Antidepressants

Question 1

Amine hypothesis

Answer 1

1. Depressive illness is induced by amine depleting agents

2. Depressive illness alleviated by agents which elevate amine levels

Question 2

Tricyclic antidepressants

Answer 2

No longer first line due to effects on multiple receptors (therapeutic inhibition of reuptake of monoamines, antihistaminergic, anticholinergic, peripheral antiadrenergic and quinidine like effects on the heart)

Toxic in overdose esp. amitryptiline and dothiepin. Lofepramine is relatively safe in OD and almost free of anticholinergic side effects)

Good absorption, large first pass effect, highly protein bound

Cardiac side-effects significant esp OD, therefore monitor ECG parameters

Question 3

Amitryptyline

Answer 3

Indications: Depression, Panic disorder, nocturnal enuresis in children, neuralgia
Adverse effects: QT prolongation with OD, sedation, postural hypotension
Interactions: Alcohol (increased sedation), SSRIs (except citalopram)-increased plasma levels of TCAs, antimuscarinics (antimuscarinics SE), antipsychotics (antimuscarinic SE and ventricular arrhythmias), MAOIs (hypertension/CNS excitation)
Half-life 9-25 hours
Pharmacokinetic interactions: Warfarin (protein-binding), Cimetidine (enzyme inhibitor), Barbituates and tobacco (enzyme inducers)

Question 4

SSRI

Answer 4

Examples: Fluoxetine, citalopram
Indication: Depression, panic disorder, phobic disorder, generalised anxiety disorder, obsessive compulsive disorder
Side effects: GI effects (nausea, diarrhoea), sexual difficulties, headache
Caution: hyponatraemia in elderly, under 18 (only fluoxetine)

Question 5

Serotonin syndrome symptoms

Answer 5

Restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions, death

Question 6

MAOI

Answer 6

Two types of MAO; MAO-A (serotonin and NA), MAO-B (dopamine)
Two types of inhibitors (irreversible and reversible)
Irreversible: Phenelzine, Isocarboxazid, Tranylcypromine (most dangerous)
Reversible: Moclobemide
Side effects: Hypotension, cheese reaction, oedema
AVOID other antidepressants, indirect-acting sympathomimetics, levodopa, opiates (pethidine), 5HT IA agonists

Question 7

Cheese reaction

Answer 7

With MAOIs (especially irreversible)
Rare fatalities when MAOIs combined with foods containing tyramine - pressor effect, can cause dangerous rise in BP
Fresh food is key!!

Question 8

St John’s Wort

Answer 8

Mild depression
MAO inhibition, reuptake inhibition of serotonin and NA, upregulation of serotonin receptors
Well tolerated (nausea, dry mouth, constipation)
Interactions with other medicines IMPORTANT
1. Reduced effect of warfarin
2. Carbamazepine metabolised more rapidly
3. OCP failure
4. Increased viral load of HIV
5. Increased serotonergic effect when combined with SSRI - avoid