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Nortriptyline response

MedGen UID:
373269
•Concept ID:
C1837159
•
Finding
Synonyms: Nortriptyline, poor metabolism of; Pamelor response
Drug:
Nortriptyline
MedGen UID:
18086
•Concept ID:
C0028420
•
Pharmacologic Substance
A tricyclic antidepressant agent used for short-term treatment of various forms of depression. Nortriptyline blocks the norepinephrine presynaptic receptors, thereby blocking the reuptake of this neurotransmitter and raising the concentration in the synaptic cleft in the CNS. Nortriptyline also binds to alpha-adrenergic, histaminergic and cholinergic receptors. Long-term treatment with nortriptyline produces a downregulation of adrenergic receptors due to the increased stimulation of these receptors. [from NCI]
Nortriptyline
 
Gene (location): CYP2D6 (22q13.2)
 
OMIM®: 608902

Definition

Nortriptyline is a tricyclic that can be identified by the secondary amine in its chemical structure. Tricyclics are commonly prescribed for psychological disorders and pain management. Genetic variants in cytochrome P450 2D6 (CYP2D6) may affect treatment success of nortriptyline or other tricyclics with the secondary amine functional group. Patients with poor metabolizer variants of CYP2D6 may require reductions in dose or alternative agents in order to circumvent common adverse anticholinergic, central nervous system, or cardiac effects. Guidelines regarding the use of pharmacogenomic tests in dosing for nortriptyline and other tricyclics have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]

Professional guidelines

PubMed

Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis.
Nuñez NA, Joseph B, Pahwa M, Kumar R, Resendez MG, Prokop LJ, Veldic M, Seshadri A, Biernacka JM, Frye MA, Wang Z, Singh B
J Affect Disord 2022 Apr 1;302:385-400. Epub 2022 Jan 2 doi: 10.1016/j.jad.2021.12.134. PMID: 34986373Free PMC Article
Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis.
Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, Li X, Cuijpers P, Coghill D, Xiang Y, Hetrick SE, Leucht S, Qin M, Barth J, Ravindran AV, Yang L, Curry J, Fan L, Silva SG, Cipriani A, Xie P
Lancet Psychiatry 2020 Jul;7(7):581-601. doi: 10.1016/S2215-0366(20)30137-1. PMID: 32563306Free PMC Article
Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials.
Hayasaka Y, Purgato M, Magni LR, Ogawa Y, Takeshima N, Cipriani A, Barbui C, Leucht S, Furukawa TA
J Affect Disord 2015 Jul 15;180:179-84. Epub 2015 Mar 31 doi: 10.1016/j.jad.2015.03.021. PMID: 25911132

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

Recent clinical studies

Etiology

Nortriptyline response in elderly depressed patients.
Kanba S, Matsumoto K, Nibuya M, Suzuki E, Kinoshita N, Shintani F, Yagi G
Prog Neuropsychopharmacol Biol Psychiatry 1992 May;16(3):301-9. doi: 10.1016/0278-5846(92)90081-o. PMID: 1589587

Therapy

Nortriptyline response in elderly depressed patients.
Kanba S, Matsumoto K, Nibuya M, Suzuki E, Kinoshita N, Shintani F, Yagi G
Prog Neuropsychopharmacol Biol Psychiatry 1992 May;16(3):301-9. doi: 10.1016/0278-5846(92)90081-o. PMID: 1589587
Relationship of free nortriptyline levels to therapeutic response.
Perry PJ, Browne JL, Alexander B, Pfohl BM, Dunner FJ, Sherman AD, Tsuang MT
Acta Psychiatr Scand 1985 Aug;72(2):120-5. doi: 10.1111/j.1600-0447.1985.tb02582.x. PMID: 4050504
Amitriptyline and nortriptyline response profiles in unipolar depressed patients.
Lehmann LS, Bowden CL, Redmond FC, Stanton BC
Psychopharmacology (Berl) 1982;77(2):193-7. doi: 10.1007/BF00431947. PMID: 6812139

Clinical prediction guides

Nortriptyline response in elderly depressed patients.
Kanba S, Matsumoto K, Nibuya M, Suzuki E, Kinoshita N, Shintani F, Yagi G
Prog Neuropsychopharmacol Biol Psychiatry 1992 May;16(3):301-9. doi: 10.1016/0278-5846(92)90081-o. PMID: 1589587
Amitriptyline and nortriptyline response profiles in unipolar depressed patients.
Lehmann LS, Bowden CL, Redmond FC, Stanton BC
Psychopharmacology (Berl) 1982;77(2):193-7. doi: 10.1007/BF00431947. PMID: 6812139

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