Pharm - Mood Disorders Flashcards
What patient should be considered for lifelong maintenance therapy for major depression?
- < 40 years old with 2+ episodes
- Any age with 3+ episodes
What is the goal of therapy?
- to prevent recurrence to prevent lifelong treatment
- Acute: 6-12 weeks, goal: remission
- Continuation: 4-9 months, goal: eliminate residual symptoms/prevent relapse
- Maintenance: 1-3 years, goal: prevent recurrence
What is the preferred medication for the initial treatment of major depression?
-combo of pharmacotherapy and psychotherapy or either alone (dependent on patient willingness/ability)
What is the initial choice and why is it preferred?
- initial choice is empirical
- SSRI usually preferred d/t more benign side effects and minimal risk of lethal effects when taken for intentional suicide
What is the initial tx for pt with comorbid anxiety disorders?
start on lower dose SSRI than normal and titrate up to minimal usual total daily dose (therapeutic dose)
What is the timeline for evaluating pt response to tx?
- early improvement/response is usually apparent in 1-2 weeks in unipolar major depression patients
- early improvement during initial treatment predicts eventual remission
What is the duration of adequate trial?
- Unipolar major depression: 6-12weeks before deciding if they’ve worked
- if they show little improvement (<25% reduction in sx) after 4-6 weeks, move to next-step tx
List the SSRIs
- citalopram
- escitalopram
- fluoxetine
- paroxetine
- sertraline (drug of choice)
List the SNRIs
- newer-generation
- tricyclic antidepressants
Newer generation:
- desvenlafaxine (active metabolite of venlafaxine)
- venlafaxine (immediate release-IR and extended release-XR)
- levomilnacipran
- milnacipran
- duloxetine (IR and XR)
Tricyclic:
- amitriptyline
- imipramine
- doxepine
- nortriptyline
- desipramine
List the NE/dopamine reuptake inhibitor
bupropion (IR, SR, XR)
List the serotonin/α2-adrenergic receptor antagonist
mirtazapine
List the MAOIs
- phenelzine
- selegiline transdermal
- tranylcypromine
List the serotonin modulators
- nefazodone
- trazodone
- vilazodone
- vortioxetine
Compare the half-life of fluoxetine with other SSRIs
- Fluoxetine has really long half-life: usually 2-4 days, most SSRIs are about 1 day
- Norfluoxetine is 7 to 15-day half-life
What is the advantage of fluoxetine’s half-life?
- treatment adherence; protects from discontinuation syndrome
- abrupt stop will not cause as many withdrawal symptoms; those are more likely with shorter half-life
List the SSRIs that have significant CYP2D6 inhibition
- best
- modest
- no effect
- other
- best: fluoxetine and paroxetine
- modest: sertraline
- no effect: citalopram and escitalopram less chance for drug-drug interactions
- Paroxetine
What is unique about Paroxetine?
it has non-linear kinetics so a high dose = very high plasma drug concentrations
Which clinical presentation is most associated with SSRI-induced sexual dysfunction?
- MC with paroxetine, moderate risk with remaining
- occurs in both men and women: decreased libido, difficulty achieving orgasm, erectile dysfunction in 37% of males
What is an appropriate tx plan for pts experiencing SSRI-induced sexual dysfunction?
- switch to non-SSRI: bupropion, mirtazapine, nefazodone (serotonin modulator)
- switch to different SSRI
- augment SSRI therapy: add bupropion/phosphodiesterase inhibitor (Viagra, sildenafil)
- -Bupropion not great as monotherapy but great in combination
% of drowsiness with SSRI use
17% - daytime sedation leads to malaise, diminished mental energy, emotional blunting
% of weight gain with SSRI use and associated risk for diabetes with long-term use
- 12% - unsure if due to SSRI or remission of depression that causes increased appetite/carb craving and change in serotonin receptor activity
- MC with paroxetine
- pt can be twice as likely to get DM 2 when used >24 months
% of increased anxiety with SSRI use
-tx
- 11% see increase in anxiety/agitation when starting SSRI
- need to anticipate this and treat highest-risk patients with antianxiety meds
- overtime SSRI doesn’t improve anxiety associated with depression
Orthostatic hypotension with SSRI use
- all cause low degree
- MC with Paroxetine
Nausea, vomiting, and diarrhea with SSRI use
- Nausea = 6%, all SSRIs associated with transient nausea/GI upset during initiation/dose increase
- MC with paroxetine/sertraline
- diarrhea: MC with sertraline
Cardiac and dosage considerations with citalopram
QTC prolongation, limit dose in elderly pts***
- dose limit in everyone = 40mg/day
- dose limit in > 60 years old = 20mg/day
- NOT recommended for patients with bradycardia, hypokalemia, hypomagnesemia, recent MI, uncompensated HF
Why are SSRI and SNRI on the Beers list?
Because of potential to cause/exacerbate SIADH or hyponatremia - monitor Na2+ closely when initiating/adjusting dose
What SSRI drugs are less likely or more common to have withdrawal symptoms?
