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Discontinuation of antipsychotics in individuals with first-episode schizophrenia and its association to functional outcomes, hospitalization and death: a register-based nationwide follow-up study

Published online by Cambridge University Press:  12 July 2022

Anne Emilie Stürup Open the ORCID record for Anne Emilie Stürup [Opens in a new window] ,
Merete Nordentoft ,
Espen Jimenez-Solem ,
Merete Osler ,
Josefine Winther Davy ,
Thomas Nordahl Christensen ,
Helene Speyer ,
Nikolai Albert  and
Carsten Hjorthøj
Anne Emilie Stürup*
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
Merete Nordentoft
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
Espen Jimenez-Solem
Affiliation:
Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology, Center for Clinical Research and Prevention, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Merete Osler
Affiliation:
Center for Clinical Research and Prevention, Frederiksberg Hospital, Denmark
Josefine Winther Davy
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
Thomas Nordahl Christensen
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
Helene Speyer
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
Nikolai Albert
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark Mental Health Center Amager, Copenhagen University Hospital, Copenhagen, Denmark
Carsten Hjorthøj
Affiliation:
Copenhagen Research Center for Mental Health – CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark
*
Author for correspondence: Anne Emilie Stürup, E-mail: [email protected]
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Abstract

Background

Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death.

Methods

Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995–2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2–5. Outcomes year 5–6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression.

Results

Among 21 351, 9.3% took antipsychotics continuously year 2–5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53–2.56 and OR 2.60, 95% CI 1.91–3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05–1.48 and 2.04, 95% CI 1.64–2.53) and no antipsychotics (OR 2.00, 95% CI 1.69–2.38 and 5.64, 95% CI 4.56–6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10–1.47) and longer admissions (IRR 1.68, 95% CI 1.30–2.16) year 5–6 compared to continuous users. Mortality during year 5–6 did not differ between groups.

Conclusion

Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.

Keywords

Antipsychoticsdiscontinuationfirst-episode schizophreniafunctionhospitalizationmortality
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 11 , August 2023 , pp. 5033 - 5041
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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References

