An introduction to the psychopharmacology of mood disorders Flashcards
What is the function of a modulatory neuron?
Changes the effects of other neurotransmitters or second messenger systems
How do mood disorder drugs act?
Altering brain function:
- change neurotransmitter function
- mimic neurotransmitters (agonist)
- block receptors (antagonist)
What are agonist drugs?
Drugs that mimic neurotransmitters
What are antagonist drugs?
Which block receptors
What is the main excitatory neurotransmitter?
Glutamate
What is the main inhibitory neurotransmitter?
GABA
What are the monoamine neurotransmitters?
- Dopamine
- Serotonin (5-HT)
- Noradrenaline
What are the targets of monoamine drugs in mood disorders?
> Serotonin system
- SSRI and SNRI antidepressants
- second generation antipsychotics -> 5HT receptor actions
> Dopamine system
- second generation antipsychotics - D2 and D3 blockade
> Noradrenaline system
- SNRIs (Venlafaxine, Duloxetine)
What is the target of Ketamine and its action?
- Targets glutamate system
- Blocks NMDA Glu receptor
- Shows promising efficacy in improving mood in patients with depression
What is the target of benzodiazepines and valproate?
GABA system
What is the target of the mood stabilisers lithium, valproate and carbamazepine?
Second messenger systems
What are the main discoveries in the history of the psychopharmacology of mood disorders?
> 1940s: Electroconvulsive therapy
> 1950s: lithium
> 1960s: First generation antidepressants: MAOIs, MARIs
> 1980s: Anticonvulsants (Carbamazepine, Lamotrigine, Valproate)
> 1990s: Second generation anti-depressants
> 2000s: Next-generation antipsychotics (Quetiapine, Olanzapine, Clozapine, Asenapine, Aripiprazole)
Why is serotonin of interest in mood disorders?
> Lowering serotonin levels -> induces depression
> Increasing serotonin levels -> can produce manic symptoms
> SSRI antidepressants and atypical antipsychotics all work in part by changing serotonin systems in brain
How does a normal serotonin system function?
> 5hT cell bodies are located in the caudal raphe nuclei (midbrain)
> Serotonin pathways have projections to the limbic system and subgenual cingulate
What are the important serotonin receptors related to mood disorders?
- 5-HT 2
- 5-HT 1A
What is the action of selective serotonin re-uptake inhibitors (SSRIs) in the synapse?
Inhibit action of 5-HT re-uptake transporter
-> increases synaptic serotonin levels
What are the 5 types of SSRI antidepressants and their usual dosage?
> Citalopram (Cipramil): 20-40mg/day
> Escitalopram: 10-20mg/day
> Sertraline: 50-200mg/day
> Paroxetine: 20-50mg/day
> Fluoxetine (Prozac): 20-60mg/day
What is the action of serotonin-noradrenaline reuptake inhibitors (SNRIs) in the synapse?
Inhibit action of 5-HT re-uptake transporter AND noradrenaline re-uptake transporter
-> increase serotonin and noradrenaline synaptic levels
What are the three types of SNRI antidepressants and their usual dosage?
> Venlafaxine (Effexor): 75-375mg/day
> Duloxetine (Cymbalta): 60mg/day
- may increase dopamine levels in PFC
> Vortioxetine (Brintelix): 10-20mg/day
How may the SNRI antidepressant Vortioxetine (Brintellix) improve cognitive impairment?
- Blocks 5HT2, 5HT7 receptors
- Stimulates 5HT1A receptor
- > may improve cognitive impairment through 5HT7 blockade
Why is dopamine relevant to mood disorders?
> Increasing synaptic dopamine levels can produce effect similar to mania
> Reducing synaptic dopamine levels improves manic symptoms but worsens depression
What is the role of dopamine antagonist antipsychotics?
- Main treatment for mania
- Used as mood stabilisers
What is the role of dopamine in mania?
Mania is a result of increases in dopamine system
- particularly in nigrostriatal and limbic systems
What is the action of dopamine antagonists in the mesolimbic pathway?
- Lowers psychotic symptoms
- Lowers manic symptoms