Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-25T18:08:11.561Z Has data issue: false hasContentIssue false
  • English
  • Français

Long-term antipsychotic use and its association with outcomes in schizophrenia – the Northern Finland Birth Cohort 1966

Published online by Cambridge University Press:  23 March 2020

J.M. Moilanen ,
M. Haapea ,
E. Jääskeläinen ,
J.M. Veijola ,
M.K. Isohanni ,
H.J. Koponen  and
J. Miettunen
J.M. Moilanen*
Affiliation:
University of Oulu, Department of Psychiatry, Research Unit of Clinical Neuroscience, Oulu, Finland Oulu University Hospital, Department of Psychiatry, Oulu, Finland Oulu University Hospital, University of Oulu, Medical Research Center Oulu, Oulu, Finland
M. Haapea
Affiliation:
Oulu University Hospital, Department of Psychiatry, Oulu, Finland Oulu University Hospital, University of Oulu, Medical Research Center Oulu, Oulu, Finland Oulu University Hospital, Department of Diagnostic Radiology, Oulu, Finland University of Oulu, Center for Life Course Health Research, Oulu, Finland
E. Jääskeläinen
Affiliation:
University of Oulu, Department of Psychiatry, Research Unit of Clinical Neuroscience, Oulu, Finland Oulu University Hospital, Department of Psychiatry, Oulu, Finland Oulu University Hospital, University of Oulu, Medical Research Center Oulu, Oulu, Finland University of Oulu, Center for Life Course Health Research, Oulu, Finland
J.M. Veijola
Affiliation:
University of Oulu, Department of Psychiatry, Research Unit of Clinical Neuroscience, Oulu, Finland Oulu University Hospital, Department of Psychiatry, Oulu, Finland Oulu University Hospital, University of Oulu, Medical Research Center Oulu, Oulu, Finland
M.K. Isohanni
Affiliation:
Oulu University Hospital, Department of Psychiatry, Oulu, Finland University of Oulu, Center for Life Course Health Research, Oulu, Finland
H.J. Koponen
Affiliation:
Helsinki University Hospital, University of Helsinki, Psychiatry, Helsinki, Finland
J. Miettunen
Affiliation:
University of Oulu, Department of Psychiatry, Research Unit of Clinical Neuroscience, Oulu, Finland Oulu University Hospital, Department of Psychiatry, Oulu, Finland Oulu University Hospital, University of Oulu, Medical Research Center Oulu, Oulu, Finland University of Oulu, Center for Life Course Health Research, Oulu, Finland
*
⁎Corresponding author. University of Oulu, Department of Psychiatry, Research Unit of Clinical Neuroscience, P.O. Box 5000, 90014 Oulu, Finland. Tel.: +358 440690706; fax: +358 8 336169. jani.m.moilanen@student.oulu.fi
Get access

Abstract

Background

Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes.

Methods

The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers.

Results

During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319 mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score.

Conclusions

In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.

Keywords

AntipsychoticsSchizophreniaLong-termOutcome
Type
Original article
Information
European Psychiatry , Volume 36 , August 2016 , pp. 7 - 14
Copyright
Copyright © European Psychiatric Association 2016

