Antidepressants 1&2

Neurotransmitter transported to the post synapse

Vesicular Monoamine Transporter (VMAT)

____ theory of depression to reverse symptoms by replenishing 5-HT and/or NE

Monoamine

What are the Nonselective, Irreversible MAO inhibitors

Iproniazid

Isocarboxacid

What are the Specific, Reversible MAO-A inhibitors

Befloxatone

Brofaromine

What are the Specific, Reversible MAO-B inhibitors

Selegiline

Which antidepressant is the last line therapy for depression

MAO inhibitors

MAO inhibitors can cause what type of toxicity due to lack of metabolization from the GI and Liver

Tyramine

What compound is found in processed meats, aged hard cheeses, and red wine

Tyramine

Accumulated Tyramine results in uncontrolled NE released which can induce what adverse effect

Hypertensive Crisis

Which reversible MAO inhibitor product reduces the risk of Tyramine-induced Hypertensive Crisis

Selegiline Transdermal Patch

What is the ADE warning for Selegiline

Suicidal thoughts and behaviors

Selegiline is contraindicated in which patient populations

Children < 12

T/F: MAO inhibitors should NOT be used with other antidepressants

True

MAO inhibitors inhibit which CYP enzymes

CYP450

Use for TCAs Reuptake inhibitors

Mod-Severe Depression

Panic disorders

Pain (low doses)

Migraines

List of Tricyclic Antidepressants (TCAs) with Tertiary amines that affects 5-HT systems

Imipramine

Amitriptyline

Clomipramine

List of Tricyclic Antidepressants (TCAs) with Secondary amines that affects NE systems

Desipramine

Nortriptyline

What is the onset duration for TCAs reuptake inhibitors

2 weeks +

TCAs reuptake inhibitors block which receptors

Alpha-Adrenergic

Histaminic

Muscarinic

ADEs of TCAs reuptake inhibitors

Life threatening arrhythmias (conduct ECG examination)

Blocks Sodium channels

Orthostatic hypotension

Drowsiness / Dizziness

Sedation

What ADE occurs if TCAs were combined with other Central Depressants (ethanol, barbiturates, benzodiazepines, opioids)

Toxic Sedation

What line of therapy are TCAs

Second line

Which specific TCA can be used for Neuropathic Pain

Amitriptyline (brand: Elavil)

List of SSRIs

Fluoxetine (Prozac)

Citalopram (Celexa)

Fluvoxamine (Luvox)

Paroxetine (Paxil)

Sertraline (Zoloft)

Escitalopram (Lexapro)

What is the MOA of Serotonin Reuptake Inhibitors (SSRIs)

Inhibits 5-HT reuptake transports to increase 5-HT levels in the extracellular space

Which receptors do SSRIs block but does not bind to?

Muscarinic

Alpha-adrenergic

Histamine H1

Which line of treatment are SSRIs for Depression and Anxiety Disorder

First Line

What is the onset time of SSRIs

2 weeks +

T/F: Between Antidepressants, SSRIs have few side effects, relatively safer outcomes in high/over doses, and does not produce CNS stimulus or mood elevations

True

Which CYP450 isoenzyme does SSRI inhibit and are substrates for?

CYP2D6 (require dose adjustments in poor metabolizers)

Serotonin Transporter Gene: SLC6A4 is a polymorphism that significantly lowers the effect of which Antidepressant?

SSRIs

T/F: SSRIs can be taken with MAO inhibitors

False; highly dangerous interaction

What are the ADE of SSRIs

GI distress

Sexual Dysfunction

Insomnia

Diarrhea (Sertraline)

Constipation (Paroxetine)

Serotonin Syndrome (rare)

Rare but dangerous elevation of 5-HT levels that can occur when both an SSRI and MAOI/SNRI are administered concurrently

Serotonin Syndrome

Symptoms of Serotonin Syndrome

Hyperthermia

Muscle Rigidity

Myoclonus

Rapid fluctuations in mental status

SSRIs can cause a “switch” from depression to mania or hypomania in which patient population

Bipolar Disorder

Which specific SSRIs have an ADE of QTx prolongation at higher dosing

Citalopram

Escitalopram

Citalopram And Escitalopram (SSRIs) should not be paired with which medications due to their CYP2C19 inhibition

PPIs

Anti-Psychotics

Anti-Epileptics

List the FIRST line SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

Venlafaxine

Desvenlafaxine

Duloxetine

List the SECOND line SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

Milnacipran

Levomilnacipran

What are the clinical use for SNRIs

Major depressive disorder

Patients that do not respond to SSRIs

Which SNRIs is approved for Depression and Pain (Fibromyalgia, Back pain, and Neuropathic pain associated with Diabetes)

Duloxetine (Cymbalta)

What CYP450 isoenzyme does Duloxetine (SNRI) inhibits

CYP2D6

Which Second line SNRI is used for Depression and Fibromyalgia

Milnacipran

Which Second line SNRI is metabolized by CYP2D6 in the liver, not recommended for hepatic insufficiency and end stage renal disease

