63. Depression Flashcards
Neurotransmitters believed to be involved in depression include ____
serotonin, NE, Epi, dopamine, glutamate, and ACh
Note: Serotonin (5-HT) may be the most important NT involved with feelings of well-being
Which tool is the most widely used depression assessment scale?
The Hamilton Depression Rating Scale (HDRS or Ham-D)
DSM-5 Criteria
A least 5 of the following symptoms present during the same 2 week period must include depressed mood or diminished interest/pleasure:
Mood - depressed
Sleep - increased/decreased
Interest/pleasure - diminished
Guilt or feelings of worthlessness
Energy - decreased
Concentration - decreased
Appetite - increased/decreased
Psychomotor agitation or retardation
Suicidal ideation
Mnemonic: M SIG E CAPS
Drugs that worsen depression
ADHD medication = Atomoxetine (Strattera)
Analgesics - Indomethacin
Antiretrovirals (NNRTIs) - efavirenz (in Atripla), Filpivirine (in Complera, Odefsey)
CV meds - beta-blockers (esp propranolol)
Hormones - hormonal contraceptives, anabolic steroids
Other - antidepressants, BZD, systemic steroids, interferons, varenciline, ethanol
Medical conditions that may contribute to depression
Stroke
Parkinson disease
dementia
MS
hypothyroidism
Low vit D levels
Metabolic conditions (e.g. hypercalcemia)
Malignancy
Overactive bladder
Infectious disease
It is necessary to rule out _____ prior to initiating antidepressant therapy for depression to avoid inducing ____ or causing ___
bipolar disorder
inducing mania
causing rapid-cycling (Cycling rapidly between bipolar depression and mania)
When depression and anxiety occur together, __ should not be used alone; they can worsen and/or mask depression and can be problematic in pts with concurrent substance abuse disorders (called Dual Diagnosis)
BZDs
Natural products used in depression
St. John’s wort
SAMe (S-adenosyl-L-methionine)
Valerian
5-HTP (5-hydroxytryptophan)
Note: St.John’s work, SAMe, and 5-HTP can incrased risk of serotonin syndrome
Valerian can cause sedation
St. John’s wort is CYP inducer - lots of DDIs
The initial choice of meds for depression should be based on side effect, safety, pt-specific symptoms. For most pts, _____ is preferred or (with specific concurrent conditions) mirtazapine or bupropion
SSRI or SNRI
First line therapy for mild depression in pregnant pts
Psycho therapy, followed by drug treatment if needed
In pregnant pts with depression, SSRIs are often used initially with the exception of ____, d/t potential ____. Although preferred, there is a warning regarding SSRI use during pregnancy and potential risk of ____
Paroxetine - d/t cardiac effects
Persistent pulmonary HTN of the newborn (PPHN)
___ helps for physical and emotional symptoms of postpartum depression (also considered beneficial for the baby)
Breastfeeding
For nursing moms that require antidepressants, _____ are generally preferred (with the exception of ___ per ACOG recommendations)
SSRIs or TCAs
exception of doxepin
___ a C-IV drug, is FDA-approved for postpartum depression (continuous IV infusion over 60 hrs, can cause excessive sedation)
Brexanolone (Zulresso)
D/t safety concerns (DDIs, drug-food interactions), MOA inhibitors such as _____ are restricted to patients unresponsive to other treatments
Phenelzine, tranylcypromine, isocarboxazid
The risk of serotonin syndrome is most severe when a ____ is administered with another serotonergic med. Higher doses increase risk.
MAOi
S/sx of serotonin syndrome
severe nausea, dizziness, HA, diarrhea, agitation, tachycardia, hallucinations, or muscle rigidity
T/F: D/c antidepressants require taper
True, should be tapered over several weeks to avoid withdrawal (s/sx: anxiety, agitation, insomnia, dizziness, flu-like symptoms)
Exception: fluoxetine (self tapers d/t long half life)
Which antidepressants have higher risk of withdrawal symptoms if not tapered to d/c?
