Depression Flashcards
What criteria is used to diagnose depression?
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition
What is the most commonly used depression assessment scale?
Hamilton Depression Rating Scale (HDRS) or (Ham-D Rating Scale)
What are s/sx of depression?
- Mood
- Sleep-more or less
- Interest/pleasure-less
- Guilt/worthlessness
- Energy-less
- Concentration-less
- Appetite- more or less
- Psychomotor agitation or retardation
- Suicidal ideation
What is required for diagnosis of depression?
> /- 5 sx present over 2 weeks including depressed mood or loss of interest/pleasure
What drugs cause/worsen depression?
- ADHD meds/methylphenidate/stimulants
- Analgesics (indomethacin)/procainamide
- Antiretroviral (NNRTIs; evafirenz, rilpivirine)
- CV meds (beta-blockers especially propranolol, clonidine)
- Antidepressants/Benzos
- Systemic steroids/ Interferons/Cyclosporine
- Ethanol
- Varenicline
- Hormones (hormonal contraceptives, anabolic steroids)
- Methadone and other opioids that can lower testosterone/estrogen levels
- Methyldopa/Parkinson’s
- Isotretinoin
What natural products are used to treat depression?
- St. John’s Wart
- SAMe
- 5-HTP
- Valerian
What are safety concerns with natural products?
- St. John’s Wart- increase risk of serotonin syndrome, broad CYP enzyme inducer, photoxicity
- SAMe- increase risk of serotonin syndrome
- 5-HTP- increase risk of serotonin syndrome
What is the 1st line therapy for mild-moderate depression in pregnancy?
Psychotherapy
What is 1st line for severe depression in pregnancy?
- if on SSRI before preg, continue if safe
- SSRIs: sertraline, escitalopram
What are warnings with SSRIs during pregnancy?
- Persistent pulmonary HTN of new born
- Cardiac effects (Paroxetine)
What are preferred treatments for post partum depression?
- SSRIs
- zuranolone PO (Zurzuvae)- C-IV
- brexanolone IV (Zulresso)- C-IV; moderate to severe PPD
What agents are restricted to patients unresponsive to other therapies due to drug-drug/drug-food interactions?
nonselective MOA inhibitors:
phenelzine, tranylcypromine, isocarboxazid
What are s/sx of serotonin syndrome?
- severe Nausea
- Dizziness
- Headache
- Diarrhea
- Agitation
- Tachycardia
- Hallucinations
- Muscle rigidity
How should all antidepressants be discontinued?
Taper over several weeks
EXCEPT fluoxetine self-tapers long half life
What are black boxed warnings with all antidepressants?
- Increase in suicidal thoughts or actions in Childrens, Teens, and young adults (changes in mood/behavior/thoughts/feelings)
- MedGuide is REQUIRED for all antidepressants
How long does it take for antidepressants to work?
when used daily, 1-2 weeks for physical symptoms and a month or longer for psychological symptoms
What is the MOA of SSRIs?
increase 5-HT by inhibiting its reuptake in the neuronal synapse
What are CIs for all SSRIs?
- DO not use with MOA inhibitors, Linezolid, IV methylene blue, or pimozide
- fluoxetine/paroxetine: do not use with thioridazine
- fluvoxamine: do not use with alosetron, thioridazine, tizanidine
- sertaline soln: do not use with disulfuram
- Brisdelle (paroxetine): pregnancy
What are warnings with all SSRIs?
- QT Prolongation: do not exceed 20mg/d in elderly (>60 y/o), liver disease, CYP2C19 poor metabolizers or inhibitors; do not exceed 10mg/d escitalopram in elderly
- SIADH/Hyponatremia, Fall Risk (caution in elderly avoid if history of falls or use of CNS depressants)
- Bleeding (additive risk)
What are SEs with all SSRIs?
- Sexual SEs (low libido, ejaculation difficulty, anorgasmia, erectile dysfunction)
- Somnolence
- Insomnia
- Nausea
- Dry mouth
- Diaphoresis (dose related)
- Weakness
- Tremor
- Headache
- osteopenia/osteoporosis
- restless leg syndrome
What agent is preferred in patients with cardiac risk?
sertraline
What agents are approved for premenstrual dysphoric disorder PMDD and how are they dosed?
