Pharm Test 2, Week 5

What is the most common psychiatric disorder?

depression

All classes of antidepressant drugs are equally ___________; differences are mainly in _________ and __________.

effective; side effects; drug interactions

What are patients taking antidepressants at risk for especially early during the treatment course?

suicide

For patients taking antidepressants at risk for suicide, what two interventions should take place?

• close observation (especially for kids, adolescents and adults under 25)

• prescriptions should be for the smallest number of doses

If suicidal thoughts emerge while a patient is taking antidepressants, what two interventions should take place?

• switch antidepressants

• consider temporary hospitalization

What is the most commonly prescribed antidepressant class?

SSRIs

How do SSRIs work?

Just like the name - blocks neuronal reuptake of serotonin, increasing concentration of serotonin in the synapse, enhancing receptor activation

SSRI ADRs

• sexual dysfunction (70% of users)

• nausea

• HA

• nervousness

• insomnia

• anxiety

• weight gain

SSRIs are _________ than TCAs and MAOIs.

safer

What is the onset of serotonin syndrome?

within 2-72 hrs of starting treatment

S/sx of Serotonin Syndrome

• agitation

• confusion

• hallucinations

• incoordination

• myoclonus

• hyperreflexia

• sweating

• tremors

• fever

What is the treatment for serotonin syndrome?

drug discontinuation

When discontinuing SSRIs/SNRIs, you should taper the dose slowly to reduce the risk of ___________.

Withdrawal Syndrome

Concurrent use of SSRIs/SNRIs and MAOIs is contraindicated because…..

it increases the risk of serotonin syndrome

Fluoxetine (an SSRI) should be administered cautiously with TCAs and Lithium because….

fluoxetine can elevate plasma levels of TCA/Lithium

Concurrent use of SSRIs and antiplatelets/anticoagulants increases risk of

GI bleeding (displaces warfarin, increasing bleeding risk)

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) MOA

blocks re-uptake of serotonin and norepinephrine

Venlafaxine (Effexor) - class, MOA

SNRI, blocks NE and 5-HT (serotonin) re-uptake, weakly blocks dopamine

Before starting an SNRI, an MAOI should be withdrawn at least ________ days prior to starting the SNRI.

14 days

Before starting an MAOI, an SNRI should be withdrawn at least _________ days prior to starting the MAOI.

7 days

Before starting an SSRI, a MAOI should be withdrawn at least __________ days prior to starting the SSRI.

14 days

Before starting an MAOI, an SSRI should be withdrawn at least __________ before starting the MAOI.

5 weeks

Tricyclic Antidepressants (TCAs) - MOA

block neuronal re-uptake of NE and serotonin

TCAs - adverse effects

• orthostatic hypotension

• sedation

• anticholinergic effects (dry mouth, blurred vision, photophobia, constipation, urinary hesitancy, tachycardia)

• cardiac toxicity (slowed conduction, risk of dysrhythmias)

• seizures (lowers threshold for seizures)

TCAs and MAOIs combination therapy should be avoided because it leads to

excessive adrenergic stimulation (creates an excess of NE) leading to severe HTN

Why is overdosing on TCAs life threatening?

Because the lethal dose is only eight times the average therapeutic dose

Symptoms of TCA toxicity:

primarily from anticholinergic and cardiotoxic actions

• dysrhythmias, blocks, vtach, vfib

• peripheral muscarinic blockade- hyperthermia, flushing, dry mouth, pupil dilation

• CNS symptoms - confusion, agitation, hallucinations, seizures, coma

Monoamine Oxidase enzyme MOA

breaks down NE, serotonin and dopamine into inactive products

inactivates tyramine and other biogenic amines in food

What are the two types of MAO Enzymes and what do they do?

MAO-A: inactivates NE and serotonin in the brain; acts on dietary tyramine in the intestine and liver

MAO-B : inactivates dopamine in the brain

MAOIs - MOA

blocks MAO enzyme thus increasing NE and 5-HT (serotonin) availability

Why would we choose to put a patient on an MAOI?

for patients with atypical depression or with depression that are unresponsive to other treatments

Patients on MAOIs need to avoid tyramine-rich foods because it can trigger

hypertensive crisis

Tyramine-rich foods include:

• aged cheeses

• cured meats

• fermented products

Patients on MAOIs should also avoid which foods (along with tyramine-rich foods)?

• caffeine (coffee, tea, chocolate)

• foods containing phenylethylamine (chocolates, wine)

Transdermal selegiline (Emsam) - class, MOA, advantage

MAOI, inhibits MAO enzyme to increase serotonin and NE levels, absorbs through the skin, lowers risk of HTN crisis from dietary tyramine at low doses

Bupropion - class, MOA, effects

class - atypical antidepressants

MOA - related to blockade of dopamine/NE reuptake

effects: similar to amphetamine - stimulant/appetite suppression

Bupropion’s effects are similar to what drug?

amphetamine

What is the most concerning side effect of bupropion?

seizures

Combined use of bupropion and CYP2D6 inhibitors (sertraline, fluoxetine, paroxetine) should be avoid because?

increases risk of seizures

Mirtazapine - class, MOA, ADRs

atypical antidepressant

increases release of serotonin and NE by blocking presynaptic a2 adrenergic receptors

somnolence, weight gain, increased appetite, elevated cholesterol

What drug just shouldn’t be combined with other antidepressants?

MAOIs

What is the differentiating factor between “baby blues” and peripartum depression?

Baby blues symptoms develop a few days after delivery and resolve by day 10

peripartum depression lasts for months and can worsen over time

What the DSM-5 diagnostic criteria for peripartum depression?

symptoms must begin within 4 weeks of delivery

What is the diagnostic criteria for postpartum depression?

symptoms must begin within 3 months of delivery

What is thought to be a major cause of peripartum depression?

• hormonal changes - estrogen and progesterone levels sharply drop after delivery

Safe antidepressants for postpartum/peripartum depression patients

sertraline (zoloft) and some TCAs (nortriptyline, desipramine)

Unsafe antidepressants for peripartum depression treatment?

fluoxetine (prozac) - reaches therapeutic levels in breastfed infants and can cause colic and impaired weight gain

How long should treatment continue for peripartum depression and why?

for at least 6 months after symptom resolution because there is a high relapse rate