The document discusses agomelatine, a novel antidepressant with melatonergic and serotonergic properties. It summarizes agomelatine's mechanism of action, clinical effects in treating depression and anxiety, indications, efficacy and tolerability profile compared to other antidepressants. Some key advantages are its well-tolerability, lack of sexual side effects, weight gain and discontinuation syndrome. However, liver function tests need monitoring and its efficacy may be modest for severe depression requiring combination therapy. The recommended dosing is 25mg once daily increased to 50mg if no response after two weeks.

1. AGOMELATINE
More Than Just Another Antidepressant
Venue: Samson H. Chowdhury Hall
Dhaka Club
Date: 19 January, 2022

2. Agomelatine
More than just another antidepressant
Dr. Ahsan Aziz Sarkar
Assistant Registrar, Psychiatry (FCPS, MCPS)
National Institute of Mental Health, Dhaka

3. Common
problems we
face with
antidepressants
Some issues
with
antidepressants
Treatment
resistance
Cardiac effect
Anticholinergic
effect, cognitive
impairment
Discontinuation
syndrome
Sexual
dysfunction,
suicide risk
Weight gain

4. History
Structural analog of melatonin.
First developed in 2005.
Got approval for clinical use in European Union in
2009.

5. Mechanism of
action
MT1 and MT2
melatonin agonist
Resynchronization
of circadian rhythm
5-HT2c antagonist
Increase
noradrenaline and
dopamine in
frontal cortex.
5-HT2A agonist
Decrease 5-HT
firing
Enhance BDNF
May promote
neurogenesis

6. Clinical effects
Antidepressant effect
Anxiolytic effect
Restoration of sleep without daytime sedation

7. Indications
Treatment of acute depression and maintenance therapy
Seasonal depression
Bipolar depression
Generalized anxiety disorder
Circadian rhythm sleep disorder
Night eating disorder

8. Efficacy and
tolerability of
agomelatine

9. Special
conditions

10. Adverse effects
Nausea
Dizziness
Somnolence
Insomnia
Migraine headaches
Anxiety
Constipation
Diarrhea
Fatigue
Back pain
Hyperhidrosis

11. Comparing
side effects
Agomelatine Nortriptyline Sertraline
Anticholinergic 0 2+ 0
Insomnia/
agitation
1+ 0 2+
QT
prolongation
0 1+ 1+
GIT symptoms 1+ 0 2+
Weight gain 0 1+ 1+
Sexual
dysfunction
0 Inadequate data 3+

12. Potentially
serious adverse
effect
Elevated transaminase in 1% of recipients (0.7% in placebo group).
Idiosyncratic reaction.
Needs to measure transaminase level at baseline, 6, 12 and 24
weeks.
Drug stoppage leads to normalization of transaminase level.

13. Contraindications
(relativeinsomecases)
Alcoholism
Non-alcoholic fatty liver disease
Mania/hypomania
Dementia
Obesity
Children
Pregnancy, lactation.

14. Drug interaction
Fluvoxamine
Ciprofloxacin
Propranolol
Estrogen

15. Advantages
Well tolerated.
Fast action.
Effective in preventive relapse.
Less chance of manic switch.
No discontinuation syndrome.
No sexual side effects.
No weight gain.
Little drug interaction.
Not cardiotoxic, safe in overdose.
Little initial agitation.

16. Concerns
Most trials are on patients with moderate to severe depression.
Modest efficacy.
In case of non-response to initial antidepressant, combination
therapy might be necessary (e.g., SSRI + agomelatine, Bupropion
+ agomelatine).
Need for LFT monitoring.

17. Dosing
Strength – 25mg
Once daily dosing at bedtime (9 PM).
Increase dose to 50mg if no response after two weeks.