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Tandon, R., Belmaker, R.H., Gattaz, W.F., Lopez-Ibor, J.J. Jr., Okasha, A., Sinqh, B. et al World Psychiatric Association pharmacopsychiatry section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia. Schizophr Res 2008;100(1–3):20–38.CrossRefGoogle ScholarPubMed
Bruijnzeel, D., Suryadevara, U., Tandon, R.Antipsychotic treatment of schizophrenia: an update. Asian J Psychiatr 2014;11:3–7.CrossRefGoogle ScholarPubMed
Young, S.L., Taylor, M., Lawrie, S.M.“First do no harm.” A systematic review of the prevalence and management of antipsychotic adverse effects. J Psychophrmacol 2015;29(4):353–362.CrossRefGoogle Scholar
Takeuchi, H., Suzuki, T., Uchida, H., Watanabupe, K., Mimura, M.Antipsychotic treatment for schizophrenia in the maintenance phase: a systematic review of the guidelines and algorithms. Schizophr Res 2012;134(2–3):219–225.CrossRefGoogle ScholarPubMed
Leucht, S., Tardy, M., Komossa, K., Heres, S., Kissling, W., Salanti, G. et al Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012;379(9813):2063–2071.CrossRefGoogle ScholarPubMed
Whitaker, R.Anatomy of an epidemic: magic bullets, psychiatric drugs, and the astonishing rise of mental illness in America New York: Broadway Paperbacks; 2010.Google Scholar
Whitaker, R.The case against antipsychotic drugs: a 50-year record doing more harm than good. Med Hypotheses 2014;62(1):5–13.CrossRefGoogle Scholar
Sohler, N., Adams, B.G., Barnes, D.M., Cohen, G.H., Prins, S.J., Schwartz, S.Weighing the evidence for harm from long-term treatment with antipsychotic medications: a systematic review. Am J Orthopsychiat 2015 [Epub ahead of print] http://dx.doi.org/10.1037/ort0000106.CrossRefGoogle Scholar
Emsley, R., Chiliza, B., Asmal, L.The evidence for illness progression after relapse in schizophrenia. Schizophr Res 2013;148(1–3):117–121.CrossRefGoogle Scholar
Fusar-Poli, P., Smieskova, R., Kempton, M.J., Ho, B.C., Andreasen, N.C., Borgwardt, S.Progressive brain changes in schizophrenia related to antipsychotic treatment?. A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev 2013;37(8):1680–1691.CrossRefGoogle ScholarPubMed
Hopper, K., Harrison, G., Wanderling, J.A.An overview of course and outcome in ISoS. In: Hopper, K., Harrison, G., Janca, A., Sartorius, N., Recovery from schizophrenia. An international perspective Oxford University Press; 2007 [Table 3.6].Google Scholar
Gilbert, P.L., Harris, M.J., McAdams, L.A., Jeste, D.V.Neuroleptic withdrawal in schizophrenic patients. A review of the literature. Arch Gen Psychiatry 1995;52:173–188.CrossRefGoogle ScholarPubMed
Sampson, S., Joshi, K., Mansour, M., Adams, C.E.Intermittent drug techniques for schizophrenia. Schizophr Bull 2013;39(5):960–961.CrossRefGoogle Scholar
Zipursky, R.B., Menezes, N.M., Streiner, D.R.Risk of symptom recurrence with medication discontinuation in first-episode psychosis: a systematic review. Schizophr Res 2014;152(2–3):408–414.CrossRefGoogle ScholarPubMed
Wunderink, L., Nieboer, R.M., Wiersma, D., Sytema, S., Nienhuis, F.J.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 2013;70(9):913–920.CrossRefGoogle ScholarPubMed
Harrow, M., Jobe, T.H.Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: a 15-year multifollow-up study. J Nerv Ment Dis 2007;195:406–414.Google Scholar
Harrow, M., Jobe, T.H., Faull, R.N.Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime?. A 20-year longitudinal study. Psychol Med 2012;42(10):2145–2155.CrossRefGoogle ScholarPubMed
Harrow, M., Jobe, T.H., Faull, R.N.Does treatment of schizophrenia with antipsychotic medication eliminate or reduce psychosis?. A 20-year multi-follow-up study. Psychol Med 2014;44:3007–3016.CrossRefGoogle ScholarPubMed
Gallego, J.A., Bonetti, J., Zhang, J., Kane, J.M., Correl, C.U.Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res 2012;138(1):18–28.CrossRefGoogle ScholarPubMed
Suokas, J.T., Suvisaari, J.M., Haukka, J., Korhonen, P., Tiihonen, J.Description of long-term polypharmacy among schizophrenia outpatients. Soc Psychiatry Psychiatr Epidemiol 2013;48:631–638.CrossRefGoogle ScholarPubMed
Correll, C.U., Rummel-Kluge, C., Corves, C., Kane, J.M., Leucht, S.Antipsychotic combinations vs. monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophren Bull 2009;35(2):443–457.CrossRefGoogle ScholarPubMed
Fleischacker, W.W., Uchida, H.Critical review of antipsychotic polypharmacy in the treatment of schizophrenia. Int J Neuropsychopharmacol 2014;17(7):1083–1093.CrossRefGoogle Scholar
Iasevoli, F., Buonaquro, E.F., Marconi, M., Di Giovambattista, E., Rapagnani, M.P., De Berardis, D. et al Efficacy and clinical determinants of antipsychotic polypharmacy in psychotic patients experiencing an acute relapse and admitted to hospital stay: results from a cross-sectional and a subsequent longitudinal pilot-study. ISRN Pharmacol 2014;2014:762127http://dx.doi.org/10.1155/2014/762127.CrossRefGoogle Scholar