Paroxetine
Venlafaxine
Most antidepressants require taper to avoid withdrawal. An exception is ____ d/t self taper from long half-life
Fluoxetine
All antidepressants carry a boxed warning of possible increase in ____ in some children, teenagers, or young adults within the first few months of treatment or when dose is changed.
suicidal thoughts or actions
T/F: antidepressant meds must be used daily and takes time to work
True
Physical symptoms of depression such as low energy will improve within ____ of medication use but psychological symptoms such as low mood may take ____
1-2 weeks
a month or longer
SSRI MOA
increase 5-HT by inhibiting its reuptake int he neuronal synapse. They weakly affect NE and DA
Examples of SSRIs
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac) (+ olanzapine (Smybyax))
Paroxetine (Paxil)
Sertraline (Zoloft)
Fluvoxamine IR/ER
Note: Paroxetine (Brisdelle) is used for mod-severe vasomotor symptoms a/w menopause
Max dose of citalopram (Celexa)
Max dose 40mg/day
Max dose in elderly (>60yo): 20 mg/day
Max dose of escitalopram (Lexapro)
Max dose 20mg/day
Max dose in elderly 10mg/day
When is fluoxetine/olanzapine (Symbyax) used?
Nightly
Contraindications with SSRIs
Do not use with MAOi, linezolid, IV methylene blue or pimozide
Fluoxetine, paroxetine: do not use with thioridazine
Fluvoxamine: do not use with alosteron, thioridazine, or tizanidine
Sertraline solution: do not use with disulfiram
Brisdelle: pregnancy
Warnings for SSRIs
QT prolongation: do not exceed citalopram 20mg/day in elderly (>60yo) or escitalopram 10mg/day in elderly
SIADH/hyponatremia, fall risk (Beers criteria)
Bleeding (additive risk)
Side effects of SSRIs
Sexual side effects
Somnolence, insomnia, nausea, dry mouth, diaphoresis (dose-related), weakness, tremor, dizziness, HA
Most activating: fluoxetine - take in AM
Most sedating: paroxetine, fluvoxamine - take in PM
Others: osteopenia/osteoporosis, restless leg syndrome
Which SSRI is most activating?
fluoxetine - take in AM
Which SSRI is most sedating?
paroxetine, fluvoxamine - take in PM
Which SSRIs are approved for premenstrual dysphoric disorder (PMDD)
Fluoxetine, paroxetine (Paxil CR) and sertraline
All SSRis are available in solution except ___
fluvoxamine
Which SSRI is preferred in pts with cardiac risk?
Sertraline
Allow a ___ washout between MAOi and SSRIs d/t risk of serotonin syndrome or hypertensive crisis
Exception is fluoxetine d/t long half-life (4-6 days). Requires ____ washout period if switching from fluoxetine
2 week wash out period
5 week wash out period
Do not initiate SSRI in pts receiving ____ d/t serotonin syndrome
linezolid or IV methylene blue
Which SSRIs most commonly cause QT prolongation?
Citalopram and escitalopram
Additive risk with other SSRIs
SSRIs and SNRIs can increase bleeding risk when used with ___
anticoag, antiplatelets, NSAIDs, ginkgo, garlic, ginger, ginseng, glucosamine, fish oils, thombolytics
Which SSRIs are CYP2D6 inhibitors?
Fluoxetine, paroxetine, and fluvoxamine
Concern with use of fluoxetine or paroxetine with tamoxifen
Tamoxifen requires conversion to active form by CYP2D6
Fluoxetine, paroxetine = CYP2D6 inhibitors
Decreased tamoxifen effectiveness if fluoxetine, paroxetine + tamoxifen
Venlafaxine (SNRI) is preferred in combination with tamoxifen
Medication with SSRI and 5-HT1A partial agonist
Vilazodone (Viibryd)
Medication with SSRI, 5-HT3 receptor antagonist, and 5-HT1A agonist
Vortioxetine (Trintellix)
Compare Vilazodone (Viibryd) and vortioxetine (Trintellix) sexual side effects compared to SSRIs and SNRIs
Less sexual side effects
If using SSRI combined mechanism meds like Vilazodone (Viibryd) and vortioxetine (Trintellix), do not use within ___ of MAOi
14 days
SNRI MOA
similar mechanism as SSRIs
Increase serotonin by inhibiting reuptake in neuronal synapse
Also inhibit NE reuptake
Examples of SNRIs
Venlafaxine (Effexor XR) - depression, GAD, panic disorder, social anxiety disorder
Duloxetine (Cymbalta) - depression, peripheral neuropathy (pain), fibromyalgia, GAD, chronic musculoskeletal pain
Desvenlafaxine (Pristiq) - depression
Levomilnacipran (Fetzima) - depression
SNRIs and MAOi can potentially cause ___ is used together
hypertensive crisis or serotonin syndrome
Washout period needed (14 days recommended) if changing between SNRIs and MAOi
Do not initiate in pts receiving linezolid or IV methylene blue d/t serotonin symdrome risk
Additive QT prolongation risk with which SNRI?
