Drilldown: Medicines

None · Codeine · 1,4-Butanediol · 1B-LSD · 1cP-LSD · 1P-LSD · 1V-LSD · 2-AI · 2-FA · 2-FDCK · 2-FMA · 25B-NBOH · 25B-NBOMe · 25C-NBOH · 25C-NBOMe · 25I-NBOH · 25I-NBOMe · 25N-NBOMe · 2C-B · 2C-B-FLY

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None (1) · Aduhelm (1) · Aimovig (1) · Ajovy (1) · Auvelity (dextromethorphan/bupropion ER) (1) · Belsomra (1) · Botox (1) · Caplyta (1) · Dayvigo (1) · Emgality (1) · Kisunla (1) · Leqembi (1) · Nuplazid (1) · Qelbree (1) · Quviviq (1) · REL-1017 / esmethadone (investigational; not yet FDA-approved as of mid-2024) (1) · Rexulti (1) · Spravato (1) · Sunosi (1) · Trintellix (US), Brintellix (formerly) (1) · Viibryd (1) · Vraylar (1) · Vyepti (1) · Wakix (1) · Zavzpret (zavegepant) (1) · Zonegran (1) · Zulresso (1) · Zurzuvae (1)

5HT1A activity than aripiprazole (1) · 5HT2A (1) · 5HT2A/D2 antagonist with proposed differential pre/post-synaptic D2 activity (1) · Anti-amyloid beta (Aβ) monoclonal antibody (3) · Anti-CGRP ligand monoclonal antibody (3) · Anti-CGRP receptor monoclonal antibody (1) · Anticonvulsant (1) · Atypical antipsychotic (3) · CGRP receptor antagonist (1) · Classic Psychedelic (1) · D2/5HT1A partial agonist with stronger α1A (1) · D2/D3/5HT1A partial agonist (1) · dissociative (1) · Dual orexin receptor antagonist (DORA) (3) · GABA-A positive allosteric modulator (1) · GABA-A positive allosteric modulator (oral) (1) · Gepant (1) · Histamine H3 receptor inverse agonist / antagonist (1) · low-trapping) (1) · Multimodal antidepressant: SERT inhibitor + 5HT1A agonist + 5HT1B partial agonist + 5HT3/5HT7 antagonist (1) · Neuroactive steroid (2) · neuromuscular blocker (presynaptic) (1) · Neurotoxin (1) · NMDA receptor antagonist (uncompetitive (1) · NMDA receptor antagonist (uncompetitive) (1) · NMDA receptor antagonist + sigma-1 agonist + NDRI (combination) (1) · non-stimulant ADHD agent (1) · Norepinephrine-dopamine reuptake inhibitor (NDRI) (1) · Phenethylamine (1) · Research material (1) · Selective 5HT2A inverse agonist (with weaker 5HT2C inverse agonism) (1) · Selective norepinephrine reuptake inhibitor (NRI) with 5HT1A partial agonism (1) · Serotonin partial agonist reuptake inhibitor (SPARI) (1) · targets protofibrils (1) · targets pyroglutamated Aβ in plaques (1) · the first approved (1) · wake-promoting agent (2)

None (12) · 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) · Competitive antagonist at OX1R and OX2R. Faster receptor association/dissociation kinetics than suvorexant (~16 sec dissociation vs ~57 sec) hypothesized to support sleep onset, with sufficient duration for maintenance. (1) · Competitive antagonist at OX1R and OX2R. First-in-class DORA. Receptor dissociation slower than lemborexant or daridorexant. (1) · Human IgG1 monoclonal antibody targeting aggregated forms of amyloid-β (Aβ), soluble oligomers and insoluble fibrils. Reduces Aβ plaque burden on PET imaging via Fc-mediated microglial clearance. Whether plaque reduction translates to clinical benefit is the core controversy. (1) · Humanized IgG1 monoclonal antibody binding CGRP peptide; IV infusion enables fastest onset of any CGRP mAb (1) · Humanized IgG2 monoclonal antibody binding both isoforms of CGRP peptide (1) · Humanized IgG2 monoclonal antibody binding the CGRP receptor (not the peptide); blocks CGRP-mediated vasodilation and nociceptive signaling (1) · Humanized IgG4 monoclonal antibody binding CGRP peptide; prevents CGRP from activating its receptor (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) · Potent 5-HT2A agonist (1) · Selective dopamine and norepinephrine reuptake inhibitor (DAT and NET inhibition). Unlike amphetamine, does not significantly release monoamines, pure reuptake inhibition. (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) · Small-molecule CGRP receptor antagonist; intranasal formulation (1) · Sodium/T-type calcium channel blocker; carbonic anhydrase inhibitor (1) · Synthetic neuroactive steroid (an analog of allopregnanolone), bioavailable orally unlike brexanolone. Positive allosteric modulator at GABA-A receptors including extrasynaptic δ-containing subtypes. (1)

