MDD/GAD Drugs Exam 1 + 2

Citalopram

Brand: Celexa
Class: SSRI

Monitor: EKG → d/c if QTc persistently >500 ms

Dose >40 mg/day NOT recommended → MAX 20 for:

• CYP2C19 poor metabolizer

• Coadminister w/ CYP2C19 inhibitors

• Pts > 60 y/o

Escitalopram

Brand: Lexapro
Class: SSRI

Best tolerated SSRI

Pearls:

• ↑ absorption with food

• GI adverse effects

• preferred during breastfeeding

Fluoxetine

Brand: Prozac
Class: SSRI

• Half Life: 4-6 days → no need to taper

• Stimulating → give in AM

• Potent CYP2D6 inhibitor

• 5 week washout required if switching to MAOI

• higher odds for birth defects

Paroxetine

Brand: Paxil, Brisdelle, Pexeva
Class: SSRI

Shortest half life (21 H) → NO active metabolite

TAPER if planning to D/C

SE:

• constipation

• dry mouth

• sedation

• weight gain

• SEX Dysfunction (possibly has the most of all SSRI)

Potent CYP2D6 Inhibitor

Pearls:

• avoid in pregnancy

• on Beer’s List

• higher odds for birth defects → 2 fold ↑ risk of cardiac malformations

Sertraline

Brand: Zoloft
Class: SSRI

Do NOT use Solution with Disulfiram

Vilazodone

Brand: Viibryd
Class: SSRI and 5-HT1a partial agonist

Pearls:

• need to take with food

• diarrhea and nausea

• may have LESS sexual SE

Vortioxetine

Brand: Trintellix
Class: SSRI and 5-HT subtype agonist/antagonist → help concentration

Pearls:

• less sexual SE

• diarrhea/constipation → GI issues

• more aware/functional

• long half life → 66 H (3 days)

• okay to abruptly d/c

21 day washout required if switching to MAOI

Venlafaxine

Brand: Effexor (XR)
Class: SNRI

Pearls:

• dose < 150 mg/day → primarily affects 5-HT → acts more like SSRI

• withdrawal upon D/C (Brain Zaps)

• XR best tolerated

• dose-dependent risk of ↑ BP

• Fatal in OD → d/t QT prolongation

• Pregnancy safe

Duloxetine

Brand: Cymbalta
Class: SNRI

Other Indication: peripheral pain, fibromyalgia, chronic musculoskeletal pain

CYP2D6 Inhibitor

Desvenlafaxine

Brand: Pristiq, Khedezla
Class: SNRI

Active Metabolite of Venlafaxine (via 2D6 metabolism)

Levomilnacipran

Brand: Fetzima
Class: SNRI

Amitriptyline

Brand: Elavil
Class: TCA

Clomipramine

Brand: Anafranil
Class: TCA

Imipramine

Brand: Tofranil
Class: TCA

Desipramine

Brand: Norpramin
Class: TCAs

Nortriptyline

Brand: Pamelor
Class: TCA

Bupropion

Brand: Wellbutrin, Aplenzin, Forfivo
Class: DNRI (dopamine NE reuptake inhibitor)

FDA approved: smoking cessation (Zyban)

Stimulating → give in AM

Avoid in: seizure disorders, eating disorders, alcoholics

Caution: pts w/ psychosis

SE:

• ↑ BP

• weight loss

• transient anxiety (worsens existing anxiety disorder)

• sweating

CYP2D6 inhibitor

Sex Dysfunction → Low Risk

Isocarboxazid

Brand: Marplan
Class: MAOIs

Phenelzine

Brand: Nardil
Class: MAOIs

Tranylcypromine

Brand: Parnate
Class: MAOIs

Selegiline

Brand: Emsam (transdermal patch)
Class: MAOIs

MOA: selective MAO-B inhibition

Reserved for: refractory depression

Formulations: transdermal patch or PO

Patch Dosing:

• 6 mg → does NOT require tyramine-free diet

• 9 and 12 mg → tyramine mediated hypertensive rxn may occur

Mirtazapine

Brand: Remeron
Class: atypical antidepressant/NaSSA (noradrenergic + specific serotonergic)

MOA: block alpha2 and H1 → ↑ 5-HT, NE, sedation

SE: sedation, ↑ appetite, weight gain

Low sex dysfunction risk

Note: ↑ dose → ↓ sedation

“CA Rocket Fuel” when combined w/ SNRI

Trazodone

Brand: Desyrel
Class: atypical antidepressant/SARIs (5-HT antagonist + Reuptake inhibitors)

