15 - Antidepressants Flashcards
What are some symptoms of depression
1) Abnormal CV function
2) Sexual dysfunction
3) Changes in brain morphology
4) Functional GI disturbances
What occurs to monoamine transport in depression
Decreased concentration of monoamine at synaptic sites produces mood disorder
Antidepressant MOA
Augment synaptic monoamine levels straight away
Downstream effects on receptor expression after weeks (likely underpinning long-term effects on symptoms)
What do all currently approved antidepressants target
Monoamine system in the brain (dopamine, noradrenaline and serotonin)
How do tri-cyclic antidepressants and SSRIs work
Inhibition of transporter enzymes at the synaptic cleft
How do MAO inhibitors work
Block the metabolism of serotonin
What are some unwanted side-effects of SSRIs (4)
Nausea
Fatigue
Reduced libido
Insomnia
What is the therapeutic window needed before a reduction in symptoms is observed
4-6 weeks
How are antidepressants used
Start with lowest dose and gradually increase
Abrupt cessation can lead to withdrawal
What is the suicide risk with antidepressants
Studies show increased suicide risk in persons taking antidepressants
Suicide by overdose may be attempted
What are the effects of antidepressants in non-depressed individuals
No euphoria
No effects in non-depressed individuals
Not likely to cause dependence
What are the effects of antidepressants in depressed individuals
Elevate mood
Increased physical activity
Improved appetite and sleep patterns
Reduce morbid preoccupation
MOA of monoamine reuptake inhibitors
Block presynaptic NA and/or 5-HT transporters
Increase levels of NA & 5-HT in the synapse
Block mACh, 5-HT and a-adrenoceptors
Where do SSRIs work
SERT
Little action on mACh and histamine receptors
MOA of MAOI
1) Inhibit breakdown of NA, 5-HT (& DA)
2) Increase cytoplasmic pool of monoamines
3) Increase leakage of monoamines into synapse/extracellular space
What is the MOA of tetracyclics
1) Block a2 adrenoceptors
2) Increased NA & 5-HT release
3) Preferred action on 5-HT1 as 5-HT2 and 5-HT3 are blocked
What occurs to neuronal circuits in depression
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
