Depression

What is the etiology of depression?

exact cause is unknown; genetics and environment play a role

What are risk factors for developing depression?

inherited (first degree relatives)

females, middle age, alone, low income/unemployed, comorbidities, stressful life event

What medical conditions can cause depression/depression like symtpoms?

• hypothyroidism

• anemia

• HIV/AIDS/STDS

• autoimmune disease

• CV disease

• neurologic disorders (epilepsy, Huntington’s, Parkinson, Alzheimer’s, post-stroke)

What medications can induce depression/ depression like symtpoms?

• cardiovascular (beta blockers, CCBs)

• hormonal (oral contraceptives, steroids)

• antiepileptic drugs (topiramate, levetiracetam)

• opioids

• stimulants, etc.

What classes of medications are first line for uncomplicated MDD?

psychotherapy OR pharmacotherapy

• SSRI

• SNRI

• bupropion

• mirtazapine

• trazadone

• vilazodone

• vortioxetine

What classes of medications are first line for complicated MDD?

psychotherapy PLUS pharmacotherapy

• SSRI

• SNRI

• bupropion

• mirtazapine

• trazadone

• vilazodone

• vortioxetine

What non-pharmacological interventions can be used in MDD?

ECT can be an option based on preference

What is generally seen as first line treatment for MDD?

SSRI or SNRI

What should be done if after 4 weeks of adequate MDD treatment, there is a 50% reduction in symptoms?

continue optimal dose and re-evaluate at 6, 8, and 12 weeks

What should be done if after 4-8 weeks of adequate MDD treatment, full symptoms persisit?

switch to an alternative antidepressant

What should be done if after 8 weeks of adequate MDD treatment, partial symptoms remain?

you can try dose increase or switch to another agent

What is the BBW for ALL antidepressants (regardless of usage)?

increase risk of suicidal thoughts and behaviors ages 24 and younger

What are the contraindications of all antidepressants?

allergy

concomitant MAO-I or MAO-I use within 14 days or less of stopping medication (needs wash out)

True or False: use of antidepressant monotherapy in patients with underlying bipolar disorder can precipitate a switch to mania

true

What DDIs do antidepressants have as a whole?

majority CYP2D6; best to run drug interaction checkers

What usually occurs by week 1 of being on an antidepressant?

improved sleep and appetite, lessening of anxiety

What usually occurs by week 3 of being on an antidepressant?

improved self-care, sex drive, memory, thinking and movements

What usually occurs by week 2-4 of being on an antidepressant?

relief of depressed mood, subsiding of hopelessness and suicidal thoughts, return of please experiences

How do you mitigate anxiety associated with use of antidepressants?

lower doses and titrate slowly

How do you mitigate insomnia or sedation associated with use of antidepressants?

switch the administration time (to morning)

How do you mitigate headaches associated with use of antidepressants?

can treat with OTC PRN for a few days trial to resolve

How do you mitigate gastrointestinal issues associated with use of antidepressants?

give dose with food

How do you mitigate weight gain associated with use of antidepressants?

explore diet/exercise or switch agents if needed

How do you mitigate sexual side effects associated with the use of antidepressants?

usually a switch is needed; alternatives include bupropion, vortioxetine, etc.

What class of medication is citalopram?

SSRI

What class of medication is escitalopram?

SSRI

What class of medication is fluoxetine?

SSRI

What class of medication is fluvoxamine?

SSRI

What class of medication is paroxetine?

SSRI

What class of medication is sertraline?

SSRI

What are the FDA indications for citalopram?

MDD

What are the FDA indications for escitalopram?

MDD, GAD

What are the FDA indications for fluoxetine?

MDD, OCD, Panic, PMDD, bulimia

What are the FDA indications for fluvoxamine?

OCD

What are the FDA indications for paroxetine?

MDD, GAD, OCD, Panic, PTSD, PMDD, SAD

What are the FDA indications of sertraline?

MDD, OCD, Panic, PTSD, PMDD, SAD, bulimia

What are the universal considerations for SSRIs?

increased bleeding, hyponatremia, serotonin syndrome, sexual side effects, seizures, activation of mania, angle closure glaucoma, discontinuation syndrome

What needs to be monitored with the first dose of SSRIs?

• cognitive/motor impairment/sedation

• allergic reactions

• first few days/weeks: increased anxiety, GI symptoms, headaches

• anticholinergic effects

What specific considerations does citalopram have?

• QT prolongation

• maximum dose for elderly over 60 years: 20 mg/day

What specific considerations does escitalopram have?

• risk of use in patients with concomitant illness

• maximum dose for elderly over 60 years: 10 mg/day

What specific considerations does fluoxetine have?

• reduced appetite and weight

• anxiety and insomnia

• long half-life (only SSRI with a once weekly dose option)

What specific considerations does fluvoxamine have?

• many significant drug interactions

• not approved for MDD

What specific considerations does paroxetine have?

• risk for us in pregnancy

• risk of bone fractures

• akathisia

• short half-life and anticholinergic side effects

What specific considerations does sertraline have?

false positive urine screens for BZDs

What are the FDA indications for desvenlafaxine?

MDD

What are the FDA indications for duloxetine?

