Antidepressants

Question 1

Types of antidepressant drug

Answer 1

There are 3 types of antidepressant drugs

• Monoamine reuptake inhibitors
• Monoamine receptor antagonists
• MAO inhibitors

Question 2

TCAs

Answer 2

Tricyclic antidepressants are non-selective competitive inhibitors of monoamine reuptake receptors (SERT & NET)

• They block NA and 5-HT reuptake back into the pre-synaptic neuron
• This increases levels of NA & 5-HT in the synaptic cleft

Question 3

Initial effects of TCAs

Answer 3

TCAs cause an immediate increase in NA/5-HT levels

However, this leads to overstimulation of post-synaptic receptors, causing a worsening of depressive symptoms

Question 4

Long-term effects of TCAs

Answer 4

Adaptive changes to the brain take a few weeks to occur

Receptor expression decreases to prevent overstimulation

Hence an antidepressant effect is seen

Question 5

Side effects of TCAs

Answer 5

NA/5-HT bind to a wide variety of receptor types, this binding causes a variety of side effects

M1 = constipation, dry mouth, blurred vision 
H1 = sedative, weight gain 
a1 = postural hypertension, dizziness

Question 6

SSRIs

Answer 6

selective serotonin reuptake inhibitors can be competitive or non-competitive inhibitors of the SERT transporter

• They block 5-HT reuptake back into the pre-synaptic neuron
• This causes an increase in 5-HT in the synaptic cleft

Question 7

Side effects of SSRIs

Answer 7

Because SSRIs are specific to the SERT transporter they tend to be better tolerated

5-HT still binds to a variety of receptors

5-HT2 = insomnia, sexual dysfunction 
5-HT3 = nausea, headache 

Associated with suicidal ideation in under 18s

Question 8

Serotonin syndrome

Answer 8

Can occur when SSRIs are taken with MAO inhibitors

An overload of serotonin leads to confusion, hallucinations, coma, nausea and tremor

Question 9

MAOIs

Answer 9

Monoamine oxidase inhibitors are non-specific, long-lasting, non-competitive inhibitors of the MAO enzyme

They target both isoforms of the enzyme

• They inhibit the metabolism of monoamine neurotransmitters
• This increases the concentration of neurotransmitter inside the synapse, reducing the concentration gradient between neuron and synapse
• Reuptake is again inhibited, increasing NA/5-HT levels

Question 10

MAOI drug interactions

Answer 10

MAOIs have both food and drug interactions

-cheese reaction = breakdown of tyramine is inhibited
Tyramine enters the systemic circulation, leading headaches & intracranial haemorrhage

-Serotonin syndrome

Question 11

MAOI side effects

Answer 11

Cause quite severe side effects & so are only used in severe depression when other therapies have failed

M1 = constipation, dry mouth, blurred vision, tremor, insomnia

Question 12

a2 receptor antagonists

Answer 12

Examples include mirtazapine

Inhibit a2 receptors which are auto-receptors

-They therefore inhibit the inhibition of NA/5-HT synthesis

Question 13

5-HT(2C) receptor antagonists

Answer 13

Examples include trazodone

-Cause increased release of dopamine & other monoamines

Question 14

5-HT3 receptor antagonsists

Answer 14

Examples include trazodone

Activation of the 5-HT3 receptor is associated with side effects

-Inhibition can make the lag period more tolerable

Question 15

Electroconvulsive therapt

Answer 15

ECT is a process in which the brain is electrically stimulated

The process is heavily regulated with muscle relaxants

Causes a rapid increase in B-receptors

Effective in 60%-80% of patients