- less likely with SSRI with longer half life
- MC with paroxetine, least common with fluoxetine
*taper drugs over 1-2 weeks
List the withdrawal symptoms
- sensory sx: paresthesia, numbness, electric-shock-like sensation, palinopsia (visual trails)
- disequilibrium: light-headedness, dizziness, vertigo
- general somatic sx: lethargy, headache, tremor, sweating, anorexia
- affective sx: irritability, anxiety/agitation, low mood, tearfulness
- GI sx: N/V/D
- sleep disturbance: insomnia, nightmares, excessive dreaming
Mnemonic for withdrawal symptoms
FINISH: Flu-like symptoms Insomnia Nausea Imbalance Sensory disturbances Hyperarousal
List the anticholinergic and adrenergic side effects of the older tricyclic antidepressants (SNRIs)
Anticholinergic: dry mouth, constipation, blurred vision, urinary retention, dizzy, tachy, memory impairment/delirium (w/high doses)
Adrenergic: orthostatic hypotension, cardiac conduction delay, AV conduction block, sever arrhythmias in overdose
List the severe Despiramine (tricyclic antidepressant, SNRI) side effects
increase death risk in pts with FHx of sudden cardiac death, cardiac conduction disturbances, dysrhythmias
Effects of the SNRI drugs on NE and serotonin reuptake
- inhibit neuronal reuptake of serotonin at low doses
- inhibit NE at higher doses
- serotonin inhibition 5x more potent that NE inhibition
What does the “washout” period refer to when switching from an SSRI/SNRI to a MAO inhibitor and vice versa?
- SNRIs are contraindicated if take MAO inhibitor in last 2 weeks because drug-drug interactions leading to serotonin syndrome
- if d/c SNRI and starting MAOI wait 2 weeks b/w last dose of SNRI and first dose of MAOI
HTN with SNRI use
- cause
- monitoring
- NE increase BP: dose related effect
- BP monitoring ongoing/regularly assessed (esp. if they have pre-existing HTN)
Which SNRIs are weight neutral?
- levomilnacipran and milnacipran
- most of their effect is on NE
- DON’T use in pt with HTN/CV disease, ESRD, glaucoma
Which SNRI increases bleeding in patients on anticoag?
Velafaxine
What is the role of bupropion in the treatment of unipolar depression?
commonly used as augmenting agent in combination with other antidepressants (SNRI or mirtaxepine) for depression treatment
Increased risk of seizures with buproprion and when it should be avoided
- side effect of seizures is dose related
- contraindicated in patients with seizure disorder
- use with caution in patients on drugs that lower seizure threshold
How can you decrease insomnia with buproprion?
Educate patient to not take drug too late in the day (example: no later than 2pm)
Weight gain with mirtazapine use
about 1-3kg weight gain in 10+%
Which drug (and class) is not associated with sexual dysfunction? -how to use
mirtazapine, a serotonin/α2-adrenergic receptor antagonist
-alternate use if pt can’t tolerate SNRI (not an adjunctive therapy)
ADR of mirtazapine
dry mouth and drowsiness are MC
*sedative action because of activity on histamine receptors
Which foods high in tyramine can precipitate a hypertensive crisis in patients taking MAOI?
- cheese
- wine
- beer
- processed meat
- coffee
- chocolate
- raisins
- fava beans
- soy sauce
- sour cream
- sauerkraut
- ripe avocado
- liver
- sardines
Why is there a high incidence of sedation with trazodone use?
Due to it being a histamine HI receptor
How do you diagnose serotonin syndrome?
- Serotonergic drug + symptom cluster
- spontaneous clonus
- inducible clonus AND agitator OR diaphoresis
- ocular clonus AND agitation OR diaphoresis
- tremor AND hyperreflexia
- hypertonia AND temperature >38°C AND spontaneous/inducible ocular clonus
Serotonergic exposure + rigid muscle tone + dry mucous membranes + dilated pupils + increased bowel sounds + hyperreflexia
Central management of serotonin syndrome
-discontinue serotonergic agents
-supportive care to stabilize vital signs
sedate with benzodiazepine
-administer serotonin antagonists
Tx of serotonin syndrome based on severity of illness
-mild
Mild: discontinue inciting meds, supportive cares, sedate with benzo
Tx of serotonin syndrome based on severity of illness
-moderate
Moderate: more aggressive tx of autonomic instability + tx with serotonin antagonist
Autonomic instability: treat HTN/tachy with short acting agents like esmolol/nitroprusside; treat hypotension from MAOIs with low doses of direct acting sympathomimetic amines; control hypothermia (immediate sedation, paralysis, intubation if >41.1°C
Tx of serotonin syndrome based on severity of illness
-hyperthermic
critically ill - paralysis and ET intubation
Tx of serotonin syndrome based on severity of illness
-supportive care
O2 to maintain SpO2≥94%, IV fluids for volume depletion, continuous cardiac monitoring, correction of vital signs
Benzos in serotonin syndrome
used for sedation to control agitation and correct mild increases in BP/HR
