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Cognitive functioning following discontinuation of antipsychotic medication. A naturalistic sub-group analysis from the OPUS II trial

Published online by Cambridge University Press:  30 July 2018

Nikolai Albert Open the ORCID record for Nikolai Albert [Opens in a new window] ,
Lasse Randers ,
Kelly Allott ,
Heidi Dorthe Jensen ,
Marianne Melau ,
Carsten Hjorthøj  and
Merete Nordentoft
Nikolai Albert*
Affiliation:
Copenhagen University Hospital, Mental Health Centre Copenhagen, Copenhagen, Denmark
Lasse Randers
Affiliation:
Copenhagen University Hospital, Mental Health Centre Copenhagen, Copenhagen, Denmark
Kelly Allott
Affiliation:
Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Australia Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia
Heidi Dorthe Jensen
Affiliation:
Copenhagen University Hospital, Mental Health Centre Copenhagen, Copenhagen, Denmark
Marianne Melau
Affiliation:
Copenhagen University Hospital, Mental Health Centre Copenhagen, Copenhagen, Denmark
Carsten Hjorthøj
Affiliation:
Copenhagen University Hospital, Mental Health Centre Copenhagen, Copenhagen, Denmark
Merete Nordentoft
Affiliation:
Copenhagen University Hospital, Mental Health Centre Copenhagen, Copenhagen, Denmark Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
*
Author for correspondence: Nikolai Albert, E-mail: nikolai.albert@regionh.dk
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Abstract

Background

The effect of antipsychotics medication on cognitive functioning in patients diagnosed with schizophrenia is poorly understood. Some studies of second generation antipsychotics indicated that they improved cognitive functioning while other studies have found that they decrease the level of cognitive functioning.

Method

We included patients with schizophrenia who were in treatment with antipsychotics 1.5 years (baseline) after initiation of treatment and followed them up 3.5 years later (n = 189). At follow-up 60 (32%) had discontinued their antipsychotic treatment and 129 (68%) were still taking antipsychotics. Using the Brief Assessment of Cognition in Schizophrenia (BACS) we assessed cognition at baseline and follow-up.

Results

The patients who discontinued their medication had a higher level of cognitive functioning in all domains at baseline, as well as Global cognitive function [mean z-score −1.50 (s.d. 1.24) v. −2.27 (s.d. 1.30), p = 0.00015]. After controlling for relevant confounders those who discontinued antipsychotic medication improved significantly more than those who remained on antipsychotic medication during the course of the follow-up on the Token Motor task [estimated mean change difference −0.46 (95% CI −0.89 to −0.04)], the Speed of Processing Domain [estimated mean change difference −0.38 (95% CI −0.68 to −0.08)] and global cognition [estimated mean change difference −0.36 (95% CI −0.66 to −0.07)].

Conclusion

Due to the naturalistic design, we cannot conclude on the direction of the relationship between antipsychotics and cognition. There is no evidence that discontinuation of medication had a negative effect on cognitive functioning. Rather, we found that that discontinuation of medication was associated with better cognitive functioning.

Keywords

Antipsychoticscognitive functioningpsychosisschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 7 , May 2019 , pp. 1138 - 1147
Copyright
Copyright © Cambridge University Press 2018 

