Neuroscience 18c - Antidepressant Drugs
Anil Chopra
1. Definitions & classification
2. Monoamine theory of depression
3. Types of antidepressant drugs
a. Tricyclic antidepressants (TCAs)
b. Monoamine oxidase inhibitors (MAOIs)
c. Selective 5-HT re-uptake inhibitors (SSRIs)
d. ‘Atypical’ antidepressants
4. Lithium
5. Electroconvulsive therapy (ECT)
Unipolar Depression
 Characterised by mood swings in the same direction.
 Is late in onset.
 Reactive Depression
o Related to a stressful event
o Non familial.
 Endogenous depression
o Not related to a stressful event
o Familial.
Bipolar Depression
 Also known as manic depression
 Characterised by oscillating depression.
 Early adult onset
 Strong hereditary tendency
Monoamine theory of Depression: this is the theory that depression is caused by
deficits in monoamine production (dopamine, noradrenaline, serotonin). The theory is
supported by the fact that:
- Monoamine oxidase inhibitors (reduce catabolism of monoamines) improve
mood.
- Tri-cyclic antidepressants (block uptake of noradrenaline) improve mood.
- Reserpine (depletes amines) causes depression in animals.
- Methyldopa (reduces noradrenaline synthesis) causes depression.
It does not however explain why:
- Amphetamines, cocaine, and L-dopa (all increase monoamines) do not affect
mood
- Atypical antidepressants (iprindole) work without affecting monoamine
systems.
- There is a delay of 2 weeks between when therapy starts and when the effects
take place.
Tricyclic Antidepressants
Names
Amitriptyline, desipramine, imipramine, protriptyline, clomipramine.
Usage
Chronic & bipolar depression.
Neuropathic pain
Nocturnal eneuresis
ADHD
Mode of Action
They block monoamine uptake (mainly noradrenaline and serotonin) from the
synaptic cleft hence increase transmission.
Side Effects
- Orally administered
- Metabolised by liver and excreted in kidney
- Long duration of action (1-3 days)
They also have actions at muscarinic receptors: (anti-muscarinic effects)
 Dry mouth and nose (salivary secretion is affected)
 Blurred vision (accommodation in the eye is affected)
 Decreased gastro-intestinal motility and secretion. This may lead to constipation
 Urinary retention or difficulty with urination
 Hyperthermia
 Sedation
 Postural hypotension
 DANGER IF OVERSOSE
 Seizures
 Cardiac dysrhythmias.
 Coma
 Respiratory depression
 Drug interactions
 Increased action by aspirin, phenytoin, neuroleptic, OCP. Also reacts with
CNS depressants and antihypertensive drugs.
Monoamine Oxidase Inhibitors
Names
Iproniazid, toloxatine, deprenyl
Usage
Depression
Mode of Action
Irreversibly block the action of mono-amine oxidase which causes decrease in
breakdown of:
- Noradrenaline (Monoamine oxidase A)
- serotonin (Monoamine oxidase A)
- dopamine (Monoamine oxidase B)
Most are non-selective so will inhibit both of them and cause an increase in
cytoplasmic NA and 5-HT (serotonin).
Side Effects and Pharmacokinetics
- Orally administered
- Long duration of action (2 weeks)
- Metabolised in the liver and excreted in the urine.
Side effects include:
 Postural hypotension
 Tremors
 Insomnia
 Siezures
 Sedation
 Weight gain
 Liver damage
 Has many drug interactions
o ‘Cheese reaction’: Tyramine-containing foods + MAOI causes
hypertensive crisis (throbbing headache, increase in blood pressure and
risk of intracranial haemorrhage)
o With TCA’s can cause hypertension
o Can react with Pethidine to produce hyperpyrexia, restlessness, coma &
hypotension
Selective Serotonin Reuptake Inhibitor
Name
Fluoxetine (Prozac)
Usage
Clinical depression
Mode of Action
Works in the same way as MAOI – inhibits the uptake of serotonin only resulting in a
less pronounced effect than MAOIs.
Side Effects and Pharmacokinetics
- Orally administered
- Long duration of action (1-3 days)
- Delayed onset of action (2 weeks)
Interacts with tri-cyclic antidepressants.
Side effects include:
 Nausea,
 Anorexia,
 Insomnia
 Loss of libido
Atypical Antidepressants
Names – maprotiline, venlafaxine, trazodone, mianserin, bupropion
Usage – Clinical depression
Mode of Action – generally unknown although some act as MAOIs.
Side Effects – rare.
Name – lithium
Usage – clinical depression & mania/bipolar depression
Mode of Action – inorganic ion taken as lithium carbonate. Not properly understood
but has numerous effects on neurotransmitter systems such as interference with IP3 an
cAMP formation (secondary messenger in dopamine receptors)
Side Effects and Pharmacokinetics
- Taken orally as lithium carbonate.
- Long plasma halflife and narrow therapeutic window.
Interacts with diuretics (enhances action)
Side effects include:
 Nausea
 Headache
 Hypothyroidism
 Tremor
 Weakness
 Mental confusion
 Polyuria
 Thirst
 Acute overdose can lead to confusions, convulsions and dysrhythmias
Electroconvulsive Therapy ECT
This is a treatment in which seizures are electrically induced in anesthetized patients
for therapeutic effect. It is used as a treatment for severe major depression which has
not responded to other treatment, and is also used in the treatment of mania (often in
bipolar disorder), catatonia, schizophrenia and other disorders.