Gibbs Mood Flashcards
definition of clinical depression
persistent sadness that interferes with normal functioning; loss of interest, low self-esteem
what is reactive sadness
a transient emotional reaction to a minor event
depressive symptoms
SIG E CAPS
sleep patterns
interests gone
guilt
energy/fatigue
concentration/memory problems
appetite (inc or dec)
psychomotor changes: agitation
suicidal thoughts
how common is depression?
over 20% of women and 12% of men will suffer a major depressive episode in their lifetime
what are some risk factors for depression?
female (esp adolescence, postpartum, older)
prior depressive episodes
medical comorbidity
SUD
lack of social support
stress
DSM-V criteria for a major depressive episode
must have 5+ symptoms in 2 week period
must include depressed mood/anhedonia
must represent change from previous functioning
cause social or occupational impairment
not due to other cause
treatment phases of depression
acute, continuation, maintenance
what are the 5 Rs
response, remission, relapse, recovery, recurrence
goals of acute phase
reduce/eliminate symptoms (6-8 weeks)
goals of continuation phase
prevent relapse or return of symptoms (6-12 months)
goals of maintenance phase
protect susceptible patients against recurrence of future depressive episodes (potential for lifelong treatment)
(3) theories about the pathophysiology of depression
monoamine hypothesis
dysregulation hypothesis
neuroendocrine hypothesis
what is the monoamine hypothesis
decreased synaptic concentrations of monoamines results in depression
what is the dysregulation hypothesis
dysregulation of neurotransmitter release results in changes in pre and post synaptic receptors results in depression
what is the neuroendocrine hypothesis
dysregulation of thyroid and HPA axis results in depression
what is the role of stress in depression?
depressed patients have increased cortisol, CRH, ACTH, abnormal circadian rhythm of cortisol, failure to respond to dexamethasone challenge
what is the significance of thyroid hormone and depression?
when the thyroid gland doesn’t produce enough thyroid hormone (hypothyroidism) the body uses energy at a SLOWER pace. symptoms: fatigue, irritability, weight changes, sleep problems
GENERAL mechanisms of antidepressants
block the reuptake of NE, 5HT, and DA into nerve terminals (reuptake inhibitors)
block the metabolism of NE and 5HT in nerve terminals (MAOIs)
(4) general characteristics of antidepressant pharmacology
1) selective alleviation of depressive symptoms instead of CNS stimulant
2) neurotransmitter levels increase soon after administration, but symptom resolution is slow
3) stopping suddenly results in rapid return of symptoms
4) do not work for every9one! 30% are non-responders
therapeutic effects seen by week 1 of antidepressant
sleep, appetite, energy, anxiety
therapeutic effects seen by week 1-3 of antidepressant
activity, drive, concentration, memoryt
therapeutic effects seen by week 4-6 of antidepressant
mood, hopelessness
what is considered an adequate trial of an antidepressant
6-8 weeks
list of (6) antidepressant classes
TCA
MAOI
SSRI
SNRI
NDRI
5HT/NE modulators
the first antidepressant agent selected is effective __% of the time
50
disadvantages of TCAs?
toxic in overdose
ADEs bad: orthostatic hypotension, tachycardia, EEG changes, anticholinergic, seizure threshold lowered, weight gain
are TCAs stimulants?
no, they do not produce euphoria in healthy people
__% of patients on TCAs improve
70%
TCA drugs
imipramine
amoxapine
desipramine
amitriptyline
nortriptyline
doxepin
clomipramine
protriptyline
trimipramine
mechanism of TCAs
-block reuptake of monoamines (NE, 5HT)
-increase neurotransmitter levels in synaptic cleft
-bind to histamine, alpha 1 & 2, GABA-A, muscarinic receptors (side effects)
TCA dosing? (generally speaking)
once daily dosing at bedtime (sedation)
because good oral absorption, long half life
TCA is inactivated by ____ metabolism
hepatic
why are TCAs not first line?