None (2) · Acute treatment of migraine with or without aura in adults (1) · ADHD in children (6+), adolescents, and adults (FDA-approved 2021 for pediatric, 2022 for adult) (1) · Alzheimer disease (FDA accelerated approval June 2021; '''withdrawn from market January 2024''' by manufacturer Biogen). At time of approval indicated for MCI or mild dementia stage of AD. (1) · Alzheimer disease (MCI or mild dementia stage), FDA-approved July 2024 (1) · Alzheimer disease (MCI or mild dementia stage); FDA accelerated approval Jan 2023 → traditional approval July 2023 (1) · Chronic migraine (≥15 headache days/month), cervical dystonia, blepharospasm, hyperhidrosis, overactive bladder, urinary incontinence, strabismus, spasticity, cosmetic problems (1) · Excessive daytime sleepiness in adults with narcolepsy or obstructive sleep apnea (OSA) (1) · Excessive daytime sleepiness or cataplexy in adults with narcolepsy (FDA-approved August 2019) (1) · Hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Investigational for psychosis in other dementias and as augmentation for depression. (1) · Insomnia (sleep onset and/or maintenance) in adults (FDA-approved August 2014). Also studied for insomnia in mild-moderate Alzheimer disease. (1) · Insomnia (sleep onset and/or maintenance) in adults (FDA-approved Dec 2019) (1) · Insomnia (sleep onset and/or sleep maintenance) in adults (FDA-approved Jan 2022) (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) · Major depressive disorder in adults (FDA-approved August 2022) (1) · Postpartum depression (PPD) in adults (1) · Postpartum depression (PPD) in adults (FDA-approved 2023) (1) · Preventive treatment of migraine in adults (1) · Preventive treatment of migraine in adults (episodic and chronic) (2) · Preventive treatment of migraine in adults; episodic cluster headache (1) · Schizophrenia (FDA-approved 2015). Acute manic or mixed episodes of bipolar I disorder. Bipolar I depression (FDA-approved 2019). Adjunctive treatment of major depressive disorder (FDA-approved Dec 2022). (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) · Treatment-resistant depression (TRD) in adults, as adjunct to oral antidepressant (FDA-approved March 2019). Depressive symptoms in adults with MDD with acute suicidal ideation or behavior (FDA-approved Aug 2020). (1)

None (2) · 1 tablet (dextromethorphan 45 mg / bupropion 105 mg) PO daily × 3 days, then increase to 1 tablet BID (1) · 10 mg (one spray) intranasally in one nostril (1) · 10 mg PO 30 min before bedtime (with ≥7 hours of sleep planned) (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) · 10 mg/kg IV every 2 weeks (1) · 100 mg IV every 3 months; may increase to 300 mg IV every 3 months (1) · 225 mg SC monthly, or 675 mg SC every 3 months (quarterly) (1) · 25 mg PO at bedtime (no titration); may increase to 50 mg if 25 mg inadequate (1) · 34 mg PO once daily (1) · 42 mg PO once daily with food (no titration) (1) · 5 mg PO at bedtime; may increase to 10 mg if inadequate (1) · 50 mg PO once daily with fatty food in the evening × 14 days (1) · 70 mg SC monthly; may increase to 140 mg monthly (1) · 700 mg IV q4w × 3 doses, then 1400 mg IV q4w; may discontinue when amyloid PET shows clearance (1) · Chronic migraine (PREEMPT protocol): 155 units divided across 31 sites in 7 head/neck muscle groups every 12 weeks (1) · Induction (TRD): 56 mg intranasal twice weekly × 4 weeks. Maintenance: 56-84 mg once weekly × 4 weeks, then 56-84 mg every 1-2 weeks. For acute suicidality: 84 mg twice weekly × 4 weeks. Administered under medical supervision in REMS-certified site. (1) · Migraine: 240 mg SC loading dose, then 120 mg SC monthly. Cluster: 300 mg SC at onset of cluster period, then monthly during cluster. (1) · Narcolepsy: 75 mg PO once daily upon awakening, titrate every 3 days. OSA: 37.5 mg PO once daily, titrate. (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) · Schizophrenia: 1.5 mg PO daily, increase to 1.5-6 mg as tolerated. Bipolar mania: 1.5 mg, may increase to 3-6 mg. Bipolar depression: 1.5 mg daily for 14 days, then 3 mg. MDD adjunct: 1.5 mg, may increase to 3 mg. (1) · Single 60-hour continuous IV infusion: 30 mcg/kg/h × 4h → 60 mcg/kg/h × 20h → 90 mcg/kg/h × 28h → 60 mcg/kg/h × 4h → 30 mcg/kg/h × 4h (1) · Trials use 25 mg or 50 mg PO daily (1) · Was 1 mg/kg IV q4w × 2, then 3 mg/kg × 2, then 6 mg/kg × 2, then 10 mg/kg q4w (1) · Week 1: 8.9 mg PO once daily in the morning. Week 2: 17.8 mg. Week 3+: 35.6 mg (max). Titrate as needed. (1)