Venlafaxine
Concern with duloxetine and tamoxifen
Duloxetine moderate CYP2D6 inhibitor
Tamoxifen requires conversion to active metabolite by CYP2D6»_space; decreased tamoxifen effectiveness
Warnings with SNRIs
SIADH/hyponatremia, fall risk (Beers)
Bleeding (additive risk)
SNRIs have similar side effects to SSRI (d/t decrease 5-HT reuptake). What additional side effects may occur with SNRIs (d/t increased NE)?
Increased HR, dilated pupils (can lead to episode of narrow angle glaucoma), dry mouth, excessive sweating, constipation
When using SNRI, there is a risk of increased ___ (greatest risk with venlafaxine when dose > 150mg/day but all have risk, esp at higher doses)
Increased BP
TCA MOA
inhibit NE and 5-HT reuptake
Blocm ACh and histamine receptors
What are the 2 main categories of TCAs? What are their differences?
Secondary amines = relatively selective for NE
Tertiary amines = slightly more effective but worse side effect profile
Examples of TCA (secondary and tertiary amines)
Tertiary amines:
amitriptyline
doxepine - for depressiona, all are generic; Silenor = insomnia; Zonalon = cream for pruritus
Others: clomipramine (Anafranil), Imipramine (Tofranil), Trimipramine
Secondaty amines:
Nortryptyline (Pmaelor)
Others: amoxapine, desipramine (Norpramin), maprotiline, protrptyline
When is Amitriptyline taken?
Nightly
Contraindications for TCAs
Do not use with MAOi, linezolid, IV methylene blue
MI
Glaucoma and urinary retention (doxepine)
Side effects of TCAs
QT prolongation with overdose (monitor for suicidal ideation, as overdose can quickly cause fatal arrhythmias) - obtain baseline ECG if cardiac risk factors or age > 50 yo
Orthostasis, tachycardia
Anticholinergic - dry mouth, blurred vision, urinary retention, constipation (taper off to avoid cholinergic rebound)
Vivid dreams, weight gain
Fall risk (Beers)
Others: sedation, sweating, myoclonus (muscle twitching - symptom of drug tox)
What type of TCAs have increased anticholinergic properties and are more likely to cause sedation and weight gain?
Tertiary amines (Amitriptyline, doxepine)
Bupropion (Wellbutrin, SR, XL) MOA in depression
Dopamine and NE reuptake inhibitor
Bupropion do not exceed ___ mg/day d/t seizure risk (up to 522mg/day with Aplenzin)
450mg/day
What is bupropion SR (Zyban) indicated for?
Smoking cessation
What is bupropion/naltrexone (Contrave) indicated for?
Weight loss
Contraindications for bupropion
Seizure disorder
Hx of anorexia/bulimia, abruption discontinuation of ethanol or sedatives
Do not use with MAOi, linezolid, Iv methylene blue, or other forms of bupropion
Side effects with bupropion for depresion
Dry mouth, CNS stimulation (insomnia, restlessness), tremors/seizures (dose-related), weight loss
Sexual dysfunction is rare (no effect on 5-HT)
Others: HA/migraine, N/V, constipation, and possible BP changes (more HTN than hypotension
Bupropion has increased risk of ___ with MAOi. Washout period ____ when concerting to a MAOi
hypertensive crisis
14 day
MAOi MOA
Inhibit MAO enzyme, which breaks down catecholamines, including 5-HT, NE, Epi, and DA (if these NTs increase dramatically, hypertensive criss and death can result
MAOi exampels
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Selegine transdermal patch (Emsam) - MAO-B selective inhibitor
MAOi warnings
Not commonly used, watch for DDIs and drug-food interactions - if missed, can be fatal
Hypertensive crisis or serotonin syndrome can occur when taken with TCAs, SSRIs, SNRIs, many other drugs and tyramine-rich foods
If using MAOi, contraindicated drugs that increase serotonin syndrome risk include ____
linezolid, lithium, tramadol, opioids, St. John’s wort
SSRIs, SNRIs, mirtazapine, trazodone, triptans, buspirone, and dextromethorphan
MAOi is contraindicated with tyramine-rich foods that increase NE. What are some examples?
