Hostname: page-component-8448b6f56d-c4f8m Total loading time: 0 Render date: 2024-04-23T19:49:03.583Z Has data issue: false hasContentIssue false
  • English
  • Français

Lifetime use of psychiatric medications and cognition at 43 years of age in schizophrenia in the Northern Finland Birth Cohort 1966

Published online by Cambridge University Press:  23 March 2020

A.P. Hulkko ,
G.K. Murray ,
J. Moilanen ,
M. Haapea ,
I. Rannikko ,
P.B. Jones ,
J.H. Barnett ,
S. Huhtaniska ,
M.K. Isohanni  and
H. Koponen
...Show all authors
A.P. Hulkko*
Affiliation:
Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000Oulu, Finland, 90014 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Department of Psychiatry, Oulu University Hospital, P.O. Box 26Oulu, Finland, 90029 OYS
G.K. Murray
Affiliation:
Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Box 189, CB2 0QQCambridge, United Kingdom Behavioural and Clinical Neuroscience Institute, University of Cambridge, Herchel Smith Building, Forvie Site, Cambridge Biomedical Campus, CB2 0SZCambridge, United Kingdom
J. Moilanen
Affiliation:
Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000Oulu, Finland, 90014 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Department of Psychiatry, Oulu University Hospital, P.O. Box 26Oulu, Finland, 90029 OYS
M. Haapea
Affiliation:
Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014Oulu, Finland Department of Diagnostic Radiology, Oulu University Hospital, P.O. Box 50Oulu, Finland, 90029 OYS
I. Rannikko
Affiliation:
Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014Oulu, Finland
P.B. Jones
Affiliation:
Department of Psychiatry, University of Cambridge, Herchel Smith Building, CB2 0SZCambridge, United Kingdom
J.H. Barnett
Affiliation:
Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Box 189, CB2 0QQCambridge, United Kingdom Cambridge Cognition Ltd, Tunbridge Court, Bottisham, Cambridge, United Kingdom
S. Huhtaniska
Affiliation:
Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000Oulu, Finland, 90014 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014Oulu, Finland
M.K. Isohanni
Affiliation:
Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014Oulu, Finland
H. Koponen
Affiliation:
Psychiatry Department, University of Helsinki and Helsinki University Hospital, P.O. Box 22, 00014Helsinki, Finland
E. Jääskeläinen
Affiliation:
Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000Oulu, Finland, 90014 Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Department of Psychiatry, Oulu University Hospital, P.O. Box 26Oulu, Finland, 90029 OYS Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014Oulu, Finland
J. Miettunen
Affiliation:
Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland Center for Life Course Health Research, University of Oulu, P.O. Box 5000, 90014Oulu, Finland
*
*Corresponding author. Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, 90014 Oulu, Finland. Fax: +3588336169. E-mail address:anja.husa@student.oulu.fi (A.P. Hulkko).
Get access

Abstract

Background:

Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia.

Methods:

Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression.

Results:

Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition.

Conclusions:

Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.

Keywords

SchizophreniaCognitionBenzodiazepineAntidepressantAntipsychoticPolypharmacy
Type
Original article
Information
European Psychiatry , Volume 45 , September 2017 , pp. 50 - 58
Copyright
Copyright © European Psychiatric Association 2017

