ANTI-DEPRESSANTS

Dr MK Ilunga
 • Antidepressants are a group of drugs used for the
treatment of major depression
• NB: They are also used to treat a broad range of
psychiatric disorders (Panic disorder, Agoraphobia, OCD,
Social phobia, GAD, PTSD, Bulimia nervosa, Premenstrual
dysphoric disorder) and other conditions such as
Enuresis in children, Neuropathic pain, Back pain,
Introduction Fibromyalgia, Smoking cessation...
• Each class of drug is different from each other with
regards to its chemical structure, mode of action, safety
profile, efficacy and adverse effects.
• There is no risk of dependency.
• Ads are the 3rd most common class of medicine
prescribed in all age groups (Analgesics and Antibiotics)
• Approximately 65-70% of patients receiving an AD will
respond within 4 to 6 weeks
Neurotransmitters
•Depression occurs due to deficits
in one of the following
transmitters:
• Serotonin
• Norepinephrine
• Dopamine
 • Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin Norepinephrine reuptake inhibitor
(SNRIs)
• Tricyclic and Tetracyclic Antidepressant
• Monoamine oxidase inhibitors
Classificatio • Norepinephrine and Dopamine reuptake inhibitors
n (NDRIs)
• Serotonin receptor antagonist/ reuptake inhibitors
• Serotonergic and Noradrenergic antidepressants
• Norepinephrine reuptake inhibitors
• Others
 Selective Serotonin Reuptake Inhibitors (SSRIs)
Indications:
First line treatment in:
• MDD (All except fluvoxamine)
• Panic disorder
• Social anxiety disorder
(sertraline & paroxetine)
• GAD (paroxetine &
escitalopram)
• OCD (All except citalopram and
escitalopram)
• PTSD (Sertraline & paroxetine)
• Bulimia nervosa (Fluoxetine)
• PMDD (Fluoxetine & sertraline)
Drugs :
Mechanism of action:
Fluoxetine (20-60mg)
Paroxetine (10-60mg)
Block 5HT transporter enzyme, thus
inhibiting presynaptic reuptake
Citalopram (10-40mg)
Escitalopram (10-20mg) Side effects:
Sertraline (25-200mg) GIT
Fluvoxamine (50-300mg) • Nausea and vomiting
. Upper GI bleeding
• Diarrhoea
• Abdominal pain
CNS
Drug Interactions: • Headache
• Insomnia
• MAOIs ( risk of fatal serotonin Black box warning: Advantages:
syndrome) • Agitation &anxiety
Antidepressants increase risk of suicidal thinking/ behavior in • Safe in pregnancy except paroxetine (safest:
• NSAIDs & Aspirin (increased risk of sertraline)
short term studies in children and adolescents with MDD. Other
bleeding) Families should be advised on the need for observation and
• Drug of choice in elderly and adolescent
• Duretics (electrolyte disturbance: communication with healthcare providers • Sexual dysfunction
(fluoxetine)
hyponatremia)
• Safer than other antidepressants when taken
in overdose
 Serotonin and Norepinephrine reuptake inhibitors
Drugs:
Venlafaxine (75-375mg) Interactions leading to
Duloxetine (60mg-120mg)
increased serotonin levels:
(may cause serotonin syndrome)
Milnacipran (50-200mg)
Indications: • MAOIs
Desvenlafaxin (50-400mg)
• MDD
Levomilnacipran (20- 120mg) Side effects:
 2nd line
GIT
 Treatment augmentation
• Nausea
 Treatment resistance
• Anorexia
 With prominent pain
symptoms Anticholinergic
• Social anxiety disorder • Constipation
• Panic disorder • Blurred vision
• Persistent depressive disorder • Dry mouth
• Diabetic neuropathic pain CNS
• Sedation
Mechanism of action: • Dizziness
SELECTIVELY Block 5HT AND NA • Anxiety
transporter enzyme, thus inhibiting
Other:
presynaptic reuptake
• Sweating
• Hypertension
• Erectile dysfunction
 Tricyclic and Tetracyclic Anti-Depressants
Drugs:
Tricyclic antidepressants
• Amytriptyline (10-200mg)
• Clomipramine (10-250mg)
• Imipramine (10-200mg)
• Trimipramine (30-300mg)
• Lofepramine (140-210mg)
Tetracyclic antidepressants (rarely
used
• Maprotiline 75-200mg
• Amoxapine
Indications:
• MDD (second line)
• Childhood enuresis
• Narcolepsy with cataplexy
• OCD
• Agoraphobia with panic
attacks
• Chronic pain
Mechanism of action:
Block the reuptake of both
norepinephrine and serotonine
Interactions:
• MAOI( serotonin syndrome)
• Clonidine (hypertensive crisis)
• CNS depressants eg alcohol,
opioids, anxiolytics (increase
sedation)
Side effects:
Anticholinergic (often severe)
• Constipation
• Urinary retention
• Dry mouth
• Blurred vision
CVS
• Palpitation
• Cardiac Conduction abnormalities
• Orthostatic hypotension and reflex
tachycardia
Other
Contraindications: • Sedation (prescribed nocte)
• Pregnancy • Weight gain
• Recent MI • Sexual dysfunction
• Cardiac arrhythmias
 Monoamine Oxidase inhibitors
Drugs:
Tranylcipromine 10-60mg
Phenelzine 15-90mg
Interactions:
Isocarboxazid 10-60mg • Most antidepressants
Selegiline 6-9mg • CNS depressants
• Anti-asthmatics
Indications:
• Antihypertensives
• MDD (atypical features,
resistance depression)
• Social anxiety disorder
• PDD Side effects:
• Panic disorder • Orthostatic hypotension
• PTSD • Insomnia
• Bulimia nervosa • Weight gain
• Oedema
Mechanism of action: Tyramine- induced hypertension • Sexual dysfunction
They inhibit monoamine oxidase Warning: Concomitant ingestion of a MAOI and substance
(enzyme responsible for the containing tyramine can lead to severe hypertension and
degradation of tyramine, serotonin, death or stroke. Wear a medical bracelet when taking a
dopamine and norepinephrine) MAOI
 Norepinephrine & Dopamine reuptake inhibitors
Drugs:
Buproprion 150-300mg Mechanism of action:
WEAK Blocker of DA AND NA
Indications: transporter enzyme, thus inhibiting
• MDD presynaptic reuptake
 2nd line
 Treatment augmentation
 With prominent hypersomnia Interactions:
&fatigue • MAOI (risk of hypertensive crisis)
 With sexual dysfunction on other • Drugs that decrease seizure
antidepressants threshold level
• Persistent depressive disorder
• Tobacco-use disorder
• ADHD Side effects:
• Headache
• Insomnia
Advantages: • Dry mouth
Minimal effect on weight gain, cardiac • Tremor
conduction or sexual drive • Nausea
• Increased sweating
 Serotonin receptor antagonist/ reuptake
inhibitors
Mechanism of action:
Block 5HT transporter
Drugs: enzyme, thus inhibiting
Trazodone 75-600mg
presynaptic reuptake
Nefazodone 50-600mg
Also cause indirect
increase in noradrenaline
release
Indications:
• MDD
• Anxiety disorders
• Insomnia (Trazodone
mostly)
Side effects:
• Sedation
• Dizziness
• Orthostatic hypotension
Blackbox Warning: • Tachycardia
• Risk of hepatotoxicity • Headache
associated with • Nausea and vomiting
nefazodone • Priaprism
 Serotonergic and Noradrenergic antidepressants
Interactions leading to a risk
Drugs: of hypertensive crisis with
Mirtazapine 15-45 mg/day MAOI