Aged cheese, pickled herring, yeast extract, air-dried meats, sauerkraut, soy sauce
Basically anything aged, fermented, pickled, smoked
Which antidepressant meds require 2 week washout period between MAOi
SSRIs, SNRIs, TCAs, bupropion
Exception: fluoxetine - 5 week wash out if switching from fluoxetine to MAOi
Mirtazapine MOA and place in therapy
Tetracyclic antidepressant - central presynaptic alpha-2 adrenergic antagonist effects»_space; increase release of NE and 5-HT
Used commonly in onc or skilled nursing facilities to help with sleep (dose QHD) and to increase appetite (can increase weight gain in frail elderly)
Trazodone MOA and place in therapy
Inhibits 5-HT reuptake, blocks H1 and alpha-1 adrenergic receptors
Rarely used as antidepressant d/t sedation; used primarily off-label for sleep (dosed QHS)
Can cause priapism (painful erection longer than 4hrs = med emergency)
Antidepressant Nefazodone (inhibits 5-HT and NE uptake, blocks 5-HT2 and alpha-1 adrenergic receptor) is rarely used d/t ___
hepatotoxicity
Selecting best antidepressant: Cardiac/QT Risk
Sertraline preferred
Do not choose QT-prolonging drug/dose (e.g. high dose of citalopram or escitalopram)
Watch for additive QT effects when SSRIs, SNRIs, TCAs, mirtazapine, or trazodone are used with other QT-prolonging drugs
Selecting best antidepressant: Smoker
Bupropion SR is FDA-approved for smoking cessation
Selecting best antidepressant: Peripheral neuropathy or pain
Consider duloxetine
Selecting best antidepressant: Taking serotonergic antidepressants
Avoid multiple serotonergic meds d/t risk of serotonin syndrome
Increases bleeding risk with anticoag, antiplatelets, NSAIDs, and some natural products (e.g. ginkgo, garlic, ginger, ginseng, glucosamine, fish oils)
Selecting best antidepressant: Seizure disorder or risk for seizures (bulimia/anorexia, recent alcohol or sedative withdrawal)
Do not use bupropion
Selecting best antidepressant: pregnant
Do not use paroxetine
Mild-moderate depression: psychotherapy first line
Severe depression: SSRIs are first-line (e.g. citalopram, escitalopram, fluoxetine, sertraline
Selecting best antidepressant: daytime sedation
do not take sedating drug early in the day (e.g. paroxetine, mirtazapine, trazodone)
Activating meds taken in the morning are preferred (e.g. fluoxetine, bupropion)
Selecting best antidepressant: Insomnia
Do not take activating drug later in the day (e.g. bupropion, fluoxetine)
Sedating meds taken at night are preferred (e.g. paroxetine, mirtazapine, trazodone)
Selecting best antidepressant: sexual dysfunction
high risk with SSRIs and SNRIs
low er risk with bupropion and mirtazapine
American Psychiatric Association (APA) guidelines state pts should receive ___ trial of med at a therapeutic dose concluding that a drug is not working
4-8 week
If pt is not improving or has incomplete response to antidepressants, what can you do?
Change to new antidepressant
Increase dose
Use combo with different MOA
Augment with buspirone or a low dose of an atypical antipsychotic (aripiprazole (Abilify), quetiapine ER (Seroquel XR) // other options: olanzapine + fluoxetine (ymbyax), , brexpiprazole (Rexulti), and cariprazine (Vraylar), esketamine (Spravato))
Augementation with lithium, thyroid hormone (i.e. T3), or inc some cases electroconvulsive therapy (ECT)
Boxed warning for antipsychotics (aripiprazole (Abilify), Quetiapine (Seroquel))
Elderly pts with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death
Contraindications for antipsychotics (aripiprazole (Abilify), Quetiapine (Seroquel))
Olanzapine/fluoxetine (Symbyax): do not use with MOAi, linezolid, IV methylene blue, pimozide, thioridazine and caution with other drugs/conditions that cause QT prolongation
Side effects of aripiprazole
Anxiety, insomnia, akathisia, constipation, agitation
Side effect of olanzapine
Sedation, weight gain, increased lipids, increased glucose, EPs, QT prolongation (lower risk)
Side effects of quetiapine
sedation, orthostasis, weight gain, increased lipids, increased glucose, EPS (lower risk)
Esketamine (Spravato) formulation and administering notes
nasal spray, must be administered under supervision of health care provider
REMS program only