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

National Institute for Health and Care Excellence Psychosis and schizophrenia in adults: treatment and management. NICE Clinical Guideline, 178. 2014.Google Scholar
Lehman, AFLieberman, JADixon, LBMcGlashan, THMiller, ALPerkins, DO, et al.Practice guideline for the treatment of patients with schizophrenia, 2nd ed., American Psychiatric Association; 2010.Google Scholar
Correll, CURummel-Kluge, CCorves, CKane, JMLeucht, SAntipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull 2009;35:443–457.CrossRefGoogle ScholarPubMed
Volz, AKhorsand, VGillies, DLeucht, SBenzodiazepines for schizophrenia. Cochrane Database Syst Rev 2007;(1):CD006391.CrossRefGoogle Scholar
Rummel, CKissling, WLeucht, SAntidepressants as add-on treatment to antipsychotics for people with schizophrenia and pronounced negative symptoms: a systematic review of randomized trials. Schizophr Res 2005;80:85–97.CrossRefGoogle ScholarPubMed
Reichenberg, ACaspi, AHarrington, HHouts, RKeefe, RSEMurray, RM, et al.Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. Am J Psychiatry 2010;167(2):160–169.CrossRefGoogle ScholarPubMed
Szöke, ATrandafir, ADupont, MEMéary, ASchürhoff, FLeboyer, MLongitudinal studies of cognition in schizophrenia: meta-analysis. Br J Psychiatry 2008;192:248–257.CrossRefGoogle ScholarPubMed
Bozikas, VPAndreou, CLongitudinal studies of cognition in first episode psychosis: a systematic review of the literature. Aust New Zealand J Psychiatry 2011;45(2):93–108.CrossRefGoogle ScholarPubMed
Zipursky, RBReilly, TJMurray, RMThe myth of schizophrenia as a progressive brain disease. Schizophr Bull 2013;39(6):1363–1372.CrossRefGoogle ScholarPubMed
Irani, FKalkstein, SMoberg, EAMoberg, PJNeuropsychological performance in older patients with schizophrenia: a meta-analysis of cross-sectional and longitudinal studies. Schizophr Bull 2011;37(6):1318–1326.CrossRefGoogle ScholarPubMed
Rajji, TKMiranda, DMulsant, BHCognition, function, and disability in patients with schizophrenia: a review of longitudinal studies. Can J Psychiatry 2014;59:13–17.CrossRefGoogle ScholarPubMed
Désaméricq, GSchurhoff, FMeary, ASzöke, AMacquin-Mavier, IBachoud-Lévi, AC, et al.Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. Eur J Clin Pharmacol 2014;70:127–134.CrossRefGoogle ScholarPubMed
Woodward, NDPurdon, SEMeltzer, HYZald, DHA meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol 2005;8:457–472.CrossRefGoogle Scholar
Mishara, ALGoldberg, TEA meta-analysis and critical review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: opening a closed book. Biol Psychiatry 2004;55:1013–1022.CrossRefGoogle ScholarPubMed
Goldberg, TEKeefe, RSEGoldman, RSRobinson, DGHarvey, PDCircumstances under which practice does not make perfect: a review of the practice effect literature in schizophrenia and its relevance to clinical treatment studies. Neuropsychopharmacology 2010;35:1053–1062.CrossRefGoogle Scholar
Husa, APMoilanen, JMurray, GKMarttila, RHaapea, MRannikko, I, et al.Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort. Psychiatry Res 2017;247:130–138.CrossRefGoogle Scholar
Husa, APRannikko, IMoilanen, JHaapea, MMurray, GKBarnett, 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;158:134–141.CrossRefGoogle ScholarPubMed
Élie, DPoirier, MChianetta, JMDurand, MGrégoire, CAGrignon, SCognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder. J Psychopharmacol 2010;24:1037–1044.CrossRefGoogle ScholarPubMed