Levomilnacipran

SNRIs adverse effects

Nausea

Loss of apeptite

Sleep problems

Weight loss

Hypertension (high dose)

Cross human placenta

Suicidal thoughts

What are possible symptoms if SNRIs are taken with MAOI or SSRIs

Hyperthermia

Neuroleptic malignant syndrome

Seizures

Death

Which first line SNRI can be used for ADHD in pediatric patients

Venlafaxine

List of Atypical Antidepressants

Nefazodone

Trazodone

Bupropion

Mirtazapine

What is the MOA of Bupropion

Stimulates the cleavage of POMC cells into alpha-Melanocyte Stimulating Hormone (Alpha-MSH) which activates Melanocortin-4 Receptor (MC4R) → decreased appetite

Which neurotransmitters does Bupropion increases the levels of?

Dopamine

Norepinephrine

Aside from depression, what can Bupropion be used for as treatment?

Nicotine withdrawals via nicotinic acetylcholine receptor antagonist

T/F: Bupropion has a long half life

False

Bupropion adverse effects

Epileptic seizures (elderly on chronic dosing)

Electroconvulsive therapy

The following contraindications are associated with which Atypical Antidepressant:

Seizure disorders

Electrolyte abnormalities

Eating disorders

Bupropion

What drugs should Bupropion should be avoided in concurrent use with

MAOI

Tamoxifen

Alcohol

Which CYP enzyme does Bupropion inhibits that prevents Tamoxifen breaking down to its active metabolite, Endoxifen

CYP2D6

Mirtazapine increase DA and NE by blocking which receptors

Pre-synaptic 5-HT(2A)

5-HT(2C)

Alpha2- Adrenergic auto receptor

What are the therapeutic uses for Atypical Antidepressant, Mirtazapine

Depression in Elderly and Weight Loss patients

Somnorific and Appetite stimulant

What drugs should Mirtazapine be avoided being used concurrently with?

MAOIs

Which Atypical Antidepressants are weak 5-HT uptake inhibitors

Nefazodone & Trazadone

What is the MOA for Nefazodone and Trazadone

Blocks pre-synaptic 5-HT(2A) and 5-HT(2C) receptors

Desensitized pre-synaptic 5-HT(1A) auto-receptors

T/F: Because Nefazodone and Trazadone are weak Serotonin uptake inhibitors, they can be used other Antidepressants without risk of Serotonin syndrome

False

Nefazodone and Trazadone can experience an increased drug effect if combined with ___

Alcohol (CNS depressants)

Which Serotonin Receptor Agonist is also considered an SSRI and 5-HT(1A) receptor partial agonist

Vilazodone (Viibryd)

T/F: Vilazodone (atypical) can be used with other antidepressants

True

T/F: Nefazodone and Trazadone can be used with other antidepressants

True

Which Serotonin Receptor Agonist is also considered an SSRI and a 5-HT(1A) partial receptor agonist

Vortioxetine

T/F: Serotonin Receptor Agonists can be used with MAOIs

False

When switching to Serotonin Receptor Agonists from a MAOI or other antidepressant, what are the precautions before starting the new treatment?

Discontinue previous antidepressant/MAOI for 14 days before starting

Ketamine blocks NMDA receptors which modulates the glutamate neurotransmission, what is released as a result to produce rapid and long-term antidepression action

Brain Derived Neurotrophic Factor (BDNF)

What is the S-enantiomer of Ketamine that is more active and has a nasal spray formulation

Esketamine

What is the use for Ketamine and Esketamine

Treatment-resistant Depression in combo with other antidepressants

All covered antidepressant classes are considered to be monoamine therapy except for ____

Ketamine/Esketamine

Antidepressant effects (acute treatment) are generally not seen until ____ of continuous therapy

2-4 weeks

Monoamine therapy has delayed antidepressant effects due to ____ via 5-HT(1A) and Alpha2-autoreceptors → concomitant decrease in synthesis and release of 5-HT and NE

Acute Feedback Inhibition

In chronic treatment for monoamine therapy, ____ of presynaptic auto-receptors no longer receives the signal to shut down and enhances neurotransmitter activity in the post-synapse

Desensitization

T/F: Electroconvulsive therapy is used for most severe cases of depression

Main mood stabilizer used to treat Mania, Bipolar Depression, and prevent future mood-disorder episodes

Lithium

Mood swings in Bipolar disorder are associated with disruptions in _______

Circadian Rhythms

MOA of Lithium

Blocks Glycogen Synthase Kinase (GSK-3Beta) and Phosphatidylinositol signaling cascade

Adverse effects of lithium

Acute intoxication via Hyponatremia or concurrent use with NSAIDs

Sudden cardiac arrest via extracellular Hyperkalemia

Nephrogenic Diabetes Insipidus via antidiuretic hormone inhibition

Hypothyroidism / Goiter via decreased Thyroxine (T4) production

T/F: Lithium is the most effective agent for Bipolar disorder

True