1. Antidepressants
Antidepressants can take between 10-20 days to begin making an effect. After
symptoms have improved they should be continued for at least 6 months at the
same dose.
1. Serotonin-selective reuptake inhibitors (SSRIs)
2. Tricyclics (TCAs)
3. Monoamine oxidase inhibitors (MAOIs)
4. Other
SSRIs
E.g. Fluoxetine, paroxetine & sertraline
1st
line Treatment
Safer in overdose than other antidepressants
Mechanism:
 Block serotonin (5-HT) reuptake at pre-synaptic membranes
 Resulting in increased synaptic 5-HT
Pharmokinetics:
 Well absorbed orally
 ½ life varies between 15-24 hrs
 Fluoxetine ½ life – 24-96 hrs
 Paroxetine & Fluoxetine increase TCA toxicity  don’t use in combination
Side Effects:
 Dry mouth
 Nausea
 Vomiting & diarrhoea
 Dizziness
 Sedation
 Sexual dysfunction
 Agitation
 Akathisia
 Parkinsonism & convulsions (both rare)

2. TCAs
E.g. Imipramine, clomipramine & amitriptyline
Possibly better than SSRIs in severe depression, however are much more toxic in
overdose!
Mechanism
They block the reuptake of 2 things:
1. 5-HT (clomipramine more 5-HT selective)
2. Noradrenaline (lofepramine more selective)
Pharmokinetics
 Rapidly absorbed orally – 90% bound to albumin
 Metabolized in the Liver
Side Effects
 Anticholinergic dry mouth, blurred vision, constipation & urinary retention
(strong with amitriptyline)
 Postural hypotension & sedation  due to being an adrenergic α receptor
antagonist
 Weight ↑ & sexual dysfunction  5HT blockade
 Day time drowsiness & difficulty concentrating
Caution in patients with:
 Close angle glaucoma
 Prostatism
 Epilepsy
 Hepatic Impairment
 Cardiac disease
SSRI Discontinuation Syndrome
Occurs most frequently if paroxetine is
suddenly stopped.
Symptoms include:
 Headache
 Dizziness
 Shock-like sensations
 Paraesthesia
 GI symptoms
 Lethargy
 Insomnia
 Changes in mood
Serotonin Syndrome
 Rare
 Potentially fatal
 Due to increased 5-HT activity
Symptoms:
 Psychological – agitation, confusion
 Neuro – nystagmus, myoclonus,
tremor, seizures
 Other – hyperpyrexia, autonomic
instability

3. MAOIs
E.g. Phenelzine & isocarboxacid
Not widely used  only in resistant depression or atypical depression
Mechanism
 Increase 5HT & Noradrenaline due to blocking there metabolism.
Side Effects
 Anticholinergic (see above)
 Weight-gain
 Insomnia
 Postural hypotension
 Tremor
 Limb parasthesia
 Peripheral oedema
Useful things to remember:
1. In pregnancy  fluoxetine or the TCAs, nortriptyline, amitriptyline &
imipramine
2. If breast-feeding  SSRIs either paroxetine or sertraline
3. If a chronic health problem is present  citalopram or sertraline as they cause
fewer interactions
4. In children  fluoxetine (after psychological input e.g. CBT)
Tyramine Reaction
Causes:
 Foods containing tyramine e.g. cheese, game,
yeast & some alcoholic drinks
 Sympathomimetic drugs e.g. non-prescription
cold remedies
Results in a severe hypertensive reaction which
can cause a subarachnoid bleed.