MOA: SSRI + H1 blocker → 😴

SE: sedation, priapism (rare)

Nefazodone

Brand: Serzone
Class: atypical antidepressant/SARIs

MOA: SSRI + 5-HT/NE reuptake blocker

BBW: hepatotoxicity

D/C if ALT/AST >3x upper limit of normal

Esketamine

Brand: Spravato
Class/MOA: NMDA receptor antagonist

C3

FDA Approved: Adjunctive to antidepressant for tx resistant depression

BBW:

• abuse/misuse

• REMS → requires:

  • only admin in healthcare w/ ≥ 2 hours monitoring

  • healthcare settings/pharmacy need certification

  • pt enrollment in registry

• suicidal thoughts and behavior

• NOT approved in peds

• dissociation → resolves about 1.5 hours post admin

• sedation → peak effect 30-45 mins

SE: ↑ BP

Olanzapine/Fluoxetine

Brand: Symbyax

Indication: Tx resistant depression

Fluvoxamine

Brand: Luvox

Class: SSRI

Approved for OCD

Inhibitor of CYP: 1A2, 2C19, 2C9, 3A4

Dextromethorphan HBr and Bupropion HCl

Brand: Auvelity

Class: DNRI

MOA:

• DM → NMDAr antagonist & sigma-1 agonist

• Bupropion → inhibit DA/NE reuptake

Fast acting → as soon as 2nd week

Bupropion Max Single Dosing

• SR → Wellbutrin SR, Zyban: 200 mg

• ER → Wellbutrin XL, Forfivo: 450 mg

• Bupropion HBr → Aplenzin: 522 mg

Trazodone Dose for Depression

150-600 mg

Trazodone Dose for Insomnia

25-150 mg

Doxepin

Brand: Sinequan

Class: TCA

Despramine

Brand: Norpramin

Class: TCA (s)

Amoxapine

Brand: Asendin

Class: TCA

Trimipramine

Brand: Surmontil

Class: TCA

MAOI Drug Interactions → Risk of Hypertensive Crisis

Sympathomimetics

• decongestants

• stimulants

• TCA

• appetite suppressants (phentermine)

• levodopa

MAOI Drug Interactions → Risk of Serotonin Syndrome

Serotonergic Agents

• SSRI, SNRI, NaSSA

• antihistamine

• opioids (tramadol, fentanyl)

• triptans

• linezolid

What are Hypertensive Crisis Sx?

• stiff neck

• HA

• vomiting

• diaphoresis

• HTN (DBP > 120)

• palpitations

• Labile HR

What is the Hypertensive Crisis Tx?

↓ BP → Phentolamine IV

CYP2D6 inhibitors and substrates?

Inhibitors:

• Bupropion

• Duloxetine

• Fluoxetine

• Paroxetine

Substrates: codeine, tramadol, clonidine, atomoxetine

What antidepressants have POTENT 2D6 inhibitory potential?

• Bupropion

• Fluoxetine

• Paroxetine

CYP1A2 inhibitors and substrates?

Inhibitor: Fluvoxamine

Substrates: caffeine, clozapine, warfarin

What antidepressants should be avoided in elderly?

Strong Anticholinergics → Paroxetine, TCA

Risk of SIADH/Hyponatremia → SSRI, SNRI, Mirtazapine, TCA

What antidepressant is 1st line in pregnancy?

SSRI → Sertraline, Citalopram

Although generally avoided d/t anticholinergic properties, what TCAs are okay to use during pregnancy?

• amitriptyline

• imipramine

• nortripyline

Zuranolone

Brand: Zurzuvae

C4

MOA: GABA-A receptor positive modulator

FDA Approved: post partum depression (PPD)

Dosing: 50 mg PO QD evening for 14 days

BBW: impaired ability to drive or engage in potentially hazardous activites

SE: somnolence, dizziness

Potential for abuse and dependence

What alternative meds/supps ↑ risk of 5-HT syndrome?

• St. John’s Wort

  • similar efficacy to low dose meds for mild/mod depression

  • CYP3A4 Inducer

• SAMe

• 5-HTP (5- hydroxytryptophan)

Folate/Folic Acid (B9) is associated with depression. True or False.

