Antidepressants Pharmacology - Krouse PART 2

Mirtazapine points

Atypical antidepressant

• Alpha-2antagonist

• Inhibits Alpha-2 antagonist at 5HT2A, 5HT3 on post synaptic neuron

• Increase Serotonin and NE

• off target of Antihistamine

UNIQUE ADVERSE EFFECTS:

• Sedation and weight gain

ALSO:

• off label for insomnia

• 20-40 hr ½ life

When would we consider Mirtazapine for a patient?

In patients who are depressed with difficulty falling asleep and have significant weight loss!

this medication helps with weight gain and sedation! it also helps with patients who have had Nause and vomiting from SSRIs!!!

Vilazadone points

Atypical Antidepressant

• Depression indication - yes

• works on SERT and 5HT1a PARTIAL agonist

• 25hr ½ life

• SE’s: Diarrhea, N/V, insomnia, dizziness

Vortioxetine points

Atypical Antidepressant

• Depression indication - yes

• works on SERT // 5HT1a PARTIAL agonist // 5HT3 antagonist

• 66 hr ½ life

• SE’s: Constipation, N/V, insomnia, dizziness

easy way to remember Vilazadone’s MOA

“Poor Mans Viibryd”

A +B = C

Escitalopram + Buspirone = Vilazadone!!!

• think that the combination of their effects

trazadone points

Atypical antidepressant

• Serotonin antagonist and reuptake inhibitor (SARI)

• Primary use is for insomnia (off label)

• No longer used in depression because:

  • Tolerability of higher doses needed to treat depression

  • Required multiple daily dosing for MDD

Gepirone points

Atypical antidepressant

• Newer gen

• Depression - yes

• too new for any other uses

• 5HT1A agonist

• Denied approval multiple times

• Unique adverse effects:

  • Qtc prolongation

• CONTRAINDICATIONS

  • QTc > 450 sec at baseline, congenital lon QT syndrome, severe hepatic impairment, POTENT CYP3A4 inhibitors

Points about Serotonin withdrawal

• More common with short t ½ antidepressants such as —— Fluvoxamine, paroxetine, venlafaxine, desvenlafaxine

• Symptoms:

  • Flu-like

  • Dizziness vertigo

  • Paresthesia, numbness, BRAIN ZAPS

  • Anxiety, agitation, mood, tremor, HA, lethargy etc

Bupropion points

Atypical antidepressant

• used for MDD

• Targets DAT and NET

• no serotonin effects!

• also used for smoking cessation

• Substrate - CYP2B6

• Inhibits CYP2D6

• AEs: tremor anxiety

DO NOT USE IN:

• eating disorders, anorexia, Bulimia, seizures, alcohol or benzodiazepines withdrawal

Auvelity points (Bupropion and DXM)

Atypical antidepressant:

• DXM - NMDA antagonist, sigma 1 agonist and serotonergic (SNRI??)

• Bupropion - DNRI with CYP2D6 inhibitor properties that increase DXM concentrations

• Risk of seizures same as Bupropion - concerns ro abuse

• Dizziness, N/V, HA, constipation, sedation Dry mouth etc

• Potentially used as quicker onset of action as early as week 1 with higher rates of response and remission at week 6

Esketmaine points

Atypical antidepressant

• Used for treatment resistant depression as monotherapy or with another antidepressant

• Intranasal admin

• Requires 2 hours of post admin monitoring

• Unique adverse effects:

  • disassociation, sedation, respiratory depression, misuse/abuse

• NOT TO BE USED IN:

  • aneurysmal vascular disorder OR intracerebral hemorrhage

What happens when blocking MAO-B?

• MAO B found in brain and platelets

• Catabolizes DA thus increases level of DA

MAOIs points

Phenelzine

• Depression- Yes

• Oral dosage

• atypical or neurotic depression

• Metabolized via oxidation

Tranylcypromine

• Depression - yes

• oral

Selgiline

• Depression - yes

• TRANSDERMAL —- avoids first pass metabolism in liver - NO NEED TO AVOID TYRAMINE IF USING PATCH!

RARELY PRESCRIBED for depression - only for treatment resistant

• too many DDIs

  • Serotonin toxicity and hypertensive crisis

  • tyramine interaction

What class of antidepressants target ALL THREE Neurotransmitters?

MAOIs !!!!

Aripiprazole points

Antipsychotic drug!!! Dopamine modulator

• has depression indication - augmenting (in addition to) antidepressants in MDD

• Also used for schizophrenia, Bipolar, mania, Tourettes, etc

• 70 hr ½ life

• Unique adverse effects

  • pathological gambling and impulse control behaviors, akathisia

• D2 partial agonist + 5Ht1a agonist + 5HT2A antagonist

Quetiapine points

Atypical 2nd gen antipsychotic

• Not an antidepressant —- only XR is FDA approved for depression AUGMENTATION

• Also used for schizophrenia, bipolar, etc

• 7 hour half life

• increases serotonin in depression augmentation

• weka D2 antagonist + 5HT2A antagonist