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Psychosis breakthrough on antipsychotic maintenance: results from a nationwide study

Published online by Cambridge University Press:  13 June 2019

Jose M. Rubio Open the ORCID record for Jose M. Rubio [Opens in a new window] ,
Heidi Taipale ,
Christoph U. Correll ,
Antti Tanskanen ,
John M. Kane  and
Jari Tiihonen
Jose M. Rubio*
Affiliation:
Division of Psychiatry Research, The Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY11004, USA Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY11550, USA The Feinstein Institute for Medical Research, Manhasset, NY11030, USA
Heidi Taipale
Affiliation:
Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Niuvankuja 65, FI-70240Kuopio, Finland Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 5th floor, SE-171 77Stockholm, Sweden School of Pharmacy, University of Eastern Finland, PO Box 1627, SE-70211Kuopio, Finland
Christoph U. Correll
Affiliation:
Division of Psychiatry Research, The Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY11004, USA Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY11550, USA The Feinstein Institute for Medical Research, Manhasset, NY11030, USA Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
Antti Tanskanen
Affiliation:
Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Niuvankuja 65, FI-70240Kuopio, Finland Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 5th floor, SE-171 77Stockholm, Sweden
John M. Kane
Affiliation:
Division of Psychiatry Research, The Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY11004, USA Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY11550, USA The Feinstein Institute for Medical Research, Manhasset, NY11030, USA
Jari Tiihonen
Affiliation:
Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Niuvankuja 65, FI-70240Kuopio, Finland Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 5th floor, SE-171 77Stockholm, Sweden Stockholm County Council, Stockholm Health Care Services, Norra Stationsgatan 69, SE-113 64Stockholm, Sweden
*
Author for correspondence: Jose M. Rubio, E-mail: jrubio13@northwell.edu
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Abstract

Background

There is uncertainty about the incidence of breakthrough psychosis in treatment adherent patients, and the role that factors, such as cumulative antipsychotic exposure, play in this phenomenon.

Methods

In a nationwide cohort of individuals treated for schizophrenia-spectrum disorders in Finland between 1 January 1996 and 31 December 2015, ‘Breakthrough Psychosis on Antipsychotic Maintenance Medication’ (BAMM) was defined as hospitalization for psychosis despite ongoing continuous treatment with long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs) for ⩾8 weeks. Incidence rates, survival curves, and risk factors were presented.

Results

In a cohort of 16 031 continuous LAI treatment episodes with virtually assured adherence [median duration = 441 days, interquartile range (IQR) = 155–1277], BAMM incidence was 31.5%. For 42 867 OAPs treatment episodes (median duration = 483 days, IQR = 167–1491), for whom adherence was modeled by the PRE2DUP method, BAMM incidence was 31.1%. Factors related to illness instability at treatment onset were associated with BAMM, although median time to BAMM was 291 days (IQR = 121–876) for LAIs and 344 days (IQR = 142–989) for OAPs, and 27.4% (N = 1386) of the BAMM events in the LAI, and 32.9% (N = 4378) in the OAP group occurred despite >1 year since last hospitalization at treatment onset. Cumulative antipsychotic exposure was not a consistent risk factor.

Conclusion

BAMM was relatively common even when adherence was confirmed with LAIs. Illness instability at treatment onset accounted for most cases, but relapse after years of continuous treatment was still prevalent. There was insufficient evidence to support causality between cumulative antipsychotic exposure and BAMM. Future research needs to address the role of symptom severity and neurobiology in BAMM.

Keywords

Adherencelong-acting injectablerelapseschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 8 , June 2020 , pp. 1356 - 1367
Copyright
Copyright © Cambridge University Press 2019

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Footnotes

*

Equal contribution.

