Atypical Antidepressants

Bupropion, Mirtazapine, Agomelatine, Trazodone, Vortioxetine, Tianeptine

1. Atypical Antidepressants
Prof. SawsanAboul-Fotouh
Department of pharmacology, faculty of Medicine, Ain-Shams University (Stahl ҆s essential psychopharmacology, 2013) (Stephen Stahl, 2015)
Vortioxetine

2. III. Atypical
Antidepressants
Bupropion
Mirtazapine
Less sexual dysfunction
Atypical Antidepressants
Agomelatine
Trazodone
Nefazodone
Vortioxetine
Tianeptine
Bupropion,
Mirtazapine,
Agomelatine
, Trazodone,
Vortioxetine,
Tianeptine

3. Bupropion
Block NE –DA reuptake
➢Same advantages of SSRIs over TCAs .
➢NO sexual dysfunction used in depressed patients
intolerant to SSRIs.
➢Use: MDD & Smoking cessationDA(craving ,Relapse)
➢BUT:Risk of convulsions
Contraindicated in pt. with history of seizures –alcohol withdrawal 

4. Mirtazapine
Block presynaptic α
2→↑NE&5HT
➢Use: MDDwith Same advantages of SSRIs over TCAs.
➢Antiemetic effect(-5HT
3in CTZ) & Rapid
➢NOsexual dysfunction (-5HT
2)used in pts intolerant to SSRIs.
➢Sedatinguseful in pts having insomnia.
➢Weight gain(appetite)
H
1antagonist

5. •MelatoninM
1&M
2receptoragonistand
5-HT
2Cantagonism(↑NE&DA)→Antidepressant
•AgomelatineisNOThypnoticlikeRamelteon
bec.it↑NEreleasevia5HT
2Cantagonism→↑
Arousal.
•Hepatotoxic“↑livertransaminases”
GITupset,Dizziness
Agomelatine

6. •Use:majordepressivedisorderinnon-respondersandintolerantstoSSRIs.
•Correctssleepcircadianrhythmdisturbanceassociatedwithdepression.

7. SARIs(5-HT
2A&Cantagonist/reuptake inhibitors) (Stahl ҆s essential psychopharmacology, 2013)
Block 5HT
2Aand 5HT
2C→ ↓↓sexual
dysfunction or insomnia/anxiety seen e SSRI
“Trazodone and Nefazodone” (Stahl ҆s essential psychopharmacology, 2013)
Mechanism:
1-SARIshaveadualaction,block5HT
2A&5HT
2C
receptorsand5-HTreuptakeinhibitor(SRI).
2-SARIsalsoblockα
1-receptors.
3-TrazodoneH
1receptorantagonism.
4-Nefazodone NE reuptake inhibition (NRI).
Indication:
1. Depression and Anxiety (SARIs)
2. Insomnia (Trazodone “Trittico” only)
Advantage over TCA:
No Anticholinergic, No Cardiotoxicity

8. Trazodone Nefazodone
Sexual
Function
Priapism
(≤0.1%)
Minimum
OrthostasisMore Less
Sedation More Less
Liver toxicity
Drug interaction
………
Potential
(CYP3A4 ----)
Priapism(ApersistentPainfulerection):
Mech:α
1-blockade→arterialdilation→venousstasis(↑intracavernosalpressure)
Treatment:
-Penileaspiration,irrigation,
-instillationofvasoactiveα
1-agentse.g.phenylephrine.

9. Serotonin multimodal (S-MM)(Stephen Stahl, 2015)
Vortioxetine
Mechanism:
Agonist at 5-HT
1A, Partial agonist at 5-HT
1B, Antagonist at 5-HT
1D&7 Receptor
→↑5-HT, NE, DA, glutamate, Ach& histamine Neurotransmitters)
“↓↓ Risk of weight gain or sexual dysfunction” & ↑ Cognition”
Vortioxetine
Sideeffects:
1.Nausea(≈20%),vomiting,constipation.
2.Rarelymaniaorseizures.
3.BlackBoxWarning:Suicidalthoughts&behaviors
▪Vortioxetine half-life 66 hours. metabolized by CYP2D6, interact CYP2D6 inhibitors. no active metabolites
Uses: MDD, GAD, Geriatric depression (improve cognition as well)

10. “Glutaminergic Modulator”
Tianeptine(Bailey et al, 2017)
Mechanism
1.inhibits NMDA receptors→↑BDNFvia mTOR signaling→
synaptic plasticity. “as Ketamine”
2. μ-opioid receptor agonist →↑Dopamine mesolimbic release
& action (antidepressant & abuse potential)
3. serotonin reuptake enhancer??!!
France
Uses: MDD, Dysthymia, Anxiety associated with depression 12.5mg3times/day
duetoshorthalf-life
SideEffects
1.Headache,dizziness,sedation,insomnia,Abnormaldreams
2.Nausea,constipation,drymouth(mildanticholinergiceffect)chemicallyasTCAsBUT………
3.Hepatotoxic↑livertransaminases
4.Tachycardia
5.ScheduleII,III??RiskofAbuse(1/1000)

11. 1. Depressivedisorders (main use)
2. Anxiety disorders.
3. Smokingcessation (bupropion).
4. Insomnia: Trazodone(Trittico) & Mirtazapine(Remeron) off-label
5. Erectile Dysfunction (ED):Trazodone (Trittico) in high doses
(150-200mg) esp. in psychogenic ED. Combined with yohimbine….
Q: Therapeutic Uses of Atypical Antidepressants?