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Doxepin response

MedGen UID:
450450
•Concept ID:
CN077978
•
Sign or Symptom
Synonym: Sinequan response
Drug:
Doxepin
MedGen UID:
3904
•Concept ID:
C0013085
•
Pharmacologic Substance
A dibenzoxepin derivative and tricyclic antidepressant (TCA) with antipruritic, antidepressive and anxiolytic activities. Doxepin blocks the reuptake of norepinephrine and serotonin (5-HT) into presynaptic terminals thereby prolonging the availability of the monoaminergic neurotransmitters within the synaptic cleft and enhancing their neurotransmission. Doxepin also has antagonistic effects on histamine H1, 5-HT2, alpha-1 adrenergic, and muscarinic receptors. The antipruritic effect of this agent is mediated through inhibition of histamine receptors. [from NCI]
Doxepin
 
Genes (locations): CYP2C19 (10q23.33); CYP2D6 (22q13.2)

Definition

Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype–directed dosing of tricyclic antidepressants. [from Clinical Pharmacogenetics Implementation Consortium]

Professional guidelines

PubMed

Insomnia Management: A Review and Update.
Shaha DP
J Fam Pract 2023 Jul;72(6 Suppl):S31-S36. doi: 10.12788/jfp.0620. PMID: 37549414
Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.
De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A
Lancet 2022 Jul 16;400(10347):170-184. doi: 10.1016/S0140-6736(22)00878-9. PMID: 35843245
Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline.
Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL
J Clin Sleep Med 2017 Feb 15;13(2):307-349. doi: 10.5664/jcsm.6470. PMID: 27998379Free PMC Article

Suggested Reading

PubMed

Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update.
Hicks JK, Sangkuhl K, Swen JJ, Ellingrod VL, Müller DJ, Shimoda K, Bishop JR, Kharasch ED, Skaar TC, Gaedigk A, Dunnenberger HM, Klein TE, Caudle KE, Stingl JC
Clin Pharmacol Ther 2017 Jul;102(1):37-44. Epub 2017 Feb 13 doi: 10.1002/cpt.597. PMID: 27997040Free PMC Article

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