Antidepressant medications Flashcards
How do antidepressants work?
Block reuptake pump (serotonin transporter OR NE transporter)
This leads to increased levels of neurotransmitters in snyapse
What causes receptors to down-regulate?
Increased level of SERT or NT in synapse
What do antidepressants impact?
Gene expression
When are MAOIs CI’d?
SSRIs SNRIs TCAs Sympathomimetics Levadopa (d/t risk of HTN crisis) Foods containing tyramine
When are MAOIs used?
MDD
Treatment resistant depression
Why are MAOIs not used anymore?
Newer safer options
How do we counsel patients on MAOIs?
Signs of HTN crisis, foods to avoid
What pumps do TCAs work on?
Serotonin
NE
Dopamine
What receptors do TCAs work on?
Muscarinic cholinergic
Histamine-1
Alpha-1
Where do TCAs block sodium channels?
Heart and brain (OD potential)
What are TCA OD sx?
Cardiac arrhymthias
Hypotension
Seizures
Coma Death
When do we avoid TCAs?
Patients with current suicidal ideations or h/o suicidal ideations or attempts
What is the MOA of MAOIs?
Nonselective and irreversible inhibitor of:
MAO A: serotonin and NE
MAO B: dopamine
Are TCAs considered “me too” drugs?
No
What levels should be checked with TCAs?
Blood levels for toxicity (not TDM)
What happens if there is abrupt withdrawal of TCAs?
Cholinergic rebound
What is the MOA for SSRIs?
Selective and potent inhibition of serotonin reuptake
Minor actions on other receptors, which accounts for differences in agents
What are TCAs?
Amitriptyline Nortriptyline Imipramine Desipramine Doxepin
What are MAOIs?
Phenelzine
Tranylcypromine
Selegiline
Which TCA is the most anticholinergic?
Amitriptyline
What is the management of acute phase agitation, anxiety, panic attacks, akathisia, “jitteriness syndrome”?
New onset: Decrease SSRI/SNRI to lower dose, titrate more slowly
What SEs do serotonin cause in the limbic cortex?
Agitation Anxiety Panic attacks Akathisia Jitteriness syndrome Insomnia
What is the management of acute phase insomnia?
Take dose in morning
What SEs does serotonin cause in the brainstem?
Nocturnal awakenings/sleep disturbances
What is the management of nocturnal awakenings/sleep disturbances?
Decrease dose, take dose in AM
What are the SEs of serotonin in the spinal cord?
Sexual dysfunction
What is the management of acute phase sexual dysfunction?
Waiting 2-8 weeks for spontaneous remission
Decrease dose
Switching to a different SSRI/non-SSRI antidepressant
What are the SEs of serotonin on the hypothalamus or brainstem?
HA
Nausea/vomiting
Reduced appetite
Wt loss
What is the management of acute phase HA?
Watch and monitor, consider APAP PRN
May consider switching to a different agent
What are the SEs of serotonin on the GI tract?
GI distress - increased bowel motility, cramps, and diarrhea
What are the management strategies for acute phase N/V?
The most commonly cited reasons for stopping antidepressant therapy in the first thirty days of treatment
Take with food
Can decrease dose, or try a different agent
What are the management strategies for acute phase reduced appetite, wt loss, and GI distress?
Take medication dose with food
Can decrease dose, or try a different agent
How do we manage acute phase dizziness, drowsiness and sedation?
Take dose in evening/near bedtime
Which SSRIs cause wt gain?
Mirtazapine > paroxetine (packs it on)
What should we do if a pt gains wt on an SSRI?
Switch to another SSRI or SNRI
What drugs are given with SSRIs for sleep disturbances?
Trazodone/Mirtazapine commonly used
What drug do we switch to if the pt experiences apathy, fatigue, and lethargy?
Bupropion > fluoxetine > SSRIs
What is the management of long term sexual dysfunction?
Switching to a different SSRI/non-SSRI
Try Bupropion, Mirtazapine, Trazodone
Paxil/Lexapro cause MORE sexual dysfunction
What are less common SEs of SSRIs?
Diarrhea
Hyponatremia in elderly
Prolonged bleeding - caution with antiplatelet agents, anticoagulants or NSAIDs
How do we treat SSRI diarrhea?
Try another agent
Which drugs cause hyponatremia?
SSRIs > SNRIs > Bupropion, mirtazapine
What is the treatment of SSRI prolonged bleeding?
Switch to mirtazapine or bupropion
How do SSRIs and SNRIs prolong bleeding time?
Decrease intra-platelet 5-HT stores and increase the risk of bleeding = monitor
What are WD sx of SSRIs?
Fatigue Lethargy Flu-like sx Dizziness HA Nausea
What do we do if a pt accidentally discontinues their SSRI?
Restart previous dose, and taper more slowly over several weeks to months
What do we do in the event of serotonin syndrome?