Hori, HNoguchi, HHashimoto, RNakabayashi, TOmori, MTakahashi, S, et al.Antipsychotic medication and cognitive function in schizophrenia. Schizophr Res 2006;86:138–146.CrossRefGoogle Scholar
Torniainen, MSuvisaari, JPartonen, TCastaneda, AEKuha, ASuokas, J, et al.Cognitive impairments in schizophrenia and schizoaffective disorder: relationship with clinical characteristics. J Nerv Ment Dis 2012;200:316–322.CrossRefGoogle ScholarPubMed
Kawai, NYamakawa, YBaba, ANemoto, KTachikawa, HHori, T, et al.High-dose of multiple antipsychotics and cognitive function in schizophrenia: the effect of dose-reduction. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1009–1014.CrossRefGoogle ScholarPubMed
Takeuchi, HSuzuki, TRemington, GBies, RRAbe, TGraff-Guerrero, A, et al.Effects of risperidone and olanzapine dose reduction on cognitive function in stable patients with schizophrenia: an open-label, randomized, controlled, pilot study. Schizophr Bull 2013;39:993–998.CrossRefGoogle ScholarPubMed
Fontanella, CACampo, JVPhillips, GSHiance-Steelesmith, DLSweeney, HATam, K, et al.Benzodiazepine use and risk of mortality among patients with schizophrenia: a retrospective longitudinal study. J Clin Psychiatry 2016;77:661–667.CrossRefGoogle Scholar
Dold, MLi, CGilliesc, DLeucht, SBenzodiazepine augmentation of antipsychotic drugs in schizophrenia: a meta-analysis and Cochrane review of randomized controlled trials. Eur Neuropsychopharmacology 2013;23:1023–1033.CrossRefGoogle ScholarPubMed
Tiihonen, JMittendorfer-Rutz, ETorniainen, MAlexanderson, KTanskanen, AMortality and cumulative exposure to antipsychotics, antidepressants, and benzodiazepines in patients with schizophrenia: an observational follow-up study. Am J Psychiatry 2016;173:600–606.CrossRefGoogle Scholar
Barker, MJGreenwood, KMJackson, MCrowe, SFCognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs 2004;18:37–48.CrossRefGoogle ScholarPubMed
Kitajima, RMiyamoto, STenjin, TOjima, KOgino, SMiyake, N, et al.Effects of tapering of long-term benzodiazepines on cognitive function in patients with schizophrenia receiving a second-generation antipsychotic. Prog Neuropsychopharmacol Biol Psychiatry 2012;36:300–306.CrossRefGoogle ScholarPubMed
Baandrup, LFagerlund, BGlenthoj, BNeurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo. Eur Arch Psychiatry Clin Neurosci 2017;267:163–171.CrossRefGoogle ScholarPubMed
Whitehead, CMoss, SCardno, ALewis, GAntidepressants for the treatment of depression in people with schizophrenia: a systematic review. Psychol Med 2003;33:589–599.CrossRefGoogle ScholarPubMed
Singh, SPSingh, VKar, NChan, KEfficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. Br J Psychiatry 2010;197:174–179.CrossRefGoogle ScholarPubMed
Vernon, JAGrudnikoff, ESeidman, AJFrazier, TWVemulapalli, MSPareek, P, et al.Antidepressants for cognitive impairment in schizophrenia - a systematic review and meta-analysis. Schizophr Res 2014;159:385–394.CrossRefGoogle ScholarPubMed
Terevnikov, VJoffe, GStenberg, JHRandomized controlled trials of add-on antidepressants in schizophrenia. Int J Neuropsychopharmacol 2015;18:1–14.CrossRefGoogle Scholar
Wang, PSBrookhart, AMUlbricht, CSchneeweiss, SThe pharmacoepidemiology of psychiatric medications. In: Tsuang, MTohen, MJones, P editors. Textbook in psychiatric epidemiology, 3rd ed., Hoboken, New Jersey, USA: Wiley-Blackwell; 2011. p. 155–165.CrossRefGoogle Scholar
Jääskeläinen, EHaapea, MRautio, NJuola, PPenttilä, MNordström, T, et al.Twenty years of schizophrenia research in the Northern Finland birth cohort 1966: a systematic review. Schizophr Res Treatment 2015. http://dx.doi.org/10.1155/2015/524875 [Article ID 524875, 12 pages].CrossRefGoogle Scholar
