Pharm 6 - Antidepressants

biogenic amine hypothesis of depression

• requires trial and error (i.e. SSRI cannot treat abnormal DA neurotransmission)

• all antidepressants increase amine neurotransmission by inhibiting transporters

antidepressant targets

• TCAs

• SSRIs

• SNRIs

• DA

• MAOI

• presynaptic alpha 2

• SNRIs have fewer AE than TCAs despite same MOA

• block presynaptic alpha 2 receptors = block negative feedback

reuptake inhibitors

• reuptake inhibited — but effects are —

amitriptyline

• class type

• MOA

• therapeutic effects

• PK

• AE

• toxicity and OD

• DI

TCA = 3 letters, 3 AE combo = antiadrenergic, antihistamine, anticholinergic

TT = TCA, AE Torsades des pointes

• can treat chronic/neuropathic pain via noradrenergic pathway

• no euphoria = low drug abuse potential

• metabolized by CYP2D6 = slowed metabolism with SSRI fluoxetine, CYP2D6 inhibitor

• increase sedative actions of alcohol via histamine receptor and CNS depressants via GABA receptor

nortriptyline

• class type

• MOA

• therapeutic effects

• PK

• AE

• toxicity and OD

• DI

TCA = 3 letters, 3 AE combo = antiadrenergic, antihistamine, anticholinergic

TT = TCA, AE Torsades des pointes

• can treat chronic/neuropathic pain via noradrenergic pathway

• no euphoria = low drug abuse potential

• metabolized by CYP2D6 = slowed metabolism with SSRI fluoxetine, CYP2D6 inhibitor
  

• increase sedative actions of alcohol via histamine receptor and CNS depressants via GABA receptor

fluoxetine

• class type

• MOA

• therapeutic effects

• PK

• AE

• toxicity and OD

• DI

• fluoxetine = CYP2D6 inhibitor

• panic disorder, OCD = CI anxiolytics

• GI AE most common

sertraline

• class type

• MOA

• therapeutic effects

• PK

• AE

• toxicity and OD

• DI

• panic disorder, OCD = CI anxiolytics
  

• GI AE most common

paroxetine

• class type

• MOA

• therapeutic effects

• PK

• AE

• toxicity and OD

• DI

• panic disorder, OCD = CI anxiolytics

• GI AE most common
  

citalopram

• class type

• MOA

• therapeutic effects

• PK

• AE

• toxicity and OD

• DI

• panic disorder, OCD = CI anxiolytics

• GI AE most common
  

duloxetine

• class type

• MOA

• therapeutic effects

• PK

• AE

AE ‘deluxe’ with duloxetine = AE hepatotoxicity, bilateral acute ACG

class types that can treat neuropathic pain

TCAs, SNRIs

phenelzine

• class type

• MOA

• therapeutic effects

• PK

• AE

• DI

• MAO-Bs also used to treat PD in low doses

• inability to metabolize tyramine = catecholamines upsurge

bupropion

• class type

• MOA

• therapeutic effects

• PK

• AE

SCATS = combined with SSRIs, AE CNS stimulation, therapeutic effects ADHD/alcoholism, AE tachycardia, CI seizures

buPROPion = can ‘prop’ it up = AE SD rare

• sometimes combined with SSRI to lower SSRI dosage = fewer AE SD

• AE CNS effects due to INC DA

mirtazapine

• class type

• MOA

• therapeutic effects

• PK

• AE

• DI

one may be full of ‘mirth’ if they are taking MIRTazapine to address both their insomnia and anxiety

mirtazapine is ‘alpha’ for solving two issues at once

• SSRI adjunct

atomoxetine

• class type

• MOA

• therapeutic effects

• PK

• AE

• preferred in children and addicts

esketamine

• class type

• MOA

• therapeutic effects

• PK

• AE

• DI

• must be taken in-clinic to monitor for > 2 hours

• last DOC after 2+ failed attempts

St John’s Wort

• may be effective in —

• do not —