Serotonin agents must be stopped and supportive care initiated
Pt should be monitored for improvement and sx of WD
What are a lot of antidepressants metabolized by?
2D6 and 3A4
Which SSRIs have minimal CYP450 interactions?
Lexapro
What are pharmacogenomic considerations of SSRIs?
Different medications work differently for different people
What are SSRIs?
Prozac
Paxil
Celexa
Lexapro
Which SSRI has the longest half-life?
Prozac
Why is prozac administered in the morning?
Activating effect
What patients do we consider prozac in?
Pts with fatigue, low-energy, non-compliance (weekly dosing available)
Which SSRI is preg cat D?
Paxil
Which SSRI is more sedating than the others?
Paxil
Which SSRI causes the most weight gain?
Paxil
What is paxil associated with?
More constipation and cholinergic rebound with abrupt WD
What can paxil be used for?
Vasomotor sx of menopause
Which SSRI has the highest QT prolongation?
Celexa
What is the dosing of Celexa in elderly/hepatic impairment?
20mg/d
Which is the most tolerable antidepressant?
Lexapro
What are SNRIs called?
Designer TCAs
What is the MOA of SNRIs?
Activity on serotonin, NE and some dopamine
Which drugs are SNRIs?
Venlafaxine
Duloxetine
Desvenlafaxin
What activity does SNRIs lack?
Significant anticholinergic, antihistamine, and alpha-1 blocking activity
How does Venlafaxine act as an SSRI?
When used at lower doses
What are the SEs of venlafaxine?
Sweating
Tachycardia
Palpitations
At high doses = increased BP
What is venlafaxine used for?
Neuropathy
Hot flashes
When do we avoid duloxetine?
Hepatotoxicity
What is duloxetine indicated for?
Pain and fibromyalgia
How do we take a patient off of duloxetine?
Taper - severe withdrawal
Does desvenlafaxine need to be titrated?
No
What is the desvenlafaxine dose?
50mg QD
What is desvenlafaxine?
Active metabolite of venlafaxine
What class is bupropion?
NE and DA Reuptake blocker
What SE is low in bupropion?
Sexual side effect potential
What are the common SE of bupropion?
Agitation Insomnia Anxiety Diminished appetite Wt loss
What is bupropion CI’d with?
Hx of seizure Eating disorders (anorexia/bolemia)
Is bupropion an activating or blocking antidepressant?
Activating
What is bupropions dose-related SE?
Seizure
What rxns can bupopion cause?
Neuropsychiatric rxn
What class is mirtazapine in?
Alpha 2 antagonist
What does the mirtazapine MOA lead to indirectly?
Increased release of both NE and serotonin
What are common SEs of mirtazapine?
Sedation Wt gain Increased appetite Dizziness Dry mouth Constipation
What is mirtazapine good for?
Depression
Insomnia
Appetite stimulation/help cause wt gain
What is the relationship of mirtazapines dose and sedation?
Inverse
What is the onset of mirtazapine vs SSRIs
Mirtazapine faster than SSRIs
What is the MOA of trazadone and nefazadone?
Block serotonin postsynaptically (more than reuptake)
What SE associated with SSRIs are decreased in nefazodone/trazodone?
Sexual dysfunciton
Insomnia
Anxiety
What toxicity is associated with nefazodone?
Hepatotoxicity
What is trazodone typically used for?
Sedative - must use HD for antidepressant effect
What are the most common SE for Trazodone?
Sedation Orthostasis HA Nausea Priapism
What is the MOA of Viibryd (Vilazodone)?
SPARI
Partial serotonin agonist + SRI
Lower risk of serotonin syndrome
What combination of drugs is similar to Viibryd?
Paxil + buspirone
How should Viibryd be tajeb?
With food - high incidence of GI SE
What is the MOA of Trintellix (vortioxetine)?
Tri = 3 mechanisms
SSRI + serotonin agonist + serotonin antagonist
What is the preferred method when switching/changing antidepressants?
Cross taper
When is a direct switch acceptable when switching antdepressants?
SRI agents
How long do MAOIs need a wash out?
2 weeks
5 weeks for prozac
How do we prevent WD sx?
Gradual tapering over several weeks
What is the starting and usual dose for prozac?
20
20-60
What is the starting and usual dose for Paxil?
20
20-60
What is the starting and usual dose for sertraline?
50
50-200
What is the starting and usual dose for fluvoxamine?
50
100-300
What is the starting and usual dose for celexa?
20
20-40
What is the starting and usual dose for lexapro?
10
10-20
What are the starting and usual dose for effexor?
37.5 -75
75-375
What is the starting and usual doses for bupropion?
100-150
300-400
What is the starting and usual dose for mirtazapine?
15
15-45
What is the starting and usual dose for duloxetine?
30-60
60-120
