Anti

depressant
drugs

By
Dr.Ali H.Saud
Definition: Depression is a psychiatric illness
characterized by mental and physical symptoms
included:

Depression of mode

Inability to take decisions

Difficulty in sleep

Feeling of guilt

loss of appetite
 Globally approximately more than 400 million

people of all ages suffer from depression (5%) .in

2024.

 Woman are affected more than man

 Depression is a major cause of disability world wide

 Depression can lead to suicide

 Pathophysiology
Genetic theory : 4 genes were implicated

 Biogenic amine theory :Depression occurs due to

disturbances in the catecholamine concentrations in

the brain including the reduction in serotonin,

noradrenaline and dopamine in certain sites in the

brain.
 Pathophysiology(Cont.)
Receptors theory :

Some receptors of 5HT receptors show up regulation

like 5-HT2A and 5-HT2C

Neurotrophic and cytokines theory :

A. Brain derived neurotrophic factor (BDNF)

B. Hypothalamic pituitary axis desregulation

C. Proinflammatory cytokines:IL-1,IL-6 and TNF

 Types of depression

1. Unipolar depression (major depressive disorder)

(MDD)

2. Bipolar depression (manic depressive disorder)

 Symptoms of depression
1.Emotional symptom
• Anhedonia: loss of interest and enjoyment of life

• Apathy and loss of self esteem

• Loss of motivation

All these symptom related to reduction in serotonin

level
 Symptoms of depression (Cont.)
2.Biological symptom

 Sleep disturbance

 loss of libido

 Chronic pain

All these symptom related to reduction in

noradrenalin level
 Classification of antidepressant agents

1. Monoamine oxidase inhibitors (MAO-I)

2. Tricyclic antidepressant (TCA)

3. Selective serotonin reuptake inhibitors (SSRIs)

4. Heterocyclic antidepressant
 Monoamine oxidase inhibitors

MAO-A enzyme

Present in the cytoplasm of neuron and peripheral

tissue like liver, it metabolized noradrenalin,
dopamine and serotonin.

MAO-B enzyme

Present mainly in the CNS and acts more on the

dopamine metabolism.
 Monoamine oxidase inhibitors

Mode of action :They act by inhibition of MAO

enzymes and increase catecholamine centrally in the
brain.

They take 2-4 weeks for clinical response to occur.

They are only used when there is no response to

other drugs.
 Monoamine oxidase inhibitors

Therapeutic uses

1.Major depression: when other drugs are ineffective

2.Parkinsonism: like selegiline

3. Used to treat anxiety and panic disorder (in past)

 Monoamine oxidase inhibitors
S/E
1. Orthostatic hypotension (postural)
2. Sexual dysfunction: delayed ejaculation
3. Serotonin syndrome: if combined with tricyclic
antidepressant or selective serotonin reuptake inhibitors
4.CNS stimulation: insomnia, tremor ,convulsion.
5. Hypertensive crisis: occurs when eating tyramine
containing food like cheese ,yogurt and banana (cheese
reaction)
 Monoamine oxidase inhibitors

Drug – Drug interaction

1. MAOIs can also inhibit the metabolism of other

drugs as barbiturates and hypoglycemic agents.

2. Cause severe hypertension when given in

combination with Adrenaline and amphetamine.

Which may lead to sub- arachnoid hemorrhage

 Monoamine oxidase inhibitors
Members of this family are:

1.Phenelzine (Nardil®)

2. Tranylcypromine (Parnate®)

3. Selegiline (Jumex®)

4. Meclobamide (not available in the USA)

5. Isocarboxazid (Marplan®)
Tricyclic antidepressant
 Tricyclic antidepressant (1970)

Mode of action :

They inhibit neuronal reuptake of both noradrenalin

and serotonin leading to accumulation of them in the

synaptic space.
 Tricyclic antidepressant
Therapeutic uses
1. Major depression

2. Chronic pain :Administered with analgesic drugs

especially in chronic pain as it improves pain control
by inhibiting pain pathway and relieving associated
depression.(Fibromyalgia)

3. Nocturnal enuresis in children. Imipramine

 Tricyclic antidepressant
S/E
1. Orthostatic hypotension (postural)
2. Sexual dysfunction: delayed ejaculation
3. Serotonin syndrome: when given with SSRIs or MAO-I
4.CNS sedation : due to atropine like effect
5.Atropin like action :commonly dry mouth ,blurred vision,
urine retention
6. Cardiac arrhythmia (common)
7. Cholestatic jaundice (hepatotoxic)
 Tricyclic antidepressant
Manifestation of TCA overdose

1. Atropine like action :dry mouth, urine

retention,…..