Gotfredsen, D. R., Wils, R. S., Hjorthoj, C., Austin, S. F., Albert, N., Secher, R. G., … Nordentoft, M. (2017). Stability and development of psychotic symptoms and the use of antipsychotic medication – Long-term follow-up. Psychological Medicine, 47(12), 2118–2129. https://doi.org/10.1017/S0033291717000563.CrossRefGoogle ScholarPubMed
Hakulinen, C., McGrath, J. J., Timmerman, A., Skipper, N., Mortensen, P. B., Pedersen, C. B., & Agerbo, E. (2019). The association between early-onset schizophrenia with employment, income, education, and cohabitation status: Nationwide study with 35 years of follow-up. Social Psychiatry and Psychiatric Epidemiology, 54(11), 1343–1351. https://doi.org/10.1007/s00127-019-01756-0.CrossRefGoogle ScholarPubMed
Harrow, M., Jobe, T. H., & Faull, R. N. (2012). Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychological Medicine, 42(10), 2145–2155. https://doi.org/10.1017/S0033291712000220.CrossRefGoogle Scholar
Helweg-Larsen, K. (2011). The Danish register of causes of death. Scandinavian Journal of Public Health, 39(7), 26–29. https://doi.org/10.1177/1403494811399958.CrossRefGoogle ScholarPubMed
Hjollund, N. H., Larsen, F. B., & Andersen, J. H. (2007). Register-based follow-up of social benefits and other transfer payments: Accuracy and degree of completeness in a Danish interdepartmental administrative database compared with a population-based survey. Scandinavian Journal of Public Health, 35(5), 497–502. https://doi.org/10.1080/14034940701271882.CrossRefGoogle Scholar
Iyer, S. N., Mangala, R., Anitha, J., Thara, R., & Malla, A. K. (2011). An examination of patient-identified goals for treatment in a first-episode programme in Chennai, India. Early Intervention in Psychiatry, 5(4), 360–365. https://doi.org/10.1111/j.1751-7893.2011.00289.x.CrossRefGoogle Scholar
Jensen, T. B., Andersen, J. T., Jimenez-Solem, E., & Lund, M. (2021). How patients in Denmark acquire their medicines: Overview, data sources and implications for pharmacoepidemiology. Basic & Clinical Pharmacology & Toxicology, 128(1), 46–51. https://doi.org/10.1111/BCPT.13472.CrossRefGoogle ScholarPubMed
Jensen, V. M., & Rasmussen, A. W. (2011). Danish education registers. Scandinavian Journal of Public Health, 39(7), 91–94. https://doi.org/10.1177/1403494810394715.CrossRefGoogle ScholarPubMed
Kroken, R. A., Kjelby, E., Wentzel-Larsen, T., Mellesdal, L. S., Jørgensen, H. A., & Johnsen, E. (2014). Time to discontinuation of antipsychotic drugs in a schizophrenia cohort: Influence of current treatment strategies. Therapeutic Advances in Psychopharmacology, 4(6), 228–239. https://doi.org/10.1177/2045125314545614.CrossRefGoogle Scholar
Le Quach, P., Mors, O., Christensen, TØ, Krarup, G., Jørgensen, P., Bertelsen, M., … Nordentoft, M. (2009). Predictors of poor adherence to medication among patients with first-episode schizophrenia-spectrum disorder. Early Intervention in Psychiatry, 3(1), 66–74. https://doi.org/10.1111/j.1751-7893.2008.00108.x.CrossRefGoogle Scholar
Leucht, S., Corves, C., Arbter, D., Engel, R. R., Li, C., & Davis, J. M. (2009). Second-generation versus first-generation antipsychotic drugs for schizophrenia: A meta-analysis. The Lancet, 373(9657), 31–41. https://doi.org/10.1016/S0140-6736(08)61764-X.CrossRefGoogle ScholarPubMed
Leucht, S., Samara, M., Heres, S., Patel, M. X., Woods, S. W., & Davis, J. M. (2014). Dose equivalents for second-generation antipsychotics: The minimum effective dose method. Schizophrenia Bulletin, 40(2), 314–326. https://doi.org/10.1093/schbul/sbu001.CrossRefGoogle ScholarPubMed
Leucht, S., Tardy, M., Komossa, K., Heres, S., Kissling, W., Salanti, G., & Davis, J. M. (2012). Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: A systematic review and meta-analysis. The Lancet, 379(9831), 2063–2071. https://doi.org/10.1016/S0140-6736(12)60239-6.CrossRefGoogle ScholarPubMed
Morgan, C., Lappin, J., Heslin, M., Donoghue, K., Lomas, B., Reininghaus, U., … Dazzan, P. (2014). Reappraising the long-term course and outcome of psychotic disorders: The AESOP-10 study. Psychological Medicine, 44(13), 2713–2726. https://doi.org/10.1017/S0033291714000282.CrossRefGoogle ScholarPubMed
Mors, O., Perto, G. P., & Mortensen, P. B. (2011). The Danish psychiatric central research register. Scandinavian Journal of Public Health, 39(7), 54–57. https://doi.org/10.1177/1403494810395825.CrossRefGoogle ScholarPubMed
National Institute for Health and Care Excellence (NICE). (2014). Psychosis and schizophrenia in adults: Prevention and management – Clinical guideline. UK: National Institute for Health and Care Excellence (NICE). Retrieved from www.nice.org.uk/guidance/cg178.Google Scholar
Pedersen, C. B. (2011). The Danish civil registration system. Scandinavian Journal of Public Health, 39(7), 22–25. https://doi.org/10.1177/1403494810387965.CrossRefGoogle ScholarPubMed
Petersson, F., Baadsgaard, M., & Thygesen, L. C. (2011). Danish registers on personal labour market affiliation. Scandinavian Journal of Public Health, 39(7), 95–98. https://doi.org/10.1177/1403494811408483.CrossRefGoogle ScholarPubMed
