Pharm III - Major Depressive Disorder

Meds associated with depression

BB, clonidine, methyldopa, OCPs, steroids, -triptans, varenicline

1st line tx for MDD

SSRIs, SNRIs (except)

Bupropion

Mirtazapine

Vortioxetine

2nd line tx for MDD

Levomilnacipran

Trazodone

Vilaodone

TCAs

MAOIs

SSRIs MOA

inhibit reuptake of serotonin (5HT)

SSRIs examples

Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

Which SSRI has the longest half life?

Fluoxetine, requires washout when switching meds

Fluvoxamine indication

OCD

SSRI with shortest half life

Paroxetine

+ more anticholinergic SE, avoid in pregnancy

What patients do you want to avoid using paroxetine in?

Pregnant pts, elderly (anticholinergic effects)

Which SSRIs are associated with QT prolongation?

Citalopram, possibly escitalopram

T/F: SSRI use w antiplatelet/anticoagulants -> an increased bleeding risk

True

Which SSRIs have the fewest DI?

Citalopram, escitalopram

SSRIs side effects

Transient anxiety/HAs

mild/transient GI effects

Insomnia

Sexual dysfunction

Weight gain

SSRI that causes the most weight gain

Paroxetine (Paxil)

++sedation

Most activating SSRI

fluoxetine (Prozac)

-dose in AM

Most sedating SSRI

paroxetine

Preferred SSRIs for pregnancy and breastfeeding

Citalopram, Escitalopram, Sertraline

Preferred SSRIs for adolescents

Escitalopram, fluoxetine, sertraline

Preferred SSRI for pts w poor adherence, slowing pts, children/adolescents

Fluoxetine (activating, long half-life)

Preferred SSRI for insomnia or underweight pts

Paroxetine

Preferred SSRI in cardiac patients

Sertraline

SSRI to use caution w agitation or insomnia

Fluoxetine

SSRI to use caution w older adults, overweight pts, pregnancy

Paroxetine

SNRIs MOA

Inhibits reuptake of serotonin and NE

SNRIs example

Desvenlafaxine, Venlafaxine

Duloxetine

Levomilnacipran (2nd line)

Venlafaxine receptor activity

< 150 mg acts on 5-HT receptor

< 150 mg acts on 5-HT and NE receptors

> 300 mg acts on dopamine receptors

FDA approved SNRI for tx of pain (peripheral neuropathy, fibromyalgia)

Duloxetine (Cymbalta)

DI in SNRIs compared to SSRIs

SNRIs have less P450 inhibitions compared to SSRIs

Duloxetine DI

CYP-2D6i

SNRIs SE

Constipation, dilated pupils, dry mouth, excessive sweating, increased BP/HR

SNRI with greatest risk for increasing BP

Venlafaxine

Bupropion MOA

Inhibits reuptake of NE and DA

*no effect on serotonin

When should you avoid bupropion

Alcohol or BZD withdrawal

Eating disorders

Head trauma

Seizure disorders

Bupropion side effects

Anxiety

Decreased appetite

N/V

Seizure risk (esp dose > 450 mg/day)

Insomnia

Tremor

When should you consider using bupropion

Concern about sexual dysfunction

Overweight or obese pts

Smokers (approved for smoking cessation)

Mirtazapine MOA

Increases 5-HT and NE

- blocks H2 receptors (sedating and weight gain)

Mirtazapine SE

Constipation

Dry mouth

Sedating

Weight gain

When should you consider using mirtazapine?

Agitation

Insomnia

Concern about sexual dysfunction

Underweight patients

*consider for older pts who need to eat/sleep more

Caution w mirtazapine

Avoid in overweight/obese patients

Vorioxetine MOA

SSRI w additional activity at serotonin receptors

- less nausea than SSRIs, slightly less sexual dysfunction

Trazodone MOA

inhibits reuptake of serotonin; antagonizes 5-HT2 receptor; also blocks a1-adrenergic and histamine receptors

Trazodone SE

Orthostatic hypotension (a1 blockade)

Sedation (5-HT blockade)

Priapism, erectile dysfunction

Vilazodone MOA

Inhibits reuptake of serotonin and partial agonist at 5-HT1a receptor

Vilazodone SE

Dizziness, GI effects, more insomnia than SSRIs

Amitriptyline MOA

Inhibits norepinephrine and serotonin reuptake; also blocks a1/h1/muscarinic receptors

Amitriptyline SE

Orthostatic hypotension, sedation, anticholinergic effects, weight gain, sexual dysfunction

Amitriptyline serious side effects

Arrhythmias, heart block

Potentially lethal in OD -> risk of sudden cardiac death, get ECG before use in kids, pts > 40, pts w cardiac risk factors

Isocarboxazid, phenelzine, tranylcypromine, transdermal selegiline MOA

Inhibit MAO which mediates degradation of monoamines (increases conc of 5-HT, NE, DA)

Selective MAO-B inhibitors

Transdermal selegiline

MAOI SE

Orthostatic hypotension

Sexual dysfunction

Weight gain

MAOI serious side effect

HTN crisis w tyramine containing foods and meds

Dietary restrictions w MAOIs

Aged cheese

Sauerkraut

Smoked/pickled fish

Dark beer

Red wine

Boxed warning for all antidepressants

Increased risk of suicidal thinking and behavior in:

- children

- adolescents

- young adults (18-24 yrs)

Classic triad of serotonin syndrome

mental status change, autonomic instability, neuromuscular abnormalities

*clonus, tremor, hyperreflexia, agitation, increased bowel sounds, tachycardia, diaphoresis, mydriasis

Serotonergic acting drugs

SNRIs, SSRIs, TCAs, MAOIs, trazodone

Monitoring for SSRIs

Serum sodium (hyponatremia)

- elderly; diuretics

Monitoring for SNRIs

BP/HR

Serum sodium (hyponatremia)

- elderly; diuretics

Monitoring for citalopram

ECG

Monitoring for duloxetine

LFTs

Pt w partial or no response to SSRI after 2 weeks, what should you do

Add bupropion

Pts w partial or no response to SSRI after 2 weeks, you want to add a non-antidepressant. What do you add?

Atypical antipsychotics

- aripiprazole, risperidone, quetiapine

Which antidepressants need a washout period

MAOIs, fluoxetine

Preferred antidepressants in elderly

SSRIs - monitor sodium

Mirtazapine

Bupropion

Preferred antidepressants in chidlren/adolescents

Fluoxetine

Escitalopram

Sertraline

Perferred antidepressants for pregnant/breastfeeding

Citalopram

Escitalopram

Sertraline