Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-22T22:41:38.624Z Has data issue: false hasContentIssue false
  • English
  • Français

Anticholinergic burden in schizophrenia and ability to benefit from psychosocial treatment programmes: a 3-year prospective cohort study

Published online by Cambridge University Press:  31 August 2016

K. O'Reilly ,
P. O'Connell ,
G. Donohoe ,
C. Coyle ,
D. O'Sullivan ,
Z. Azvee ,
C. Maddock ,
K. Sharma ,
H. Sadi  and
M. McMahon
...Show all authors
K. O'Reilly
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland Department of Psychiatry, Trinity College Dublin, Ireland
P. O'Connell
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland Department of Psychiatry, Trinity College Dublin, Ireland
G. Donohoe
Affiliation:
Department of Psychology, National University of Ireland, Galway, Ireland
C. Coyle
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland
D. O'Sullivan
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland
Z. Azvee
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland
C. Maddock
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland
K. Sharma
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland
H. Sadi
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland
M. McMahon
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland
H. G. Kennedy*
Affiliation:
National Forensic Mental Health Service, Central Mental Hospital, Dundrum, Dublin, Ireland Department of Psychiatry, Trinity College Dublin, Ireland
*
*Address for correspondence: Professor H. G. Kennedy, Central Mental Hospital, Dundrum, Dublin, Ireland. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown.

Method

Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS).

Results

Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by −0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for.

Conclusions

Anticholinergic burden has a significant impact on patients’ ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.

Keywords

Anticholinergic burdencognitionMCCBpsychosocial treatmentsschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 15 , November 2016 , pp. 3199 - 3211
Copyright
Copyright © Cambridge University Press 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