- Fluoxetine
- Paxil CR
- Sertraline
Continuous dosing or cyclical (luteal phase)
When should SSRIs be taken?
In the morning: fluoxetine (most awakening), others if not sedating
At night: paroxetine (most sedating), others if sedating
Which SSRI is not available in a solution?
fluvoxamine
What drugs interact with SSRIs?
- fluoxetine, paroxetine, and fluvoxamine are CYP2D6 inhibitors and decrease tamoxifen effectiveness
- antipsychotic drugs that are CYP2D6 substrates
- Other drugs that prolong QT interval
- increased bleeding risk NSAIDs/ anticoagulants/ antiplatelet/ gingko/garlic/ginger/ginseng/glucosamine/fish oil
What is the maximum dose of citalopram?
40mg /d
What is the maximum dose of escitalopram?
20mg/day
fluoxetine + olanzapine for treatment resistant depression
Symbyax
paroxetine for moderate- severe vasomotor symptoms
Brisdelle
How long is the washout period between SSRIs and MAO inhibitors/serotonin syndrome/ HTN crisis?
- 2 week washout period between MAO inhibitors and SSRIs
- 5 week washout period between MAOi and fluoxetine
- do not initiate in patients receiving methylene blue or linezolid
What is the MOA of vilazodone (Viibryd, Viibryd Starter Pack)?
SSRI and 5HT1A partial agonist
What is the MOA of vortioxetine (Trintellix)?
SSRI, 5HT1A agonist, and 5HT3 antagonist
What are CIs with 5HT partial agonists and antagonists?
- Do not use within 14 days of MAO inhibitors
- do not use with linezolid or IV methylene blue
What are warnings with 5HT partial agonists and antagonists?
Avoid with hx of seizure
What are SEs with 5HT partial agonists and antagonists?
- N/V/D
- decreased libido (less sexual SE compared to SSRI/SNRI)
What are SEs with vortioxetine?
- constipation
- decrease dose by 50% when used with strong CYP2D6 inhibitors (bupropion, fluoxetine, paroxetine, quinidine)
What is an important counseling point with vilazodone?
Take with food
What is the MOA of SNRIs?
increase 5HT and NE by inhibiting reuptake in the neuronal synapse
What is venlafaxine indicated for?
- Depression
- GAD
- panic disorder
- Social anxiety disorder
What is duloxetine indicated for?
- Depression
- Peripheral neuropathy
- Fibromyalgia
- GAD
- Chronic musculoskeletal pain
What is the max dose of venlafaxine?
375mg/d (IR)
225mg/d (ER)
What are CIs to using SNRIs?
- Lethal drug interaction WITH MAO INHIBITORS CAUSING HTN CRISIS
- do not use with linezolid or IV methylene blue
What are warnings with SNRIs
- SIADH/Hyponatremia, Fall Risk (caution in elderly avoid if history of falls or use of CNS depressants)
- Bleeding (additive risk)
- can affect urethral resistance; caution in those prone to obstructive urinary disorders
- high BP risk greatest with >150mg venlafaxine or other high-dose SNRIs; can decrease dose/ use antiHTN meds/change therapy
- do not use levomilnacipran CrCl<15
- do not use duloxetine CrCl<30
- Pristiq can leave a ghost tablet
What are SEs with SNRIs?
- same as SSRIs
- Increased HR
- Dialated pupils (lead to narrow angle glaucoma)
- Dry mouth
- Excess sweating
- Constipation
- High BP
- osteoporosis
- restless leg syndrome
Levomilnacipran
Fetizma
What are DIs with SNRIs?
- Additive QT prolongation
- Duloxetine moderate CYP2D6 inhibitor
- increased bleeding risk
- HTN crsis and serotonin syndrome with MAOi, methylene blue IV, and linezolid
What is the MOA of TCAs?
block Ach and H receptors
Secondary amines: selective for NE
Tertiary amines: more effective with worse SEs
What are CIs to using TCAs?
