Depressive

disorders
Neurotransmitters- endogenous
chemical signals

● Excitatory: 5-HT,NE,EPI,GLUTAMATE
● Inhibitory: GABA, GLYCINE
● Both: Dopamine
ASSOCIATED WITH:
⬇ Serotonin
⬇ Dopamine
⬇ Norepinephrine

These monoamines are

the target of
treatment= ⬆
Major depressive disorder
Mdd : diagnostic criteria (adult)
Note:
DYSTHYMIA
Pathology: MONOAMINE
HYPOTHESIS
pathology: NEUROTROPHIC
HYPOTHESIS
The hippocampus
Antidepressant classification
1st Gen (Traditional):
Cyclic antidepressants and MAO Inhibitors

2nd Gen:
5-HT2 antagonists

3rd Gen:
SSRI, SNRI (SSNRI), Miscellaneous
Cyclic antidepressants

MOA: inhibit 5-HT and NE reuptake inhibitors

Less selective than SNRIs due to blockade

of H1, M, and alpha receptors.
Cyclic antidepressants
Pharmacokinetic and drug interaction:
-interactions with inducers and inhibitors
-long half-lives

Toxicities:
-block α and M
-sedation
-weight gain
-overdose
-arrhythmias
-seizures
triCyclic antidepressants
OTHER TCA
clomipramine
tetraCyclic antidepressants
Monoamine oxidase inhibitors
(MAOIS)
Believed to be the “1st modern class”
of antidepressants

Has greater potential for toxicity via drug

and food interactions

MOA: Inhibits degradation of

monoamines by inhibiting MAO enzymes
Monoamine oxidase types
MAO-A
brain, liver, gut, placenta
NE, Epi, 5-HT degradation
MAO-B
brain, liver, and platelet
DA, tyramine, 5-HT degradation
Inactive Metabolites:
NE and Epi (precursor Tyrosine)
Vanillylmandelic Acid
(VMA)
DA (precursor Tyrosine)
Homovanillic Acid (HVA)
5-HT (precursor Tryptophan)
5-hydroxyl-indole-acetic acid
Monoamine oxidase inhibitors

Phenelzine, Isocarboxazid, Tranylcypromine

Moclobemide
Monoamine oxidase
inhibitors

Selegiline
Pharmacokinetics and drug interaction:
-hypertension with tyramine and
sympathomimetics
-serotonin syndrome with SSRIs
-very long half-lives

Toxicities:
-hypertension, insomnia
5-HT2 antagonists

MOA: inhibits 5-HT2 receptors

Prevents downregulation of receptors in treatment-resistant

depression to increase SSRI efficacy
Trazodone

Nefazodone
*Role of 5-HT2A receptors in depression
>G-protein linked postsynaptic receptor

>inhibition -> antianxiety, antipsychotic, and

antidepressant effects

>activation -> hallucinogenic and anxiogenic

(causes anxiety)
SELECTIVE SEROTONIN
REUPTAKE INHIBITORS (SSRIs)
Most commonly used antidepressant today

MOA: Inhibits SERT in neurons

SSRI
Fluoxetine
norfluoxetine

● Sertraline, Paroxetine,
● Fluvoxamine, Escitalopram,
● Citalopram
Clinical application:
-Major depression
-Chronic pain
-OCD, PTSD, PMDD (premenstrual dysphoric disorder)
-bulimia

Pharmacokinetics and drug interactions:

-CYP2D6 and 3A4 inhibitors (fluoxetine, paroxetine); 1A2
(fluvoxamine)
-half-life: 15+ hrs.
Toxicities:
-sexual dysfunction
SEROTONIN-NOREPINEPHRINE
REUPTAKE INHIBITORS (SNRIs)
Newer agents

MOA: selectively inhibits the reuptake of serotonin

and norepinephrine

Venlafaxine, Desvenlafaxine, Duloxetine

 Clinical application:
-Major depression, chronic pain, fibromyalgia,
menopausal symptoms

Pharmacokinetics and drug interactions:

-half-lives: 10+ hrs.

Toxicities:
-anticholinergic, sedation, HTN (venlafaxine)
 BUPROPION

🡪
🡪
Indications for antidepressants
MDD and Anxiety Disorders
Indications for antidepressants

Imipramine
Desmopressin
CAUTION!

Anti-depressants if taken alone may

trigger manic episodes in patients with
BD, as mania is associated with elevated
DA and NE levels.
Indications for antidepressants
 Drug Tx:
Fluoxetine
 Anorexia Nervosa
Starving on purpose to have a
skeletal like body
Patients are very thin or emaciated
most of the time
Patients prefer to starve or eat less
May result in conditions like
amenorrhea, osteoporosis,
infertility, etc.
Bulimia Nervosa
Binge eating followed by purging,
resulting in average or overweight
body due to the residual amount of
calorie
Patients usually have an average
weight ideal for their height and
age, or in some cases an obese body
Patients eat heavy meal followed by
purging
May result in heart failure and
damage to esophagus and teeth
ADVERSE EFFECTS OF ANTIDEPRESSANTS

SSRIs usually cause:

paroxetine

Paroxetine
The activity of TCAs on other receptors may cause:
TOXIC EFFECTS OF ANTIDEPRESSANTS
Dx Int: SEROTONIN SYNDROME

MAOIs + other antidepressants

Fluoxetine,
MAOI, TYRAMINE, AND SYMPATHOMIMETICS
MUST-KNOW INFORMATION