References

Addington, DE, Patten, SB, McKenzie, E and Addington, J (2013) Relationship between relapse and hospitalization in first-episode psychosis. Psychiatric Services 64, 796–799.CrossRefGoogle ScholarPubMed
Alphs, L, Nasrallah, HA, Bossie, CA, Fu, D-J, Gopal, S, Hough, D and Turkoz, I (2016) Factors associated with relapse in schizophrenia despite adherence to long-acting injectable antipsychotic therapy. International Clinical Psychopharmacology 31, 202–209.CrossRefGoogle ScholarPubMed
Baumann, P, Hiemke, C, Ulrich, S, Eckermann, G, Gaertner, I, Gerlach, M, Kuss, HJ, Laux, G, Müller-Oerlinghausen, B, Rao, ML, Riederer, P, Zernig, G; Arbeitsge-meinschaft fur neuropsychopharmakologie und pharmakopsychiatrie (2004) The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 37, 243–265.CrossRefGoogle Scholar
Carbon, M and Correll, CU (2014) Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues in Clinical Neuroscience 16, 505–524.Google Scholar
Correll, CU, Citrome, L, Haddad, PM, Lauriello, J, Olfson, M, Calloway, SM and Kane, JM (2016) The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. The Journal of Clinical Psychiatry 77(suppl. 3), 1–24.CrossRefGoogle ScholarPubMed
Correll, CU, Rubio, JM and Kane, JM (2018) What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry 17, 149–160.CrossRefGoogle ScholarPubMed
Csernansky, JG, Mahmoud, R and Brenner, R (2002) A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. New England Journal of Medicine 346, 16–22.CrossRefGoogle ScholarPubMed
De Cuyper, H, Bollen, J, van Praag, HM and Verstraeten, D (1986) Pharmacokinetics and therapeutic efficacy of haloperidol decanoate after loading dose administration. The British Journal of Psychiatry 148, 560–566.CrossRefGoogle ScholarPubMed
Demjaha, A, Murray, RM, McGuire, PK, Kapur, S and Howes, OD (2012) Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. The American Journal of Psychiatry 169, 1203–1210.CrossRefGoogle ScholarPubMed
Demjaha, A, Lappin, JM, Stahl, D, Patel, MX, MacCabe, JH, Howes, OD, Heslin, M, Reininghaus, UA, Donoghue, K, Lomas, B, Charalambides, M, Onyejiaka, A, Fearon, P, Jones, P, Doody, G, Morgan, C, Dazzan, P and Murray, RM (2017) Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors. Psychological Medicine 47, 1981–1989.CrossRefGoogle ScholarPubMed
Dold, M, Fugger, G, Aigner, M, Lanzenberger, R and Kasper, S (2015) Dose escalation of antipsychotic drugs in schizophrenia: a meta-analysis of randomized controlled trials. Schizophrenia Research 166, 187–193.CrossRefGoogle ScholarPubMed
Forsman, J, Taipale, H, Masterman, T, Tiihonen, J and Tanskanen, A (2018) Comparison of dispensed medications and forensic-toxicological findings to assess pharmacotherapy in the Swedish population 2006 to 2013. Pharmacoepidemiology and Drug Safety 27, 1112–1122.CrossRefGoogle ScholarPubMed
Foti, DJ, Kotov, R, Guey, LT and Bromet, EJ (2010) Cannabis use and the course of schizophrenia: 10-year follow-up after first hospitalization. The American Journal of Psychiatry 167, 987–993.CrossRefGoogle ScholarPubMed
Goff, DC, Falkai, P, Fleischhacker, WW, Girgis, RR, Kahn, RM, Uchida, H, Zhao, J and Lieberman, JA (2017) The long-term effects of antipsychotic medication on clinical course in schizophrenia. The American Journal of Psychiatry 174, 840–849.CrossRefGoogle Scholar
Harrow, M, Jobe, TH and Faull, RN (2014) Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. Psychological Medicine 44, 3007–3016.CrossRefGoogle ScholarPubMed
Hasan, A, Falkai, P, Wobrock, T, Lieberman, J, Glenthoj, B, Gattaz, WF, Thibaut, F, Möller, HJ; World Federation of Societies of Biological Psychiatry (WFSBP) Task Force on Treatment Guidelines for Schizophrenia (2012) 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. The World Journal of Biological Psychiatry 13, 318–378.CrossRefGoogle ScholarPubMed
Howes, OD and Kapur, S (2014) A neurobiological hypothesis for the classification of schizophrenia: type A (hyperdopaminergic) and type B (normodopaminergic). The British Journal of Psychiatry 205, 1–3.CrossRefGoogle Scholar
Kahn, RS, van Rossum I, Winter, Leucht, S, McGuire, P, Lewis, SW, Leboyer, M, Arango, C, Dazzan, P, Drake, R, Heres, S, Díaz-Caneja, CM, Rujescu, D, Weiser, M, Galderisi, S, Glenthøj, B, Eijkemans, MJC, Fleischhacker, WW, Kapur, S, Sommer, IE; OPTiMiSE study group (2018) Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study. The Lancet. Psychiatry 5, 797–807.CrossRefGoogle ScholarPubMed
Kane, JM, Kishimoto, T and Correll, CU (2013) Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry 12, 216–226.CrossRefGoogle ScholarPubMed
Kishimoto, T, Nitta, M, Borenstein, M, Kane, JM and Correll, CU (2013) Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. The Journal of Clinical Psychiatry 74, 957–965.CrossRefGoogle ScholarPubMed
Kishimoto, T, Robenzadeh, A, Leucht, C, Leucht, S, Watanabe, K, Mimura, M, Borenstein, M, Kane, JM and Correll, CU (2014) Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophrenia Bulletin 40, 192–213.CrossRefGoogle ScholarPubMed
