Ch. 62 Depression

Stabinsky

background

people with depression usually suffer with persistent feelings

causes

neurotransmitters involved include 5-HT, NE, epi, dopamine, glutamate, and acetylcholine

5-HT may be the most important

diagnosis

diagnostic and statistical manual of mental disorders, 5th edition (DSM-5-TR)

HDRS, also known as Ham-D is the most widely used depression assessment scale

DSM-5 criteria

at least 5 of the following symptoms present during the same two week period (must include depressed mood or diminished interest/pleasure):

Sleep - increased or decreased

Interest/pleasure - diminished

Guilt of feelings of worthlessness

Mood - depressed

Energy - decreased

Concentration - decreased

Appetite - increased or decrease

Psychomotor agitation or retardation

Suicidal ideation

** remember --> SIG ME CAPS

concurrent bipolar or anxiety disorders

must rule out bipolar disorder before initiating antidepressant therapy to avoid inducing mania or causing rapid-cycling

benzos should not be used alone; can be problematic in patients with concurrent SUD --> risk for physiological dependence, withdrawal symptoms, and respiratory depression and death

key drugs that can cause or worsen depression

ADHD meds --> atomoxetine (strattera)

analgesics --> indomethacin

antiretrovirals (NNRTIs) --> efavirenz, rilpivirine

CV meds --> beta-blockers (esp. propranolol)

hormones --> contraceptives, anabolic steroids

other -->

antidepressants

benzos

systemic steroids

interferons

varenicline

ethanol

medical conditions --> stroke, PD, dementia, MS, hypothyroidism, low vitamin D, metabolic conditions, malignancy, OAB, ID

natural products

st. john's wort --> enzyme inducer

SAMe

5-HTP

** all increase the risk for serotonin syndrome

drug treatment

the initial choice is based on side effect profile, safety concerns, and patient-specific symptoms

for most patients, SSRI or SNRI is preferred

depression in pregnancy and postpartum depression

psychotherapy is first line for depression during pregnancy

medications may be necessary --> SSRIs are first line options --> there is a warning for use during pregnancy and risk of persistent pulmonary hypertension of the newborn

paroxetine should be avoided due to cardiac effects

SSRIs are preferred for treating postpartum depression

safety issues with antidepressants

MAOIs such as phenelzine, tranylcypromine, and isocarboxazid is restricted

serotonin syndrome can occur with the admin of one or more serotonergic meds --> risk is most severe when an MAOI is combined with another serotonergic med --> higher doses also increase risk

if a med is being DC, it should be tapered over several weeks --> an exception to this rule is fluoxetine because of its long half-life

symptoms of serotonin syndrome

severe nausea

dizziness

HA

diarrhea

agitation

tachycardia

hallucinations

muscle rigidity

BBW and med guides

all antidepressants carry a BBW of possible increase in suicidal thoughts or actions in children, teens, or young adults

medguides are required

lag effect and suicide prevention

all meds must be taken daily and will take time to work

physical symptoms such as low energy will improve within 1-2 weeks but psych symptoms may take a month or longer

SSRIs

increase serotonin

SSRI drugs

citalopram (celexa) --> max dose 40mg/day (20mg/day if >60yo)

escitalopram (lexapro) --> max dose 20mg/day (10mg/day if >60yo)

fluoxetine (proxac) + olanzapine (symbyax) --> take symbyax at night

paroxetine (paxil) --> brisdelle: for vasomotor symptoms

sertraline (zoloft)

SSRI CIs

do not use with MAOIs or linezolid

brisdelle --> pregnancy

SSRI warnings

QT prolongation --> do not exceed citalopram 20mg/day or escitalopram 10mg/day in elderly (>60yo)

SIADH/hyponatremia, fall risk

bleeding

SSRIs SEs

sexual side effects

somnolence, insomnia, nausea, dry mouth, diaphoresis, weakness, tremor, dizziness, HA

most activating --> fluoxetine (take in AM)

most sedating --> paroxetine (take in PM)

SSRI notes

fluoxetine, paxil CR, and sertraline are also approved for PMDD

sertraline is preferred in patients with cardiac risk

SSRI drug interactions

MAOIs and serotonin syndrome or HTN crisis --> do not initiate in patients receiving linezolid or methylene blue due to serotonin syndrome risk

allow a 2 week washout period between MAOIs and SSRIs --> fluoxetine is the only exception due to its long half-life (needs a 5-week washout)