Lochmaan van Bennekom, M.W., Gijsman, H.J., Zitman, F.G.Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness. J Psychopharmacol 2013;27(4):327–336.CrossRefGoogle Scholar
Tiihonen, J., Suokas, J.T., Suvisaari, J.M., Haukka, J., Korhonen, P.Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiatry 2012;69:476–483.CrossRefGoogle ScholarPubMed
Moilanen, J., Haapea, M., Miettunen, J., Jääskeläinen, E., Veijola, J., Isohanni, M. et al Characteristics of subjects with schizophrenia spectrum disorder with and without antipsychotic medication – a 10-year follow-up of the Northern Finland 1966 Birth Cohort study. Eur Psychiatry 2013;28(1):53–58.CrossRefGoogle ScholarPubMed
Moilanen, J., Huhtaniska, S., Haapea, M., Jääskeläinen, E., Veijola, J., Isohanni, M. et al Brain morphometry of individuals with schizophrenia with and without antipsychotic medication – the Northern Finland Birth Cohort 1966 study. Eur Psychiatry 2015;30(5):598–605.CrossRefGoogle ScholarPubMed
Nykänen, S., Puska, V., Tolonen, J.-P., Salo, H., Isohanni, M., Koponen, H. et al Use of psychiatric medications in schizophrenia and other psychoses in a general population sample. Psychiatry Res 2015, http://dx.doi.org/10.1016/j.psychres.2015.11.013.CrossRefGoogle Scholar
Wang, P., Brookhart, A., Ulbricht, C., Schneeweiss, N.The pharmacoepidemiology of psychiatric medications. In: Ming, T.Tsuang, M.T., Tohen, M., Jones, P.B., editors. Textbook in psychiatric epidemiology 3rd ed, John Wiley & Sons, Ltd; 2011.p. 155–165.CrossRefGoogle Scholar
Jääskeläinen, E., Haapea, M., Rautio, N., Juola, J., Penttilä, M., Nordström, T. et al Twenty years of schizophrenia research in the Northern Finland Birth Cohort 1966 – a systematic review. Schizophr Res Treatm 2015;2015:524875.CrossRefGoogle ScholarPubMed
Husa, A.P., Rannikko, I., Moilanen, J., Haapea, M., Murray, G.K., Barnett, J. et al Lifetime use of antipsychotic medication and its relation to change of verbal learning and memory in midlife schizophrenia – an observational 9-year follow-up study. Schizophr Res 2014;158(1–3):134–141.CrossRefGoogle ScholarPubMed
Veijola, J., Guo, J.Y., Moilanen, J.S., Jääskeläinen, E., Miettunen, J., Kyllönen, M. et al Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication. PLoS One 2014;9:e101689.CrossRefGoogle ScholarPubMed
Penttilä, M., Jääskeläinen, E., Haapea, M., Tanskanen, P., Veijola, J., Ridler, K. et al Association between duration of untreated psychosis and brain morphology in schizophrenia within the Northern Finland 1966 Birth Cohort. Schizophr Res 2010;123(2–3):145–152.CrossRefGoogle ScholarPubMed
Kroken, R.A., Johnsen, E., Ruud, T., Wentzel-Larsen, T., Jørgensen, H.A.Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry 2009;9:24.CrossRefGoogle ScholarPubMed
Spitzer, R.L., Gibbon, M., Endicott, J.Global Assessment Scale (GAS), Global Assessment of Functioning (GAF) scale, Social and Occupational Functional Assessment Scale (SOFAS). In: Rush, J.A., et al., editors. Handbook of Psychiatric Measures Washington: American Psychiatric Association; 2000. p. 96–100.Google Scholar
Kay, S.R., Fiszbein, A., Opler, L.A.The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.CrossRefGoogle Scholar
Andreasen, N.C., Carpenter, W.T., Kane, J.M., Lasser, R.A., Marder, S.R., Weinberger, D.R.Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 2005;162:441–449.CrossRefGoogle ScholarPubMed
Guy, W.EDCEU Assessment Manual for Psychopharmacology–Revised (DHEW Pupl No ADM 76 338). Rockville, MD, U.S: Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976. p. 534–537.Google Scholar
Kampman, O., Lehtinen, K.Compliance in psychoses. Acta Psychiatrica Scandinavica 1999;100:167–175.CrossRefGoogle ScholarPubMed
Llorca, P.-M.Partial compliance in schizophrenia and the impact on patient outcomes. Psychiatry Res 2008;161(2): 235–247.CrossRefGoogle ScholarPubMed
Harrow, M., Jobe, T.H.Does long-term treatment of schizophrenia with antipsychotic medications facilitate recovery. Schizophr Bull 2013;39(5): 362–365.CrossRefGoogle ScholarPubMed
American Psychiatric Association, Practice guideline for the treatment of patients with schizophrenia. Washington, DC: APA; 2010.Google Scholar
Dold, M., Leucht, S.Pharmacotherapy of treatment-resistant schizophrenia: a clinical perspective. Evid Based Ment Health 2014;17(2):33–37.CrossRefGoogle ScholarPubMed
Arranz, M.J., Rivera, M., Munro, J.C.Pharmacogenetics of response to antipsychotics in patients with schizophrenia. CNS Drugs 2011;25(11):933–969.CrossRefGoogle ScholarPubMed
Xu, Q., Wu, X., Xiong, Y., Xing, Q., He, L., Qin, S.Pharmacogenetics can improve antipsychotic treatment in schizophrenia. Front Med 2013;7(2):180–190.CrossRefGoogle Scholar
Supplementary material: PDF

Moilanen et al. supplementary material

Table S1

Download Moilanen et al. supplementary material(PDF)
PDF 8.8 KB
Submit a response

Comments

No Comments have been published for this article.