Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2017

Open Access 01-12-2017 | Case report

Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report

Authors: Seenae Eum, Mark E. Schneiderhan, Jacob T. Brown, Adam M. Lee, Jeffrey R. Bishop

Published in: BMC Psychiatry | Issue 1/2017

Login to get access

Abstract

Background

Given the complex nature of symptom presentation and medication regimens, psychiatric clinics may benefit from additional tools to personalize treatments. Utilizing pharmacogenetic information may be helpful in assessing unique responses to therapy. We report herein a case of wearing-off phenomena during treatment with aripiprazole long-acting injectable (LAI) and a proof of concept strategy of how pharmacogenetic information may be used to assess possible genetic factors and also hypothesize potential mechanisms for further study.

Case presentation

A 51-year-old African American male with schizoaffective disorder was referred to a psychiatric clinic for medication management. After unsuccessful trials of multiple antipsychotics, oral aripiprazole was initiated (up to 30 mg/day) and transitioned to aripiprazole LAI with symptom improvement. At a high dose of aripiprazole LAI (400 mg Q3wks), the patient experienced breakthrough symptoms approximately 3 days prior to his next injection. Various considerations were examined to explain his atypical dose requirements, including but not limited to pharmacogenetic influences. Pharmacogenetic testing ruled out genetic influences on drug metabolism but noted a -141C Del variant in the dopamine-D2 receptor (DRD2) gene associated in prior studies of poor-response to antipsychotics. At this time, a new formulation, aripiprazole lauroxil, was explored due to its availability in higher dose options. Transition to the new formulation (882 mg Q4wks) greatly improved and stabilized the patient’s symptoms with no breakthrough psychosis. Comparable daily dose equivalents were achieved with two different formulations due to the Q3wks vs Q4wks dosing strategies, although the two agents have some differences in pharmacokinetic profiles.

