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None (7) · Amitriptyline (hydrochloride) (1) · Ascorbic acid (vitamin C) (1) · Bisacodyl (1) · Docusate (sodium or calcium) (1) · Doxepin (hydrochloride) (1) · Lactulose (1) · Mirtazapine (1) · Nortriptyline (hydrochloride) (1) · Omega-3-acid ethyl esters (1) · Polyethylene glycol 3350 (PEG 3350) (1)

Caplyta (1) · Colace (sodium), Surfak (calcium); many generics OTC (1) · Dulcolax, Correctol, Bisac-Evac (1) · Elavil (US brand discontinued; generic widely available), Endep, Tryptizol (1) · Generic; huge OTC presence (1) · Kristalose, Constulose, Generlac, Enulose (1) · Lovaza, Omtryg (1) · MiraLAX (OTC), GlycoLax, GoLYTELY (with electrolytes for bowel prep), CoLyte, MoviPrep, NuLYTELY (1) · Nuplazid (1) · Pamelor (US brand discontinued; generic widely available), Aventyl (1) · Qelbree (1) · REL-1017 / esmethadone (investigational; not yet FDA-approved as of mid-2024) (1) · Remeron (US brand discontinued; generic widely available), Remeron SolTab (ODT) (1) · Rexulti (1) · Sinequan (oral antidepressant, US brand discontinued), Silenor (low-dose for insomnia), Prudoxin / Zonalon (topical cream) (1) · Trintellix (US), Brintellix (formerly) (1) · Viibryd (1)

None (10) · Partial agonist at D2 and 5HT1A. Antagonist at 5HT2A, α1A, α1B, α2C. More potent 5HT2A antagonism, 5HT1A partial agonism, and α1 antagonism (relative to D2 partial agonism) than aripiprazole, proposed to reduce akathisia and enhance affective/cognitive effects. (1) · Selective inverse agonist at 5HT2A receptors with weaker activity at 5HT2C. Has no significant dopamine D2 affinity, unique among approved antipsychotics. Inverse agonism (rather than antagonism) reduces constitutive 5HT2A receptor activity below baseline. (1) · Selective NET inhibitor (no significant DAT activity, distinguishes from amphetamine/methylphenidate). Also: 5HT1A receptor partial agonism, 5HT2B and 5HT7 receptor antagonism. The serotonergic actions may underlie better tolerability and possibly different efficacy spectrum than atomoxetine. (1) · '"`UNIQ--vote-00000019-QINU`"' Therapeutic plasma-level monitoring is standard practice for TCAs given the narrow therapeutic index and the established plasma-level-efficacy correlation. CYP2D6 substrate; CPIC PGx guidance applies for dose individualization'"`UNIQ--ref-0000001A-QINU`"'. (1) · '"`UNIQ--vote-0000004E-QINU`"' The EPA+DHA mix is biochemically and clinically distinct from icosapent ethyl'"`UNIQ--ref-0000004F-QINU`"'. (1) · '"`UNIQ--vote-00001067-QINU`"' Chronic use is associated with cathartic colon (colonic dilation, loss of haustration), hypokalemia, and laxative dependence; reserved for short-term use or bowel prep with breaks between courses'"`UNIQ--ref-00001068-QINU`"'. (1) · '"`UNIQ--vote-0000132D-QINU`"' Electrolyte-balanced bowel-prep formulations are designed to be iso-osmotic with plasma so the volume passes through without net fluid or electrolyte shifts, the basis of their safety for whole-bowel evacuation. (1)

