Details of the Drug

General Information of Drug (ID: DM6F1PU)

Drug Name

Vortioxetine

Synonyms

VORTIOXETINE; 508233-74-7; 1-(2-((2,4-Dimethylphenyl)thio)phenyl)piperazine; Lu AA21004; UNII-3O2K1S3WQV; 3O2K1S3WQV; CHEBI:76016; Trintellix; 1-{2-[(2,4-dimethylphenyl)sulfanyl]phenyl}piperazine; Piperazine, 1-[2-[(2,4-dimethylphenyl)thio]phenyl]-; Brintellix (TN); 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine; 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine; 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine; CHEMBL2204360; 1-[2-[(2,4-Dimethylphenyl)thio]phenyl]piperazine; Lu-AA21004

Indication

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[1], [2]
Mood disorder	6A60-6E23	Phase 3	[3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

298.4

Topological Polar Surface Area (xlogp)

4.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The drug present in the plasma can be removed from the body at the rate of 5.8 mL/min/kg [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 66 hours [4]
Metabolism: The drug is metabolized via the cytochrome P450 isozymes [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [4]
Vd: The volume of distribution (Vd) of drug is 2600 L [6]

Chemical Identifiers

Formula: C18H22N2S
IUPAC Name: 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine
Canonical SMILES: CC1=CC(=C(C=C1)SC2=CC=CC=C2N3CCNCC3)C
InChI: InChI=1S/C18H22N2S/c1-14-7-8-17(15(2)13-14)21-18-6-4-3-5-16(18)20-11-9-19-10-12-20/h3-8,13,19H,9-12H2,1-2H3
InChIKey: YQNWZWMKLDQSAC-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 9966051
ChEBI ID: CHEBI:76016
CAS Number: 508233-74-7
DrugBank ID: DB09068
TTD ID: D03WEX
VARIDT ID: DR01102
INTEDE ID: DR1712
ACDINA ID: D00735

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[2], [3], [7], [2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
Cytochrome P450 2D6 (CYP2D6)_{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[9]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Substrate	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[8]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Substrate	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Major depressive disorder

ICD Disease Classification

6A70.3

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serotonin transporter (SERT)	DTT	SLC6A4	8.76E-01	7.18E-05	6.19E-04
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	5.57E-01	-7.89E-02	-7.93E-01
Cytochrome P450 2B6 (CYP2B6)	DME	CYP2B6	4.32E-01	4.39E-02	4.30E-01
Cytochrome P450 2A6 (CYP2A6)	DME	CYP2A6	8.99E-01	4.59E-03	2.19E-02
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.57E-01	9.43E-03	1.29E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	9.62E-01	2.57E-02	1.10E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	2.35E-01	2.78E-02	2.09E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.76E-01	1.26E-01	8.27E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Vortioxetine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Additive serotonergic effects by the combination of Vortioxetine and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[76]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Vortioxetine caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[77]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Vortioxetine caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[77]
Oliceridine	DM6MDCF	Moderate	Additive serotonergic effects by the combination of Vortioxetine and Oliceridine.	Acute pain [MG31]	[78]
Inotersen	DMJ93CT	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Inotersen.	Amyloidosis [5D00]	[79]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Vortioxetine caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[77]
Lumacaftor	DMCLWDJ	Moderate	Increased metabolism of Vortioxetine caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[77]
Eslicarbazepine	DMZREFQ	Moderate	Increased risk of hyponatremia by the combination of Vortioxetine and Eslicarbazepine.	Epilepsy/seizure [8A61-8A6Z]	[80]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Tazemetostat.	Follicular lymphoma [2A80]	[79]
Avapritinib	DMK2GZX	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[79]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Vortioxetine caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[81]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Vortioxetine caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[82]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Vortioxetine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[83]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Vortioxetine caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[77]
Dacomitinib	DMOH8VY	Major	Decreased metabolism of Vortioxetine caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[77]
Acalabrutinib	DM7GCVW	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[79]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Vortioxetine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[84]
Ozanimod	DMT6AM2	Moderate	Additive serotonergic effects by the combination of Vortioxetine and Ozanimod.	Multiple sclerosis [8A40]	[85]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Vortioxetine caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[86]
Rolapitant	DM8XP26	Moderate	Decreased metabolism of Vortioxetine caused by Rolapitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[87]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[79]
Insulin degludec	DMPL395	Moderate	Increased risk of hypoglycemia by the combination of Vortioxetine and Insulin degludec.	Type-1/2 diabete [5A10-5A11]	[88]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Vortioxetine caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[77]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Vortioxetine and Betrixaban.	Venous thromboembolism [BD72]	[79]
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⏷ Show the Full List of 24 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 10 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Vortioxetine 15 mg tablet	15 mg	Oral Tablet	Oral
Vortioxetine 10 mg tablet	10 mg	Oral Tablet	Oral
Vortioxetine 20 mg tablet	20 mg	Oral Tablet	Oral
Vortioxetine 5 mg tablet	5 mg	Oral Tablet	Oral
Vortioxetine Hydrobromide eq 15mg base tablet	eq 15mg base	Tablet	Oral
Vortioxetine Hydrobromide eq 10mg base tablet	eq 10mg base	Tablet	Oral
Vortioxetine Hydrobromide eq 5mg base tablet	eq 5mg base	Tablet	Oral
Vortioxetine Hydrobromide eq 20mg base tablet	eq 20mg base	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7351).
2	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
3	Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacol Biochem Behav. 2013 Apr;105:41-50.
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
6	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
7	A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012 Jun;15(5):589-600.
8	Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos. 2012 Jul;40(7):1357-65.
9	Vortioxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2018 Jun;57(6):673-686.
10	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
11	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
12	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
13	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
14	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
15	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
16	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
17	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
18	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
19	Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
20	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
21	Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
22	Psychotropic drug interactions with valproate. Clin Neuropharmacol. 2005 Mar-Apr;28(2):96-101.
23	The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
24	Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
25	CYP2A6- and CYP2A13-catalyzed metabolism of the nicotine delta-5'(1')iminium ion. J Pharmacol Exp Ther. 2012 Nov;343(2):307-15.
26	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
27	Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
28	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
29	Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
30	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
31	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
32	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
33	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
34	Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
35	Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
36	Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
37	Drug Interactions Flockhart Table
38	Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
39	Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
40	Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
41	Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
42	Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
43	Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
44	Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
45	Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
46	Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
47	PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
48	Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
49	Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
50	Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
51	Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
52	Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
53	New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
54	A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
55	A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
56	Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
57	Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
58	Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
59	Drugs that may have potential CYP2B6 interactions.
60	Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
61	Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
62	PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
63	Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
64	High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
65	Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
66	CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
67	Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
68	Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
69	Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
70	Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
71	Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
72	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
73	Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
74	Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
75	Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
76	Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
77	Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America, Lincolnshire, IL.
78	Vizcaychipi MP, Walker S, Palazzo M "Serotonin syndrome triggered by tramadol." Br J Anaesth 99 (2007): 919. [PMID: 18006535]
79	Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
80	Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
81	Product Information. Givlaari (givosiran). Alnylam Pharmaceuticals, Cambridge, MA.
82	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
83	Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
84	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
85	Alvine G, Black DW, Tsuang D "Case of delirium secondary to phenelzine/L-tryptophan combination." J Clin Psychiatry 51 (1990): 311. [PMID: 2365671]
86	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
87	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
88	Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7. [PMID: 11678792]