Atypical antidepressants have several advantages over traditional antidepressants: 1. They have fewer side effects like sexual dysfunction and weight gain. 2. Bupropion is used for major depressive disorder and smoking cessation. Mirtazapine is used for depression and insomnia. 3. Other atypical antidepressants include trazodone, nefazodone, agomelatine, and vortioxetine which are used for depression and related conditions.

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?