15 - Antidepressants

Question 1

What are some symptoms of depression

Answer 1

1) Abnormal CV function
2) Sexual dysfunction
3) Changes in brain morphology
4) Functional GI disturbances

Question 2

What occurs to monoamine transport in depression

Answer 2

Decreased concentration of monoamine at synaptic sites produces mood disorder

Question 3

Antidepressant MOA

Answer 3

Augment synaptic monoamine levels straight away

Downstream effects on receptor expression after weeks (likely underpinning long-term effects on symptoms)

Question 4

What do all currently approved antidepressants target

Answer 4

Monoamine system in the brain (dopamine, noradrenaline and serotonin)

Question 5

How do tri-cyclic antidepressants and SSRIs work

Answer 5

Inhibition of transporter enzymes at the synaptic cleft

Question 6

How do MAO inhibitors work

Answer 6

Block the metabolism of serotonin

Question 7

What are some unwanted side-effects of SSRIs (4)

Answer 7

Nausea
Fatigue
Reduced libido
Insomnia

Question 8

What is the therapeutic window needed before a reduction in symptoms is observed

Answer 8

4-6 weeks

Question 9

How are antidepressants used

Answer 9

Start with lowest dose and gradually increase

Abrupt cessation can lead to withdrawal

Question 10

What is the suicide risk with antidepressants

Answer 10

Studies show increased suicide risk in persons taking antidepressants
Suicide by overdose may be attempted

Question 11

What are the effects of antidepressants in non-depressed individuals

Answer 11

No euphoria
No effects in non-depressed individuals
Not likely to cause dependence

Question 12

What are the effects of antidepressants in depressed individuals

Answer 12

Elevate mood
Increased physical activity
Improved appetite and sleep patterns
Reduce morbid preoccupation

Question 13

MOA of monoamine reuptake inhibitors

Answer 13

Block presynaptic NA and/or 5-HT transporters
Increase levels of NA & 5-HT in the synapse
Block mACh, 5-HT and a-adrenoceptors

Question 14

Where do SSRIs work

Answer 14

SERT

Little action on mACh and histamine receptors

Question 15

MOA of MAOI

Answer 15

1) Inhibit breakdown of NA, 5-HT (& DA)
2) Increase cytoplasmic pool of monoamines
3) Increase leakage of monoamines into synapse/extracellular space

Question 16

What is the MOA of tetracyclics

Answer 16

1) Block a2 adrenoceptors
2) Increased NA & 5-HT release
3) Preferred action on 5-HT1 as 5-HT2 and 5-HT3 are blocked

Question 17

What occurs to neuronal circuits in depression

Answer 17

1) Information is processed in partially overlapping neural networks in healthy brain
2) In depression, information processing in some networks does not function properly
3) Antidepressant treatment enhances connectivity in neural networks
4) Activity-dependent pruning of synapses selects out and stabilises the active synapses and networks