Bupropion, Mirtazapine, Agomelatine, Trazodone, Vortioxetine, Tianeptine

1. Atypical Antidepressants
Prof. Sawsan Aboul-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
Bupr
Mirt
Agom
, Traz
Vorti
Tiane

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 α2→↑NE&5HT
➢ Use: MDD with Same advantages of SSRIs over TCAs.
➢ Antiemetic effect (-5HT3 in CTZ) & Rapid
➢ NO sexual dysfunction (-5HT2) used in pts intolerant to SSRIs.
➢ Sedating  useful in pts having insomnia.
➢ Weight gain ( appetite)
H1 antagonist

5. • Melatonin M1&M2 receptor agonist and
5-HT2C antagonism (↑ NE & DA)→ Antidepressant
• Agomelatine is NOT hypnotic like Ramelteon
bec. it ↑ NE release via 5HT2C antagonism→↑
Arousal.
• Hepatotoxic “↑ liver transaminases”
GIT upset, Dizziness
Agomelatine

6. • Use: major depressive disorder in non-responders and intolerants to SSRIs.
• Corrects sleep circadian rhythm disturbance associated with depression.

7. SARIs (5-HT2A&C antagonist/reuptake inhibitors)
(Stahl ҆s essential psychopharmacology, 2013)
Block 5HT2A and 5HT2C→ ↓↓ sexual
dysfunction or insomnia/anxiety seen e SSRI
“Trazodone and Nefazodone”
(Stahl ҆s essential psychopharmacology, 2013)
Mechanism:
1-SARIs have a dual action, block 5HT2A &5HT2C
receptors and 5-HT reuptake inhibitor (SRI).
2- SARIs also block α1- receptors.
3- Trazodone H1 receptor antagonism.
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
Orthostasis More Less
Sedation More Less
Liver toxicity
Drug interaction
……… Potential
(CYP3A4 ----)
Priapism (A persistent Painful erection):
Mech: α1-blockade → arterial dilation → venous stasis (↑ intracavernosal pressure)
Treatment:
- Penile aspiration, irrigation,
- instillation of vasoactive α1-agents e.g. phenylephrine.

9. Serotonin multimodal (S-MM)
(Stephen Stahl, 2015)
Vortioxetine
Mechanism:
Agonist at 5-HT1A, Partial agonist at 5-HT1B, Antagonist at 5-HT1D&7 Receptor
→↑5-HT, NE, DA, glutamate, Ach & histamine Neurotransmitters)
“↓↓ Risk of weight gain or sexual dysfunction” & ↑ Cognition”
Vortioxetine
Side effects:
1. Nausea (≈20%) , vomiting, constipation.
2. Rarely mania or seizures.
3. Black Box Warning: Suicidal thoughts & 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 →↑BDNF via 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 12.5 mg 3 times/day
due to short half-life
Side Effects
1. Headache, dizziness, sedation, insomnia, Abnormal dreams
2. Nausea, constipation, dry mouth (mild anticholinergic effect) chemically as TCAs BUT ………
3. Hepatotoxic ↑ liver transaminases
4. Tachycardia
5. Schedule II, III ?? Risk of Abuse (1/1000)

11. 1. Depressive disorders (main use)
2. Anxiety disorders.
3. Smoking cessation (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?