Conclusions

We report a case of a patient experiencing wearing-off symptoms with aripiprazole LAI who benefited from switching to aripiprazole lauroxil. Pharmacogenetic testing revealed normal activity for relevant metabolism pathways but a DRD2 -141C variant that may influence brain D2 expression and antipsychotic responsiveness. The clinical utility of DRD2 information and what to do with genotyping results has not been previously addressed, despite availability on clinical test panels. Our case report suggests further investigations of altered dosing strategies and receptor genotype sensitivities to pharmacokinetic factors may be helpful in understanding symptom re-emergence observed in some patients taking LAI antipsychotics.
Literature
1.
Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13:318–78.CrossRefPubMed
2.
3.
Drozda K, Müller DJ, Bishop JR. Pharmacogenomic testing for neuropsychiatric drugs: current status of drug labeling, guidelines for using genetic information, and test options. Pharmacotherapy. 2014;34:166–84.CrossRefPubMedPubMedCentral
4.
5.
Eum S, Lee AM, Bishop JR. Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations. Dialogues Clin Neurosci. 2016;18:323–37.
6.
Zhang J-P, Lencz T, Malhotra AK. D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis. Am J Psychiatry. 2010;167:763–72.CrossRefPubMedPubMedCentral
7.
Pouget JG, Müller DJ. Pharmacogenetics of antipsychotic treatment in schizophrenia. Methods Mol Biol. 2014;1175:557–87.CrossRefPubMed
8.
9.
Rohde M, M Rk N, Håkansson AE, Jensen KG, Pedersen H, Dige T, et al. Biological conversion of aripiprazole lauroxil - An N-acyloxymethyl aripiprazole prodrug. Results Pharma Sci. 2014;4:19–25.CrossRefPubMedPubMedCentral
10.
Spanarello S, La Ferla T. The pharmacokinetics of long-acting antipsychotic medications. Curr Clin Pharmacol. 2014;9:310–7.CrossRefPubMed
11.
Jönsson EG, Nöthen MM, Grünhage F, Farde L, Nakashima Y, Propping P, et al. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry. 1999;4:290–6.CrossRefPubMed
12.
Arinami T, Gao M, Hamaguchi H, Toru M. A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum Mol Genet. 1997;6:577–82.CrossRefPubMed
13.
Meltzer HY, Risinger R, Nasrallah HA, Du Y, Zummo J, Corey L, et al. A randomized, double-blind, placebo-controlled trial of aripiprazole lauroxil in acute exacerbation of schizophrenia. J Clin Psychiatry. 2015;76:1085–90.CrossRefPubMed
14.
Yin J, Collier AC, Barr AM, Honer WG, Procyshyn RM. Paliperidone Palmitate Long-Acting Injectable Given Intramuscularly in the Deltoid Versus the Gluteal Muscle: Are They Therapeutically Equivalent? J Clin Psychopharmacol. 2015;35:447–9.PubMed
15.
Procyshyn RM, Banasch JL, Barr AM, Honer WG. Breakthrough symptoms after switching long-acting injectable paliperidone palmitate from the gluteal to the deltoid site of administration. J Psychiatry Neurosci. 2016;41:E56–7.CrossRefPubMedPubMedCentral
16.
Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, et al. Pharmacogenetics: from bench to byte--an update of guidelines. Clin Pharmacol Ther. 2011;89:662–73.CrossRefPubMed
17.
Sáiz PA, García-Portilla MP, Arango C, Morales B, Arias B, Corcoran P, et al. Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an association study. Prog Neuro-Psychopharmacol Biol Psychiatry. 2010;34:26–31.CrossRef
18.
Xiao L, Shen T, Peng D-H, Shu C, Jiang K, Wang G-H. Functional -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter and schizophrenia in a Chinese Han population. J Int Med Res. 2013;41:1171–8.CrossRefPubMed
19.
Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–7.CrossRefPubMedCentral
20.
Mallikaarjun S, Kane JM, Bricmont P, McQuade R, Carson W, Sanchez R, et al. Pharmacokinetics, tolerability and safety of aripiprazole once-monthly in adult schizophrenia: an open-label, parallel-arm, multiple-dose study. Schizophr Res. 2013;150:281–8.CrossRefPubMed
21.
Remenar JF. Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics. Mol Pharm. 2014;11:1739–49.CrossRefPubMed
22.
Turncliff R, Hard M, Du Y, Risinger R, Ehrich EW. Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia. Schizophr Res. 2014;159:404–10.CrossRefPubMed
23.
Takase M, Kanahara N, Oda Y, Niitsu T, Watanabe H, Iyo M. The impacts of dopamine D2 receptor polymorphism and antipsychotic dosage on dopamine supersensitivity psychosis in schizophrenia. Schizophr Res. 2017; doi:10.​1016/​j.​schres.​2017.​03.​014.
24.
Lencz T, Robinson DG, Xu K, Ekholm J, Sevy S, Gunduz-Bruce H, et al. DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am J Psychiatry. 2006;163:529–31.CrossRefPubMed
25.
26.
27.
Walkup JT, McAlpine DD, Olfson M, Labay LE, Boyer C, Hansell S. Patients with schizophrenia at risk for excessive antipsychotic dosing. J Clin Psychiatry. 2000;61:344–8.CrossRefPubMed
28.
Lehman AF, Steinwachs DM. Patterns of usual care for schizophrenia: initial results from the Schizophrenia Patient Outcomes Research Team (PORT) Client Survey. Schizophr Bull. 1998;24:11–20. discussion 20–32CrossRefPubMed
29.
Segal SP, Bola JR, Watson MA. Race, quality of care, and antipsychotic prescribing practices in psychiatric emergency services. Psychiatr Serv. 1996;47:282–6.CrossRefPubMed
Metadata
Title
Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report
Authors
Seenae Eum
Mark E. Schneiderhan
Jacob T. Brown
Adam M. Lee
Jeffrey R. Bishop
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2017
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-017-1396-x

Other articles of this Issue 1/2017

BMC Psychiatry 1/2017 Go to the issue

Research article

Hypnotic susceptibility and affective states in bipolar I and II disorders

Research article

Jump step - a community based participatory approach to physical activity & mental wellness

Research article

Examining differences in cognitive and affective theory of mind between persons with high and low extent of somatic symptoms: an experimental study

Research article

Mental health care and delivery system at Temeke hospital in Dar es Salaam, Tanzania

Study protocol

Effectiveness and cost-effectiveness of a guided Internet- and mobile-based intervention for the indicated prevention of major depression in patients with chronic back pain—study protocol of the PROD-BP multicenter pragmatic RCT

Research article

The disease burden of suicide in Ecuador, a 15 years’ geodemographic cross-sectional study (2001–2015)