Depressive Spectrum Flashcards
Mneumonic for symptoms of depression
S leep disturbance I nterest loss G uilt E nergy loss C oncentration difficulties A ppetite disturbance P sychomotor retardation/ agitation S uicidality
Meds than can cause depression
Clonidine Methyldopa Propranolol Prazosin Alcohol Alpha interferson Corticosteroids
what endocrine condition is a big cause of depression
hypothyroidism
depression results from dysregulation of what 3 NTs?
Norepinephrine (NE)
Serotonin (5-HT)
Dopamine (DA)
What happens to post-synaptic 5-HT, DA, and NE receptors when the amount of these neurotransmitters is decreased?
Up-regulation of post-synaptic receptors
Decreased receptor sensitivity
Altered genetic expression
how does reserpine induce depression?
depletion of monoamines
depression reverse by 5-HT precursor
with loss of serotonin what happens
loss of impulse control
with loss of dopamine what do you lose?
drive
with loss of norepi what do you loss?
energy/ interest
Increased glucocorticoids may result from what?
severe stress
Hippocampus has negative feedback on the _______ _________
Glucocorticoids trigger this negative feedback
HPA loop
Potent regulator of plasticity of adult neurons and glia
Important for survival of neurons
BDNF- Brain Derived Neurotrophic Factor
where in the brain is the dopaminergic pathway
nucleus accumbens
amygdala
Mediates numerous functions ie., sleep, appetite, circadian rhythms, interest in sex
Hypothalamus
primary medication of choice for depression
SSRI
What are MAOIs reserved for now?
Parkinsons
TCAs have what type side effects
anticholinergic
what are the SSRIs (6)
Fluoxetine Sertraline Paroxetine Fluvoxamine Citalpram Escitalopram
MOA of SSRIs
block reuptake of serotonin
are SSRIs titrated?
No
how are SSRIs dosed
once in the morning
common ADRs of SSRIs
Nausea
HA
sleep disturbances (not as common if take in am)
agitation/ increased anxiety (initially)
what SSRI has a very long 1/2 life
you could possibly abruptly stop because it could self taper
fluoxetine
SSRI more likely to cause sedation, constipation, dry mouth
paroxetine
type of paroxteine that has less GI side effects
paroxetine CR
SSRI that may cause GI distress, insomnia or activation
Sertraline
does any one SSRI have more propensity to cause sexual dysfunction than another SSSRI?
No
which SSRI has the shortest 1/2 life meaning it need to be tapered
paroxetine
Antidepressant discontinuation syndrome
flu/ malaise dizziness, GI ADRs transient changes in modd, affect, appetite, sleep "shock-like" in upper extremities vivid dreams/ nightmares poor concentration
MOA of TCAs
Block the reuptake of NE and 5-HT (NE > 5-HT)
also block Ach and histamine at bit
dosing for TCAs
once daily dosing (1/2 life is ~24 hours)
how are TCAs metabolized?
P450 (potential for drug interactions)
what are the secondary amines (TCAs)
notriptyline
despramine
protriptyline
amoxapine
What are the tertiary amines
Amitriptyline
imipramine
clomipramine
doxepin
what TCAs may need levels monitored?
nortriptyline
despramine
(draw blood sample 12 hours past last dose)
ADRs of TCAs
Tachycardia orthostasis weight gain sedation sexual dysfunction ach effects (dry, urinary retention)
Cardiac conduction of TCAs
prolongated of QRS, ST depression, flatttened or inverted T-waves
what should you get on each patient before starting TCAs
baseline EKGs
what TCAs have worse anticholingeric, antihistamine, hypotensive effects
tertiary amines
Drug that is a potent and direct alpha-2 receptor antagonist
Enhances 5-HT and NE transmission
Blocks 5-HT2 and 3 receptors
Results in enhances 5-HT1 reception
Mirtazapine
benefit of mirtazapine
less nausea and sexual dysfunction than SSRIs
dosing for mirtazapine
once daily at bedtime due to sedation
what is soltab?
