W12 MENTAL HEALTH 2 Flashcards
What is depression?
A mental illness that can linger for for more than 2 weeks; it significantly affects one’s ability to work, play, love
Sx of depression
Having five of the following symptoms may inform a diagnosis of depression: depressed mood for 2+ weeks, loss of interest in things normally enjoyed, changes in appetite, changes in sleep patterns, restlessness or slowness, poor concentration, feelings of worthlessness or guilt, suicidal ideation or thoughts.
intangible sx
Depression has physical manifestations, seen in the naked eye, or x-ray… provide examples
smaller frontal lobe and hippocampus, blunted circadian rhythms (REM/slow wave sleep cycles), abnormal regulation of hormones (high cortisol, deregulation of thyroid hormones)
Which neurotransmitters are abnormally released/depleted during depression?
serotonin, norepinephrine, dopamine
potential causes
mainly unknown, though, thought to be a genetic & environmental impact
treatment options for depression
medications and behavioural-cognitive therapy to boost brain chemicals; in extreme cases, electro-simulation
how does depression compare to general feelings of sadness
General sadness is a mood that comes and goes in most individuals. It is a natural part of life but is usually not as long lasting or as impactful as depression.
Which neurotransmitters and brain structures mentioned as being of key interest in the physiology of depression?
The key interest in physiology of depression includes abnormal levels of certain monoamine neurotransmitters, blunted circadian rhythms and sleep patterns, as well as hormonal abnormalities. Smaller frontal lobes and hippocampal volumes of the brain are also important to note.
list the processes during 5-HT nerve transmission
- serotonin (5-HT) is synthesised from tryptophan and loaded into vesicles via the vesicular monoamine transporter (VMAT)
- it then undergoes calcium-mediated exocytosis and is released into the synaptic cleft
- 5-HT then binds to the 5-HTr to induce a serotonergic effect
- 5-HT is then reabsorbed into the presynaptic cell via the serotonin transporter (SERT) and is reloaded into vesicles or degraded by monoamine oxidase (MOA)
what does VMAT stand for, and what is its function
vesicular monoamine transporter; it is responsible for the uptake of cystosolic monoamines into synaptic vesicles in monoaminergic neurons
what MAO stand for, and what is its function
monoamine oxidase; an enzyme involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain.
what is the monoamine theory of depression?
it states there is a deficiency of monoamine neurotransmitters within the brain. Deficiencies of key monoamines including serotonin (5-HT) and noradrenaline lead to symptoms of depression.
what are TCAs
tricyclic antidepressants.
what are available TCA medications (-ine, -in) (6)
[A, C, D, D, I, N]
amitriptyline, clomipramine, dosulepin, doxepin, imipramine, nortryptiline
what is the overall effect of TCAs
Tricyclic antidepressants (TCAs) block the reuptake of serotonin (5-HT) and noradrenaline (NA) in presynaptic terminals, which leads to increased concentration of these neurotransmitters in the synaptic cleft, which leads to their anti-depressive effect. Additionally, they act as competitive antagonists on post-synaptic cholinergic, muscarinic, and histaminergic receptors (H1).
what are the side effects of TCAs (6)
dry mouth, constipation, difficulty urinating, sedation, sexual complications, weight gain.
it is not a good idea to drink alcohol when depressed as it tends to worsen the depression. it also interacts with TCAs, increasing sedation.
the side effects of TCAs are largely due to the…
interactions w non-monoamine associated receptors; the most common adverse effects including constipation, dizziness, and xerostomia (dry mouth)
TCA side effects: Due to its blockade of cholinergic receptors, these drugs can lead to…
blurred vision, constipation, xerostomia, confusion, urinary retention, and tachycardia.
TCAs may also cause cardiovascular complications, including arrhythmias, such as QTc prolongation, ventricular fibrillation, and sudden cardiac death in patients with pre-existing ischemic heart disease.
TCA side effects: Due to its blockade of alpha-1 receptors…
it can cause orthostatic hypotension and dizziness
TCA side effects: Due to its blockade of histamine (H1) receptors…
causes sedation, increased appetite, weight gain, and confusion.
Noting the side-effects of TCAs, what other conditions could they be used to treat? (8)
migraine prophylaxis, obsessive-compulsive disorder (OCD), insomnia, anxiety, and chronic pain, especially neuropathic pain conditions such as myofascial pain, diabetic neuropathy, and postherpetic neuralgia. TCAs are also the second-line treatment for fibromyalgia after the failure of other treatments.
what are SNRIs
serotonin and noradrenaline reuptake inhibitors (SNRIs); antagonises reuptake transporters of both noradrenaline and serotonin
what are current SNRIs available in Australia (-xine, -xetine) (3)
venlafaxine, desvenlafaxine, and duloxetine
describe the mechanism of action of SNRI medication
SNRIs antagonism both 5-HT and noradrenergic re-uptake transporters, increasing the concentrations of both neurotransmitters in synapses.
