Antidepressants Flashcards
vortioxetine (Trintellix)
Indication: Major Depression
Dose: 10mg daily (increase to 20mg); 5mg to tolerate anxiety/nausea
Mechanism: multi-modal SRI (5HT1A agonist; antagonist of 5HT3A, 5HT1D, and 5HT7)
Advantages: low sexual ADE; pro-cognitive effects (originally Brintellix (“bring intelligence”)
Disadvantages: higher doses to reach efficacy
ADEs: severe nausea, headache, GI, dry mouth, anti-platelet
Off-Label: GAD; other anxiety
Serotonin Receptors
5HT2A Agonists – induces psychosis, dissociation, and pain (think LSD, psilocybin, and MDMA)
but, also induces self-transcendence and mild antidepressant effects
5HT2A Antagonism – Treats depression, anxiety, and psychosis (think mirtazapine, trazodone, and cyproheptadine)
5HT2C Agonism – Increases risk of suicide (explains why antidepressants create the effect early, but then reduces over time as the serotonin receptors down-regulate)
5HT2B Agonism – responsible for valvular heart disease (like with LSD)
brexanolone (Zulresso)
Indication: Postpartum Depression
Dose: IV dosing only; 30mcg/kg/hr for hrs 0-4; 60mcg for hrs 4-24; 90mcg for grs 24-52; 60mcg for hrs 52-56; 30mcg for hrs 56-60
Monitoring: pulse oximetry
Mechanism: GABA-A modulator; neurosteroid identical to allopregnanolone which rises during pregnancy and falls abruptly after birth
Advantages: fast-acting; high maintenance response rate (94%)
Disadvantages: expensive ($34k); requires REMS enrollment as a facility; requires inpatient monitoring; 60% response rate; Schedule IV medication
ADEs: sedation; somnolence; dry mouth; loss of consciousness; flushing; hypoxia
bupropion (Wellbutrin)
Indication: MDD, SAD; smoking cessation
Dose: (IR): 100mg BID, increase to TID after 3d; separate dose by >6hrs to reduce seizure risk
(SR): 150mg QAM, increase to BID at d4; separate dose by >8hrs to reduce seizure risk
(ER): 150mg QAM, increase to 300mg on d4
Monitoring: No monitoring required.
Mechanism: dopamine and norepinephrine reuptake inhibitor
Advantages: Absence of sexual ADEs and weight gain; best for those with fatigue and poor concentration; effective for anxious depressions
Disadvantages: seizure risk at high doses (mitigated by keeping below 450mg/d); false positive for amphetamines; used as a drug of abuse (snorting crushed tablets); cannot crush ER or SR tablets; avoid in renal impairment (active metabolites excreted through kidney)
ADEs: avoid in eating disorder patients (esp. bulimia); agitations; insomnia; headache; nausea; tremor; tachycardia; dry mouth; weight loss; seizures
Off-Label: ADHD; sexual dysfunction in ADT; bipolar depression
clomipramine (Anafranil)
Indication: OCD
Dose: Start 25mg at QHS and increase by 25mg/d weekly to a target of 150mg/d in divided doses; MAX=250mg/d; requires taper to discontinue
Monitoring: EKG
Mechanism: Serotonin and norepinephrine reuptake inhibitor (mostly serotonin); only TCA with an indication for OCD
Advantages: most effective medication for OCD
Disadvantages: OD toxicity on 10d supply; pharmacokinetics are non-linear, so there are higher levels and accumulations at the higher dose ranges
ADEs: sedation; dry mouth; constipation; weight gain; sexual ADEs; urinary hesitation; blurred vision; seizure at doses>250mg/d; orthostasis; QT prolongation; AV block; arrythymias
Off-Label: cataplexy (esp. in narcolepsy); sleep terrors; sleepwalking; MDD; panic disorder; pain
Fun Facts: on the WHO model list of essential medications
desvenlafaxine (Pristiq)
Indication: MDD (isomer of venlafaxine)
Dose: Start 50mg daily; Dosages up to 400mg/d; No researched benefit over 50mg
Monitoring: Periodic BP
Mechanism: Serotonin and norepinephrine reuptake inhibitor (SNRI)
Advantages: None.