MDD, GAD, fibromyalgia, musculoskeletal pain, neuropathic pain

What are the FDA indications for venlafaxine?

MDD, GAD, panic disorder, social phobia

What are the FDA indications for levomilnacipran?

MDD

What class of medication is desvenlafaxine?

SNRI

What class of medication is duloxetine?

SNRI

What class of medication is venlafaxine?

SNRI

What class of medication is levomilnacipran?

SNRI

True or False: all SNRI agents may pose increased risk of BP elevation

true

What medication class is amitryptyline?

TCA

What medication class is amoxapine?

TCA

What medication class is clomipramine?

TCA

What medication class is desipramine?

TCA

What medication class is doxepin?

TCA

What medication class is imipramine?

TCA

What medication class is nortrptyline?

TCA

What medication class is maprotiline?

TCA (tetracyclic?)

What are the FDA indications of amitriptyline?

MDD

What are the FDA indications of amoxapine?

MDD

What are the FDA indications of clomipramine?

OCD

What are the FDA indications of desipramine?

MDD

What are the FDA indications of doxepin?

MDD

What are the FDA indications of imipramine?

MDD

What are the FDA indications of nortyptyline?

MDD

What are the FDA indications of maprotiline?

MDD

What unique considerations does amitriptyline have?

• tertiary amine

• may cause urine discoloration

What unique considerations does amoxapine have?

EPS (TD) and NMS reported with use

What unique considerations does clomipramine have?

• side effects and availability of other agents with less risk limits use

• can cause blood dyscrasias

What unique considerations does desipramine have?

• metabolite of imipramine

• secondary amine

What unique considerations does doxepin have?

• Silenor (low dose doxepin) brand name only for insomnia, not depression

What unique considerations does imipramine have?

tertiary amine

What unique considerations does nortriptyline have?

• metabolite of amitriptyline

• secondary amine

What unique considerations does maprotiline have?

not readily available

What class of medication is isocarboxazid?

MAOi

What class of medication is selegiline?

MAOi

What class of medication is phenelzine?

MAOi

What class of medication is tranylcypromine?

MAOi

What unique considerations does isocarboxazid have?

• nonselective irreversible MAO inhibitor

• increases 5HT, NE, and DA in synapse

• contraindications: CVD, HTN or treatment with BP meds, hepatic impairment, severe renal impairment, history of headache, excessive caffeine intake

What unique considerations does selegiline have?

• irreversible selective MAO-B inhibitor (selectivity dose dependent; MAO-B at clinical doses, MOA-A at higher doses)

• patch avoids first pass metabolism; must rotate sites

• cannot be used in children under the age of 12

True or False: all MAOis available in the US are irreversible

true

What does MAO-A inhibition reduce?

the breakdown of primarily serotonin, norepinephrine, and dopamine

What does MAO-B inhibitor reduce?

the breakdown mainly of dopamine and phenethylamine

Which MAOi subtype does not have dietary restrictions?

MAO-Bi

Which MAOi are nonselective?

phenelzine and tranylcypromine

What is the wash out period from antidepressants before starting MAOis?

2 weeks

What is the wash out period for MAOis from fluoxetine?

5 weeks

What unique considerations does phenelzine have?

• nonselective irreversible MAO inhibitor

• contraindication: heart failure, hypertension or treatment with BP meds, hepatic impairment, severe renal impairment

• avoid in pregnancy

• peripheral neuropathy reported (influences pyridoxine metabolism); can give supplemental B6 if observed

What unique considerations does tranylcypromine have?

• nonselective irreversible MAO inhibitor

• has additional effects like amphetamines

• contraindications: CVD, HTN or treatment with BP meds, hepatic impairment, history of headache

• hypoglycemia reported in diabetes

What are contraindications for MAOis?

• allergy

• concomitant MAOi or MAOi use within 14 days or less of stopping SNRI

• pheochromocytoma

• concomitant use of sympathomimetics or serotonergic agents

• tyramine containing foods

• discontinue for no less than 10 days prior to elective surgery

What are tyramine examples?

aged cheeses, aged meats, wine, tofu, soy sauce, pickled foods, etc. 

What class of medication is bupropion?

NDRI

What additional contraindications does bupropion have?

seizure disorder or any other condition predisposing risk

current or prior diagnosis of bulimia or anorexia

What unique considerations does bupropion have?

• may increase blood pressure

• wakefulness/activation and insomnia

• associated with less sexual side effects compared to other AD

• do not exceed dose prescribed per administration and separate twice daily doses by no less than 8 hours unless clinically directed otherwise

• many different brands have different max dose per administration

• consider neuropsychiatric adverse events suicide risk (smoking cessation)

• transaminase elevations have been reported

What is the MOA of buproprion?

inhibits NE and DA transporters, increasing their concentrations in the synapse; no notable serotonergic effects

What unique considerations does bupropion with dextromethorphan have?

• risk of serotonin syndrome is grater, embryo-fetal toxicity, may cause hyperhidrosis

• warn patients not to take more than 2 ER tablets a day and allow minimum of 8-hour intervals between doses

What is the purpose of bupropion with dextromethorpan?

boost through CYP2D6 inhibition