- MAO inhibitors, linezolid, IV methylene blue
- myocardial infarction
- glaucoma
- urinary retention (doxepin)
What are SEs with TCAs?
- QT prolongation with Overdose (monitor for Suicidal Ideation as OD can quickly cause Fatal Arrhythmia): obtain baseline ECG if cardiac risk factors >50 yr
- Orthostasis/tachycardia
- Dry mouth
- Blurred vision
- Urinary retention
- Constipation
- Weight gain
- vivid dreams
- sedation
- sweating
- myoclonus (muscle twitching- indicated toxicity)
- Fall risk
- Seizures (high doses increase risk)
What are warnings with TCAs?
- Tertiary amines have increased anticholinergic PROPERTIES AND ARE MORE LIKELY TO CAUSE SEDATION AND WEIGHT GAIN
- taper off to avoid cholinergic rebound
What is typical dosing for amitriptyline?
100-300mg/day QHS or divided doses
What drugs are tertiary amine TCAs?
- amitriptyline
- doxepin
- clomipramine
- imipramine
- trimipramine
Doxepin
Silenor (insomnia)
Zonalon (topical for pruritis)
What drugs are secondary amine TCAs?
- nortriptyline
- amoxapine
- desipramine
- maprotiline
- protriptyline
Nortriptyline
Pamelor
What are DIs with TCAs?
- MAOi and HTN crisis: 2-week washout period
- additive QT prolongation
- metabolized by CYP2D6
What are CIs to using bupropion?
- Seizure disorder
- Hx anorexia/bulimia
- Use with MAOi, linezolid, IV methylene blue, other forms of bupropion
- abrupt discontinuation of alcohol/sedatives
What are warnings with bupropion?
Neuropsychiatric adverse events possible when used for smoking cessation (mood changes, hallucination, paranoia, aggression, anxiety)
What are SEs with bupropion?
- Dry mouth
- CNS stimulation (Insomnia, Restlessness)
- Tremors/Seizure (dose-related)
- Weight loss
- headache/migraine
- N/V
- constipation
- BP changes (HTN>hypotension)
- sexual dysfunction rare (preferred over other antidepressants
- dizziness, excessive sweating (Auvelity)
What is the maximum dose of bupropion/ day?
450mg/day (522mg /day with Aplenzin) due to seizure risk
Bupropion
Wellbutrin SR (BID)
Wellbutrin XL (QD)
Aplenzin
Forfivo XL
Bupropion + Dextromethorphan ER
Auvelity (depression)
Bupropion + naltrexone
Contrave (weight management)
Bupropion SR
Zyban (smoking cessation)
What forms of bupropion are approved for seasonal affective disorder (SAD)?
Wellbutrin XL
Aplenzin
What are DIs with bupropion?
- Do not use multiple formulations
- HTN crisis and MAOi: 14 day wash out
What drugs are MAOIs?
- isocarboxazid
- phenelzine
- tranylcypromine
- selegiline (MAO B)
What is the MOA of MAOIs?
inhibit monoamine oxidase; prevents breakdown of NE, 5HT, DA, EPI
What are CIs to using MAOIs?
- History of CV disease, cerebrovascular defect, headache, hepatic disease, pheochromocytoma
- Use with sympathomimetics and related compounds
- Severe renal disease (isocarboxazid, phenelzine)
What are warnings with MAOIs?
Watch for DIs could be fatal
What are SEs with MAOIs?
- anticholinergic effects (taper off)
- orthostasis
- sedation (except tranylcypromine causes stimulation)
- sexual dysfunction
- weight gain
- headache
- insomnia
What are CIs with selegiline (MAOBi)?
- Use with other serotonergic agents
- pheochromocytoma
What are SEs with selegiline (MAOBi)?
- constipation/gas
- dry mouth
- loss of appetite
- sexual dysfunction
Isocarboxazid
Marplan
Phenelzine
Nardil
Tranylcypromine
Parnate
Selegiline
Emsam (transdermal patch)
Zelapar ODT (parkinsons disease)
What are DIs with MAOIs?