Indications:
Advantages:
• MDD
 1st or 2nd line
• Limited sexual side effect
 Treatment augmentation • Used in patient with
cardiac condition defect
 With prominent insomnia
• General anxiety disorder Side effects:
• Panic disorder • Increased appetite
• Social anxiety disorder • Weight gain
• Seasonal depression • Dry mouth
• Constipation
Mechanism of action:
Mirtazapine is a central presynaptic • Dizziness
alpha 2 blocker and blocks also 5HT2 • Headache
and 5HT3 receptors ,that to an
• Sedation
increase release of norepinephrine
and 5HT1A mediated serotonergic
transmission. • Oedema
Norepinephrine reuptake inhibitors

Drugs:
Interactions leading
Atomoxetine (40-
to increased
100mg)
serotonin levels:
Reboxetine (4-10mg)
(may cause serotonin
syndrome)
• MAOI (type A)

Indications:
• MDD
• ADHD (Atomoxetine) Side effects:
• Abdominal
discomfort
• Anorexia
• Sexual
dysfunction
 • Vortioxetine (10-20mg) – is a newer agent
that is a serotonin reuptake inhibitor

• Vilazodone (10-40mg) – has as mechanism

of action, selective reuptake inhibition with
Others partial agonist activity at the 5HT 1A.

• Agomelatine (25-50mg) – is a melatonin

agonist
 CAUSE: ABRUPT discontinuance of antidepressants, especially those with short half lives eg
Paroxetine, fluvoxamine, venlafaxine
SYMPTOMS: usually appear after 6 weeks of antidepressant discontinuance and
spontaneously resolve within 3 weeks
 Dizziness, weakness, nausea
 Rebound depression, anxiety, insomnia, poor concentration

Discontinuation  Headache, migraine-like symptoms, paraesthesias

 Upper respiratory symptoms
syndrome PREVENTION: ALWAYS taper antidepressants slowly before discontinuation
TREATMENT:
 Restart medication at same dose and taper down slowly
 Choose drugs with a longer half life eg fluoxetine
 Treat symptoms
 • Use SSRIs as first line (titrate from lowest minimal
effective dose to maximal dose)
Use of • If no response after 4 weeks, switch to another
antidepressant from a different class. Always
Antidepressants taper down before switching
• If treatment fails, consider:
• Augmentation strategies with
• Lithium
• Antipsychotic (Aripiprazole, olanzapine, quetiapine)
• Another AD (SSRIs + bupropion, SSRIs + mirtazapine)
• Second choice for augmentation: add ketamine
• ECT
 • The Mausley: Prescribing Guidelines in
Psychiatry 14th Edition
• Introduction Textbook of Psychiatry 6th
References Edition
• Manual of Clinical Psychopharmacology 8th
Edition
Thank you !!!