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References

Albert, N, Melau, M, Jensen, H, Emborg, C, Jepsen, J, Fagerlund, B, Gluud, C, Mors, O, Hjorthøj, C and Nordentoft, M (2017) Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II). BMJ 356. Available at https://doi.org/10.1136/bmj.i6681.Google Scholar
Allott, K, Fraguas, D, Bartholomeusz, C, Diaz-Caneja, C, Wannan, C, Parrish, E, Amminger, G, Pantelis, C, Arango, C, McGorry, P and Rapado-Castro, M (2017) Duration of untreated psychosis and neurocognitive functioning in first-episode psychosis: a systematic review and meta-analysis. Psychological Medicine 48, 1592–1607.Google Scholar
Andreasen, NC (1984) Scale for Assessment of Negative Symptoms/Scale for Assessment of Positive Symptoms. Iowa City: University of Iowa Press.Google Scholar
Bozikas, VPP and Andreou, C (2011) Longitudinal studies of cognition in first episode psychosis: a systematic review of the literature. Australian & New Zealand Journal of Psychiatry 45, 93–108.Google Scholar
Désaméricq, G, Schurhoff, F, Meary, A, Szöke, A, Macquin-Mavier, I, Bachoud-Lévi, AC and Maison, P (2014) Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. European Journal of Clinical Pharmacology 70, 127–134.Google Scholar
Elie, D, Poirier, M, Chianetta, J, Durand, M, Gregoire, C and Grignon, S (2010) Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder. Journal of Psychopharmacology 24, 1037–1044.Google Scholar
Faber, G, Smid, HGOM, Van Gool, AR, Wiersma, D, Van, RJ and Bosch, D (2011) The effects of guided discontinuation of antipsychotics on neurocognition in first onset psychosis. European Psychiatry 27, 275–280.Google Scholar
Fett, AKJ, Viechtbauer, W, Dominguez, M, de, G, Penn, DL, van Os, J and Krabbendam, L (2011) The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neuroscience and Biobehavioral Reviews 35, 573–588.Google Scholar
Fink-Jensen, A, Rasmussen, I, Viuff, A, Larsen, J, Scmidt, M, Peacock, L, Stenstrøm, A, Glintborg, D, Brøsen, K, Gudik-Sørensen, M, Glenthøj, B, Pagsberg, A and Baandrup, L (2016) Behandlingsvejledning for medicinsk behandling af psykotiske tilstande hos voksne. RADS – Raadet for Anvendelse Af Dyr Sygehusmedicin.Google Scholar
Gardner, DM, Murphy, AL, O'Donnell, H, Centorrino, F and Baldessarini, RJ (2010) International consensus study of antipsychotic dosing. American Journal of Psychiatry 167, 686–693.Google Scholar
Glenthøj, L, Fagerlund, B, Randers, L, Hjorthøj, C, Wenneberg, C, Krakauer, K, Vosgerau, A, Gluud, C, Medalia, A, Roberts, D and Nordentoft, M (2015) The FOCUS trial: cognitive remediation plus standard treatment versus standard treatment for patients at ultra-high risk for psychosis: study protocol for a randomised controlled trial. Trials 16, 1–10.Google Scholar
Harrow, M, Jobe, TH and Faull, RN (2012) Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychological Medicine 42, 2145–2155.Google Scholar
Harvey, PD and Keefe, RSE (2001) Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. American Journal of Psychiatry 158, 176–184.Google Scholar
Husa, A, Rannikko, I, Moilanen, J, Haapea, M, Murray, G, Barnett, J, Jones, P, Isohanni, M, Koponen, H, Miettunen, J and Jääskeläinen, E (2014) 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. Schizophrenia Research 158, 134–141.Google Scholar
Keefe, RSE, Goldberg, TE, Harvey, PD, Gold, JM, Poe, MP and Coughenour, L (2004 a) The brief assessment of cognition in schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophrenia Research 68, 283–297.Google Scholar
Keefe, R, Seidman, LJ, Christensen, BK, Hamer, RM, Sharma, T, Sitskoorn, M, Lewine, R, Yurgelun-Todd, D, Gur, R, Tohen, M, Tollefson, G, Sanger, T, Lieberman, J and HGDH Research Group (2004 b) Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. The American Journal of Psychiatry 161, 985.Google Scholar
Knowles, EEM, David, AS and Reichenberg, A (2010) Processing speed deficits in schizophrenia: reexamining the evidence. The American Journal of Psychiatry 167, 828–835.Google Scholar
Leucht, S, Arbter, D, Engel, RR, Kissling, W and Davis, JM (2009) How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Molecular Psychiatry 14, 429–447.Google Scholar
