Antidepressants

What is the first line of treatment for depression?

SSRIs

What is the MOA of SSRIs?

Allosterically binds and inhibits SERT receptor → inhibits reuptake of serotonin

Why does it take 4-6 weeks to see effects of SSRIs?

It takes 4-6 weeks for BDNF to be up-regulated and synaptic remodeling to occur

What are the most common side effects of SSRIs?

-Sexual dysfunction

-Weight gain

-GI complaints

How can you mitigate the GI side effects of SSRIs?

Take medication with food

Which SSRI is best used for the treatment of OCD?

Fluvoxamine

Which medication is absolutely contraindicated with SSRIs?

MAOIs

Which class of antidepressants have the highest risk of serotonin syndrome?

MAOIs

Which is the most activating SSRI?

Fluoxetine (Prozac)

Which SSRI is the least activating?

Paroxetine

Why does Paroxetine cause significantly worse sexual dysfunction?

Inhibits nitric oxide (NO) synthase

Which SSRI has the highest risk of EPS effects?

Paroxetine

Which SSRI has the highest affinity for 5-HT receptors:?

Paroxetine

When would you start a patient on Paroxetine?

Only if the patient had a previous good response

Why is constipation a side effect seen with Paroxetine?

Has anticholinergic effects (blocks M1 receptors)

What are the major side effects of Paroxetine?

-Weight gain

-Constipation

-Sexual dysfunction

What type of patients should you avoid the use of Fluoxetine in?

Patients with agitation, insomnia or anxiety

What are the MOAs of Fluoxetine that cause its activating properties?

5-HT-2C antagonism → increases NE and dopamine

What is good about Escitalopram's formulation?

Removes the unwanted R enantiomer

What is considered the best tolerated SSRI?

Escitalopram

What is bad about Citalopram's formulation?

Contains both R and S enantiomers

What side effects are commonly associated with the S enantiomer of SSRIs?

-Sedation

-Weight gain

Which SSRI is good for treating atypical depression?

Sertraline

Which drug is a SPARI?

Vilazodone

What is the MOA of Vilazodone?

Combined SERT inhibitor with 5-HT1A partial agonist → causes an increase release of serotonin on downstream post-synaptic receptor

What about Vilazodone's MOA causes an immediate increase in serotonin when compared to SSRIs?

5HT-1A partial agonism

What are the SNRIs?

-Duloxetine

-Desvenlafaxine

-Venlafaxine

-Milnacipran

-Levomilnacipran

What is the MOA of SNRIs?

Binds both 5-HT and NE reuptake transporters

What are some common side effects seen with SNRIs?

-Hypertension

-Tachycardia

-Insomnia

-Anxiety

-Agitation

Dose-related hypertension is seen with which SNRI?

Venlafaxine

What type of patients are good candidates for SNRIs?

Patients with depression and concomitant neuropathic pain

Which is the best SNRI?

Duloxetine

What are the TCAs?

-Amitriptyline

-Clomipramine

-Desipramine

-Doxepin

-Impramine

-Nortriptyline

What is the MOA of TCAs?

-Inhibits 5-HT and NE reuptake

-H1 antagonist

-Alpha adrenoreceptor antagonist

What are the most common side effects seen with TCAs?

-Dry mouth

-constipation

-Sedation

-Weight gain

-Orthostatic hypotension

-Cardiac arrhythmias

What type of patients should you avoid the use of TCAs in?

Elderly and people with overdose risk

Which TCA is best used in the treatment of OCD?

Clomipramine

What is the anticholinergic toxidrome?

-Fever ("hot") due to ↓ sweating

-Dry skin/mucosa due to ↓ secretions

-Mydriasis/blurry vision due to pupil dilation + cycloplegia

-Flushed skin due to vasodilation

-Delirium/agitation

What are the common findings of a TCA overdose?

-Widened QRS

-Seizures

-Hypotension

-Anticholinergic toxidrome

What is the treatment for a TCA overdose?

-Sodium bicarbonate for ECG abnormalities

-Vasopressors for hypotension

-Benzodiazepines for seizures

What are the MAOIs?

-Isocarboxazid

-Phenelzine

-Selegiline

-Tranylcypromine

What is the MOA of MAOIs?

Mitigates the action of monoamine oxidase in the neurons

What are the most common side effects of MAOIs?

-Orthostatic hypotension

-Weight gain

-SEVERE sexual dysfunction

-Insomnia

Which antidepressant is best for patients with insomnia and concomitant anorexia?

Mirtazapine

What is the MOA of Trazedone?

-H1 receptor antagonist

-Weak selective inhibitor of SERT

-5-HT2A antagonist

What condition does Trazedone best treat?

Insomnia

What is the MOA of Bupropion?

Increases the presynaptic release of NE and dopmaine and inhibits the reuptake

What is the pro of Bupropion?

No sexual dysfunction or weight gain

In what patients is Bupropion absolutely contraindicated?

History of seizures or anorexics

What is a major benefit with Ketamine treatment for MDD?

Results are seen immediately

Which SSRI has the longest half life?

Fluoxetine