2. Metabolic acidosis

3. Cardiac arrhythmia : sinus tachycardia with first

degree AV block , wide QRS, long QT interval

 Tricyclic antidepressant

Treatment of TCA toxicity

1.NAHCO3 vial in order to correct acidosis

2.Lidocain giving I.V to treat arrhythmia

3.Is hemodialysis effective in treatment of TCA

overdose? Knowing that most TCA have Vd around 25

L/kg .
 Tricyclic antidepressant
Members of this family are :

1.Imipramin (Tofranil®)

2. Clomipramine (Anafranil®)

3. Amitriptyline (Tryptizol®)

4. Nortriptyline ( Aventyl®)
 Selective serotonin reuptake inhibitors

Mode of action :

They selectively inhibit serotonin reuptake leading

to accumulation of serotonin in the brain tissue

 Selective serotonin reuptake inhibitors

Therapeutic uses

1.Major depression (MDD)

2.Obssesive compulsive disorder (OCD)

3.Generlized anxiety disorder (GAD)

 Selective serotonin reuptake inhibitors
S/E
1. Orthostatic hypotension

2. Sexual dysfunction: delayed ejaculation

3. Serotonin syndrome: if combined with tricyclic

antidepressant or monoamine oxidase inhibitors So C/I

4.CNS sedition or stimulation: at initiation of therapy

but tolerance will occurs with time
 Selective serotonin reuptake inhibitors
S/E (cont.)
5.GIT irritation :Very common . How can treat it?
6.Cardiac arrhythmia: less than TCA (increase QT interval) .
7. All SSRIs are potent microsomal enzyme inhibitor except
sertraline and citalopram
 SSRIs should be stopped gradually over one month to avoid
relapse .
 Sertraline :Its antidepressant of choice after MI
 Dapoxetine : is drug of choice in treatment of PE
 Selective serotonin reuptake inhibitors
 Members of this family are:

1.Fluoxetine (PROZAC®)

2. Paroxetine (Seroxat®)

3.Sertraline (Zoloft®)

4. Dapoxetine (Priligy®) not approved by FDA

5.Citalopram (Cipralex®)

6. esCitalopram
 Heterocyclic antidepressant
A. NA and 5-HT reuptake inhibitors
 Venlafaxine used in treatment of MDD, general anxiety disorder
and social anxiety disorder
 Duloxetine used for neuropathy
B. Receptor blocker
 Trazodone : Acts by antagonism at serotonin receptors (5-HT2A or
5-HT2C)
 Mirtazapine: Block presynaptic α2 adrenoceptor and 5-HT2C
increased catecholamine secretion. Less to cause sexual
dysfunction and less GIT upset and act more rapidly than other
antidepressants and has sedative effects.
.
 Heterocyclic antidepressant

 Maprotiline: Is a tetracyclic compound similar in action to

the tricyclic compounds, has a long half-life and can be given

in a single daily dose.

 Amoxapine: Causes less cardiac toxicity but may cause

extra-pyramidal symptoms due to blockage of dopamine

receptor .
 Lithium
Effective in the treatment of manic-depression.

Acts by replace Na+ ions which lead to altered

neuronal function, it also interacts with second
messengers (G-proteins) and causes inhibition of
inositol triphosphate

Available as lithium carbonate.

 Lithium
Diuretics reduce renal clearance

Not bound to plasma proteins

Low therapeutic index (0.5mmol/l to 1.5mmol/l) so

requires serum level monitoring during treatment

All these considered as pharmacokinetics

 Lithium
S/E
1. GIT: nausea, vomiting and diarrhea
2. Cardiovascular: hypotension and cardiac dysrhythmias
3. Nephrogenic diabetes insipidus (block effect of ADH)
4. CNS: drowsiness, dizziness, ataxia, tremor, coma and
convulsions
5. Thyroid enlargement, sometimes associated with
hypothyroidism.