Lingjaerde, O, Ahlfors, U, Bech, P, Dencker, S and Elgen, K (1987) The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatrica Scandinavica Supplementum 334, 1–100.Google Scholar
Lynge, E, Sandegaard, JL and Rebolj, M (2011) The Danish National Patient Register. Scandinavian Journal of Public Health 39 (Suppl. 7), 30–33.Google Scholar
Marshall, M, Lewis, S, Lockwood, A, Drake, R, Jones, P and Croudace, T (2005) Association between duration of untreated psychosis and outcome in cohorts of first-episode patients. Archives of General Psychiatry 62, 975–983.Google Scholar
Melau, M, Jeppesen, P, Thorup, A, Bertelsen, M, Petersen, L, Gluud, C, Krarup, G and Nordentoft, M (2011) The effect of five years versus two years of specialised assertive intervention for first episode psychosis – OPUS II: study protocol for a randomized controlled trial. Trials 12, 72.Google Scholar
Mesholam-Gately, RI, Giuliano, AJ, Goff, KP, Faraone, SV and Seidman, LJ (2009) Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology 23, 315–336.Google Scholar
Moilanen, J, Haapea, M, Miettunen, J, Jääskeläinen, E, Veijola, J, Isohanni, M and Koponen, H (2013) 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. European Psychiatry: The Journal of the Association of European Psychiatrists 28, 53–58.Google Scholar
Morosini, PL, Magliano, L, Brambilla, L, Ugolini, S and Pioli, R (2000) Development, reliability and acceptability of a new version of the DSM-IV social and occupational functioning assessment scale (SOFAS) to assess routine social functioning. Acta Psychiatrica Scandinavica 101, 323–329.Google Scholar
Murray, R, 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. British Journal of Psychiatry 209, 361–365.Google Scholar
Nuechterlein, KH, Barch, DM, Gold, JM, Goldberg, TE, Green, MF and Heaton, RK (2004) Identification of separable cognitive factors in schizophrenia. Schizophrenia Research 72, 29–39.Google Scholar
Perkins, DO, Gu, H, Boteva, K and Lieberman, JA (2005) Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. The American Journal of Psychiatry 162, 1785–1804.Google Scholar
Potkin, SG, Fleming, K, Jin, Y and Gulasekaram, B (2001) Clozapine enhances neurocognition and clinical symptomatology more than standard neuroleptics. Journal of Clinical Psychopharmacology 21, 479–483.Google Scholar
Schaefer, J, Giangrande, E, Weinberger, DR and Dickinson, D (2013) The global cognitive impairment in schizophrenia: consistent over decades and around the world. Schizophrenia Research 150, 42–50.Google Scholar
Statistics Denmark (n.d.) “The DREAM database, Statistics Denmark”. Available at http://www.dst.dk/da/TilSalg/Forskningsservice/Data/Andre_Styrelser.aspx#.Google Scholar
Szoke, A, Trandafir, A, Dupont, M, Meary, A, Schurhoff, F and Leboyer, M (2008) Longitudinal studies of cognition in schizophrenia: meta-analysis. British Journal of Psychiatry 192, 248–257.Google Scholar
Takeuchi, H, Suzuki, T, Remington, G, Bies, R, Abe, T, Graff-Guerrero, A, Watanabe, K, Mimura, M and Uchida, H (2013) Effects of risperidone and olanzapine dose reduction on cognitive function in stable patients with schizophrenia: an open-label, randomized, controlled, pilot study. Schizophrenia Bulletin 39, 993–998.Google Scholar
Weickert, TW, Goldberg, TE, Marenco, S, Bigelow, LB, Egan, MF and Weinberger, DR (2003) Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds. Neuropsychopharmacology 28, 1491–1500.Google Scholar
Wils, R, Gotfredsen, D, Hjorthøj, C, Austin, S, Albert, N, Secher, R, Thorup, A, Mors, O and Nordentoft, M (2016) Antipsychotic medication and remission of psychotic symptoms 10 years after a first-episode psychosis. Schizophrenia Research 182, 42–48.Google Scholar
Wing, JK, Sartorius, N and Üstun, TB (1998) WHO Diagnosis and Clinical Measurement in Psychiatry. A Reference Manual for SCAN. Cambridge: Cambridge University Press.Google Scholar
World Health Organization (1993) The ICD-10 Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research, 1st Edn. Geneva: World Health Organization.Google Scholar
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.Google Scholar
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