Antidepressants Flashcards
How long do you wait for a response to an antidepressant before considering a switch to another agent, or an augmenting agent?
Typical response time to SSRIs is 3-6 weeks, if no response after 8 weeks, switch. If partial response, consider dose adjustment, adding augmenting agent, or switching.
What are the major classes of antidepressants?
Tricyclic Antidepressants (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
Novel antidepressants (other)
What are the major worrisome aspects of TCAs?
- Lethal at fairly low doses (a week’s supply can be lethal)
- can have QT prolongation even at blood levels within what’s considered therapeutic range
- Lots of side effects: antihistiminic, anticholinergic, antiadrenergic. Potentially lots of discomfort for patients.
What’s a tertiary TCA and what are some examples?
- They have tertiary amine side chains. So what? Those side chains interact with a variety of receptors that cause the effects we’d rather not see patients experience (euphemistically known as side effects)
- Examples: imipramine, amitriptyline, doxepin, clomipramine
- These also have active metabolites: desipramine, nortriptyline
Describe the undesired effects (side effects) by receptor type (i.e. antihistaminic SEs, anticholinergic, and antiadrenergic)
antihistamine: sedation and weight gain
anticholinergic: dry mouth, dry eyes, constipation, memory problems, possibly delirium)
antiadrenergic: orthostatic hypotension, sedation, sexual dysfunction
What is the believed mechanism of the therapeutic action of TCAs?
They act on serotonin receptors
What are the secondary TCAs? How are they believed to function?
- These are the active metabolites of some of the tertiary TCAs. Examples: desipramine, nortriptyline
- Primarily by blocking NE reuptake. Dopaminergic tone in the frontal cortex decreases as NE is uptaken (not sure if that’s a word) so blocking NE reuptake is thought to increase dopamine activity in this brain region.
How are MAOIs believed to work?
They irreversibly bind to monoamine oxidase, an enzyme that metabolizes monoamines (NE, DA, 5HT) in the synaptic space, purportedly leading to higher levels of these biogenic amines.
What are some of the undesired effects of MAOIs?
- Orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction, sleep disturbance.
- If combined with a serotonergic medication, can lead to serotonin syndrome
- Hypertensive crisis (usually if not adhereing to an MAOI diet)
Explain the diet-related complication associated with MAOIs?
- Hypertensive crisis: earliest symptom is usually headache or visual disturbance.
- Eating tyramine-rich foods (aged cheeses, many alcoholic drinks–red wine, beer, aged/fermented foods (things that have been pickled) or things like salami and pepperoni
What OTC medications do you need to warn pts about if they’re going on an MAOI?
- Sympathomimetics: dextromethorphan (found in cough medicine), epehdrine, pseudoephedrine, phenylpropanolamine (these last three are usually in cold medicine and sometimes diet pills)
- taking this with an MAOI can cause HTN crisis
What is the usual wash-out period for starting an MAOI? Which SSRI is the exception (you have to wait longer than usual?)
- Usual washout period is two weeks–meaning you don’t start the MAOI until someone has been off of their serotonergic medication for at least two weeks.
- The exception is fluoxetine (which has a longer half-life) and the recommendation is to wait 5 weeks.
Name some MAOIs.
tranylcypromine
isocarboxazid (Marplan)
phenelzine (Nardil)
tranylcypromine (Parnate)
selegiline transdermal (Emsam)*
linezolid (Zyvox)**
* often prescribed to patients with dementia or Parkinson’s
**this is an antibiotic often used when people have allergies to vancomycin
!!!! Take home point is that there are MAOIs that are not used for mental health reasons so be on the lookout for these anytime you’re thinking about prescribing a serotonergic agent to a patient
Describe serotonin syndrome.
Symptoms include abdominal pain and diarrhea (there are lots of 5HT receptors in the GI tract), diaphoresis, hyperpyrexia (elevated temp not due to fever–not due to infection), tachycardia, HTN, myoclonus, delirium, irritability/agitation
How are SSRIs believed to work?
They block presynaptic uptake of serotonin, thus increasing synaptic availability of this NT, not clear why/if this is how they work. If it were a direct effect, you wouldn’t see the 4-8 week lag before symptoms improve.
What are SSRIs used for?
Most commonly depressive (unipolar depression, and cautiously in bipolar depression) and anxiety disorders (including GAD, panic, OCD, PTSD)
What’s the major safety advantage to SSRIs versus older antidepressants?
They are far less cardiotoxic in overdose than TCAs or MAOIs.
What are the most common undesired effects of SSRIs?
- GI upset like nausea and diarrhea, less common to see vomiting (lots of 5HT receptors in the gut, can usually mitigate this with slower up-titration and taking it with food)
- Sexual side effects (up to 30%, do not forget to talk with patients about this–part of informed consent); for some this means decreased libido, anorgasmia, or both
- Restlessness, nervousness, anxiety, possibly akathisia (more pronounced subjective sense of restlessness that is associated with increased risk for violent behavior and suicide)
- Insomnia (often depends on when it’s dosed, usually don’t give SSRIs in the PM or at HS)
- Fatigue/sedation
- Dizziness, tremors, headache
What is the black box warning associated with SSRIs?
- There is an association with increase in suicidal thoughts in some subset of people who take SSRIs (mostly documented in adolescents).
- You need to warn patients of this and instruct them what to do if this occurs (are they going to call you? call the crisis line? go to the ED?)
What should you tell patients about stopping SSRIs and when should you tell them this?
- Tell them before they start taking it (this is part of informed consent) that it is not recommended to stop these abruptly
- There are discontinuation syndromes associated with SSRIs; these vary in terms of severity. Some people don’t experience much, others develop pretty severe flu-like symptoms (nausea, aches, disequilibrium, dysphoria, agitation). For some people this can be pretty severe and may require lengthy tapers so warn people up-front.
Name the most common SSRIs
paroxetine (Paxil)
fluoxetine (Prozac)
citalopram (Celexa)
sertraline (Zoloft)
escitalopram (Lexapro); s-enantiomer of citalopram
fluvoxamine (Luvox)
vilazodone (Viibryd); newer, not used much yet
What is the dosing for paroxetine (Paxil)?
paroxetine: start 10-20/day, incr by 10mg increments weekly; max of 60mg daily
ER formulation: 25mg to start, can go up to 62.5mg/day by increasing 12.5mg/week
What are things you should consider before usuing paroxetine specifically?
- Has a shorter half-life with some auto-inhibition of metabolism at higher doses so it’s believed to have the worst withdrawal syndrome of the SSRIs
- significant CYP2D6 inhibition which means more likely to have drug-drug interactions (I wouldn’t prescribe this for anyone with HIV or cancer as the drugs they may get to treat those conditions are likely to be affected by paroxetine)
- more anticholinergic than most SSRIs, so pt’s are more likely to gain weight and more likely to have sexual side effects
- more sedating than others so may be a good choice for someone with insomnia and you can consider dosing it at night; however, can cause insomnia in someone who didn’t have it before
What is the typical dosing for fluoxetine?
-can start 10-20mg daily (usually in the AM as it can be activating for some people); can go up to 80mg daily; usually done ~10mg/week increments
