Antidepressants

first line drug treatment for depression

second gen antidepressants (SSRIs, SNRIs)

boxed warning for antidepressants

suicidal thoughts and behaviors in peds and adolescents within first few mos of Tx or when dose is changed

SSRI MOA

selectively bind to and block serotonin reuptake pumps (SERT), increasing the concentration in the cleft and enhancing signaling in the postsynaptic receptors

weakly affect NE and DA

SSRI common ADEs

sexual dysfunction, somnolence, insomnia, nausea, dry mouth, diarrhea (most serotonin in gut)

headache, weakness, dizziness

wt gain, risk of bleeding if taken with other meds that increase bleeding risk

SSRI rare ADEs

serotonin syndrome - excess serotonin, life-threatening

sx (can be mild or severe): autonomic dysfunction, neuromuscular dysfunction (clonus, rigidity, hyperreflexia), mental status fluctuations

SSRI discontinuation

taper down over several wks

SSRI withdrawal sx

anxiety, agitation, insomnia, dizziness, flu-like sx

SSRI exception to tapering discontinuation

Fluoxetine - it has a very long half life, so it usually tapers down on its own

Citalopram (SSRI)

QT prolongation risk

Escitalopram (SSRI)

QT prolongation risk

why do we avoid giving higher doses of Citalopram and Escitalopram to elderly pts?

both meds have a higher risk of causing QT prolongation

Sertraline (SSRIs)

preferred in pts with cardiac risk

Fluvoxamine

only approved for OCD

Fluoxetine (SSRI)

least likely to cause wt gain (avoid in wt loss pts), most activating/energizing (take in AM), long half life - better for pts with adherence issues

Paroxetine (SSRI)

most anticholinergic SEs (most sedating), most likely to cause discontinuation sx (short half life)

SNRI MOA

selectively bind to and block SERT and NET, preventing the reuptake of serotonin and NE, increasing their concentration in the cleft and enhancing postsynaptic receptor signaling

SNRI common ADEs

same as SSRIs plus increased BP/HR, urinary hesitation or retention, dry mouth, excess sweating constipation

Duloxetine (SNRI)

avoid in pts with low renal function

also for peripheral neuropathy, fibromyalgia, anxiety, chronic MSK pain - good for pts with associated pain

Venlafaxine (SNRI)

also for anxiety, panic disorder, social anxiety disorder

why do both desvenlafaxine and venlafaxine have higher risk of discontinuation syndrome?

both of their half lives are shorter

tricyclic antidepressants MOA

inhibit presynaptic reuptake of serotonin (SERT) and NE (NET), Ach antagonist

secondary amines (TCAs)

more selective for NE

nortrip

tertiary amines (TCAs)

more selective for serotonin

can be more effective, but has worse SEs

amitriptyline, doxepin, imipramine, clomipramine

TCA ADEs

QT prolongation, orthostasis, tachycardia

anticholinergic ADEs: dry mouth, blurry vision, urinary retention, constipation

wt gain, sedation (more common in tertiary)

Beers List

inappropriate for older adults due to high anticholinergic properties that could lead to sedation and risk of orthostatic hypotension (TCAs)

atypical antidepressants

bupropion - minimum/no risk of causing serotonin syndrome, can be used in combo with a serotonergic agent

mirtazapine and bupropion - little risk of sexual dysfunction compared to SSRIs

Bupropion MOA

blocks NET and DA reuptake transporter (DAT), some metabolites active at nicotinic Ach receptors

Bupropion clinical uses

smoking cessation, wt management in combo pill with naltrexone

Bupropion ADEs

lower compared to other antidepressants

seizures - lowers threshold, so avoid in anyone with hx of seizure disorder

lower sedative risk and sexual dysfunction

may avoid in pts with anxiety or current/hx of anorexia/bulimia

Mirtazapine MOA

block presynaptic alpha2-adrenergic receptors, antagonist at serotonin (5HT2, 5HT3) and histamine (H1) receptors

allows increased release of serotonin and NE

FDA approved indication - depression

Mirtazapine ADEs

increased appetite and wt gain

anticholinergic sx - dry mouth, sedation

lower doses - block H1 receptor, antihistamine effects are stronger and more likely to promote drowsiness

higher doses - more serotonergic and adrenergic activity, less sedative

Trazodone MOA

inhibit SERT on presynaptic neurons to prevent reuptake

antagonizes 5-HT2A, 5-HT2C, H1 receptors

Trazodone clinical uses and ADEs

primarily used off label for sleep

sedation (from blocking H1), orthostasis, priapism

monoamine oxidase inhibitors (MAOIs) MOA

inhibits the enzyme monoamine oxidase, preventing the breakdown of serotonin, NE, epinephrine, and dopamine

MAOI clinical uses

rarely used as antidepressant, more for Parkinson’s

HTN crisis and death can occur due to dramatic increase in neurotransmitters

MAOI contraindications

do not give to those with hx of CV disease, hepatic disease, or severe renal disease

do not eat foods high in tyramine (i.e aged cheese, yeast extract, red wine, beer on tap)

MAOI adverse effects

anticholinergic effects, orthostasis, sedation, sexual dysfunction, wt gain, headache, insomnia

what antidepressant would you choose for a pt who has severe insomnia, or a different need for a sedating agent?

Mirtazapine

what antidepressant would you choose for a pt who has hypersomnia or a lack of energy?

Bupropion, Vilazodone

what antidepressant would you choose for a pt who has depression related wt loss or the need for wt gain?

Mirtazapine

what antidepressant would you choose for a pt who is wt neutral or wants to lose wt?

Bupropion

what antidepressant would you choose for a pt who wants to quit smoking?

Bupropion

what antidepressant would you choose for a pt who has concomitant pain?

SNRI, TCA

what antidepressant would you choose for a pt who has a concern about sexual dysfunction or related SEs?

Bupropion, Mirtazapine, possibly an SNRI

what antidepressant would you AVOID for a pt who has HTN?

Venlafaxine

what antidepressant would you AVOID for a pt who has seizures?

Bupropion

what antidepressant would you AVOID for a pt who has CV disease?

TCAs, Trazodone

what antidepressant would you AVOID for a pt who has orthostatic HTN?

TCAs, Trazodone

what antidepressant would you AVOID for a pt who has a condition that causes a prolonged QT interval?

Citalopram, Escitalopram

what antidepressant would you AVOID for a pt who has a kidney impairment or low kidney function, possibly due to severe kidney disease?

Duloxetine

what antidepressant would you AVOID for a pt who has hyponatremia?

SSRIs, SNRIs