HubBytes: Mechanism of Action and Psychopharmacology of Mirtazapine

Presented by: Sunil Regge, Consultant Psychiatrist

5-HT2A receptor antagonism:
- Located in limbic system, reticular activating system, and basal ganglia.
- Effects: Anti-anxiety, anti-akathisia, does not lead to emotional blunting, releases dopamine in frontal and subcortical areas.
- Promotes slow-wave sleep (similar to agomelatine).
5-HT2C receptor antagonism:
- Responsible for sexual function.
- Used for sexual dysfunction related to SSRIs/SNRIs.
5-HT3 receptor antagonism:
- Located in the gut and nausea/vomiting center in the hypothalamus.
- Provides anti-nausea properties.
- Effective at 15-30 mg doses.

Alpha-2 presynaptic antagonism:
- Releases norepinephrine in the prefrontal cortex and serotonin from serotonergic neurons.
- Can cause serotonin syndrome but less so than SSRIs/SNRIs.

5-HT1A receptor agonism:
- Increases dopamine in prefrontal cortex.
- Effective at higher doses.

Low Dose (7.5-15 mg):
- Treats insomnia, anxiety, has mild antidepressant effect.
- Useful in cancer patients for sedation and anti-nausea.
High Dose (30-60 mg):
- Treats more severe forms of depression (melancholic depression).
- Starts with 15 mg at bedtime and increases by 15 mg weekly.
- Watch for mixed states, bipolarity to avoid side effects like activation, agitation, akathisia, insomnia.
Augmentation:
- Can be combined with SSRIs, SNRIs, vortioxetine, agomelatine, psychostimulants like armodafinil, dexamphetamine, methylphenidate.

Common: Sedation, weight gain (antihistaminergic effect).
Higher doses: Constipation, dry mouth, noradrenergic and dopaminergic associated side effects.

Mirtazapine is a novel, dual-action antidepressant.
Effective for anxiety, akathisia, sleep disorders, sexual dysfunction, anti-nausea.
Versatile in augmentation strategies for severe depression.

Stay safe and see you in another edition of HubBytes.