Baker, LA, Cheng, LY, Amara, IB (1983). The withdrawal of benztropine mesylate in chronic schizophrenic patients. British Journal of Psychiatry 143, 584–590.Google Scholar
Boustani, M, Campbell, N, Munger, S, Maidment, I, Fox, C (2008). Impact of anticholinergics on the aging brain: a review and practical application. Aging Health 4, 311–320.CrossRefGoogle Scholar
Buchanan, RW, Davis, M, Goff, D, Green, MF, Keefe, RS, Leon, AC, Nuechterlein, KH, Laughren, T, Levin, R, Stover, E, Fenton, W, Marder, SR (2005). A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophrenia Bulletin 31, 5–19.Google Scholar
Buchanan, RW, Keefe, RS, Umbricht, D, Green, MF, Laughren, T, Marder, SR (2011). The FDA-NIMH-MATRICS guidelines for clinical trial design of cognitive-enhancing drugs: what do we know 5 years later? Schizophrenia Bulletin 37, 1209–1217.Google Scholar
Campbell, N, Boustani, M, Limbil, T, Ott, C, Fox, C, Maidment, I, Schubert, CC, Munger, S, Fick, D, Miller, D, Gulati, R (2009). The cognitive impact of anticholinergics: a clinical review. Clinical Interventions in Aging 4, 225–229.Google Scholar
Carr, A (2009). What Works with Children, Adolescents and Adults? A Review of Research on the Effectiveness of Psychotherapy. Routledge: London and New York.Google Scholar
Chang, WC, Ming Hui, CL, Yan Wong, GH, Wa Chan, SK, Ming Lee, EH, Hai Chen, EY (2013). Symptomatic remission and cognitive impairment in first-episode schizophrenia: a prospective 3-year follow-up study. Journal of Clinical Psychiatry 74, 1046–1053.Google Scholar
Chew, ML, Mulsant, BH, Pollock, BG, Lehman, ME, Greenspan, A, Mahmoud, RA, Kirshner, MA, Sorisio, DA, Bies, RR, Gharabawi, G (2008). Anticholinergic activity of 107 medications commonly used by older adults. Journal of American Geriatrics Society 5656, 1333–1341.Google Scholar
Chudasama, Y, Dalley, JW, Nathwani, F, Bouger, P, Robbins, TW (2004). Cholinergic modulation of visual attention and working memory: dissociable effects of basal forebrain 192-IgG-saporin lesions and intraprefrontal infusions of scopolamine. Learning and Memory 11, 78–86.Google Scholar
Davoren, M, Abidin, Z, Naughton, L, Gibbons, O, Nulty, A, Wright, B, Kennedy, HG (2013). Prospective study of factors influencing conditional discharge from a forensic hospital: the DUNDRUM-3 programme completion and DUNDRUM-4 recovery structured professional judgement instruments and risk. BMC Psychiatry 13, 185.Google Scholar
Davoren, M, O'Dwyer, S, Abidin, Z, Naughton, L, Gibbons, O, Doyle, E, McDonnell, K, Monks, S, Kennedy, HG (2012). Prospective in-patient cohort study of moves between levels of therapeutic security: the DUNDRUM-1 triage security, DUNDRUM-3 programme completion and DUNDRUM-4 recovery scales and the HCR-20. BMC Psychiatry 12, 80.Google Scholar
Dawes, RM (1979). The robust beauty of improper linear models in decision making. American Psychologist 34, 571–582.Google Scholar
Desmarais, JE, Beauclair, L, Annable, L, Bélanger, MC, Kolivakis, TT, Margolese, HC (2014). Effects of discontinuing anticholinergic treatment on movement disorders, cognition and psychopathology in patients with schizophrenia. Therapeutic Advances in Psychopharmacology 4, 257–267.Google Scholar
Deutsch, D (2011). The Beginning of Infinity: Explanations that Transform the World. Viking Press: New York.Google Scholar
Drimer, T, Shahal, B, Barak, Y (2004). Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients. International Clinical Psychopharmacology 19, 27–29.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). Biometrics Research, New York State Psychiatric Institute: New York.Google Scholar
Gibbons, AS, Scarr, E, Boer, S, Money, T, Jeon, WJ, Felder, C, Dean, B (2013). Widespread decreases in cortical muscarinic receptors in a subset of people with schizophrenia. International Journal of Neuropsychopharmacology 16, 37–46.Google Scholar
Grant, PM, Huh, GA, Perivoliotis, D, Stolar, NM, Beck, AT (2011). Randomized trial to evaluate the efficacy of cognitive therapy for low-functioning patients with schizophrenia. Archives of General Psychiatry 69, 121–127.Google Scholar
Gray, SL, Anderson, ML, Dublin, S, Hanlon, JT, Hubbard, R, Walker, R, Yu, O, Crane, PK, Larson, EB (2015). Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Internal Medicine 175, 401–407.Google Scholar