10 mg PO once daily × 7 days, then 20 mg × 7 days, then 40 mg as target dose (take with food) (1) · 10 mg PO once daily; may increase to 20 mg as tolerated, or decrease to 5 mg if needed (1) · 100-200 mg PO once or twice daily; pediatric weight-based (1) · 15 mg PO at bedtime, titrate to 30-45 mg/day after 1-2 weeks. '''Counterintuitive dose paradox''': lower doses (7.5-15 mg) are more sedating than higher doses because H1 antihistamine effect dominates at low dose (1) · 34 mg PO once daily (1) · 4 g PO daily (as 4 x 1 g capsules once daily, or 2 capsules BID) (1) · 42 mg PO once daily with food (no titration) (1) · 5-15 mg PO once at bedtime; 10 mg PR for faster effect; bowel prep regimens use higher single doses (1) · Constipation: 15-30 mL PO daily (titrate to 1-2 soft stools/day); hepatic encephalopathy: 20-30 g (30-45 mL) PO/PR every 1-2 hours acutely until soft stools, then BID-QID to target 2-3 soft stools/day (1) · Constipation: 17 g (one capful) PO daily dissolved in 4-8 oz fluid; bowel prep: 4 L of PEG-electrolyte solution split-dose evening before and morning of procedure (1) · Depression (rarely used now): 25-75 mg PO at bedtime, titrate to 150 mg/day. Neuropathic pain / migraine prophylaxis: 10-25 mg at bedtime, titrate by 10-25 mg weekly to 50-100 mg/day. Elderly: 10 mg at bedtime (Beers-list cautions apply) (1) · Depression: 25 mg PO TID-QID or 75 mg at bedtime, titrate to 75-150 mg/day. Neuropathic pain: 10-25 mg at bedtime, titrate to 50-100 mg/day. Elderly: 10 mg at bedtime (Beers-list cautions, though less than amitriptyline) (1) · Depression: 25-75 mg/day to start, titrate to 75-150 mg/day at bedtime. Insomnia (Silenor): 3 mg PO 30 minutes before bedtime, max 6 mg. Topical (Prudoxin): apply to affected area every 3-4 hours (1) · General supplementation 75-90 mg/d (RDA); scurvy treatment 100-1000 mg/d for several weeks; megadose claims unsupported (1) · Pediatric 6-11: 100 mg PO daily, titrate weekly to max 400 mg. Adolescent 12-17: 200 mg, max 400 mg. Adult: 200 mg, max 600 mg. (1) · Schizophrenia: 1 mg PO daily × 4 days, then 2 mg daily × 3 days, then 4 mg daily. MDD adjunct: 0.5-1 mg daily, increase to 2 mg max. AD agitation: 0.5 mg daily, titrate to 2-3 mg daily. (1) · Trials use 25 mg or 50 mg PO daily (1)

0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablets (1) · 1 g soft gelatin capsules containing ~465 mg EPA + ~375 mg DHA as ethyl esters (1) · 10 g/15 mL solution (Constulose); 10 g, 20 g powder packets (Kristalose) (1) · 10 mg, 20 mg, 40 mg tablets (1) · 10 mg, 34 mg capsules/tablets (1) · 100 mg, 150 mg, 200 mg extended-release capsules (can be sprinkled on food) (1) · 100, 250, 500, 1000 mg tablets, chewables, gummies, effervescent; IV (specialty) (1) · 17 g (OTC) and 14 g (Rx) powder packets; 238, 510, 527 g bottles; PEG-electrolyte preparations 4 L (GoLYTELY, NuLYTELY) (1) · 42 mg capsules (1) · 5 mg enteric-coated tablets; 10 mg rectal suppositories; OTC and Rx (1) · 5 mg, 10 mg, 20 mg tablets (1) · 50, 100, 250 mg capsules; 50 mg/5 mL syrup; OTC (1) · Capsules 10, 25, 50, 75 mg; oral solution 10 mg/5 mL (1) · Capsules 10, 25, 50, 75, 100, 150 mg; oral concentrate 10 mg/mL; Silenor tablets 3, 6 mg; topical cream 5% (Prudoxin, Zonalon) (1) · Investigational oral capsule (1) · Tablets 10, 25, 50, 75, 100, 150 mg (1) · Tablets 7.5, 15, 30, 45 mg; orally disintegrating tablets (SolTab) 15, 30, 45 mg (1)

150 mg/day; therapeutic plasma-level monitoring recommended (target 50-150 ng/mL window) (1) · 20 mg/d (1) · 30 mg/d for short-term use (1) · 300 mg/day (depression, hospitalized); 150 mg/day outpatient; 6 mg/day for insomnia (1) · 300 mg/day (historical hospitalized inpatient depression); 150 mg/day outpatient typical ceiling (1) · 34 mg/d (1) · 4 g/d (1) · 4 mg/d (schizophrenia); 3 mg/d (AD agitation); 3 mg/d (MDD adjunct) (1) · 40 mg/d (1) · 400 mg/d (pediatric); 600 mg/d (adult) (1) · 42 mg/d (1) · 45 mg/day (1) · Indication-specific; bowel prep regimens reach 4 L cumulative (1) · Indication-specific; HE may require high-volume dosing (1) · Not yet approved (1) · UL 2000 mg/d in adults (1) · ~500 mg/d typical (1)

especially in acute HE) (1) · IV (1) · Oral (17) · rectal (2) · rectal (enema (1) · topical (1)