Disadvantages: lower risk of drug interactions than venlafaxine
ADEs: nausea; dizziness; insomnia; excessive sweating; constipation; dry mouth; somnolence; decreased appetite; anxiety; sexual ADEs; dose-related increases in systolic AND diastolic BP
Off-Label: fibromyalgia; vasomotor symptoms of menopause; GAD; social anxiety disorder; panic disorder; PTSD; PMDD
Fun Facts: Two products: Pristiq (a succinate salt) and Khedezla (a base)
duloxetine (Cymbalta)
Indication: MDD; GAD (7+); diabetic peripheral neuropathic pain; fibromyalgia; chronic musculoskeletal pain (including OA and chronic low back pain)
Dose: MDD/GAD: Start 40mg/d (may be divided); target=60mg/d; MAX=120mg, but >60mg not shown to be more effective.
Fibromyalgia: Start 30mg/d; MAX=60mg/d
Diabetic Neuropathic Pain: 60mg/d
Monitoring: LFTs if history of liver disease or heavy alcohol use
Mechanism: Serotonin and norepinephrine reuptake inhibitor (SNRI)
Advantages: None.
Disadvantages: Has potential for serious hepatic side effects; cannot split/open pills
ADEs: Nausea; dry mouth; constipation; decreased appetite; diarrhea; vomiting; fatigue; insomnia; dizziness; agitation; sweating; headache; urinary hesitation/retention; sexual ADEs; SERIOUS: hepatic failure (rare, but transaminases >20x without jaundice); orthostatic hypotension
Off-Label: Other neuropathic or pain disorders; other anxiety disorders; urinary incontinence (approved in Europe, but not the US)
esketamine (Spravato)
Indication: Treatment-resistant depression (with another antidepressant); CONTRAINDICATED in aneurysmal vascular disease and history of intracerebral hemorrhage
Dose: Induction: (weeks 1-4) 56mg on day one, then 56mg or 84mg 2x/wk; Maintenance: 56mg or 84mg every two weeks (or weekly); five-minute rest between devices (28mg/device)
Monitoring: NPO for two hours prior to administration; must be monitored by a healthcare professional for two hours after administration; check BP before dose and 40min after each dose
Mechanism: NMDA receptor antagonist
Advantages: Often a rapid response
Disadvantages: Requires a REMS order; frequent office visits; Schedule III medication
ADEs: sedation; dissociation (primarily depersonalization and derealization); increased BP (transient – about 4 hours); cognitive impairment; impaired driving; SERIOUS: hypertensive crisis
Off-Label: Pain; migraine HAs
Fun Facts: given breakthrough status by the FDA (suggests it provides substantial improvement over existing treatments
ketamine
Indication: Anesthesia
Dose: 0.5mg/kg over 40min IV (2mg/kg is anesthesia dose); 2-3x weekly over (4) weeks
Monitoring: EKG; BP; O2 sat
Mechanism: NMDA receptor antagonist
Advantages: ultra-rapid antidepressant effect
Disadvantages: IV use and need for anesthesiology; effects attenuate after a week; 90% relapse in 4 weeks after administration
ADEs: confusion; blurred vision; poor coordination; dissociative properties; spikes in BP; tachycardia; delirium; respiratory depression
Off-Label: MDD; chronic pain; severe agitation (in ICU)
Fun Facts: was a “buddy drug” in Vietnam while awaiting AirEvac
levomilacipran (Fetzima)
Indication: MDD
Dose: Start 20mg daily; increase to 40mg daily after 2d; then by 40mg/d every 2d; MAX=120mg/d
Monitoring: Periodic BP and pulse
Mechanism: serotonin and norepinephrine reuptake inhibitor (SNRI)
Advantages: greater norepinephrine effects
Disadvantages: cannot cut/open pills
ADEs: nausea (often significant); constipation; sweating; elevated pulse (10bbm) to tachycardia; erectile dysfunction; dose-related urinary hesitation and retention (which can be severe); increased BP
Off-Label: fibromyalgia; anxiety disorders; vasomotor symptoms of menopause; diabetic peripheral neuropathy; chronic musculoskeletal pain
Fun Facts: enantiomer of milnacipran (a SNRI approved for fibromyalgia in Europe, but not US)
mirtazapine (Remeron)
Indication: MDD
Dose: Start at 15mgQHS; increase by 7.5-15mg weekly; MAX=45mg/d; reduce in renal impairment
Monitoring: Weight; CBC
Mechanism: central pre-synaptic alpha-2 adrenergic receptor antagonist and post-synaptic 5HT2 and 5HT3 antagonism
Advantages: possible faster action; useful for anxiety and insomnia complaints; benefits those who need appetite stimulation (like in the elderly and cancer patients); comes in an ODT form
Disadvantages: weight gain often poses a problem
ADEs: somnolence; increased appetite; weight gain; SERIOUS: reversible agranulocytosis or neutropenia (rare);
Off-Label: panic disorder; PTSD; GAD; insomnia; nausea; appetite stimulant
Monoamine Oxidase Inhibitors (MAOIs)
Indication: MDD
Equivalents: 20mg of tranylcypromine = 40mg of isocarboxazid = 45mg of phenelzine
Monitoring: No clinical monitoring required.