None (2) · 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablets (1) · 1.5 mg, 3 mg, 4.5 mg, 6 mg capsules (1) · 10 mg, 20 mg, 40 mg tablets (1) · 10 mg, 34 mg capsules/tablets (1) · 10 mg/spray nasal solution (1) · 100 mg, 150 mg, 200 mg extended-release capsules (can be sprinkled on food) (1) · 100 mg/20 mL vial, single-use (1) · 100 mg/mL vial for IV infusion (1) · 120 mg/mL prefilled syringe or autoinjector (1) · 20 mg, 25 mg, 30 mg capsules (1) · 200 mg/2 mL, 500 mg/5 mL vials for IV infusion (1) · 225 mg/1.5 mL prefilled syringe or autoinjector (1) · 25 mg, 50 mg tablets (1) · 28 mg/device (each dose uses 2 devices) (1) · 350 mg/20 mL vial for IV infusion (1) · 4.45 mg, 17.8 mg tablets (1) · 42 mg capsules (1) · 5 mg, 10 mg tablets (1) · 5 mg, 10 mg, 15 mg, 20 mg tablets (1) · 5 mg, 10 mg, 20 mg tablets (1) · 50, 100, or 200 unit vials of lyophilized powder for reconstitution (1) · 70 mg/mL or 140 mg/mL prefilled autoinjector (1) · 75 mg, 150 mg tablets (1) · Dextromethorphan 45 mg + bupropion 105 mg ER tablets (1) · Investigational oral capsule (1) · Was: 170 mg/1.7 mL, 300 mg/3 mL vials for IV infusion (1)

None (2) · 10 mg per 24 h (1) · 10 mg/d (1) · 10 mg/kg q2w (1) · 140 mg/month (1) · 1400 mg q4w (1) · 150 mg/d (1) · 195 units/treatment for chronic migraine; max varies by problem (1) · 2 tablets/day (dextromethorphan 90 mg / bupropion 210 mg) (1) · 20 mg/d (2) · 240 mg loading + 120 mg/month for migraine; 300 mg/month for cluster (1) · 300 mg/quarter (1) · 34 mg/d (1) · 35.6 mg/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) · 50 mg/d (1) · 50 mg/d × 14 d (1) · 6 mg/d (psychosis/mania); 3 mg/d (depression adjunct) (1) · 675 mg/quarter (1) · 84 mg per session (1) · Not yet approved (1) · Single 60-hour course (1) · Withdrawn 2024 (1)

None (2) · Intramuscular (PREEMPT injections for migraine) (1) · Intranasal (1) · Intranasal (under direct medical supervision) (1) · Intravenous (continuous infusion in a REMS-certified facility) (1) · Intravenous infusion (1) · IV infusion (60 min) every 2 weeks; outpatient or infusion-center setting (1) · IV infusion every 4 weeks (2) · Oral (15) · Subcutaneous (3)

None (2) · 1–2 weeks for muscle effects; preventive migraine benefit accrues over 12-week cycles (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) · Amyloid PET clearance within months; cognitive benefit over 18 months (1) · Antidepressant effect within hours of infusion start; sustained at 30 days (1) · Antipsychotic effect over weeks (1) · Benefit over weeks of dosing (1) · Day 3 of dosing in trials; sustained through day 45 (1) · Effect demonstrated within 24 hours in some patients (1) · Onset of preventive effect over weeks; some patients respond after first dose (1) · Over weeks (2) · Pain relief reported within 15 min in trials (1) · PET Aβ reduction over months (1) · Rapid (within 1 week in trials) (1) · Significant antidepressant response by week 1 in trials (faster than monoaminergic antidepressants which take 4-6 weeks) (1) · Slowing of cognitive decline over 18 months (modest effect, ~27% relative slowing) (1) · Typical antidepressant 4-6 week onset (1) · Wake-promoting effect over weeks of titration (1) · Weeks for psychosis/depression; AD agitation benefit emerges over weeks (1) · Weeks for psychosis/mood efficacy (1) · Within hours of first administration (1) · ~30 min (3) · ~30-60 min (1)