1-3 days (1) · 4-6 weeks for full antidepressant effect (claimed earlier onset for some patients due to 5HT1A partial agonism) (1) · ADHD symptom improvement reported within 1-2 weeks (faster than atomoxetine which takes 4-6 weeks) (1) · Antipsychotic effect over weeks (1) · Benefit over weeks of dosing (1) · Constipation: 1-3 days; bowel prep: 1-3 hours after starting (1) · Constipation: 24-48 hours; HE: ammonia reduction within hours of stool production (1) · Days for symptom improvement in scurvy (1) · Pain and migraine prophylaxis effect 1-4 weeks; antidepressant effect 4-6 weeks (1) · PO 6-12 hours; PR 15-60 minutes (1) · Rapid (within 1 week in trials) (1) · Sleep effect from first dose; analgesic and migraine-prophylaxis effect 1-4 weeks; antidepressant effect 4-6 weeks (1) · Sleep effect from first dose; antidepressant effect over 1-4 weeks (2) · Triglyceride lowering at 2-4 weeks; max at 8 weeks (1) · Typical antidepressant 4-6 week onset (1) · Weeks for psychosis/depression; AD agitation benefit emerges over weeks (1)

18-44 hours'"`UNIQ--ref-00000020-QINU`"' (1) · 20-40 hours'"`UNIQ--ref-00000023-QINU`"' (1) · Amitriptyline 10-50 hours (highly variable); nortriptyline active metabolite 18-44 hours'"`UNIQ--ref-00000026-QINU`"' (1) · Not formally established (1) · Not meaningfully described (1) · Not meaningfully described (negligible systemic absorption) (1) · Not meaningfully described — lactulose is not significantly absorbed (1) · Not well characterized; tissue incorporation over weeks'"`UNIQ--ref-00000051-QINU`"' (1) · Variable; effect dependent on local intestinal action rather than systemic kinetics'"`UNIQ--ref-0000106B-QINU`"' (1) · ~10-20 days (steady-state body pool); single dose plasma ~2 hours (1) · ~15 hours (parent); nordoxepin active metabolite ~30 hours'"`UNIQ--ref-00000020-QINU`"' (1) · ~18 hours (terminal) (1) · ~25 hours (1) · ~57 hours (parent), ~200 h (active metabolite) (1) · ~66 hours (1) · ~7 hours (1) · ~91 hours (1)

<0.1% systemic absorption (PEG 3350 is too large to absorb intact) (1) · <3% systemic absorption (the basis of the safety and mechanism)'"`UNIQ--ref-00000F5E-QINU`"' (1) · Adequate oral bioavailability with extended-release formulation (1) · Improved with food'"`UNIQ--ref-00000052-QINU`"' (1) · Limited but adequate; take with food (1) · Local action; minimal systemic effect (1) · Low systemic absorption (enteric coating delivers drug to colon)'"`UNIQ--ref-0000106C-QINU`"' (1) · Not characterized; oral dosing once daily (1) · Oral bioavailability suitable for daily dosing (1) · ~30% (oral)'"`UNIQ--ref-00000021-QINU`"' (1) · ~50% (oral)'"`UNIQ--ref-00000021-QINU`"' (1) · ~50% (oral)'"`UNIQ--ref-00000027-QINU`"' (1) · ~50% (oral; substantial first-pass)'"`UNIQ--ref-00000024-QINU`"' (1) · ~70-90% at typical doses; saturable at high doses (>500 mg) (1) · ~72% (with food); much lower fasting (~36%) (1) · ~75% (1) · ~95% (1)

Investigational (1) · OTC (MiraLAX) and [[USLegal:Prescription only|Rx-only]] (electrolyte solutions for bowel prep) in US (1) · OTC in US (3) · Rx (4) · Rx, '''not a controlled substance''' (no DEA scheduling) (1) · Rx. FDA black-box warning for increased mortality in elderly patients with dementia-related psychosis (class warning shared with all antipsychotics) (1) · [[USLegal:Prescription only|Rx-only]] in US (2) · [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults'"`UNIQ--ref-00000022-QINU`"' (2) · [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults'"`UNIQ--ref-00000025-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults'"`UNIQ--ref-00000028-QINU`"' (1)