Green, AI, Canuso, CM, Brenner, MJ, Wojcik, JD (2003). Detection and management of comorbidity in patients with schizophrenia. Psychiatric Clinics of North America 26, 115–139.Google Scholar
Green, MF, Kern, RS, Braff, DL, Mintz, J (2000). Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the ‘right stuff’? Schizophrenia Bulletin 26, 119–136.Google Scholar
Haddad, P, Lambert, T, Lauriello, J (2010). Antipsychotic Long-Acting Injections. Oxford University Press: London.CrossRefGoogle Scholar
Harvey, PD, Bowie, CR (2012). Cognitive enhancement in schizophrenia: pharmacological and cognitive remediation approaches. Psychiatric Clinics of North America 35, 683–698.Google Scholar
Hayes, AF (2013). Introduction to Mediation, Moderation and Conditional Process Analysis: A Regression-Based Approach. The Guilford Press: New York.Google Scholar
Hori, K, Konishi, K, Tani, M, Tomioka, H, Akita, R, Kitajima, Y, Aoki, M, Yokoyama, S, Azuma, K, Ikuse, D, Akashi, N, Hosoi, M, Jinbo, K, Hachisu, M (2014). Serum anticholinergic activity: a possible peripheral marker of the anticholinergic burden in the central nervous system in Alzheimer's disease. Disease Markers. Published online: 9 February 2014 doi: 10.1155/2014/459013.CrossRefGoogle ScholarPubMed
Jääskeläinen, E, Juola, P, Hirvonen, N, McGrath, JJ, Saha, S, Isohanni, M, Veijola, J, Miettunen, J (2013). A systematic review and meta-analysis of recovery in schizophrenia. Schizophrenia Bulletin 39, 1296–1306.Google Scholar
Jauhar, S, McKenna, PJ, Radua, J, Fung, E, Salvador, R, Laws, KR (2014). Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias. British Journal of Psychiatry 204, 20–29.Google Scholar
Jones, DR, Macias, C, Barreira, PJ, Fisher, WH, Hargreaves, WA, Harding, CM (2004). Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatric Services 55, 1250–1257.Google Scholar
Kahn, RS, Keefe, RS (2013). Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry 70, 1107–1112.Google Scholar
Kahn, RS, Sommer, IE, Murray, RM, Meyer-Lindenberg, A, Weinberger, DR, Cannon, TD, O'Donovan, M, Correl, CU, Kane, JM, van Os, J, Insel, TR (2015). Schizophrenia. Nature Reviews Disease Primers. Published online: 12 November 2015 doi: 10.1038/nrdp.2015.67.Google Scholar
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.Google Scholar
Kennedy, HG, O'Neill, C, Flynn, G, Gill, P (2010). The DUNDRUM Toolkit. Dangerousness Understanding, Recovery and Urgency Manual (The DUNDRUM Quartet) V1.0.21 (18/03/10), Four Structured Professional Judgment Instruments for Admission Triage, Urgency, Treatment Completion and Recovery Assessments. Trinity College Dublin: Dublin. (http://hdl.handle.net/2262/39131)Google Scholar
Keshavan, MS, Anderson, S, Pettegrew, JW (1994). Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? The Feinberg hypothesis revisited. Journal of Psychiatry Research 28, 239–265.Google Scholar
Kim, YK, Lee, AR, Hur, JW, Yoon, HK, Lee, BH, Ko, YH (2008). Cognitive factors for predicting treatment response in schizophrenic patients: one-year follow-up study. Psychiatry Investigation 5, 106–114.Google Scholar
Kubota, M, van Haren, NE, Haijma, SV, Schnack, HG, Cahn, W, Hulshoff Pol, HE, Kahn, RS (2015). Association of IQ changes and progressive brain changes in patients with schizophrenia. JAMA Psychiatry 72, 803–812.Google Scholar
Kurtz, MM (2011). Neurocognition as a predictor of response to evidence-based psychosocial interventions in schizophrenia: what is the state of the evidence? Clinical Psychology Review 31, 663–672.Google Scholar
Lertxundi, U, Domingo-Echaburu, S, Hernandez, R, Peral, J, Medrano, J (2013). Expert-based drug lists to measure anticholinergic burden: similar names, different results. Psychogeriatrics 13, 17–24.Google Scholar
Leucht, S, Tardy, M, Komossa, K, Heres, S, Kissling, W, Davis, JM (2012). Maintenance treatment with antipsychotic drugs for schizophrenia. The Cochrane Library. Published online 16 May 2012. doi:10.1002/14651858.CD008016.pub2.Google Scholar
Lezak, MD, Howieson, DB, Bigler, ED, Tranel, D (2012). Neuropsychological Assessment, 5th edn. Oxford University Press: New York.Google Scholar
Mancama, D, Arranz, MJ, Landau, S, Kerwin, R (2003). Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 119, 2–6.Google Scholar
Michel, NM, Goldberg, JO, Heinrichs, RW, Miles, AA, Ammari, N, McDermid Vaz, S (2013). WAIS-IV profile of cognition in schizophrenia. Assessment 20, 462–473.Google Scholar
