Oct15 A3-Antidepressants Flashcards
categories of antidepressants
- SSRIs and SNRIs
- TCAs
- atypical antidepressants
- MAOIs
categories of mood stabilizers
- lithium
- anticonvulsants
- atypical antipsychotics
charact of adt tx
- only makes you feel less bad, not great
- takes few weeks before improvement (6 to 12 weeks before full benefit)
- third people good resp, third = slight improvement, third = no improvement
- most SEs are in beginning and improve later
- need daily tx for >6 mo after remission to prevent relapse
what’s the monoamine theory of mood and anxiety disorders
- most adts in market modulate monoamine neurotransmission
- monoamine = NE, 5HT and dopamine
- this DOESN’T mean that depression and anxiety are caused by low monoamine lvl
- 5HT linked to obsessions and OCDs + anxiety and impulsivity
- NE = fatigue and concentration issues
- dopamine = reward chemical (drugs, sex, gambling)
- it is WRONG to say that depression is caused by low dopa and 5HT
- we DON’T KNOW if adts modify dz or modulate sx
serotonin system
- cell bodies in rostral and caudal Raphe nuclei
- project neurons to prefrontal cortex, limbic system, spinal cord, etc.
- 5HT is made of tryptophan which comes from diet
- ejected in synaptic vesicles
- act on post syn 5HT Rs. (14 types of them, only some are active in the brain)
- 5HT1A is the most associated with antidepressant effect
- 5HT pumped back in pre syn cell after synapse
SSRIs work how
increase amount of serotonin in the synapse by blocking SERT (serotonin transporter for reuptake)
SSRIs main benefit in depression
main effect is on increased negative affect (feeling bad)
- dysphoria (state of unease, general dissatisfaction with life)
- guilty ruminations
- anxiety
- irritability
- suicidal ideation
- obsessions
diseases where SSRIs are indicated
- major depressive disorder
- anxiety disorders
- PTSD
- OCD
- premenstrual dysphoric disorder
- bulimia nervosa
- bipolar depression (antipsychotic + SSRI)
off label uses of SSRIs
- premature ejaculation
- anxiety assoc with certain personality disorders (ie. obsessive compulsive personality, avoiding personality, etc.)
- somatic symptom disorder
SSRI mnemonic (EFSPC)
effective for sadness panic compulsions
common SEs of SSRIs
- GI upset
- headache
- sexual dysfunction = decreasd interest, orgasm. is the MAIN problem.
uncommon but serious SEs of SSRIs
- switch into mania (if use on bipolar pt)
- increased bleeding risk like NSAIDs
- apathy and emotional numbling
- hyponatremia
duration of SEs with SSRIs
1-2 weeks
-apathy and sexual dysfunction are short term
SNRIs are what
SEROTONIN norepinephrine reuptake inhibitors
SNRIs general action
dual action by blocking both NE and 5HT reuptake
noradrenergic system (norepinephrine)
- nuclei (so cell bodies) in the locus coeruleus in the brainstem
- projects to brain, limbic system, spinal cord
- NE comes from tyrosine changing to dopamine
- NE pumped out in syn vesicles
- then reuptake
main effect of blocking NE and dopamine reuptake transporters (NOREPINEPHRINE TRANSPORTER = NET) (SNRIs block 5HT and NE reuptake transporters)
help for reduced positive affect
other use of SNRIs
use for chronic pain conditions because they reduce pain via descending NE and 5HT pathways
- related to central sensitization theory for pain
- this theory is that in chronic pain, brain gets worse at filtering out painful stimuli
- brain receives painful signals
- signal go back down spine to inhibit pain (inhibitory signals)
- these signals stop working in chronic pain (the inhibitory ones)
- we get them working again by increasing NE and 5HT pathways (blocking their NET and SERT) with SNRIs
SEs of SNRIs that are related to blocking NET specifically (increasing NE)
- NE beta R: tremor, htn, tachycardia
- NE alpha R: dry mouth, constipation, urinary retention, sweating
SEs of SNRIs related to NET blocking are similar to what med + how to diff
like anticholinergics. diff is
- anticholinergics = dry skin
- noradrenergic = sweating
TCAs charact
tricyclic antidepressants
- block SERT and NET
- more SEs bc also block H1 (histamine), alpha 1 (adrenergic) and mAch (muscarinic Ach) Rs.