Dietary Restrictions: avoid foods high in tyramine, tryptophan, phenylalanine, or tyrosine. Examples: aged cheeses, cured meats (e.g., salami), fava or broad bean pods, tap/draft beers, sauerkraut, soy sauce, or spoiled foods
Mechanism: non-selective monoamine oxidase inhibitors
Advantages: more effective than TCAs for atypical depression (overeating, oversleeping, rejection sensitivity, and mood reactivity)
Disadvantages: Dietary restrictions; No use for two weeks after last ADT (5 weeks for fluoxetine); regeneration of inhibited enzymes takes 2-3 weeks, so you need to also wait two weeks after stopping MAOIS before a different ADT; discontinue ten days before surgeries; antihypertensives exaggerate hypotensive effects
ADEs: dizziness; headache; drowsiness; orthostatic hypotension; dry mouth; tremor; sweating; peripheral edema; weight gain; SERIOUS: Hypertensive crisis
Off-Label: treatment-resistant depression; panic disorder; social anxiety disorder
Fun Facts: isoniazid was found to have antidepressant properties and was an MAOI, launching MAOIs as the first antidepressants.
MAOI Medications
isocarboxazid (Marplan):
* Start 10mg BID; increase by 10mg q2-4d to 40mg at end of first week; after first week, may increase by 20mg weekly; MAX=60mg. Caution at doses >40mg
phenelzine (Nardil):
* Start 15mg BID; increase by 15mg q2-4d; MAX=60-90mg daily (divided). * More ADEs than others
tranylcypromine (Parnate):
* Start 10mg BID; increase by 10mg q2-3 WEEKS; MAX=30mg BID. * More stimulating (structurally like amphetamine) * More likely to cause “cheese reaction”
selegiline transdermal (Emsam)
Indication: MDD
Dose: Start 6mg/d; increase by 3mg/d every two weeks; MAX=12mg/d; Apply to clean, dry skin in upper torso, upper thigh, or outer surface of upper arm; rotate location to avoid rash; wash hands after use.
Monitoring: No routine monitoring required.
Mechanism: non-selective MAOI
Advantages: compliance easier; less risk for suicide; no need for dietary restrictions at the 6mg dose (and maybe higher doses as well); less weight gain
Disadvantages: patch may contain metal (avoid heat sources); complications with antidepressants, serotonergic agents, stimulants, pain medications, and antihypertensives; dietary counseling; B6 deficiency possible (especially with phenelzine)
ADEs: headache; insomnia; application site rashes; hypotension; dry mouth; SEVERE: orthostatic hypotension
Off-Label: treatment-resistant depression; panic disorder; treatment-resistant anxiety disorders
nefazodone (Serzone)
Indication: MDD
Dose: Start 50mg BID; increase by 50-100mg/d weekly; usual dosage 300-500mg/d; MAX=600mg/d
Monitoring: LFTs; BP
Mechanism: serotonin and norepinephrine reuptake inhibitor (SNRI) plus 5HT2 antagonist
Advantages: minimal sexual ADEs
Disadvantages: off market now because of liver effects (but still generic)
ADEs: nausea; somnolence; dry mouth; dizziness; lightheadedness; constipation; blured vision; confusion; orthostasis; SERIOUS: black box warning for hepatic toxicity (1/300k – 3-4x general medication incidence) not associated with increased LFTs (some have resulted in transplant need or death)
Off-Label: anxiety; insomnia
Fun Facts: removed from almost all markets
