Antidepressants Flashcards
Describe the broad physiologic goal of all antidepressant medications.
Increase the concentration of neurotransmitters in the synapse
By what mechanism do anti-depressants have their effect?
There is disagreement –> some say the increased concentration of the neurotransmitters in the synapse lead to the anti-depressive effect while others argue that the effect comes from down regulation of receptors on the pre-synaptic neuron.
What evidence is there that down regulation of receptors is the reason anti-depressant medications are effective?
Because anti-depressant medications take 3-4 weeks to be effective, meaning the down regulation of receptors is likely more responsible.
List neurotransmitters (NTs) found in the synapse of CNS neurons
Epinephrine, norepinephrine, serotonin, dopamine, acetylcholine
What are two ways the body removes neurotransmitters from the synapse?
- Reuptake: recycling NTs by pumping them back into the pre-synaptic neuron
- Enzymes: acetylcholinesterase and monoamine oxidase chew up NTs in the synapse
Which class of antidepressant medications is most effective?
No one class is more effective than another –> what determines use is side effects the patient experiences
What was the original class of antidepressant medications?
Monoamine oxidase inhibitors (MAOIs)
Name two MAOIs on the market today.
Phenelzine and Tranylcypromine
What is the mechanism of action of MAOIs?
They block action of monoamine oxidase thereby increase CNS synapse levels of epi, norepi, and dopamine
What are two isoforms of MAOIs and which has the most antidepressive effect?
MAO-A and MAO-B –> MAO-A has the greatest antidepressive effect
What is the GI related AE of MAOIs and how is it mitigated?
MAO in the colon metabolizes vasoactive substances that we eat (tyramine) before they enter the bloodstream. MAOIs allow absorption of these vasoactive chemicals. Patient must adhere to a special diet or suffer risk of hypertensive emergency and urgency.
List common AEs of MAOIs other than the GI related AE.
Many drug interactions, orthostatic hypotension, palpitations, tachycardia, erectile dysfunction
Differentiate between Phenelzine and Tranylcypromine and state how it is clinically relevant.
Phenelzine: more sedating –> prescribe to people with insomnia
Tranylcypromine: more activating –> prescribe to people that sleep too much
When, after discontinuing use of MAOIs, do you no longer worry about AEs?
3 weeks after stopping medication
When should MAOIs be combined with other antidepressant medications?
Only under care of psychiatrist –> mixing more than one drug class can lead to serotonin syndrome
T/F: MAOIs are considered first line therapy for depression.
False –> patients on an MAOI have issues
What are two medications previously discussed in class that have weak MAOI properties?
Linezolid (antibiotic) and St. John’s Wort (OTC antidepressant)
Describe the use and mechanism of tricyclic antidepressants (TCAs).
- They are not commonly used –> they are dirty drugs (lots of side effects)
- They indiscriminately block NT reuptake
Why are TCAs still kept on the market?
Off label uses such as insomnia (Anti-Ach sedation), neuropathic pain, enuresis (bed wetting)
What are the three primary results of TCA toxicity?
- Tonic-clonic seizures
- Cardiac arrhythmias
- Anti-cholinergic effects (constipation, dry mouth, urinary retention, sedation, tachycardia)
How should you counsel patients when starting them on a TCA?
Anti-Ach side effects will start immediately but the antidepressant effects will not be seen for three weeks
What is the father of TCAs?
Imipramine
What is the hallmark ECG finding of TCA toxicity and what is the antidote?
Toxicity causes QRS widening on the ECG. The antidote is Bicarbonate
What are the two broad categories of TCAs?
Secondary Amines: desipramine, nortriptyline, exs
Tertiary Amines: amitriptyline, imipramine, exs
Which TCAs are more well tolerated by patients?
Secondary because the tertiary amines are typically metabolized into the secondary amines. Tertiary amines stay around longer.
Patients with what past medical history should have TCAs prescribed cautiously?
Seizure patients –> TCAs decrease seizure threshold
What class of antidepressant medications is most commonly prescribed?
Selective Serotonin Reuptake Inhibitors (SSRIs)
What is the father of SSRIs?
Fluoxetine
Name SSRIs (other than the father of the class) commonly prescribed
Paroxetine, Sertraline, Citalopram, Fluvoxamine, Escitalopram
Compare the AEs of SSRIs to the AEs of TCAs and MAOIs
Fewer AEs than other antidepressants –> no anti-ach effects or cardiovascular effects
What is the primary AE associated with SSRIs?
Erectile dysfunction
T/F: SSRIs are commonly lethal in overdose.
False: A patient would have to take a lot of SSRIs to overdose
Other than depression, what other pathology is SSRIs used for?
Anxiety
What is an increasingly common risk associated with SSRIs?
Suicidal ideation –> fluoxetine most common
Describe serotonin syndrome.
Confusion, sweating, fever, rigidity, tachycardia, hypotension, and possibly death that typically results when two agents that increase serotonin levels are combined or begun in succession without an adequate washout period
List two SSRIs that also have some serotonin 1-a receptor agonism and state how this is clinically relevant.
Vilazodone and Vortioxetine –> cause more down regulation of receptors and thus may be more potent than other SSRIs
What are the advantages of prescribing Vilazodone?
Causes less erectile dysfunction and has no effect on weight (SSRIs tend to cause weight gain)
What is the mechanism of bupropion?
It is a weak inhibitor of dopamine reuptake with no effect on norepinephrine or serotonin
What is the major advantage of prescribing bupropion?
No effect on sexual function
What is the common off-label use of bupropion?
Smoking cessation and other addiction disorders
What is the major AE associated with bupropion?
Decreases seizure threshold –> cannot use in PMH of seizure or in eating disorders (hyponatremia decreases seizure threshold)
Describe the mechanism of action of trazodone?
It is a weak SSRI and an antagonist of one specific type of serotonin receptor.
What is the most common use of trazodone?
Insomnia –> the drug is highly sedating
What AEs are associated with trazodone
Orthostatic hypotension (fall risk) and priapism (rare)
Name three drugs that are Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
Venlafaxine, Duloxetine, and Levomilnacipran
What was the first SNRI and what are its risks of use?
Venlafaxine –> causes HTN and increased lipids. Not great for patients with vascular disease
Differentiate venlafaxine from desvenlafaxine.
Desvenlafaxine is the same drug but is dosed qd where venlafaxine is multiple doses per day
Differentiate duloxetine from venlafaxine.
Duloxetine is an SNRI with less norepinephrine activity
What are the primary uses of duloxetine other than as an antidepressant?
Peripheral neuropathy, fibromyalgia, and urinary incontinence
What is the disadvantage of duloxetine?
High cost
Name and describe three miscellaneous antidepressant medications.
- Mirtazapine: highly sedating
- St John’s Wort: herbal antidepressant
- Amphetamines: may be added to antidepressant meds in low doses for severe depression
What is different about the way St. John’s Wort can be marketed?
Because it is an herbal, company cannot make the claim that it is an antidepressant. They can only say it may reduce depression.