None (2) · 14-day course; effect persists after discontinuation in trials (1) · 3-month dosing interval (1) · Acute effect ~24 hours; cumulative effect builds with repeated dosing (1) · Daily dosing (7) · Daily dosing; active metabolites with very long half-lives (up to 1-3 weeks) (1) · Daily morning dosing (1) · Monthly dosing (2) · Monthly or quarterly dosing (1) · Ongoing dosing (1) · Single infusion course (1) · Sustained with twice-daily dosing (1) · Treatment can be discontinued upon achieving amyloid clearance (1) · Withdrawn (1) · ~12 weeks (1) · ~48 h sustained pain freedom in responders (1) · ~7-8 hours (3) · ~9 hours (1)

None (2) · Cariprazine ~2-4 d; major active metabolites desmethyl-cariprazine (DCAR) ~1-3 weeks → 'oral depot' effect with delayed steady-state and reduced effect of missed doses (1) · Dextromethorphan ~22 h (when CYP2D6 inhibited); bupropion ~21 h (1) · Not formally established (1) · Tissue half-life not formally measured; clinical effect ~12 weeks (1) · ~12 hours (1) · ~12.1 days (1) · ~16-23 hours (1) · ~17-19 hours (longer than daridorexant) (1) · ~18 hours (terminal) (1) · ~20 hours (1) · ~25 days (1) · ~25 hours (1) · ~27 days (2) · ~28 days (1) · ~31 days (1) · ~5-7 days (1) · ~57 hours (parent), ~200 h (active metabolite) (1) · ~6.6 h (1) · ~66 hours (1) · ~7 hours (1) · ~7-12 hours (1) · ~7.1 hours (1) · ~8 hours (shorter than suvorexant and lemborexant) (1) · ~9 hours (terminal) (1) · ~91 hours (1)

None (2) · 100% (IV) (5) · Adequate (food-dependent, must take with fatty meal) (1) · Adequate oral bioavailability (1) · Adequate oral bioavailability with extended-release formulation (1) · Limited but adequate; take with food (1) · Local (intramuscular) (1) · Not characterized; oral dosing once daily (1) · Not formally characterized for the combination (1) · Not formally established (1) · Not formally established (high SC) (1) · Not formally established; oral once-daily adequate (1) · Oral bioavailability suitable for daily dosing (1) · ~44% (1) · ~48% intranasal (1) · ~5% intranasal (1) · ~62% (1) · ~72% (with food); much lower fasting (~36%) (1) · ~75% (1) · ~82% (1) · ~82% SC (1) · ~95% (2)

None (2) · Avoid; may cause fetal harm (1) · Category C; limited data (1) · Discontinued/withdrawn (1) · Investigational (1) · Limited data (4) · Limited data; avoid (10) · Limited data; avoid in pregnancy. Lactation: present in milk; consider risks (1) · Limited data; National Pregnancy Registry available (1) · Limited data; National Pregnancy Registry for Atypical Antipsychotics (1) · Limited data; pitolisant may reduce hormonal contraceptive efficacy (1) · Limited data; pregnancy exposure registry available (1) · Limited data; weigh benefits/risks (2) · Medicine is structurally identical to endogenous allopregnanolone; pregnancy considerations relate to breastfeeding during/after infusion. Limited data; brief interruption of breastfeeding considered (1)

None (2) · Investigational (1) · Rx (11) · Rx, '''not a controlled substance''' (no DEA scheduling) (1) · Rx, '''not a controlled substance''' (unique among wake-promoting agents) (1) · Rx, Schedule III (US). REMS program required. (1) · Rx, Schedule IV (US) (5) · Rx. FDA black-box warning for increased mortality in elderly patients with dementia-related psychosis (class warning shared with all antipsychotics) (1) · Rx; ARIA monitoring required (1) · Rx; black-box warning for distant spread of toxin effect (1) · Rx; REMS program required (excessive sedation/loss of consciousness during infusion) (1) · Rx; REMS-like program for ARIA monitoring (1) · Withdrawn from US market January 2024 (1)