PHAR: Antidepressants & Mood Stabilisers

Question 1

Alterations in the activities of which six neurotransmitters may contribute towards depression?

Which two neurotransmitters are most commonly manipulated by antidepressants?

Answer 1

1. Serotonin.
2. NA.
3. Dopamine.
4. Acetylcholine.
5. Glutamate.
6. GABA.

Serotonin and NA.

SSRIs and SNRIs are first-line treatment for anxiety and depression.

Question 2

What are the different classifications of antidepressant drugs? Name an example of each

Answer 2

• SSRI (Selective serotonin reuptake inhibitor) - fluoxetine
• NRI (Noradrenaline reuptake inhibitor) - reboxetine
• SNRI (Serotonin & noreadrenaline reuptake inhibitor) - venlafaxine
• RIMA (Reversible inhibitor of monoamine oxidase A) - moclobemide
• NaSSA (Noradrenaline-serotonin specific antidepressant) - mirtazapine
• NDRI (noradrenaline dopamine reuptake inhibitor) - bupropion (weak)

Very powerful but not frontline:

• TCA (tricyclic antidepressant) - desipramine
• MAOI (monoamine oxidase inhibitors) - phenelzine

Question 3

What is the 5-HT receptor a receptor for?

Answer 3

Serotonin.

Question 4

• Give an example of an SSRI.
• What is the mechanism of action of an SSRI?

Answer 4

• Fluoxetine (Prozac).
• Selective inhibition of the 5-HT (dopamine) transporter (SERT).
  
  • SERT transports serotonin from the synaptic cleft to the presynaptic neuron.

Question 5

Discuss the safety of SSRIs, relative to TCAs.

• Impairment of cardiac conduction?
• Therapeutic index?
• Safety in overdose?

Answer 5

• Do not impair cardiac conduction significantly.
  
  • Lack affinity for muscarinic receptors, α₁- adrenoceptors, and H₁-receptors.
• SSRIs have higher therapeutic indices than TCAs and are therefore safer and easier to prescribe.
• SSRIs are much safer than TCAs in overdose.

Question 6

How long is the lag period before antidepressants ‘kick in’?

Answer 6

2-4 weeks.

Question 7

1. What are some of the side effects of SSRIs?
2. What are these side effects due to?

Answer 7

1.

• Gastrointestinal:
  
  • Nausea, anorexia, diarrhoea.
• CNS
  
  • Insomnia, anxiety, irritability, restlessness, tremor, headache, fatigue.
• Sexual
  
  • Decreased libido, delayed orgasm, anorgasmia.
• Other
  
  • Weight gain, fever, sweating, bleeding.
  • Increased suicidal ideation may occur in some patients (such as young adults) at the start of treatment.

2.

• Overstimulation of some 5-HT receptors.

Question 8

What is the action of TCAs on monoamine transporters?

Answer 8

• TCAs are reversible negative allosteric modulators of NA & 5-HT transporters on axon terminals
• Prevent NA and Serotonin reuptake (immediately)
• Delayed increase in:
  
  • transcription factor CREB (cAMP response element binding protein)
  • BDNF (brain derived neurotrophic factor)

Question 9

What is the mechanism of serotonin & noradrenaline reuptake inhibitors (SNRIs) such as venlafaxine?

Answer 9

SNRIs = reversible, negative allosteric modulation of the 5-HT transporter (SERT) & NA transporter (NET) on axon nerve terminals and dendrites