Rantakallio, PGroups at risk in low birth weight infants and perinatal mortality. Acta Paediatr Scand 1969;Suppl. 193:1–71.Google ScholarPubMed
Haapea, MMiettunen, JLindeman, SJoukamaa, MKoponen, HAgreement between self-reported and pharmacy data on medication use in the Northern Finland 1966 Birth Cohort. Int J Methods Psychiatr Res 2010;19:88–96.Google ScholarPubMed
Moilanen, JMHaapea, MJääskeläinen, EVeijola, JMIsohanni, MKKoponen, HJ, et al.Long-term antipsychotic use and its association with outcomes in schizophrenia–the Northern Finland Birth Cohort 1966. Eur Psychiatry 2016;36:7–14.CrossRefGoogle ScholarPubMed
Nykänen, SPuska, VTolonen, JPSalo, HIsohanni, MKoponen, H, et al.Use of psychiatric medications in schizophrenia and other psychoses in a general population sample. Psychiatry Res 2016;235:160–168.CrossRefGoogle Scholar
Glahn, DCCannon, TDGur, RERagland, JDGur, RCWorking memory constrains abstraction in schizophrenia. Biol Psychiatry 2000;47:34–42.CrossRefGoogle Scholar
Delis, DCKramer, JHKaplan, EOber, BACalifornia Verbal Learning Test New York: Psychological Corporation; 1987Google Scholar
Glahn, DCGur, RCRagland, JDCensits, DMGur, REReliability, performance characteristics, construct validity, and an initial clinical application of a visual object learning test (VOLT). Neuropsychology 1997;11:602–612.CrossRefGoogle Scholar
Lezak, MDHowieson, DBLoring, DWNeuropsychological assessment, 4th ed., Oxford University Press, Inc; 2004. p. 2004.Google Scholar
Wechsler, DWMS-III - Wechsler Memory Scale, 3rd ed., New York: The Psychological Corporation. Helsinki, Finland: psykologien Kustannus Oy; 2008.Google Scholar
Wechsler, DWechsler Adult Intelligence Scale, Third edition: manual, Helsinki, Finland: Psykologien Kustannus Oy; 2005.Google Scholar
WHO Collaborating Centre for Drug Statistics Methodology Guidelines for ATC classification and DDD assignment 2016. Oslo; 2016.Google Scholar
van der Gaag, MHoffman, TRemijsen, MHijman, Rde Haan, Lvan Meijel, B, et al.The five-factor model of the Positive and Negative Syndrome Scale II: a ten-fold cross-validation of a revised model. Schizophr Res 2006;85(1–3):280–287.CrossRefGoogle ScholarPubMed
Rubin, DMultiple imputation for nonresponse in surveys New York: Wiley; 1987CrossRefGoogle Scholar
IBM Corp, IBM SPSS Statistics for Windows, Version 24. 0 Armonk, NY: IBM Corp; 2016Google Scholar
Tannenbaum, CPaquette, AHilmer, SHolroyd-Leduc, JCarnahan, RA systematic review of amnestic and non-amnestic mild cognitive impairment induced by anticholinergic, antihistamine, GABAergic and opioid drugs. Drugs Aging 2012;29:639–658.Google ScholarPubMed
Barker, MJGreenwood, KMJackson, MCrowe, SFPersistence of cognitive effects after withdrawal from long-term benzodiazepine use: a meta-analysis. Arch Clin Neuropsychol 2004;19:437–454.CrossRefGoogle ScholarPubMed
Kontis, DTheochari, EKleisas, SKalogerakou, SAndreopoulou, APsaras, R, et al.Doubtful association of antipsychotic polypharmacy and high dosage with cognition in chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:1333–1341.CrossRefGoogle ScholarPubMed
Tiihonen, JSuokas, JTSuvisaari, JMHaukka, JKorhonen, PPolypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiatry 2012;69:476–483.CrossRefGoogle ScholarPubMed
Andreasen, NCLiu, DZiebell, SVora, AHo, BCRelapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry 2013;170:609–615.CrossRefGoogle ScholarPubMed
Fusar-Poli, PSmieskova, RKempton, MJHo, BCAndreasen, NCBorgwardt, SProgressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav R 2013;37:1680–1691.CrossRefGoogle ScholarPubMed
