Depression

SSRI’s =?

Selective Serotonin reuptake inhibitors

SNRI’s =?

Serotonin norepinephrine reuptake inhibitors

TCA’s =?

Tricyclic antidepressants

MAOI’s =?

Monoamine oxidase inhibitors

NDRI’s =?

Norepinephrine and dopamine reuptake inhibitor

NaSSA’s =?

Serotonin antagonists and reuptake inhibitors

5HT1A =?

Serotonin 1A agonists

NMDA’s =?

N-methyl-D-aspartate antagonists

The other 2 depression drug class without abbreviations.

Serotonin modulators and Neuroactive steroids

What is the adverse effects for ALL antidepressants?

Increased suicidal thoughts/behavior, mania, and discontinuation syndrome

The adverse effect of discontinuation syndrome is most common in which agents?

agents that affect serotonin specifically SNRIs and SSRIs

List the SSRI drugs.

Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

What is the MOA for SSRI’s?

They block the reabsorption of serotonin in the presynaptic nerve ending

For SSRI’s what are the transient adverse effects?

N/V/D, anxiety, headaches, sleep disturbances

For SSRI’s what are the persistent adverse effects?

Hyponatremia, Bleeding risk, sexual dysfunction, weight gain, serotonin syndrome

List the SNRI drugs.

Desvenlafaxine, duloxetine, venlafaxine, levomilnacipran

What is SNRI’s MOA?

They inhibit the reuptake of serotonin and norepinephrine by blocking their transporters (SERT and NET) in the presynaptic membrane

What are the adverse effects of SNRI’s?

Same as SSRI’s plus increased BP/HR and Diaphoresis

SNRI’s and TCA’s improve depression. What else can they improve?

Neuropathic pain

List the TCA drugs.

Amitriptyline, desipramine, doxepin, imipramine, nortriptyline

What is the MOA for TCA drugs?

They block the serotonin/NE reuptake transporters and the histamine/muscarinic acetyl-CoA receptors

What are the ADRs for TCA drugs?

Anticholinergic effects, arrthythmia, heart block, orthostatic hypotension, weight gain, dosed related seizure activity, hyponatremia

With TCA’s which ADR is potentially toxic in overdose situations?

cardiac arrhythmias

List the MAOI drugs.

Isocarboxazid, Phenelzine, Tranylcypromine, Selegiline

What is the MOA for MAOI’s?

They inhibit monoamine oxidase (MAO-A/B) which blocks the break down of serotonin, NE, and dopamine

Non-selective MAOI blocks what?

MAO-A and B; Serotonin, NE, and dopamine

Selective MAOI blocks what?

MAO-B; dopamine

What are the ADRs for MAOI’s?

Postural hypotension, hypertensive crisis in DDI or tyramine foods, tachycardia, sedation, insomnia, weight gain, sexual dysfuntion, and anticholinergic effects

List the drugs for NDRI’s?

Bupropion

What is the MOA for NDRI drugs?

It inhibits the reuptake of NE and dopamine by blocking their transporters (NET and DAT) in the presynaptic neuron.

What are the ADRs for NDRI’s?

Increased risk of seizures, weight loss, N/V, insomnia, tremor, dry mouth, mild BP increases, anxiety

What is buproprion contraindicated with? Why?

Eating disorders, seizure disorders, and patients undergoing abrupt discontinuation of alcohol and antiepileptics

List the NASSA drugs.

Mirtazapine

What is mirtazapines MOA? What additional blocking does it do?

It blocks presynaptic α2-adrenergic receptors which increases NE and serotonin release; also blocks 5-HT2, 5-HT3, and H1 receptors which reduces N/V and certain serotonergic side effects

List the mirtazapines ADRs.

Sedation, weight gain, hypertriglyceridemia

List the SARI drugs.

Nefazodone, Trazodone

What is the MOA for SARI’s?

Blocks 5-HT2A and 5-HT2C receptors while activating 5-HT1A receptors; also inhibits serotonin reuptake.

List the ADRs for SARI’s.

Orthostatic hypotension, liver toxicity, cognititve slowing, dizziness

Which SARI drug has a Black Box Warning (BBW) for hepatotoxicity?

Nefazodone

What specific side effect can Trazodone cause?

Priapism

List the Serotonin Modulator drugs.

Vortioxetine and Vilazodone

What is the MOA for Serotonin Modulators?

Inhibits serotonin reuptake and directly modulates serotonin receptors to enhance serotonergic activity.

What are the ADRs for Serotonin Modulators?

Serotonin syndrome, nausea, dizziness, insomnia, decreased libido, bleeding risk, hyponatremia

List the Serotonin Agonist 5HT1A drug.

Gepirone

What is Gepirone’s MOA?

It modulates serotonin neurotransmission in the post/presynaptic neuron to produce antidepressant effects.

What are the ADRs for Gepirone?

QTC prolongation, dizziness, nausea, drowsiness, insomnia, headache

List the NMDA drugs.

Esketamine, Ketamine, Dextromethorphan/bupropion

What is the MOA for NMDA drugs?

They block NMDA receptors which decrease glutamate-mediated signaling while promoting synaptic plasticity and producing antidepressant effects.

What are the ADRs for NMDA drugs?

Dissociation, sedation, N/V, brief psychosis, elevations in BP, cognitive and motor impairment

List the Neural Steroid drugs.

Zuranolone, Brexanolone

What is the MOA for Neural Steroids?

Positive allosteric modulation of GABA-A receptors that increases inhibitory neurotransmission which decreases neuronal excitability.

What are the ADRs for Neural Steroid drugs?

Headache, dizziness, somnolence, risk of abuse/dependence

Brexanolone has a BBW and a mandatory REM program for a certain side effect. What is it? What do we monitor?

Excess sedation of loss of consciousness, monitor for hypoxia

Zuranolone has a BBW. What is it for?

Impaired ability to drive or engage in other hazardous activity

There are alot of DDI with MAOI’s. Which drugs cause an increase in norepinephrine resulting in a higher risk of a hypertensive crisis?

Decongestants, Stimulants, Sympathomimetics, SNRIs, TCAs, bupropion, atomoxetine, phentermine

There are a lot of DDI with MAOI’s. Which drugs cause an increase in serotonin resulting in a higher risk of serotonin syndrome?

Antidepressants, dextromethorphan, opioids, antihistamines

What ingredient in food causes DDI’s with MAOI’s? Give a few examples.

Tyramine; aged cheeses, chicken liver, fermented food, red wine, tap beer

What exactly does Tyramine do to MAOI’s?

It can cause dangerous elevations of BP due to it increasing the release of NE and the MAOI stopping the breakdown of NE resulting in vasoconstriction and hypertension