Lally, J, Ajnakina, O, Di Forti, M, Trotta, A, Demjaha, A, Kolliakou, A, Mondelli, V, Reis Marques, T, Pariante, C, Dazzan, P, Shergil, SS, Howes, OD, David, AS, MacCabe, JH, Gaughran, F and Murray, RM (2016) Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses. Psychological Medicine 46, 3231–3240.CrossRefGoogle ScholarPubMed
Leucht, S and Davis, JM (2017) Do antipsychotic drugs lose their efficacy for relapse prevention over time? The British Journal of Psychiatr 211, 127–129.CrossRefGoogle ScholarPubMed
Leucht, S, Tardy, M, Komossa, K, Heres, S, Kissling, W, Salanti, G and Davis, JM (2012) Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 379, 2063–2071.CrossRefGoogle ScholarPubMed
Mallikaarjun, S, Kane, JM, Bricmont, P, McQuade, R, Carson, W, Sanchez, R, Forbes, RA and Fleischhacker, WW (2013) Pharmacokinetics, tolerability and safety of aripiprazole once-monthly in adult schizophrenia: an open-label, parallel-arm, multiple-dose study. Schizophrenia Research 150, 281–288.CrossRefGoogle ScholarPubMed
Mitchell, M, Kothare, P, Bergstrom, R, Zhao, F, Jen, KY, Walker, D, Johnson, J and McDonnell, D (2013) Single- and multiple-dose pharmacokinetic, safety, and tolerability profiles of olanzapine long-acting injection: an open-label, multicenter, nonrandomized study in patients with schizophrenia. Clinical Therapeutics 35, 1890–1908.CrossRefGoogle ScholarPubMed
Mojtabai, R, Lavelle, J, Gibson, PJ and Bromet, EJ (2003) Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes. Schizophrenia Bulletin 29, 519–530.CrossRefGoogle ScholarPubMed
Mouchlianitis, E, Bloomfield, MA, Law, V, Beck, K, Selvaraj, S, Rasquinha, N, Waldman, A, Turkheimer, FE, Egerton, A, Stone, J and Howes, OD (2016) Treatment-resistant schizophrenia patients show elevated anterior cingulate cortex glutamate compared to treatment-responsive. Schizophrenia Bulletin 42, 744–752.CrossRefGoogle ScholarPubMed
Murray, RM, Quattrone, D, Natesan, S, van Os, J, Nordentoft, M, Howes, O, Di Forti, M and Taylor, D (2016) Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? The British Journal of Psychiatry 209, 361–365.CrossRefGoogle ScholarPubMed
Robinson, D, Woerner, MG, Alvir, JM, Bilder, R, Goldman, R, Geisler, S, Koreen, A, Sheitman, B, Chakos, M, Mayerhoff, D and Lieberman, JA (1999) Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Archives of General Psychiatry 56, 241–247.CrossRefGoogle ScholarPubMed
Rossenu, S, Cleton, A, Hough, D, Crauwels, H, Vandebosch, A, Berwaerts, J, Eerdekens, M, Herben, V, De Meulder, M, Remmerie, B and Francetic, I (2015) Pharmacokinetic profile after multiple deltoid or gluteal intramuscular injections of paliperidone palmitate in patients with schizophrenia. Clinical Pharmacology in Drug Development 4, 270–278.CrossRefGoogle ScholarPubMed
Rubio, JM and Kane, JM (2017) Psychosis breakthrough on antipsychotic maintenance medication (BAMM): what can we learn? NPJ Schizophrenia 3, 36.CrossRefGoogle ScholarPubMed
Samaha, A-N, Seeman, P, Stewart, J, Rajabi, H and Kapur, S (2007) ‘Breakthrough’ dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. The Journal of Neuroscienc 27, 2979–2986.CrossRefGoogle ScholarPubMed
Seeman, P and Lee, T (1975) Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217–1219.CrossRefGoogle ScholarPubMed
Seeman, P, Weinshenker, D, Quirion, R, Srivastava, LK, Bhardwaj, SK, Grandy, DK, Premont, RT, Sotnikova, TD, Boksa, P, El-Ghundi, M, O'dowd, BF, George, SR, Perreault, ML, Männistö, PT, Robinson, S, Palmiter, RD and Tallerico, T (2005) Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. Proceedings of the National Academy of Sciences 102, 3513–3518.CrossRefGoogle ScholarPubMed
Takeuchi, H, Siu, C, Remington, G, Fervaha, G, Zipursky, RB, Foussias, G and Agid, O (2018) Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia. Neuropsychopharmacology 44, 1036–1042.CrossRefGoogle ScholarPubMed
Tanskanen, A, Taipale, H, Koponen, M, Tolppanen, A-M, Hartikainen, S, Ahonen, R and Tiihonen, J (2015) From prescription drug purchases to drug use periods – a second generation method (PRE2DUP). BMC Medical Informatics and Decision Making 15, 21.CrossRefGoogle Scholar
Thien, K and O'Donoghue, B (2018) Delays and barriers to the commencement of clozapine in eligible people with a psychotic disorder: a literature review. Early Intervention in Psychiatry 13, 18–23.CrossRefGoogle ScholarPubMed
Tiihonen, J, Mittendorfer-Rutz, E, Majak, M, Mehtälä, J, Hoti, F, Jedenius, E, Enkusson, D, Leval, A, Sermon, J, Tanskanen, A and Taipale, H (2017) Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29823 patients with schizophrenia. JAMA Psychiatry 74, 686–693.CrossRefGoogle Scholar
Wilson, WH (2004) A visual guide to expected blood levels of long-acting injectable risperidone in clinical practice. Journal of Psychiatric Practice 10, 393–401.CrossRefGoogle ScholarPubMed
Wunderink, L, Nieboer, RM, Wiersma, D, Sytema, S and Nienhuis, FJ (2013) Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry 70, 913–920.CrossRefGoogle ScholarPubMed
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