Veijola, JGuo, JYMoilanen, JSJääskeläinen, EMiettunen, JKyllönen, M, et al.Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication. Plos One 2014;9(7):e101689. http://dx.doi.org/10.1371/journal.pone.0101689.CrossRefGoogle ScholarPubMed
Abbott, CCJaramillo, AWilcox, CEHamilton, DAAntipychotic drug effects in schizophrenia: a review of longitudinal fMRI investigations and neural interpretations. Curr Med Chem 2013;20:428–437.Google Scholar
Knowles, EEDavid, ASReichenberg, AProcessing speed deficits in schizophrenia: reexamining the evidence. Am J Psychiatry 2010;167:828–835.CrossRefGoogle ScholarPubMed
Rijcken, CAWMonster, TBMBrouwers, J.R.B.J.de Jong-van den Berg, LTWChlorpromazine equivalents versus defined daily doses: how to compare antipsychotic drug doses?. J Clin Psychopharmacol 2003;23:657–659.CrossRefGoogle ScholarPubMed
Harrow, MJobe, THFaull, RNDoes treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study. Psychol Med 2014;44:3007–3016.CrossRefGoogle ScholarPubMed
Wunderink, LNieboer, RMWiersma, DSytema, SNienhuis, FJRecovery 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;70:913–920.CrossRefGoogle ScholarPubMed
Moilanen, JHaapea, MMiettunen, JJääskeläinen, EVeijola, JIsohanni, 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;28:53–58.CrossRefGoogle ScholarPubMed
Winton-Brown, TTElanjithara, TPower, PCoentre, RBlanco-Polaina, PMcGuire, PFive-fold increased risk of relapse following breaks in antipsychotic treatment of first episode psychosis. Schizophr Res 2017;179:50–56.CrossRefGoogle ScholarPubMed
Harvey, PDLoewenstein, DACzaja, SJHospitalization and psychosis: influences on the course of cognition and everyday functioning in people with schizophrenia. Neurobiol Dis 2013;53:18–25.CrossRefGoogle ScholarPubMed
Terry, AVMahadik, SPTime-dependent cognitive deficits associated with first and second generation antipsychotics: cholinergic dysregulation as a potential mechanism. J Pharmacol Exp Ther 2007;320:961–968.CrossRefGoogle ScholarPubMed
Nestler, EJHyman, SEMalenka, RCMolecular neuropharmacology: a foundation for clinical neuroscience, 2nd ed., New York: The McGraw-Hill Companies; 2009.Google Scholar
Liemburg, EJKnegtering, HKlein, HCKortekaas, RAleman, AAntipsychotic medication and prefrontal cortex activation: a review of neuroimaging findings. Eur Neuropsychopharmacol 2012;22:387–400.CrossRefGoogle ScholarPubMed
Sakurai, HBies, RRStroup, STKeefe, RSRajji, TKSuzuki, T, et al.Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data. Schizophr Bull 2013;39:564–574.CrossRefGoogle ScholarPubMed
Stahl, SMAntipsychotics and mood stabilizers: Stahl's essential psychopharmacology, 3rd ed., New York: Cambridge University Press; 2008.Google Scholar
Vinkers, CHOlivier, BMechanisms underlying tolerance after long-term benzodiazepine use: a future for subtype-selective GABAA Receptor modulators?. Adv Pharmacol Sci 2012. http://dx.doi.org/10.1155/2012/416864416864 [Article ID 416864].CrossRefGoogle Scholar
Rannikko, IHaapea, MMiettunen, JVeijola, JMurray, GKBarnett, JH, et al.Changes in verbal learning and memory in schizophrenia and non-psychotic controls in midlife: a nine-year follow-up in the Northern Finland Birth Cohort study 1966. Psychiatry Res 2015;228:671–679.CrossRefGoogle ScholarPubMed
Supplementary material: File

Hulkko et al. supplementary material

Hulkko et al. supplementary material
Download Hulkko et al. supplementary material(File)
File 23.5 KB
Submit a response

Comments

No Comments have been published for this article.