Classification of Antidepressants & “Diagnosis & Pathophysiology of Depression”

Depression is classified into:

1. Unipolar depression
Major depressive Disorder (17%)

2. Bipolar manic depressive disorder (~ 2%)
Episodes of depression alternating with episodes of mania or hypomania.

Manic attacks (≥1w)
-↓need of sleep, euphoria, Grandiosity
lack of judgment , flights of ideas& hyper-talkativeness,
psychotic symptoms (hallucinations, delusions & agitation)

1. Prof. SawsanAboul-Fotouh
Department of pharmacology, Faculty of Medicine, Ain-Shams University
Classification of Antidepressants
“Diagnosis & Pathophysiology of Depression”

2. Depression is classified into:
1. Unipolar depression
Major depressive Disorder (17%)
2. Bipolar manic depressive disorder(~ 2%)
Episodes of depression alternating with episodes of mania or
hypomania.
Manic attacks (≥1w)
-↓need of sleep, euphoria, Grandiosity
lack of judgment , flights of ideas& hyper-talkativeness,
psychotic symptoms (hallucinations, delusions & agitation)

3. EPIDEMIOLOGY
•Lifetime prevalence ̴17% (Highest PD)
•Womenare ̴twice men.
•The average age at onset is the mid-twenties.
•Most patients with MDD also suffer from comorbidpsychiatric
disorders, esp. anxietydisorders and substance-use disorders.

4. CLINICAL PRESENTATION AND DIAGNOSIS
Severely depressed pts may experience Psychoticsymptoms: Hallucinations• Delusions.
•Patients present with combined emotional, physical, & cognitive symptoms
Emotional:
1.Sadness –inability to experience pleasure (Anhedonia)
2.Suicidal ideation/ Death wishes
3.Loss of interest
4.Guilt / worthlessness/ hopelessness –despair .
Physical:
1.Disturbed sleep (↓ or ↑)
2.Disturbed appetite/weight (↓ or ↑)
3.Psychomotor agitation or retardation, ↓energy/Fatigue
Cognitive:
1.↓ concentration
2.↓ memory & Indecisiveness

5. ❑Diagnostic criteria (MDD) include the presence of at least five
symptoms, for at least two consecutive weeks ( DSM5 -ICD 10 )
Core symptoms (1 0r 2)
Other symptoms
Impairment
Differential diagnosis
5 symptoms / 2Wks
Bipolar

6. Atypical Depression
DSM-5

7. Used to determine patient’s Severity of depression
before, during, and after treatment.
Hamilton Depression Rating Scale (HDRS)
Prof. Max Hamilton
(1912–1988)

8. Treatment of Depression

9. Non-Pharmacological
Psychotherapy
Electroconvulsive
therapy (ECT)
TMS
Physical exercise
Vagal nerve
stimulation
Pharmacological
TCA
MAOI
SSRI
SNRI
Atypical

10. Pathophysiology of Depression
•Monoamines (Most applicable) oldest, 1960s
•Glutamate (EsKetamine)
•GABA (Brexanolone)
2019
2019

11. Monoamine Theory of Depression
(Schildkraut, 1965 and van Proag, 1970)
Depression
NE -5HT
Antidepressants
NE -5HT

12. Mechanism of Action of Antidepressants
1. ↑ brain Monoamines “5-HT, NE, DA” (within 12 hours).
2. Downregulation of & 5-HT
2Receptors(delayed 2-4 wks).
3. ↑ Neurotrophic factors (e.g. BDNF) essential for survival &
function of neurons (Neuroplasticity).

13. CLASSIFICATION OF ANTIDEPRESSANTS

14. Amine Pump Inhibitors
InhibituptakeIofbiogenicaminesinto
neuronsresultingintheiraccumulation
insynapticcleft,potentiatingtheiraction
atpostsynapticreceptors.
1. TCAs: Imipramine-amitriptyline.
2. SSRI: Fluoxetine–sertraline
3. NDRI: Bupropion.
4. SNRI: Venlafaxine-duloxetine.
MAO Inhibitors
Inhibit metabolism of biogenic
amines by MAO enzyme inside nerve
endings stores available for
release.
1. Nonselective: Tranylcypromine.
Phenelzine
2. Selective on MAO-A:
Moclobemide.
Presynaptic 
2Blockers (Main action)
e.g. Mirtazapine
NA & 5-HT release into synaptic cleft by preventing 
2auto-inhibition.
Antidepressant Site(s) of Action

15. Antidepressant Site(s) of Action
SNRIs

16. Atypical Antidepressants
I. SARIs (Serotonin 2 antagonist/reuptake inhibitors)
“Trazodoneand Nefazodone” (Stahl ҆s essential psychopharmacology, 2013)
Blocking 5HT
2Aand 5HT
2C→ ↓↓sexual dysfunction or insomnia/anxiety seen e SSRIs

17. Agomelatine
(Stahl ҆s essential psychopharmacology, 2013) II. Melatonin multi-modal (Mel-MM),
Agonistatmelatonergic1andmelatonergic2receptors,Antagonistat5HT2Creceptors
“Agomelatine”
Atypical Antidepressants (Stahl ҆s essential psychopharmacology, 2013)
Block 5HT
2Creceptors →↑ NE & DA release
Less Sexual Dysfunction

18. III. Serotonin multimodal (S-MM)
Vortioxetine
Atypical Antidepressants(Stephen Stahl, 2015)
Vortioxetine
(Agonist at 5-HT
1A, Partial agonist at 5-HT
1B, Antagonist at 5-HT
1D& 5-HT
7receptors)
“↓↓ Risk of weight gain or sexual dysfunction” & ↑ Cognition
(↑5-HT, NE, DA,
glutamate, Ach&
histamine
Neurotransmitters)

19. “Glutaminergic/ GABAergic drugs”
Esketamine
Brexanolone
Fast Onset “hours” , Both Approved in Mar 2019
NMDA-Receptor Blocker
Brexanolone
GABA A –Receptor enhancer

20. Delayed onset
Antidepressants, including
SSRIs, take at least 2 weeksto
produce significant
improvement in mood, and
maximum benefit may require
up to12 weeks.

21. Response to Antidepressants
First Few Days
⚫May ↑agitation
/anxiety
⚫Improve sleep
& psychomotor
⚫Appetite
improves
1-3 weeks
⚫↑ activity, sex drive
⚫Self-care habits
improve
⚫Conc. and memory
normalize
⚫Sleeping and eating
patterns normalize
2-4 weeks
(up to 8 weeks)
⚫Relief of
depressive mood
⚫Begin to feel
pleasure
⚫↓hopeless
⚫Thoughts of
suicide subside