- HTN crisis/serotonin syndrome/psychosis with drugs that increase concentrations of NE, DA, Epi, 5HT
- CI with drugs that increase 5HT: linezolid, Lithium, Tramadol, Opioids, St. John’s Wort, Antidepressants
- CI tyramine-rich foods: Aged cheese, Pickled herring, Yeast extract, Air-dried meats, Sauerkraut, Soy sauce; Aged, Fermented, Pickled, Smoked foods
- CI drugs that increase NE: levodopa, linezolid, methylene blue, stimulants, OTC/herbal diet pills
What is the MOA of mirtazapine?
presynaptic alpha-2 adrenergic antagonist ; helps with sleep when dosed QHS and increases appetite
What are CIs with mirtazapine?
- MAOIs
- Linezolid
- IV methylene blue
What are warnings with mirtazapine?
- anticholinergic effects
- QT prolongation (additive)
- blood dyscrasias
- CNS depression
What are SEs with mirtazapine?
- Sedation
- Increased appetite/Weight gain
- dry mouth
- dizziness
- agranulocytosis (rare)
What is the MOA of trazodone?
SSRI, blocks H1 and alpha-1 adrenergic receptors
What are CIs with trazodone?
- MAOIs
- Linezolid
- IV methylene blue
What are SEs with trazodone?
- Sedation (ER less sedating)- used for sleep>depression
- orthostasis
- sexual dysfunction/ Priapism
- additive QT prolongation
What is the MOA of nefazodone?
inhibits 5HT and NE reuptake, blocks 5HT2 and alpha -1 adrenergic receptors
Mirtazapine
Remeron
Remeron SolTab
What boxed warnings does nefazodone have?
Hepatotoxicity
What are CIs with nefazodone?
- hepatic disease
- MAOIs
- carbamazepine
- cisapride
- pimozide
- triazolam
What are SEs with nefazodone?
- Sedation (less sedating vs. trazodone)
- orthostasis
- sexual dysfunction/ Priapism
What is treatment resistant depression?
not responsive to 2 full treatment trials (4-8 week trial at therapeutic dose)
What should be considered if someone is not responding to antidepressant therapy?
- change med
- increase dose
- use combination of antidepressants with different MOA
- augment with buspirone or atypical antipsychotic
- augment with lithium thyroid hormone T3 or electroconvulsive therapy
What are boxed warnings with atypical antipsychotics?
- Elderly patients with dementia related psychosis increase risk of death
- Increased risk of suicidal behavior
What are warnings with atypical antipsychotics?
- neuropleic malignant syndrome
- tardive dyskinesia
- leukopenia/neutropenia
- falls
- Multiorgan hypersensitivity (eosinophilia/DRESS)
- pathological gambling/compulsive behavior
What are SEs with aripiprazole?
- Anxiety
- Insomnia
- Akathisia
- constipation
- agitation
- orthostasis/dizziness/weight gain/diabetes- less
What are SEs with olanzapine?
- Sedation
- Weight gain
- High lipids/glucose
- EPS
- QT prolongation- less
- orthostasis/dizziness/diabetes
What are SEs with quetiapine?
- Sedation
- Weight gain
- High lipids/glucose
- EPS- less
- Orthostasis
- dizziness/diabetes
What are SEs with brexpiprazole?
- weight gain
- dyspepsia
- diarrhea
- agitation
- orthostasis/dizziness/weight gain/diabetes
What are SEs with cariprazine?
- EPS
- dystonias
- headache
- insomnia
- orthostasis/dizziness/weight gain/diabetes
What is the MOA of esketamine?
NMDA rec antagonist
What are boxed warnings with esketamine?
- sedation and dissociative/ perceptual changes
- abuse potential
- suicidality
What is required for esketamine administration?
- Must be under medical supervision
- restricted distribution under REMS program
Aripiprazole
Abilify
Abilify Maintena
Abilify MyCite
Oral route only for treatment resistant depression
Quetiapine
Seroquel
Seroquel XR
Brexpiprazole
Rexulti
Cariprazine
Vraylar
Esketamine
Spravato (nasal spray; CIII)
Fluoxetine
Prozac
Sarafem
Saelfemra