neuro: depression Flashcards
TCA egs and moa
amitriptyline -> nortriptyline
imipramine -> desipramine
dothiepin
clomipramine
block reuptake of NE and 5HT + anticholinergic + H1 and a-adrenergic antagonism
TCA side effects
GI and sexual dysfunction
anticholinergic, sedation, orthostatic hypoTN, arrhythmias, seizure
FATAL on overdose
clomipramine indicated for
OCD
SSRI eg and moa
fluoxetine -> norfluoxetine
fluvoxamine
escitalopram/citalopram
sertraline
paroxetine
blocks reuptake of 5HT selectively
SSRI adr
gi and sexual dysfunction
headache, transient nervousness during initiation
hyponatremia (SIADH)
bleeding risk
escitalopram/citalopram
qtc prolongation, esp in elderly women at high doses
paroxetine
most anticholinergic, sedating, incr weight, t1/2 short
fluvoxamine dosing
on, sedating
fluoxetine
OM: alerting
t1/2 long 4-6d, then 4-16d for norfluoxetine
SNRI egs and moa
venlafaxine -> desvenlafaxine
duloxetine
blocks reuptake of NE and 5-HT
SNRI moa
(same as SSRI)
gi and sexual dysfunction
headache, transient nervousness during initiation
hyponatremia (SIADH)
bleeding risk
- venlafaxine: incr bp!!!!
- duloxetine: urinary hesitation
duloxetine indicated for
diabetic peripheral neuropathy, fibromyalgia, chronic musculoskeletal pain
SMS
serotonin modulator and stimulator
SMS egs and moa
vortioxetine
altering the activity of various post-synaptic serotonin (5-HT) receptors, in addition to inhibiting the reuptake of serotonin via the same mechanism as selective serotonin reuptake inhibitors (SSRIs)
- vortioxetine is also a 5HT1a agonist
SMS adr
gi and sexual dysfunction
headache, transient nervousness during initiation
low Na levels (SIADH)
bleeding risk
NaSSA
Noradrenergic and specific serotonergic antidepressants
NaSSA eg and moa
mirtazapine
a2-adrenergic antagonist, incr 5HT and NE, 5HT2&3 + H1 antagonism
NaSSA adr
somnolence, incr appetitie, weight gain
NaSSA is able to ____________________ of SSRI/SNRI
reverse SI and sexual SE
NDRI
norepinephrine–dopamine reuptake inhibitor
NDRI egs and moa
bupropion
blocks reuptake of NE and DA
NDRI adr
seizure, insomnia, psychosis
not suitable for eating disorder
decr sexual SE of SSRI/SNRI
bupropion also used for
smoking cessation aid
MAOI
moclobemide: reversible MOAI-B
trazadone
blocks reuptake of 5HT
antagonises 5HT2A,H1 and a1-adrenoceptor
used for insomnia than depression
same adr as ssri + sedation _ orthostatic hypoTN + rare SE: priapism
agomelatine
MT-1, MT-2 agonist
5HT2c antagonist
adr: GI, incr LFTs (check at baseline at week 3,6,12,24)
c/i: fluvoxamine, ciprofloxacin
for all antidepressants, what is a transient side effect?
jittery (sudden release of neurotransmitter at synapse)
- to start at a lower dose for pt w anxiety issue
for all SSRI, what is a SE to take note for
hyponatremia (particularly common and bad in the elderly - check renal panel at baseline, 2 weeks, 4 weeks, 3 months)
> SIADH: cramps, muscle twitching, confusion, seizures
BZD moa
potentiates GABA
- anxiolytic
- hypnotic
- muscle relaxant
- anticonvulsant
- amnesia
BZD side effects
sedation, drowsiness
muscle weakness, ataxia, amnesia
less commonly: slurred speech, vertigo, headache, confusion
how to minimise risk for dependence of BZD?