True

• adjunctive → improves depression scores in SSRI nonresponders

L-methylfolate

Brand: Deplin

MOA: active form of folic acid

Rx product → “medical food”

Time to Onset of Effects - What changes in the 1st week?

• anxiety

• sleep

• appetite

• energy

Time to Onset of Effects - What changes in the 2nd week?

• self-care

• memory

• concentration

• movements

• sex drive

Time to Onset of Effects - What changes in the 4rd week?

• depression

• feelings of hopelessness

Time to Onset of Effects - What changes in the 4th week?

• FULL RESPONSE

• less helpless

• less suicidal thoughts

What antidepressants induce anxiety?

• Bupropion

• SSRI

• SNRI

What antiseizure meds induce anxiety?

• carbamazepine

• phenytoin

What dopamine agonist meds induce anxiety?

• amantadine

• levodopa

What substances induce anxiety?

• ecstasy

• cannabis

• cocaine

What stimulants induce anxiety?

• amphetamines

• methylphenidate

• caffeine

• nicotine

• cocaine

What bronchodilators induce anxiety?

• albuterol

• Theophylline

What somatic meds induce anxiety?

• quinolones

• prednisone

• pseudophedrine

• phenylephrine

• levothyroxine

BZDs - MOA, Result, Use, SE, PK

MOA: enhance GABA inhibitory effects by binding to allosteric site on GABA-A receptor → ↑ affinity of GABA binding

Result: Rapid relief, Short-term tx, Acute anxiety

Uses: Anxiolysis, Insomnia, Seizures, Muscle relaxant activity

SE: drowsiness, ataxia, ↓ alertness/concentration

PK:

-  All → hepatic metabolism (CYP3A4)

-  Dose dependent highly sedating → low dose (sedating), high (hypnotic)

Flumazenil

Brand: Romazicon

Class: BZD Antidote

MOA: competitive GABA receptor antagonist

Use: counteract AE of BZDs

Admin IV

Potential to cause seizures & arrhythmias

PK: Rapid onset → may induce w/drawls

Short DOA

Buspirone

Brand: BuSpar

MOA: unknown; affinity for 5-Ht1A & 5-HT2 receptors

Non-BZD or CNS depressant

Non-sedating anti-anxiety agent

SE: dizziness, drowsiness, nausea, HA, tachycardia, nervousness

CI: MAOI → ↑ risk of serotonin syndrome

Avoid in severe liver or kidney impairment

Major CYP3A4 substrate:

• ↓ dose if used with inhibitor (diltiazem, itraconazole)

• ↑ dose if used with inducer (rifampin)

Propanolol

Brand: Inderal, InnoPran

MOA: competitive, non-selective beta 1 & 2 adrenergic blocker

Result: blocks “fight or flight” of heart and lungs → ↓ palpitations, fast HR, dizziness, shaking, sweaty palms

Treats physical sx of anxiety only !!!

Off-Label (low dose): stage fright & performance anxiety

PK:

-  Fast onset → within 1 hour

-  Effects last → 3-4 hours

SE: hypotension, bradycardia, arrhythmias, bronchospasm

Alprazolam

Brand: Xanax

Class: BZD

Clonazepam

Brand: Klonopin

Class: BZD

Diazepam

Brand: Valium

Class: BZD

Lorazepam

Brand: Ativan

Class: BZD

Chlordiazepoxide

Brand: Librium

Class: BZD

Clorazepate

Brand: Tranxene

Class: BZD

Oxazepam

Brand: Serax

Class: BZD

Temazepam

Brand: Restoril

Class: BZD

Advantages of BuSpar

• no potential for abuse, tolerance, or dependence

• anxiolytic effects as effective as BZD

• chronic anxiety

• long term tx

• no marked sedation

• less psychomotor impairments

• abrupt D/C does NOT cause rebound or w/drawls

Disadvantages of BuSpar

• slow or delayed onset

• takes 3-4 weeks to work

• not suitable for PRN or immediate relief

Pregabalin

Brand: Lyrica

MOA: doesn’t bind GABA/BZD receptors → ↓ Ca influx → inhibits GABA release

Off-Label GAD

C-5

Onset: Immediate

Serious SE: suicidal thoughts

Monitor: dizziness/somnolence

Hydroxyzine

Brand: Vistaril

FDA approved → NO tx for underlying condition

Dose: 50-100 mg QID PRN

AE: anticholinergic, sedation

Avoid in >65 y/o (Beer’s List)