The document reviews atypical antidepressants, detailing their classification, mechanisms of action, indications, and side effects. It covers various types of antidepressants, including monoamine oxidase inhibitors, tricyclics, SSRIs, SNRIs, and specific atypical agents like mirtazapine, trazodone, and bupropion. The document also discusses the pathophysiology of depression, emphasizing the role of neurotransmitter imbalances.

1. Atypical Anti-depressants
Brajesh Lahri
Final Professional MBBS Student
All India Institute of Medical
Sciences (AIIMS), Bhopal

2. By the end of discussion you should be able to…
• Classify anti-depressants
• Enlist atypical anti-depressants
• Know about the mechanism of action of atypical anti-depressants
• Know about the indications of atypical anti-depressants
• Know about the side effects of atypical anti-depressants

3. Introduction
• Major Depression and Mania are two extremes of affective disorders,
referring to pathological change in mood state.
• Depression is characterized by symptoms like sad mood, loss of
interest and pleasure in activities, low energy, feeling of guilt,
agitation, change in appetite, sleep disturbances, suicidal thoughts
etc.
• Anti-Depressants are drugs which help to elevate mood in depressive
illness.

4. Pathophysiology of depression
• Many theories are given, most accepted is Monoamine Hypothesis.
• It states that deficiencies in various monoamine neurotransmitters
are responsible for corresponding symptoms of depression.
• According to the monoamine hypothesis, Serotonin, norepinephrine,
and dopamine are the neuro-transmitters associated in
pathophysiology of depression.
**(Serotonin, Nor-epinephrine and Dopamine levels are decreased in
depression)

5. Classification of Anti-Depressants
Anti-Depressants
Reversible Inhibitors of
MAO-A (RIMAs)
Examples: Moclobemide,
Clorgyline
Tri-Cyclic Anti-depressants
(TCAs)
Examples: Imipramine,
Amitriptyline,
Clomipramine
Selective Serotonin
Reuptake Inhibitors (SSRIs)
Examples: Fluoxetine,
Paroxetine, Sertaline,
Citalopram, Dapoxetine
Serotonin and Nor-
adrenaline Reuptake
Inhibitors (SNRIs)
Examples: Venlafaxine,
Duloxetine
Atypical Anti-depressants
Examples: Trazodone,
Mirtazapine, Bupropion,
Tianeptine

6. Atypical Anti-depressants
• Mirtazapine
• Trazodone
• Bupropion
• Tianeptine
• Agomelatine

7. Mirtazapine
• Mechanism of Action
Blocks α-1 receptors (present on NA neurons) and Hetero receptors (5HT-2)
(present on 5-HT neurons), enhancing both NA and 5HT release.
** Also, Mirtazapine is said to have some affinity for α-2 receptors, which is
claimed to be related to their therapeutic efficacy, but this point is
questionable.
**(It is also a H1 blocker and quite sedative)
• Adverse Effects
- Increased appetite
- Weight gain
- Agranulocytosis (Rare)
Indications : Depression,
OCD, Panic disorder, PTSD,
SAD

8. Trazodone
• Mechanism of Action
Prominent α-1 adrenergic and weak 5-HT2A antagonistic action. Also
acts by blocking uptake of 5HT.
• Adverse Effects
- Excessive Sedation
-Inappropriate, prolonged and painful penile erection (Priapism)
- Postural Hypotension (Due to α1 adrenergic blockade)
Indications : Generalized
anxiety disorders (GAD),
Panic Disorder, Eating
Disorders

9. Bupropion
• Mechanism of Action
Inhibits re-uptake of Dopamine and Nor-Adrenaline. In addition may also
increase the release of NA and DA.
**(It has excitant rather than sedative activity)
• Adverse Effects
-Insomnia and agitation
- Decreases Seizure threshold
Indications : Depression,
Eating Disorder, Cannabis
dependence, Cocaine
dependence, Nicotine
dependence

10. Agomelatine
• Mechanism of action:
It acts as melatonin receptor agonist at MT1 and MT2 receptors. It
also acts as a weak antagonist at 5-HT2c receptors
• Adverse Effects :
- Nausea and Dizziness
- Increase in liver enzyme levels
Indications : Depression,
resynchronization of disturbed
circadian rhythm

11. Tianeptine
• Mechanism of Action :
It increases serotonin/5-HT uptake in the brain (in contrast with most
antidepressant agents) and reduces stress-induced atrophy of neuronal
dendrites.
• Adverse Effects:
- Nausea, Constipation, Abdominal Pain
- Dizziness, Headache
- Hepatoxicity (Rare)
Indications : Useful in
anxio-depressive states
,as well as in
endogenous depression

12. Serotonin and Nor-Adrenaline reuptake
inhibitors (SNRIs)
• Venlafaxine
• Duloxetine
Mechanism of Action : Inhibit uptake of both Nor-adrenaline and
Serotonin, but do not interact with cholinergic, adrenergic or histaminergic
receptors.
Adverse Effects :
- Dizziness ,Insomnia
- Rise in BP (More common with Venlafaxine )
- Associated with increased risk of
Cardiac arrhythmias(Clinical significance is still unclear)
Indications:
-Depression (Both)
-Neuropathic pain
(Duloxetine)

13. Reversible Inhibitors of MAO-A (RIMAs)
• Moclobemide
• Clorgyline
Mechanism of Action:
Inhibit MAO-A enzyme which deaminates 5-HT and NA.
Adverse Effects :
-Nausea
- Dizziness, Insomnia
- Liver damage (Rare)
Indications:
Depression and Social
Phobia

14. References
• Clinical Pharmacology-11th Edition - Bennett, Brown and Sharma
• Goodman-Gilman’s -The Pharmacologic basis of Therapeutics- 12th
Edition – Brunton, Chabner, Knollmann
• Essential Medical Pharmacology-7th Edition - K.D. Tripathi
• Essential Evidence based Psychopharmacology- 2nd Edition- Stein ,
Lerer and Stahl

15. Thank You