Pottegård, A., Schmidt, S. A. J., Wallach-Kildemoes, H., Sørensen, H. T., Hallas, J., & Schmidt, M. (2017). Data resource profile: The Danish national prescription registry. International Journal of Epidemiology, 46(3), 798. https://doi.org/10.1093/ije/dyw213.Google ScholarPubMed
Schennach-Wolff, R., Jäger, M., Seemüller, F., Obermeier, M., Messer, T., Laux, G., … Riedel, M. (2009). Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders. Schizophrenia Research, 113(2–3), 210–217. https://doi.org/10.1016/j.schres.2009.05.032.CrossRefGoogle ScholarPubMed
Schmidt, M., Schmidt, S. A. J., Sandegaard, J. L., Ehrenstein, V., Pedersen, L., & Sørensen, H. T. (2015). The Danish National patient registry: A review of content, data quality, and research potential. Clinical Epidemiology, 7, 449–490. https://doi.org/10.2147/CLEP.S91125.CrossRefGoogle ScholarPubMed
Schneider-Thoma, J., Efthimiou, O., Huhn, M., Krause, M., Reichelt, L., Röder, H., … Leucht, S. (2018). Second-generation antipsychotic drugs and short-term mortality: A systematic review and meta-analysis of placebo-controlled randomised controlled trials. The Lancet Psychiatry, 5(8), 653–663. https://doi.org/10.1016/S2215-0366(18)30177-9.CrossRefGoogle ScholarPubMed
Strålin, P., & Hetta, J. (2019). Medication, hospitalizations and mortality in 5 years after first-episode psychosis in a Swedish nation-wide cohort. Early Intervention in Psychiatry, 13(4), 902–907. https://doi.org/10.1111/eip.12697.CrossRefGoogle Scholar
Strømme, M. F., Mellesdal, L. S., Bartz-Johannesen, C., Kroken, R. A., Krogenes, M., Mehlum, L., & Johnsen, E. (2021). Mortality and non-use of antipsychotic drugs after acute admission in schizophrenia: A prospective total-cohort study. Schizophrenia Research, 235, 29–35. https://doi.org/10.1016/J.SCHRES.2021.07.009.CrossRefGoogle ScholarPubMed
Taipale, H., Tanskanen, A., Mehtälä, J., Vattulainen, P., Correll, C. U., & Tiihonen, J. (2020). 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry, 19(1), 61–68. https://doi.org/10.1002/WPS.20699.CrossRefGoogle Scholar
Thompson, A., Winsper, C., Marwaha, S., Haynes, J., Alvarez-Jimenez, M., Hetrick, S., … Sullivan, S. A. (2018). Maintenance antipsychotic treatment versus discontinuation strategies following remission from first episode psychosis: Systematic review. BJPsych Open, 4(4), 215–225. https://doi.org/10.1192/bjo.2018.17.CrossRefGoogle ScholarPubMed
Thygesen, L. C., Daasnes, C., Thaulow, I., & Brønnum-Hansen, H. (2011). Introduction to Danish (nationwide) registers on health and social issues: Structure, access, legislation, and archiving. Scandinavian Journal of Public Health, 39(7), 12–16. https://doi.org/10.1177/1403494811399956.CrossRefGoogle ScholarPubMed
Tiihonen, J., Haukka, J., Taylor, M., Haddad, P. M., Patel, M. X., & Korhonen, P. (2011). A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. American Journal of Psychiatry, 168(6), 603–609. https://doi.org/10.1176/appi.ajp.2011.10081224.CrossRefGoogle ScholarPubMed
Tiihonen, J., Mittendorfer-Rutz, E., Torniainen, M., Alexanderson, K., & Tanskanen, A. (2016). Mortality and cumulative exposure to antipsychotics, antidepressants, and benzodiazepines in patients with schizophrenia: An observational follow-up study. American Journal of Psychiatry, 173(6), 600–606. https://doi.org/10.1176/appi.ajp.2015.15050618.CrossRefGoogle ScholarPubMed
Tiihonen, J., Tanskanen, A., & Taipale, H. (2018). 20-Year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. American Journal of Psychiatry, 175(8), 765–773. https://doi.org/10.1176/appi.ajp.2018.17091001.CrossRefGoogle ScholarPubMed
Torniainen, M., Mittendorfer-Rutz, E., Tanskanen, A., Björkenstam, C., Suvisaari, J., Alexanderson, K., & Tiihonen, J. (2015). Antipsychotic treatment and mortality in schizophrenia. Schizophrenia Bulletin, 41(3), 656–663. https://doi.org/10.1093/SCHBUL/SBU164.CrossRefGoogle ScholarPubMed
Uggerby, P., Østergaard, S. D., Røge, R., Correll, C. U., & Nielsen, J. (2013). The validity of the schizophrenia diagnosis in the Danish psychiatric central research register is good. Danish Medical Journal, 60(2), 1–4.Google ScholarPubMed
Wils, R. S., Gotfredsen, D. R., Hjorthøj, C., Austin, S. F., Albert, N., Secher, R. G., … Nordentoft, M. (2017). Antipsychotic medication and remission of psychotic symptoms 10 years after a first-episode psychosis. Schizophrenia Research, 182, 42–48. https://doi.org/10.1016/j.schres.2016.10.030.CrossRefGoogle Scholar
Wunderink, L., Nieboer, R. M., Wiersma, D., Sytema, S., & Nienhuis, F. J. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy. JAMA Psychiatry, 70(9), 913. https://doi.org/10.1001/jamapsychiatry.2013.19.CrossRefGoogle ScholarPubMed
Zipursky, R. B., Menezes, N. M., & Streiner, D. L. (2014). Risk of symptom recurrence with medication discontinuation in first-episode psychosis: A systematic review. Schizophrenia Research, 152(2–3), 408–414. https://doi.org/10.1016/j.schres.2013.08.001.CrossRefGoogle ScholarPubMed
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