PSYC 02: MDD Pharmacology

Why don’t SSRIs work instantly (why do they take weeks to have effect)

A sudden influx of serotonin ends up making the autoreceptors OVERSTIMULATED, so they stop firing serotonin

—> Effect doesn’t take place until the receptors “chill out” and downregulate and start shooting again

1) SSRI side effects (6)

2) SSRI Drug-Drug interactions (2) [Not including obvious ones like antipsychotics/antidepressants)

3) One important caveat to remember

1) SIDE EFFECTS:

• Sympathetic (fight/flight)

• Nausea

• Dry mouth

• Headache

• Insomnia/Somnolence

• Sexual dysfunction

2) DDI:

• Tramadol (opioid + SNRI)

• Triptans (migraine medications)

3) Interaction w/ antiplatelets / anticoagulants

• Serotonin is involved with platelet activation

• INCREASE BLEEDING RISK

SNRI: Do the following inhibit 5HT more or NE more

Venlafaxine

Levomilacipran

Venlafaxine = 5HT

Levomilnacipran = NE

SNRIs:

Other than the side effects associated with SSRIs, whats something big that SNRIs have (2 things that are connected)

Activation syndrome

• LOTS OF fight/flight

  • Restlessness

  • Anxiety

  • Agitation

AND

• Noradrenergic effects of:

  • INCREASE BP

  • INCREASE HR

  • SWEATING

Bupropion Norepinephrine/Dopamine Reuptake Inhibitors

1) Use as adjunct therapy for who (3)

2) Allows for prolonged activity of NE and DA where

3) At low doses, does it block more NE or DA reuptake

4) At high doses, does it block more NE or DA reuptake

5) Therapy is contraindicated in what patients / monitor lots (2)

1) Sexual dysfunction w/ SSRIs, smoking cessation , weight loss

2) Synaptic cleft

3) Low = dopamine

4) High = Norepinephrine

5) Eating disorders (weight loss) seizures (decreases threshold)

Which medication is contraindicated in eating disorders

Bupropion (ED weight loss)

Which medication needs to be carefully monitored / not ideal for seizures

Bupropion (seizure)

Mirtazapine (NASSAs) HAs a burger (MEALtazapine)

1) What 3 receptors does this antagonize (be specific: don’t just list the neurotransmitterd)

2) Who should use this (good option for ppl who experience what common side effect) is it better to switch or augment with this medication

3) Whats an important caveat (side effect)

4) Does it have more Alpha-2 blockage or H1 blockage activity at LOW DOSES

5) At what dose (low or high) is it sedating

6) What does it do to eating / weight

1) The receptors:

1. Alpha-2 (blocking this increases NE)

2. Histamine-1 (weight gain, sedation)

3. 5-HT2A (selectively) (decrease anxiety, lets 5HT bind to 1A instead, increasing serotonin)

2) Ppl who experience sexual dysfunction (switch to this rather than augment)

3) SEDATION/hypnotic side effects

4) Histamine blocking at lower doses

5) Sedating at lower doses (due to more histamine blockage)

6) Increases appetite , therefore weight gain

Trazodone: SARI Serotonin Antagonist/Reuptake Inhibitors

1) What 2 receptors does it antagonize

2) Whats the other MOA

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Vilazodone: SPARI Serotonin 1A Agonist / Serotonin Reuptake Inhibitor

3) What are the two main MOA

4) Why is it not considered an SSRI

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5) SIDE EFFECTS FOR BOTH (Trazodone + Vilazodone)

1) 5HT-2A receptor (anxiolytic) Antagonist + Histamine antagonist

2) 5HT reuptake inhibitor

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3) 5HT1a AGONISM + SSRI

4) Because it partially agonizes other serotonin receptors (not selective)

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5) Histamine blocking effects… AND

• Orthostatic HYPOtension

• Priapism

TCAs:

1) Which receptor does nortriptyline affect the most

2) Which receptor does amitriptyline affect the most

3) What type of “receptor” side effects most present

1) NE

2) Serotonin 5HT

3) Anticholinergic + Antihistamine

• Dry mouth

• Constipation

• Blurred vision

• Urinary retention

• Dizziness

• Tachcardia

• Weight Gain

• Sedation

MAOI

1) Caveat to remember (DDI with what and why)

2) Which drugs are NOT selective for MAO-A or B

3) Which drugs are selective for MAO-B inhibitor

4) MAO-A substrate

5) MAO-B substrate

1) DDI: Tyramine (Hypertensive crisis; can’t metabolize it)

2) MAO-A/B = Phenelzine & Tranylcypromine

3) MAO-B = selegiline + rasagiline

4) Serotonin + norepinephrine

5) Dopamine

Moclobemide (RIMA) Monoamine Oxidase Inhibitor Reversible

1) When would you ever use this

2) Selectively inhibits what (which MAO)

3) Inhibiting that ^ leads to increased levels of what

4) How long does MAO inhibition last for before it can start breaking down neurotransmitters again

5) What lifestage is this good for and why

1) Ppl who can’t tolerate SSRI/SNRI

2) MAO-A (which metabolizes 5HT + NE)

3) Increase in NE and 5HT

4) ~24 hours

5) Elderly; less anticholinergic effects

What’s good for depression + pain (neuropathy, fibromyalgia)

SNRIs

Which SSRI has rapid absorption, therefore more side effects at the start and more severe withdrawal

Paroxetine

What’s something to keep in mind for sertraline

SQUIRTraline

• GI effects

• Diarrhea

• Nausea

**Take with meals

Which antidepressant needs to be monitored for QTc prolongation

Escitalopram/Citalopram

What’s good for depression + pain (MIGRAINE / NEUROPATHIC)

Tricyclic Antidepressants (amitriptyline, etc)

If someone is super skinny / no appetite and would benefit from gaining weight, which antidepressant should you use

Mirtazapine

SSRI MOA: Inhibits reuptake by ____ to the ____ ____ of SERT

Inhibits reuptake by binding to the CENTRAL CAVITY of SERT