy, what might be another treatment for depression
electroconvulsive therapy (ECT and TMS) and deep brain stimulation (Helen Mayberg)
monoamines are _________ for their receptors, and their receptors are the _______________
agonists, g-protein coupled receptors
list 6 monoamines relevant to this
- dopamine (DA)
- norepinephrine (NE)
- serotonin (5HT)
- melatonin
- histamine
- trace amines
what do monoamines regulate (10)
- mood
- sleep
- appetite
- peristalsis
- arousal (awakeness)
- sexual function
- cognition
- reward
- motivation
- aggression
(sometimes w opposing effects between dopamine and serotonin)
state the similarities/features of monoamines (4)
- all derived from amino acids in similar synthetic processes and are degraded by the same/similar enzymes
- all packaged into synaptic vesicles by VMAT2 (vesicular monoamine transporter 2)
- act on metabotropic, g-protein coupled receptors
- all cleared from the synapse by plasma membrane transporters; another way to clear is through enzymes that will degrade them (monoamine oxidase)
what does monoamine oxidase degrade
serotonin, norepinephrine, adrenaline, dopamine, tyramine (cheese effect is too much tyramine)
how do monoamine oxidase inhibitors affect levels of nt (serotonin, norepinephrine, adrenaline, dopamine, tyramine)
they increase levels of this bc monoamine oxidase is what degrades them; more serotonin means you can package more and so it increases levels of the NT
what are 2 examples of monoamine oxidase inhibitors
phenelzine (also a drug for tb) and moclobemide (reversible)
what is the moa of phenelzine (MAOI)
irreversible inhibitor of monoamine oxidase, once it binds the enzyme it permanently inactivates it and there is no more enzyme until the cell makes more
describe the concerns of phenelzine (MAOI)
highly effect but only used as last resort bc nuremous drug drug interactions that cause hypertensive crisis (excess adrenaline) and serotonin syndrome (too much) that can be fatal
High BP = brain cannot handle a “firehouse” of blood going through it. The blood vessels will burst = stroke
describe the relationship of hypertensive crisis and tyramine
tyramine can cause hypertensive crisis
foods that contain tyramine are cheese wine beer sauerkraut thus you have to have a strict diet while on MAOIs
compare reversible and irreversible MAOIs
phenelzine is irreversible and reversible is moclobemide.
phenelzine is highly effective with serious adverse effects and moclobemide are also effective and much safer but doctors have reluctance prescribing
they have the same drug drug interactions and diet
how were tricyclic antidepressant discovered
the drugs were initially made for schizophrenia patients. After chlorpromazine (schizophrenia med) was discovered - all pharma companies wanted chlorpromazine made many chemicals similar (imipramine) –> gave it to psychiatrist, tried it on schizophrenia patients and didn’t work, and just randomly tested out on his depressed patients.
didn’t want to make more bc there was no market, but a stockholder and pharma owner had a wife w depression so they kept it.
what is the primary therapeutic benefit of TCAs
they have several targets. primary benefit is thought to be due to blocking (antagonist) the reuptake of both serotonin and norepinephrine (inhibit NET and SERT)
list the receptors (7) and channels (2) that TCAs are antagonists for
receptors:
1. 5ht2a
2. 5ht2c
3. 5ht6
4. 5ht7
5. a1 adrenergic
6. antihistamine
7. anticholinergic
channels
1. sodium
2. calcium
what are the adverse effects of TCAs blocking ion channels
cause of death from overdose is from cardiotoxicity, prolonged heart rhythms
what are the adverse effects of TCAs antagonizing the receptors
histamine receptor antagonist causes drowsiness, anti-muscarinic cholinergic receptor causes dry mouth and dry eyes
safety profile of ________ preferred over TCAs
SSRIs
name 2 examples of tcas
imipramine, amitriptyline
what are the first line of treatment for depression and anxiety
ssri
list examples of ssri (4)
fluoxetine eg prozac
paroxetine eg paxil
citalopram eg celexa
sertraline eg zoloft
fluoxetine is the ________ selective and first line for __________ and have a ______ half life
least, adolescents, long (the lost half life may lead to dosing problems
paroxetine has _______________ effects, _____ weight gain
anti-cholinergic effects, most
t/f we know how ssri causes weight gain, if so, how
false, we don’t know, all of them cause weight gain after 6 months
citalopram is the _____ selective for SERT
most
sertraline is an __________ of DAT (dopamine transporter)
antagonist
ssris were the first class of drugs developed by what design, and what did this design mean
rational drug design; screened for ability to inhibit sert and elevate serotonin based on actions of tcas and maois
what is the typical half life of ssri and what is the outlier
around 24-30 hours, fluoxetine is 48-96 hours, active metabolites have half lives of several days
contrast between the timelines of adverse effects and beneficial effects of ssris
Beneficial effects take several weeks to occur and you get the adverse effects from day 1 (the weight gain is later)
note that many or most of the adverse effects diminish with continued use
list the adverse effects of ssris (11)
- headache
- insomnia
- gi disturbance (nausea, cramping, diarrhea)
- sexual dysfunction (reduced libido, anorgasmia)
- weight gain
- dizziness
- weakness
- fatigue
- tremor
- agitation
- anxiety
Note that the less common effects are at the end of the list
how to deal with discontinuation syndrome and its effects
effects: anxiety, insomnia, headache, nausea
how to deal: taper off treatment by reducing dose and then taking on alternating days
snri inhibits what transporters
sert and net
for depression, are ssri or snri more effective
snri
examples of snris 2
venlafaxine (effecor)
duloxetine (cymbalta)
why is bupropion (wellbutrin) a different kind of antidepressant (diff class altogether)
little action on sert, but blocks dat and net
what is serotonin syndrome caused by
drug drug interactions of ssri and maoi –> too much released that you can’t clear it
ssri + cough med (dextromethorphan)
ssri + tryptans (migraine med) or some opiods (aalgesics)
can also be caused by ecstasy (mdma)
what are the adverse effects of serotonin syndrome (10) and the fatal effects (3)
adverse:
agitation or restlessness, hyper reflexes, diarrhoea, fast heart beat, high bp, hallucinations, increase body temperature, loss of coordination, nausea, vomiting
fatal: hyperthermia, tachycardia, lactic acidosis (too acidic) from muscle contraction
list the related disorders that also respond to anti-depressants (8)
dysthymia, postpartum depression, atypical depression (overeat, oversleep, inability to react positively, oversensitivity to rejection), SAD, anxiety disorders (gad, panic, ptsd, social), ocd, neuropathic pain, eating disorders (bulimia but not anorexia nervosa)
hallucinogens (as antidepressants) have more ______ antidepressants effects
rapid
how must hallucinogens (as antidepressants) be delivered
in a clinic with someone guiding them
how might ketamine act as an antidepressant
antagonist of nmda type of glutamate receptors - increases synapse density within 1h of treamtent. given intravenously every 1-4 weeks
how might psilocybin act as an antidepressant
chemical in psilocybes (magic mush) converted to psilocin in body - agonist of 5ht2a serotonin receptor
how might lsd (lysergic acid diethylamide) act as an antidepressant
chemical dervied from ergot mold - agonist of 5ht2a serotonin receptor
how might mdma (3,4-methylenedioxymethamphetamine) act as an antidepressant
acts in same way as amphetamine
selective for sert - reverse transports serotonin