limit to 2 weeks PRN, short course therapy, at lowest effective dose
Z-hypnotics
zolpiclone (Imovane 7.5) - hypnotic + anxiolytic
zolpidem (Stilnox 6.25) - hypnotic only
preferentially binds to bzd-binding sites with y and a1 subunits, causes sedation
z-hypnotics adr
n/v, dizziness, drowsiness, dry mouth, headache
rarely: amnesia, confusion, hallucinations, nightmares, complex sleep-walking behaviours
zolpiclone: taste disturbance
antihistamine
H1 antagonism
adr: sedation, anticholinergic (dry mouth, constupation)
SGA
second gen antipsychotics
5HT2a antagonishm, 5HT1a partial agonism
aripiprazole/brexpiprazole: EPSE
quetiapine, olanzapine: metabolic SE
Spravato nasal spray
Esketamine, NMDA receptor antagonist
adr: dissociation, dizziness, nausea, sedation, anxiety, incr BP
first line antidepressant
monotherapy: SSRI, SNRI, mirtazapine, bupropion
switch to alt antidepressant when
ineffective or intolerable to adequate dose in 1-4wks
if cross-titration, watch for
serotonin syndrome, if combining serotonergic agents
if direct switch
one SSRI can be stopped totally and the next serotonergic agent initiated
If switching from a Serotonergic antidepressant used daily for the past 2 months to a Nonserotoninergic
agent (e.g. switching from SSRI/SNRI to Bupropion),
gradual cross-tapering
over several weeks can reduce risk of Antidepressant Discontinuation Syndrome
washout period required for MAOIs
If switching from Moclobemide to another antidepressant: 24 hour washout.
If switching from another antidepressant
approaches to manage partial/no response
switching, augmentation, treatment-resistant depression
treatment-resistant depression
Symbyax oral capsule: olanzapine 6mg + fluoxetine 25mg per cap
Spravato Nasal Spray (Esketamine 28mg per vial), as an adjunct to ssri/snri treatment
breastfeeding
may consider sertraline or mirazapine
elderly
avoid TCAs and anticholinergic, CNS, hypotensive or other SE
post-MI depression
may consider sertraline
hepatic impairment
avoid agomelatine
if mild-moderate: consider vortioxetine
renal impairment
may consider vortioxetine
bipolar depression
lithium, lamotrigine, lurasidone, quetiapine
pregnancy
may consider nortriptyline in late pregnancy
antidepressant with fewer CYP interactions
mirtazapine, escitalopram, venlafaxine, desvenlafaxine, vortioxetine
serotonin syndrome
acute onset: within 6-8hrs
causes: concomittant rx of high-dose serotonergic meds (eg. triptans, sibutramine, opioids, dextromethorphan, linezolid, ritonavir)
mild: insomnia, anxiety nausea, diarrhea, HTN, tachycardia, hyper-reflexia
moderate: agitation, myoclonus, tremor, mydriasis, flushing, diaphoresis, low fever<38.5
severe: severe hyperthermia, confusion, rigidity, resp failure, coma, death
SSRIs: incr risk of bleeding by at least 1-2 folds
higher risk in elderly on NSAID, warfarin, steroids
- consider adding PPI
- consider stopping serotonergic antidepressant 2 weeks before surgery if high bleeding risk
- agomelatine safest
BZD + opioids
incr mortality, cns depression
- avoid combi if possible, or limit doeses and duration
antidepressant discontinuation syndrome
worse with abrupt discontinuation of long-term regular therapy
- esp w short t1/2 antidepressants: paroxetine, venlafaxine
- onset: 36-72hrs
- duration: 3-7 days but typically resolves over 1-2 weeks without treatmentd
FINISH
- flu-like sx: fatigue, muscle aches, headache
- insomina
- nausea
- imbalance: dizziness
- sensory: electric shock sensations, paresthesia
- hyperarousal: anxiety, agitation
if you need to stop a long-term antidepressant therapy after daily tx >= 8 weeks
recommend to gradually taper over at least 4 weeks
- fluoxetine, bupropion: generally unnecessary because of their v long t1/2
- for the rest, taper by 25% every 1-2 weeks, or as gradually as clinically indicated
bzd: gradual discontinuation of long-term. high-dose use
decr dose by 25% weekly until reaching 50% dose, thenr educe 1/8 every 4-7 days, or as gradually as clinically indicated
space alc how long apart from antidepressants
4-6hrs
antidepressants w less sexual dysfunction side effect
mirtazapine, bupropion, agomelatine
antidepressants order
SSRI, SNRI, NaSSA > bupropion > agomelatine, vortioxetine > TCA > MAOIs
mirtazapine may be beneficial for
insomnia and poor appetite: can cause sedation and weight gain
bupropion not suitable for
h/o seizures, psychosis or eating disorder
