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Medicines > duration : Daily dosing or Hours or ~12 weeks

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mechanism:
None (7) · Cleaves SNAP-25 protein in presynaptic motor and autonomic nerve terminals, blocking acetylcholine release; in chronic migraine, hypothesized to inhibit peripheral sensitization of trigeminovascular nociceptors (1) · 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-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)
uses:
ADHD in children (6+), adolescents, and adults (FDA-approved 2021 for pediatric, 2022 for adult) (1) · Chronic migraine (≥15 headache days/month), cervical dystonia, blepharospasm, hyperhidrosis, overactive bladder, urinary incontinence, strabismus, spasticity, cosmetic problems (1) · Hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Investigational for psychosis in other dementias and as augmentation for depression. (1) · Investigational for major depressive disorder; trials underway (phase 3 mixed results) (1) · Major depressive disorder in adults (FDA-approved 2011) (1) · Major depressive disorder in adults (FDA-approved 2013). Notable for evidence of cognitive benefit (processing speed) that distinguishes it from other antidepressants. (1) · Schizophrenia (FDA-approved 2015). Adjunctive treatment of major depressive disorder (2015). '''Agitation associated with dementia due to Alzheimer disease''' (FDA-approved May 2023, first agent specifically approved for this problem). Investigational for PTSD (combined with sertraline). (1) · Schizophrenia (FDA-approved Dec 2019). Bipolar depression as monotherapy or adjunct to lithium/valproate (FDA-approved Dec 2021). (1) · '"`UNIQ--vote-00000050-QINU`"' (1) · '"`UNIQ--vote-00000F5C-QINU`"', '"`UNIQ--vote-00000F5D-QINU`"' (1) · '"`UNIQ--vote-00001069-QINU`"', '"`UNIQ--vote-0000106A-QINU`"' (1) · '"`UNIQ--vote-000012E5-QINU`"', '"`UNIQ--vote-000012E6-QINU`"', '"`UNIQ--vote-000012E7-QINU`"', '"`UNIQ--vote-000012E8-QINU`"' (1) · '"`UNIQ--vote-0000132E-QINU`"', '"`UNIQ--vote-0000132F-QINU`"', '"`UNIQ--vote-00001330-QINU`"' (1) · '"`UNIQ--vote-00001341-QINU`"', '"`UNIQ--vote-00001342-QINU`"' (1)
starting dose:
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) · 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) · Chronic migraine (PREEMPT protocol): 155 units divided across 31 sites in 7 head/neck muscle groups every 12 weeks (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) · 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)
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