Antidepressants

MAOIs

Phenelzine, selegiline patch, tranylcypromine

MAOI MOA/indications

Reserved for tx-resistant depression

A - metabolizes serotonin and norepinephrine

B - metabolizes dopamine

Boost noradrenergic, serotonergic, and dopaminergic neurotransmission

MAOI contraindications

Do NOT use w/in 2 weeks of other antidepressants (5 weeks for fluoxetine, 3 for vortioxetine)

Combination with stimulants or opioids

MAOI ADE

Hypertensive crisis - occipital headache, stiff/sore neck, dilated pupils, chest pain

MAOI food interaction

Tyramine rich foods - aged cheese, avocado, cured/smoked meats/fish, beer, fermented foods, overripe fruits, wine

TCAs

Amitriptyline, nortriptyline, clomipramine, desipramine, doxepine, imipramine

TCA indications

Migraine prophylaxis, neuropathic pain, fibromyalgia

TCA MOA

Block reuptake pump for norepinephrine and serotonin primarily (dopamine to lesser degree)

Block other receptors - histamine, muscarinic cholinergic receptors, alpha 1, sodium channels (in heart and brain)

TCA contraindications

Acute recovery phase following MI

Caution in pts w/ heart block, arrhythmias, prolonged QT interval

Avoid in pts w/ suicidal ideation

TCA ADE

Anticholinergic

Antihistaminic - sedation, wt gain

Alpha 1 blocking - dizziness, orthostatic hypotension, reflex tach

Sodium channel blockade - major OD risk, QTc prolongation

TCA OD

Prominent anticholinergic and antimuscarinic effects can cause cardiac arrhythmias, hypotension, seizures, coma, death

Tx - supportive, emesis, activated charcoal

Doxepin

TCA available as topical cream for pruritus

TCA dosing

Must taper off due to risk of cholinergic rebound

SSRIs

Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

SSRI MOA

Selective and potent inhibition of serotonin reuptake

Decrease dose

SSRI ADE management - agitation, anxiety, panic attacks, jitteriness

Morning dose

SSRI ADE management - insomnia

Decrease dose, morning dose

SSRI ADE management - nocturnal awakenings/sleep disturbances

Wait (2-8 weeks), decrease dose

SSRI ADE management - sexual dysfunction

Monitor, acetaminophen, switch

SSRI ADE management - headache

N/V

MC reasons for stopping SSRIs in first 30 days

Take w/ food, decrease dose, switch

SSRI ADE management - GI distress

Evening dose

SSRI ADE management - dizziness, drowsiness, sedation

Switch, paroxetine

SSRI ADE management - significant weight gain

Switch to activating (fluoxetine, bupropion)

SSRI ADE management - apathy, fatigue, lethargy

Stop med

SSRI ADE management - SIADH (elderly)

Mirtazapine, bupropion

SSRI ADE management - prolonged bleeding

SSRI withdrawal

Most problem w/ short half-life agents

Tx - restart previous dose and taper more slowly

FINISH (flu-like, insomnia, nausea, imbalance, sensory disturbance, hyperarousal)

SSRI dosing

May take 4-6 weeks to see beneficial effects

ADE will be seen w/in days to weeks

Lower doses needed for GAD, higher for OCD (relative to MDD)

Citalopram

SSRI w/ highest QTc prolongation risk

Preferred SSRI for pregnancy

Escitalopram

SSRI that is one of the most tolerable

Fewest drug-drug interactions

Preferred SSRI for pregnancy

Fluoxetine

Activating SSRI that needs to be taken in the morning to prevent insomnia

Not a preferrable SSRI during pregnancy

Wait 5 weeks between MAO-I use

Fluvoxamine

SSRI that is beneficial in pediatric anxiety disorders and OCD

Considered one of most tolerable

Improves sleep quality

Not preferred in pregnancy

Paroxetine

SSRI most associated w/ anticholinergic and sedating ADE

Frequently used for vasomotor sxs of menopause

Not recommended during pregnancy (one of worst)

Sertraline

SSRI that is a good first-line choice due to cardiovascular safety

Well-tolerated ADE

Preferred SSRI for pregnancy

SNRIs

Desvenlafaxine, duloxetine, levomilnacipran, milnacipran, venlafaxine

SNRI MOA

TCA by MOA but w/o cholinergic, histaminic, and alpha-1 receptor drawbacks

Venlafaxine

SNRI w/ HTN ADE

Different effects at different doses

Similar ADE to SSRIs

May be used in pregnancy for depression but not migraine prophylaxis

Duloxetine, milnacipran

SNRIs w/ hepatotoxicity ADE

SNRI drug interactions

Serotonergic agents, anticoagulants, NSAIDs

Duloxetine

SNRI similar to venlafaxine, but w/ serotonin and NE reuptake throughout dosage range

Hepatotoxic

Use tapering strategy to avoid severe withdrawal

May be used in pregnancy

Desvenlafaxine

SNRI that is active metabolite of venlafaxine

NE reuptake actions greater than w/ venlafaxine

Fewer drug interactions w/ desvenlafaxine

NO titration needed

Dual mechanism antidepressants

Bupropion, bupropion + dextromethorphan, mirtazapine, trazadone, vilazodone, vortioxetine

Bupropion

Dual mechanism antidepressants

Used in smoking cessation and as augment to other antidepressants

Norepinephrine and dopamine reuptake inhibitor

Mirtazapine

Dual mechanism antidepressants

Central alpha2 adrenergic antagonist

Histamine-1 muscarinic antagonism - anticholinergic effects

Minimal CYP interactions

Use w/ pts w/ insomnia or wt loss

Used in headache chronic tension-type and panic d/o

Trazadone

Dual mechanism antidepressants

Used in insomnia

SARI

More for augmentation

Priapism, orthostasis, sedation

Bupropion contraindications

Dual mechanism antidepressants

Seizures, EDs, pts undergoing abrupt discontinuation of ethanol or sedatives, MAO-I use, pt on linezolid

Bupropion ADE

Dual mechanism antidepressants

Activating - agitation, anxiety, insomnia

Psychiatric changes - smoking cessation

Decreased appetite and wt loss

Lower prevalence of sexual side effects

Increased

At what dose is Mirtazapine more sedating?

Mirtazapine special pop

Dual mechanism antidepressants

Elderly:

Safer than TCA from CV standpoint

Exacerbate/cause SIADH/hyponatremia

Increased risk of nightmares

Vilazodone

SPARI

Dual mechanism protects against serotonin syndrome

Sertraline, paroxetine

Medication preferred in pregnancy

Medication to avoid in pregnancy