what is the difference between TCAs and SNRIs
The major differences between TCAs and SNRIs comes down to their reduced side effects. SNRIs have minimal affinity and therefore minimal antagonism for the H1 histaminergic and muscarinic receptors. This means there are reduced sedation and cardiovascular effects.
what are SSRIs
selective serotoninergic reuptake inhibitors (SSRIs)
what are current SSRIs available in Australia (-pram, -xetine…) (6)
citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
which type of medication for depression is usually first-line
SSRIs
what do SSRIs mainly act on
serotonergic synapses
what transporter do SSRIs block
SERT (serotonin reupdate transporter)
what is the result of SSRI
increased serotonin available for postsynaptic nerve transmission
what are some common side effects of SSRI
nausea (esp. in the first wk of treatment), difficulty going to sleep, nervousness, headaches, sexual problems.
what is an example of a pre-synaptic autoreceptor on serotonergic neurons
5-HT1A
what is the role of autoreceptors
they detect the presence of serotonin that is released into the synaptic gap following an action potential by the serotonergic neuron itself
Activation of the autoreceptor leads to gradual _________ in serotonin release – a ________ feedback process.
reduction; negative
Activation of postsynaptic 5-HT1A receptors mediates _______ (e.g., _______) properties, whereas activation of _____ autoreceptors is implicated in delay of therapeutic onset of antidepressants.
therapeutic; antidepressant; raphe
hypothalamic 5-HT1A receptors are involved in ____________ and ___________ control
thermoregulation; neuroendocrine
septum/___________ receptors control ___ release and aspects of memory function
hippocampal; ACh
SSRI treatment results in ______ concentrations of _________ and over time it is thought the auto-receptors are downregulated and ___________.
higher; serotonin; desensitised
why do antidepressants take 2-4 weeks to be effective
the 5-HT1A autoreceptor desensitization model: inhibition of serotonin reuptake increases serotonin concentration, which causes a downregulation of 5HT1A receptors. After the number of 5HT1A receptors is reduced, the neuron is less inhibitided to release more serotonin in the synaptic space.
what are MAOIs
irreversible monoamine oxidase inhibitors (MAOIs) (the oldest drug class of antidepressants)
what MAOIs are currently available in Aus (2)
phenelzine, tranylcypromine
summarise the MAOI mechanism of action
MAOIs prevent monoamine degradation, so they are packaged more quickly into synaptic vesicles for re-release. this enhances the speed with which the pre-synaptic neuron can respond to an action potential and therefore alleviates the presumed deficiency
what is the difference between MAO-A and MAO-B
MAO-A: works on noradrenaline and serotonin
MAO-B: metabolises dopamine within the CNS
where is else is MAO-A located and what does it metabolise
digestive tract; tyramine
list some food that contain tyramine
cheese, yeast, beer, some wines, avocados, yoghurt, soy sauce
what is the interaction between food that contain tyramine and MAOIs
as MAOIs inhibit MAO-A, the normal metabolism of tyramine is inhibited. tyramine will then be absorbed into the blood supply, making its way to the BBB. tyramine can then pass through the reuptake transporters for noradrenaline and subsequently displace NA from its synapses, lading to its unregulated release into synapses. this can lead to a hypertensive crisis. which could be fatal due to its sudden increase in blood pressure, heart rate, heart palpitations, and sweating.
how can you avoid a MAOI induced hypertensive crisis
tyramine-restricted diet, consideration of administration of MAOIs via a transdermal patch [it does not inhibit MAO-A]
common side effects of MAOIs
dry mouth, nausea, diarrhoea or constipation, headache, insomnia, drowsiness, dizziness or light-headedness, and possible skin reactions at the patch site
less common side effects of MAOIs
hypotension, reduced sexual desire/difficulty achieving orgasm, weight gain, muscle cramps
what are NASSAs
noradrenergic and specific serotonergic antidepressants (NASSAs)
what is one example of NASSA
mirtazapine
summarise NASSA mechanism of action [2 mechanism of actions]
In adrenergic neurons, NASSAs have an affinity for and antagonist effects against the NA alpha2 autoreceptors, which leads to downregulation/desensitization in the long term and a net increase in noradrenaline release in synapses.
In serotonergic neurons, NA influences increase synaptic release of 5-H. NASSAs are antagonists of postsynaptic 5-HT2 and 5-HT3 receptors. This leads to increased action on the 5-HT1 receptors, which stabilises mood.
list side effects of NASSAs [7]
dry mouth, increased appetite and weight gain, headaches, drowsiness, nausea, vomiting, diarrhoea, and constipation
how long should we try a treatment before we know whether it is working or not?
allowing time to observe clinical response, some agents may require 2-3 month trial. These changes may be positive, non-optimal or negative due to side effects experienced. The GP may continue the current dose, alter it up or down, or discontinue and/or switch to a new drug class. The goal is to achieve “remission” of the severe depressive symptoms such that other means of support can be added (e.g., counselling, mindfulness).