anticholinergic, cardiac side effects (because of blockade of other receptors)
MAOI mechanism
increase neurotransmission by increasing NE, 5HT, DA levels in nerve terminal
inhibition of MAO is irreversible
non selective MAOIs
phenelzine, tranylcypromine, isocarboxazid
selective MAOIS
SELEGILINE
selective for MAO-B
why does selegiline have reduced dietary restrictions
because it is more selective for MAO-B; avoids inhibition of MAO-A
which MAOI has a transdermal patch
selegiline (EmSam)
serious food interaction with MAOIs
they inactivate biogenic amines present in food (tyramine– aged cheese/cured meats, wine) and drugs (decongestants in OTC cold remedies)
what happens with failure to avoid tyramine with MAOIs?
hypertensive crisis
must avoid (except not necessary with EmSam)
most common side effects of MAOIs
orthostatic hypotension
insomnia
serotonin syndrome (overdose, combo w/ SSRI)
dry mouth, constipation, blurred vision, etc
what is serotonin syndrome
a potential fatal drug interaction resulting in over-potentiation of serotonin effects that causes GI, CNS, CV, and psych symptoms
what drugs are the SSRIs
fluoxetine
paroxetine
sertraline
fluvoxamine
citalopram
escitalopram
which SSRI is most selective
citalopram
escitalopram is the ____ of citalopram
active S-enantiomer
what is the first line antidepressant for most patients
SSRIs (as effective as TCA but safer side effect profile)
common SSRI side effects
GI disturbances, CNS excitation (insomnia, restlessness– except paroxetine which causes sedation), weight loss early on, weight gain later on, decreased libido/sexual dysfunction
what is SSRI discontinuation syndrome
a withdrawal syndrome consisting of flu-like symptoms, GI effects, dizziness, paresthesia, mood/appetite, sleep changes
how to mitigate SSRI discontinuation syndrome
gradually taper dose over several weeks
which drug is NDRI
bupropion
which drugs are SNRIs
venlafaxine
duloxetine
desvenlafaxine
which drugs are 5HT/NE modulators
trazodone
nefazodone
mirtazipine
mechanism of bupropion
norepinephrine/dopamine reuptake inhibition
weak blocker of DA uptake, even weaker blocker of NE uptake, virtually no effect on 5HT
bupropion is also used for?
ADHD, smoking cessation
bupropion side effects
generally well tolerated
nausea, restless, insomnia, anxiety
high risk of seizure activity at 450 mg/day
may precipitate psychotic episodes
why is there lower incidence of sedation, hypotension, etc with bupropion
no muscarinic, alpha, or histaminic receptor effects
SARIs
trazodone, nefazodone
serotonin antagonist and reuptake inhibitors
5HT2 antagonist and 5HT reuptake blocker
trazodone place in therapy
very sedating, useful for patients with insomnia but not highly effective as antidepressant
NSSA
mirtazapine
noradrenergic & specific serotoninergic antidepressant
mirtazapine mechanism
serotonin & NE modulator
blocks alpha2 autoreceptors resulting in increased NA release
antagonizes 5HT2 receptor
enhances activity at 5HT1 receptor
blocks H1 and muscarinic receptors
mirtazapine side effects
sedation (histamine blockade)
increased appetite, weight gain
why does antagonism of 5HT2 receptors treat depression?
5HT2 receptors are excitatory
increase in 5HT2 receptor expression increases depression
decreasing 5HT2 receptor expression decreases depression
what is the role of 5HT1 receptors in depression?
5HT1 are presynaptic inhibitory autoreceptors– meaning they reduce 5HT release from serotonergic neurons (work against SSRIs)
sustained activation: results in DESENSITIZATION so that effect decreases over time and this is why SSRIs take weeks to become fully effective
strategies for treatment resistant depression
non pharm like ECT, light therapy, etc
pharm: lithium, thyroid supplement, stimulants, atypical antipsychotics, anticonvulsants, esketamine
ketamine mechanism
non-competitive NMDA receptor antagonist
most commonly used anesthetic in the world
esketamine role in treatment resistant depression
S(+) enantiomer of ketamine
FDA approved for treatment resistant depression, breakthrough therapy
also acts as partial DA reuptake inhibitor
which atypical antipsychotics have FDA approval as adjunctive treatment for MDD in combo w/ current antidepressant therapy
aripiprazole, quetiapine