QT prolongation mostly noted with citalopram and escitalopram --> careful for additive QT prolongation risk

increase bleeding risk when used with anticoagulants, antiplatelets, NSAIDs, 5 Es, fish oils

fluoxetine and paroxetine are CYP2D6 inhibitors --> tamoxifen requires conversion to its active form by CYP2D6 --> decreased tamoxifen --> venlafaxine is preferred in combo with tamoxifen

SSRI combined mechanism

SSRI and 5-HT1A partial agonist --> vilazodone (viibryd) --> take with food

SSRI, 5-HT3 receptor antagonist, and 5-HT1A agonist --> vortioxetine (trintellix)

SSRI combo details

CIs --> do not use within 14 days of MAOIs

SEs --> decreased libido, but less sexual SEs than SSRIs and SNRIs

SNRIs

increase 5-HT and inhibit the reuptake of NE

SNRI drugs

venlafaxine (effexor XR) --> depression, GAD, panic disorder, social anxiety --> max dose: 375mg/day (IR)

duloxetine (cymbalta) --> depression, peripheral neuropathy, fibromyalgia, GAD, chronic musculoskeletal pain

desvenlafaxine (pristiq)

levomilnacipran (fetzima)

SNRI CIs

SNRIs and MAOIs

SNRI warnings

SIADH/hyponatremia

fall risk

bleeding

SNRI SEs

similar to SSRIs

increased HR

dilated pupils

dry mouth

excessive sweating

constipation

increased BP (all have risk, especially at higher doses)

SNRI drug interactions

SNRIs and MAOIs can cause HTN crisis or serotonin syndrome if used together --> a washout period is needed

do not initiate in patients receiving linezolid or IV methylene blue due to risk of serotonin syndrome

additive QT prolongation risk with venlafaxine

duloxetine is a moderate 2D6 inhibitor

increased bleeding risk with other drugs that increase bleeding risk

TCAs

block ACh and histamine receptors

secondary amines are selective for NE

tertiary amines are more effective, but have a worse side effect profile

TCA tertiary amines

amitriptyline --> QHS

doxepin --> silenor for insomnia

TCA secondary amines

nortriptyline (pamelor)

amoxapine

desipramine

maprotiline

protriptyline

TCA CIs

do not use with MAOIs, linezolid, or IV methylene blue

TCA SEs

cardiotoxicity --> QT prolongation with overdose (monitor for suicidal ideation, as overdose can quickly cause fatal arrhythmias); orthostasis

anticholinergic --> dry mouth, blurred vision, urinary retention, constipation

weight gain

seizures

falls

TCA notes

tertiary amines have increased anticholinergic properties

TCA drug interactions

MAOIs and HTN crisis --> 2 week washout

additive QT prolongation

DA and NE reuptake inhibitor

bupropion (wellbutrin SR, wellbutrin XL) --> do not exceed 450mg/day due to seizure risk

wellbutrin XL is also approved for seasonal affective disorder

bupropion SR (zyban) --> for smoking cessation + naltrexone (contrave) --> for weight loss

bupropiion SIs

seizure disorder

hx of anorexia/bulemia

use with MAOIs, linezolid, IV methylene blue or other forms of bupropion

bupropion SEs

dry mouth

insomnia, restlessness

tremors/seizures (dose related)

weight loss

sexual dysfunction is rare

bupropion drug interactions

do not use multiple forms of bupropion

increased risk of HTN crisis with MAOIs

MAOIs

inhibit monoamine oxidase, which breaks down catecholamines --> can lead to HTN crisis

MAOI drugs

isocarboxazid (marplan)

phenelzine (nardil)

tranylcypromine (parnate)

selegiline transdermal patch (emsam) --> MAO-B selective

MAOI warnings

DDI and DFI --> if missed, it could be fatal

HTN crisis or serotonin syndrome can occur when taken with TCAs, SSRIs, SNRIs, many other drugs, and tyramine-rich foods

MAOI drug interactions

to avoid HTN crisis and serotonin syndrome, MAOIs cannot be used with drugs that increase epi, NE, DA, or serotonin