If medication(s) can be optimised for the patient, it is likely that “maintenance” will be achieved for at least _ months – __.
9; 1 year
when are relapses more likely to happen when taking anti-depressants
12 weeks - 9 months
in depression, remission can also be associated with…
return to euthymia - feeling true to oneself
When a patient is in remission/recovery for more than ___ year, their medication may be reduced gradually over a - week period.
one; 4-6
what is recurrence in depression
where symptoms reuturn after recovery
what is serotonin syndrome
elevated serotonin levels; mild or severe
what causes serotonin syndrome
antidepressant medications, St. John’s Wort, some cough medications, MDMA, migraine medications and other drugs, and intentional overdose of antidepressant medications
mild sx of serotonin syndrome
sweating, fever, agitation, confusion, anxiety, tachycardia, diarrhoea, tremors, poor coordination
full sx of serotonin syndrome
hyperthermia, shivering diaphoresis
hypomania, hyper-vigilance
hypertension
hyperflexia, clonus, myoclonus
severe sx of serotonin syndrome
hyperthermia (>40 degrees C), seizures, coma, death, rigidity
psychotherapy is a non-pharmacological ways to improve mental health, this involves:
cognitive behavioural therapy (CBT), stress mgt, relaxation strategies, effective sleep habits
electroconvulsive therapy (ECT) is a non-pharmacological way to improve mental health, this is:
a fast treatment for severe depression when the situation is thought to be life-threatening or after all other treatment options have failed.
what is a side effect of ECT
mild memory loss
T/F
ECT is one of the most effective treatments for depression
T
T/F
the effects of ECT are long-term without the requirement of further pharmacological/non-pharmacological assistance like antidepressants and therapy
F
During ECT the patient is placed under light _______ ______ and given _______ ______
general anaesthetics; muscle relaxants
T/F
antidepressants improve sx in about 40-60 out of 100 people
T
about __% of people who took an antidepressant had a relapse in 1-2 years
23
T/F
there may be strong components within families for depression
T
Deficiencies of which two central nervous system neurotransmitters may be linked to depressed mood, and which drugs are generally the first choice for the treatment of depression?
noradrenaline and serotonin; SSRIs
T/F
increased intraventricular conduction time is a side effect associated with TCAs as a result of blocking adrenergic receptors, muscarinic cholinergic receptors, or H1 receptors?
F
The ‘cheese reaction’ is characterised by flushing of the skin, sweating, and tachycardia when taking oral antidepressants. It is directly related to the effect of:
tyramine. which displaces noradrenaline from presynaptic vesicles, leading to a sympathetic response
The ‘cheese reaction’ is characterised by flushing of the skin, sweating, and tachycardia when taking oral antidepressants. It is directly related to the effect of:
elevated levels of 5-HT and NA caused by re-uptake inhibition and receptor blockade
anxiety is a reaction to our _____; a stop-reaction to the impulses that ____ and other core emotions create inside the body
emotions; fear
physical and psychological sx of anxiety
Feeling nervous, restless, or tense
Having a sense of doom
Increased heart rate
Shortness of breath
Sweating
Dizziness
Ear ringing
Trouble concentrating
Trouble sleeping
Gastrointestinal (GI) distress
Having difficulty controlling worry/ruminating
Having the urge to avoid things that trigger anxiety
Feeling insecure
physical and psychological sx of anxiety
Feeling nervous, restless, or tense
Having a sense of doom
Increased heart rate
Shortness of breath
Sweating
Dizziness
Ear ringing
Trouble concentrating
Trouble sleeping
Gastrointestinal (GI) distress
Having difficulty controlling worry/ruminating
Having the urge to avoid things that trigger anxiety
Feeling insecure
physical sx anxiety and depression share [3]
GI upset
Appetite and weight changes
Sleep difficulty
mental sx anxiety and depression share [2]
Difficulty concentrating
Irritability
how do stress and anxiety compare?
stress is short-term and is a response to a recognised threat
anxiety is long term where there is not an identifiable trigger
generalised anxiety disorder (GAD) is characterized by
increased motor tension (eg, fatigability, trembling, restlessness, muscle tension), autonomic hyperactivity (eg, shortness of breath, rapid heartbeat, high heart rate, dry mouth, cold hands, dizziness), and increased vigilance and scanning (eg, feeling keyed up, increased startling, impaired concentration)
T/F
in GAD men experience more psychologic sx (i.e. irritability, sense of impending doom), whereas women develop more physical pain (i.e. chest pain, palpitations, and shortness of breath)
T
list risk factors for GAD [8]
gender, childhood trauma, physical illness, stress, personality disorder, genetics, substance abuse, family discord
define generalised anxiety disorder (GAD)
persistent and excessive worry that tends to interfere w daily activities
