Details of the Drug Combination

General Information of Drug Combination (ID: DC05J0L)

• Drug Combination Name: Escitalopram + Mirtazapine
• Indication: Major Depressive Disorder; Status: Phase 1 [1]
• Component Drugs:
  Escitalopram (DMFK9HG): Small molecular drug
  Mirtazapine (DML53ZJ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Escitalopram

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[2]

Escitalopram Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[4]

Escitalopram Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[7]

Escitalopram Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Increases ADR	[8]

Indication(s) of Mirtazapine

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[3]

Mirtazapine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Antagonist	[9]

Mirtazapine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[11]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[12]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[12]

Mirtazapine Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[13]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[14]
Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4)	OTJZG0LD	GLUT4_HUMAN	Increases Expression	[15]
Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5)	OTZNYEKF	GTR5_HUMAN	Increases Expression	[15]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[13]

References

• [1] ClinicalTrials.gov (NCT01764867) Algorithm Guided Treatment Strategies for Major Depressive Disorder
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] 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: 7241).
• [4] Antidepressants and sleep: a review. Perspect Psychiatr Care. 2009 Jul;45(3):191-7.
• [5] PharmGKB summary: citalopram pharmacokinetics pathway. Pharmacogenet Genomics. 2011 Nov;21(11):769-72.
• [6] CYP2D6 P34S Polymorphism and Outcomes of Escitalopram Treatment in Koreans with Major Depression. Psychiatry Investig. 2013 Sep;10(3):286-93.
• [7] Escitalopram pharmacogenetics: CYP2C19 relationships with dosing and clinical outcomes in autism spectrum disorder. Pharmacogenet Genomics. 2015 Nov;25(11):548-54.
• [8] Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression. Eur Neuropsychopharmacol. 2009 Jun;19(6):451-6. doi: 10.1016/j.euroneuro.2009.01.010. Epub 2009 Mar 9.
• [9] Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
• [10] A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Fall;7(3):249-64.
• [11] Impact of the CYP2D6 ultrarapid metabolizer genotype on mirtazapine pharmacokinetics and adverse events in healthy volunteers. J Clin Psychopharmacol. 2004 Dec;24(6):647-52.
• [12] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [13] Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett. 2006 Mar 13;395(3):185-90. doi: 10.1016/j.neulet.2005.10.096. Epub 2005 Dec 1.
• [14] [Gynecomastia-galactorrhea during treatment with mirtazapine]. Presse Med. 2004 Apr 10;33(7):458. doi: 10.1016/s0755-4982(04)98631-9.
• [15] Effects of different antipsychotics and the antidepressant mirtazapine on glucose transporter mRNA levels in human blood cells. J Psychiatr Res. 2006 Jun;40(4):374-9. doi: 10.1016/j.jpsychires.2005.04.016. Epub 2005 Jul 5.