CI --> linezolid, lithium, tramadol, opioids, St. John's wort

CI with tyramine-rich foods --> aged cheese, pickled herring, yeast extract, air-dried meats, sauerkraut, soy sauce

foods become high in tyramine when they have been aged, fermented, pickled, or smoked

MAOIs --> keep them separated

to avoid serotonin syndrome and HTN crisis -->

2 week washout is required between MAOIs and SSRIs, SNRIs, TCAs, and bupropion

5 week washout is required when changing from fluoxetine to an MAOI

mirtazapine

remeron

TCA

can help with sleep and appetite as well

CI --> MAOIs, methylene blue, linezolid

SEs --> sedation, increased appetite, weight gain

trazadone

inhibits 5-HT reuptake, blocks H1 and alpha-1 receptors

taken at night for sleep

CI --> MAOIs, methylene blue, linezolid

SEs --> sedation, priapism

nefazodone

inhibits 5-HT and NE reuptake, blocks 5-HT2 and alpha-1 receptors

rarely used due to hepatotoxicity --> BBW

selecting the best antidepressant

the antidepressant selected should incorporate patient-specific info and history

did it work? if an antidepressant was taken at a reasonable dose for 4-8 weeks and did not work well, do not use it again

was it well tolerated? do not choose a treatment that was poorly tolerated in the past

does the patient have comorbid conditions that make a drug a good or poor choice?

cardiac/QT risk

sertraline preferred

do not choose a QT-prolonging drug/dose (high doses of citalopram or escitalopram)

watch for additive QT effects when SSRIs, SNRIs, TCAs, mirtazapine or trazadone are used with other QT prolonging drugs

smoker

bupropion SR is FDA approved for smoking cessation

peripheral neuropathy or pain

consider duloxetine

taking serotonergic antidepressants

avoid multiple serotonergic meds due to risk of serotonin syndrome

increased bleeding risk with anticoagulants, antiplatelets, NSAIDs, and some natural produts

seizure disorder or at risk for seizures

do not use bupropion

pregnant

do not use paroxetine

mild-moderate depression --> psychotherapy is first line

certain SSRIs (escitalopram, sertraline) are first line if using drug therapy

daytime sedation

do not take a sedating drug early in the day (paroxetine, mirtazapine, trazodone)

activating medications taken in the morning are preferred (fluoxetine, bupropion)

insomnia

do not take an activating drug later in the day (bupropion, fluoxetine)

sedating meds taken at night are preferred (paroxetine, mirtazapine, trazodone)

sexual dysfunction

high risk with SSRIs and SNRIs

lower risk with bupropion and mirtazapine

treatment-resistant depression

APA guidelines state that a patient should receive a 4-8 week trial of medication at a therapeutic dose

after this, you can:

increase the dose

augment with buspirone or an atypical antipsychotic --> approved agents are aripiprazole, olanzapine + fluoxetine, quetipaine ER

augment with lithium

antipsychotics

aripiprazole (abilify)

olanzapine + fluoxetine (symbyax)

quetiapine (seroquel)

brexpiprazole (rexulti)

cariprazine (vraylar)

antipsychotic BBW

elderly patients with dementia-related psychosis are at increased risk of death

antipsychotic CI

symbyax --> do not use with MAOIs, linezolid, or methylene blue

antipsychotic SEs

aripiprazole --> anxiety, insomnia, akathisia

olanzapine --> sedation, weight gain, increased lipids, increased glucose

quetiapine --> sedation, orthostasis, weight gain, increased lipids, increased glucose

NMDA receptor antagonist

esketamine --> nasal spray

must be taken under supervision of HCP

REMS

all antidepressant counseling

can cause suicidal ideation

medguide required

can take 1-2 weeks to feel a benefit from this drug and 6-8 weeks to feel the full effect on mood

SSRI counseling

can cause sexual dysfunction and serotonin syndrome

fluoxetine --> take in the morning

SNRI counseling

can cause increased BP, increased sweating, sexual dysfunction, and serotonin syndrome

ghost tablet in stool (pristiq)

TCA counseling

can cause anticholinergic effects and orthostasis

bupropion counseling

can cause insomnia

MAOI counseling

can cause serotonin syndrome

many drug interactions

other antidepressant counseling

trazodone --> take at bedtime; can cause priapism

mirtazapine --> take at bedtime