Dissolvable tablet of mirtazapine
ADRs of mirtazapine
Somnolence (increased risk w/ lower dose) dry mouth constipation orthostasis increased appetite and weight gain
Inhibits reuptake of NE and 5-HT
Also inhibits DA reuptake (to lesser extent)
Venlafaxine (Effexor)
ADRs w/ venlafaxine
Nausea HA somnolence sexual dysfunction Increase in DBP (dose dependent) insomnia agitation
Active metabolite for venlafaxine
No mechanistic advantage
Wrong answer on exam… shouldn’t be prescribed
Desvenlafaxine
Potent 5-HT NE reuptake inhibitor
Can be dosed 1-2 daily
duloxetine
other uses of duloxetine
urinary incontinence
diabetic neuropathic pain
ADRs of duloxetine
nausea (most reported) diarrhea insomnia/ sedation urinary hesitancy hepatotoxicity Increase in BP
Believed to block reuptake of dopamine and norepinephrine
No clinically significant effect on 5-HT
considered a first line agent
Bupropion (Wellbutrin)
ADRs w/ bupropion
increased risk of seizures as threshold reduced (dose related)
anxiety, sweating, HA
GI problems
weight loss
Serotonin reuptake inhibitor plus potent 5-HT2 receptor antagonist
Enhanced 5-HT1
Hepatotoxicity risk
nefazodone (Serzone)
ADRs w/ nefazodone
Heptatotoxicity- need baseline levels sedation, orthostasis dry mouth, nausea blurred vision (occur less commonly than w/ SSRIs)
Blocks 5-HT2A receptors (potently); Blocks 5-HT reuptake less potently
Also has antihistaminic properties → Sedation
Trazodone
Block the break down of NE, 5-HT, DA, and epinephrine
monoamine oxidase inhibitors (MAOIs)
2 indications for trazodone
depression
insomnia
2 types of MAOIs
A- (EPI, NE, 5-HT, DA, tyramine)
B- (DA, tyramine, benzylamine, phenylethylamine)
what type MAOI is used for parkinsons
MAOI-B
what type MAOI is used for depression
mixed
what are the irreversible mixed MAOIs
phenelzine
isocarboxazid
what is the reversible MAOI inhibitor
tranylcypromine
Irreversible inhibitor of MAO-B; inhibits A and B in higher doses (>10 mg/day)
available as a patch
Transdermal selegiline
Drug food interaction w/ MAOIs
Aged, hard cheeses and strongly flavored cheeses contraindicated
ADRs w/ AMOIs
orthostasis dizziness mydraisis piloerection edema sexual dysfunction
what 2 things are there a high risk of w/ MAOIs
serotonin syndrome
hypertensive crisis
Drug interactions w/ MAOIs
other antidepressants including herbals buspirone meperidine dextromethorphan sympathomimetics (L-dopa, epinephrine, tyramine, ampetamines) cocaine
An adverse effect due to excessive serotonin in the periphery
Serotonin syndrome (toxicity)
Symptoms of serotonin syndrome (sternbach criteria)
neuromuscular hyperactivity
autonomic hyperactivity
cognitive/ behavior changes
when will most people have an onset of response w/ antidepressants
4 weeks
if no response up the dose and wait another 2-3 weeks
a trial of an antidepressants shouldn’t last longer than how
8 weeks
if an SSRI needs to be d/c what should happen
tapered down before d/c or class switch (except FLX due to long 1/2 life)
patients who show a partial response to antidepressants can be treated for how long?
up to 12-16 weeks to see if there’s a response
BBW for SSRIs
Suicide for children and adolescents
first line antidepressants in geriatrics
SSRIs
what drugs shouldn’t be used in geriatrics w/ depression
TCAs
antidepressants to be used for pregnancy/ lactation
SSRIs or TCAs
FLX most studied