- weakly block Na+ channels so can cause seizures and cardiac arrhythmias in overdose. MAIN WORRY IS PT CAN DECIDE TO COMMIT SUICIDE BY OVERDOSING ON IT (which is not possible with SSRIs)
- block 5HT2 Rs so additional benefit in chronic pain, fibromyalgia, migraine
TCAs use today
chronic pain conditions mostly
SEs of TCAs
- alpha1 and beta adrenerg = dizziness and drowsiness
- antihistamine effect = weight gain and drowsiness
- antichol effect = constipation, dry mouth, blurred vision
atypical antidepressants MOA
- bupriopion weakly blocks dopa and NE reuptake = more transmission
- another one called mirtazapine, diff MOA (dnm)
- quetiapine (diff MOA, dnm)
- vortioexetine (diff MOA, dnm)
SEs of atypical atds
- bupriopion = rarely helpful in anxiety disorders, decreases seizure threshold
- mirtazapine = weight gain and sedation
- quetiapine = weight gain and sedation
- vortioxetine = GI SEs
main reason to use atypical atds
reduced risk of sexual SEs (common benefit to all atypical atds) + one marketed for smoking cessation (one benefit of bupriopion)
monoamine oxidase inhibitors (MAOIs) use today
rarely used
- rarely by experts for very tx resistant depression
- rarely for some anxiety disorders
MAOIs 2 types
irreversible and reversible (less effective, less risk of 5HT syndrome and no risk of tyramine htn crisis)
(imp) main SE of MAOIs
2 life threatening drug interaction reactions
- serotonin syndrome
- hypertensive crisis
(imp) cause of 5HT syndrome
when combined with SSRIs and other serotonergic meds or certain drugs of abuse (like MDMA and certain opiates), MAOIs can give the syndrome
(imp) cause of hypertensive crisis with MAOI
when combined with sympathomimetics and tyramine containing foods (aged cheese, dried meats, soy sauce, draft beer)
(imp) tyramine hypertensive crisis def
severe, life threatening hypertension
(imp) tyramine hypertensive crisis pathophgy
- MOA needed for NE degradation
- NE in cells of liver and gut not degradated
- tyramine enters cells of liver and gut and kicks out NE which increases BP
- high tyramine in diet contributes to that
(imp) serotonin syndrome pathophgy
- SERT and MAO are both blocked
- 5HT accum in synapses and over stim post syn Rs
- 6-8 hrs after starting or increasing drug
- tachycardia, agitation, autonomic instability, clonus and tremor, etc.
atds and suicidality
- atds decrease the risk of completed suicide
- atds increase the risk of suicidal behavior but NOT of complete suicide in people <25
- tx of depression in adolescents DECREASES the risk of suicide
why atds increase the risk of suicidal behavior but NOT of complete suicide in people <25
- bc these people have some type of bipolar disorder
- you’re activating them into an agitated state
- a mood stabilizer is better for these pts
(imp) what meds can give a true serotonin syndrome
MOAIs ONLY
-SSRIs and SNRIs can both give serotonin effects (bad headaches, feeling unwell), especially if combine them but not 5HT syndrome
considerations in initial tx of depression
- first line meds are SSRIs, SNRIs, bupriopion, vortioxetine and mirtazapine
- the 3 atypical atds for less risk of sexual SEs
lithium used for what
tx of mania and prevention of mood episodes in bipolar disorder
(also in combination with atds for tx resistant depression)
(may reduce suicidal thinking and aggression)
lithium MOA
- is a salt, given as lithium carbonate
- interacts with 2nd messenger systems inside the cell
- promotes neuronal survival and synaptongenesis, neural plasticity, neural protection
- no metab by liver. excreted unchanged by the kidney
SEs of lithium
- short term: GI, tremor, polyuria, polydipsia
- long term (after years): 10-20% nephrogenic diabetes insipidus, 20% CKD (chronic renal insufficiency), hypoT
(imp) bad SEs of lithium
teratogenic, risks for pregnancy
- cardiac malformations
- assoc with Epstein abnormality (a specific cardiac abnormality)
- also not compatible with lactation
lithium toxicity
- narrow therapeutic index
- toxicity possible in dehydration and diarrheal illnesses
- sx of lithium toxicity = GI sx, ataxia, confusion, seizures, renal failure, arrhythmias
- no tx = long term neuro problems
tx of lithium toxicity
IV fluids, hemodialysis maybe
mnemonic for lithium SEs
- L = leukocytosis
- I = insipidus (diabetes)
- T = tremors
- H = hypothyroid
- I = increased urine (polyuria)
- M = mom’s beware (teratogenicity)
anticonvulsant used for tx of mania and prevention of mood episodes
valproate (epival, depakote)
-anticonvulsant and antimigraine effec ttoo
MOA of valproic acid
- block Na and Ca channels
- increases GABA
- inhibits histone deacetylace
- modulates 2nd messengers
SEs of valproate
- GI
- weight gain
- sedation
- polycystic ovary
contraindication of valproate use
pregnancy
- neural tube defects
- dev delay
- CAN lactate while taking it however
anticonvulsant used to prevent depressive episodes in bipolar disorder
lamotrigine (lamictal)
- well tolerated
- MOA = block Na channels leading to decreased glutamate release
SEs of lamotrigine
- drowsiness
- rashes
- rare Steven-Johnson syndrome (severe life threatening rash)
antipsychotics in bipolar disorders
- can be used to tx mania no matter if pt has psychosis or not
- used when pts are agitated (works faster than lithium and valproate)
- long acting injectable format available
- some antidepressant effects also
antipsychotics MOA
decrease dopamine activity (increased dopamine is probably the cause of manic episodes in bipolar disorders)
considerations in tx of bipolar disorder
- lithium (classic manic depressive illness, not in pt with kidney prob)
- valproate (irritability and mixed states, migraine, epilepsy. but teratogenic)
- lamotrigine (prevents depression, helps epilepsy)
- 2nd generation antipsychotics (tx and prevent mania. watch out for sedation)
main categories of antidepressants
- SSRIs
- SNRIs
- TCAs
- MAOIs
- novel antidepressants
what all currently prescribed atds do
modulate monoamine ntrs (dopa, 5HT, NE) synaptic transmission
meds used to tx bipolar disorders
- lithium
- valproate
- lamotrigine
- 2nd generation antipsychotics