Mori, K, Yamashita, H, Nagao, M, Horiguchi, J, Yamawaki, S (2002). Effects of anticholinergic drug withdrawal on memory, regional cerebral blood flow and extrapyramidal side effects in schizophrenic patients. Pharmacopsychiatry 35, 6–11.Google Scholar
Morris, SB, DeShon, RP (2002). Combining effect size estimates in meta-analysis with repeated measures and independent-groups designs. Psychological Methods 7, 105–125.Google Scholar
Nebes, RD, Pollock, BG, Meltzer, CC, Saxton, JA, Houck, PR, Halligan, EM, DeKosky, ST (2005). Serum anticholinergic activity, white matter hyperintensites, and cognitive performance. Neurology 65, 1487–1489.Google Scholar
Newell, KA, Zavitsanou, K, Jew, SK, Huang, XF (2007). Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 31, 225–233.Google Scholar
Nielsen, RE, Levander, S, Kjaersdam Telléus, G, Jensen, SO, Østergaard Christensen, T, Leucht, S (2015). Second-generation antipsychotic effect on cognition in patients with schizophrenia–a meta-analysis of randomized clinical trials. Acta Psychiatrica Scandinavica 131, 185–196.Google Scholar
Nuechterlein, KH, Green, MF, Kern, RS, Baade, LE, Barch, DM, Cohen, JD, Essock, S, Fenton, WS, Frese, FJ III, Gold, JM, Goldberg, T, Heaton, RK, Keefe, RS, Kraemer, H, Mesholam-Gately, R, Seidman, LJ, Stover, E, Weinberger, DR, Young, AS, Zalcman, S, Marder, SR (2008). The MATRICS consensus cognitive battery, part 1: test selection, reliability, and validity. American Journal of Psychiatry 165, 203–213.Google Scholar
O'Reilly, K, Donohoe, G, Coyle, C, O'Sullivan, D, Rowe, A, Losty, M, McDonagh, T, McGuinness, L, Ennis, Y, Watts, E, Brennan, L, Owens, E, Davoren, M, Mullaney, R, Abidin, Z, Kennedy, HG (2015). Prospective cohort study of the relationship between neuro-cognition, social cognition and violence in forensic patients with schizophrenia and schizoaffective disorder. BMC Psychiatry 15, 155.Google Scholar
O'Reilly, K, Donohue, G, O'Sullivan, D, Coyle, C, Mullaney, R, O'Connell, P, Maddock, C, Nulty, A, O’ Flynn, P, O'Connell, C, Kennedy, HG (2016). Study protocol: a randomised controlled trial of cognitive remediation for a national cohort of forensic mental health patients with schizophrenia or schizoaffective disorder. BMC Psychiatry 16, 5.Google Scholar
Ogino, S, Miyamoto, S, Tenjin, T, Kitajima, R, Ojima, K, Miyake, N, Funamoto, Y, Arai, J, Tsukahara, S, Ito, Y, Tadokoro, M, Anai, K, Tatsunami, S, Kubota, H, Kaneda, Y, Yamaguchi, N (2011). Effects of discontinuation of long-term biperiden use on cognitive function and quality of life in schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 15, 78–83.Google Scholar
Patel, MX, Arista, IA, Taylor, M, Barnes, TRE (2013). How to compare doses of different antipsychotics: a systematic review of methods. Schizophrenia Research 149, 141–148.Google Scholar
Pollock, BG (2000). Geriatric psychiatry: psychopharmacology: general principles. In Comprehensive Textbook of Psychiatry (ed. Saddock, B. J. and Saddock, V. A.). Williams & Wilkins: Baltimore.Google Scholar
Raedler, TJ, Knable, MB, Jones, DW, Urbina, RA, Gorey, JG, Lee, KS, Egan, MF, Coppola, R, Weinberger, DR (2003). In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. American Journal of Psychiatry 160, 118–127.Google Scholar
Rybarczyk, B (2011). Social and occupational functioning assessment scale (SOFAS). In Encyclopedia of Clinical Neuropsychology, vol. 1 (ed. Kreutzer, J., DeLuca, J. and Caplan, B.). Springer: New York.Google Scholar
Salahudeen, SM, Duffull, SB, Nishtala, PS (2015). Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review. BMC Geriatrics 15, 31.Google Scholar
Sarter, M, Hasselmo, ME, Bruno, JP, Givens, B (2005). Unravelling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Research Reviews 48, 98–111.Google Scholar
Scarr, E, Gibbons, AS, Neo, J, Udawela, M, Dean, B (2013). Cholinergic connectivity: its implications for psychiatric disorders. Frontiers in Cellular Neuroscience 7, 1–26.Google Scholar
Sekar, A, Bialas, AR, de Rivera, H, Davis, A, Hammond, TR, Kamitaki, N, Tooley, K, Presumey, J, Baum, M, Van Doren, V, Genovese, G, Rose, SA, Handsaker, RE, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly, MJ, Carroll, MC, Stevens, B, McCarroll, SA (2016). Schizophrenia risk from complex variation of complement component 4. Nature 530, 177–183.Google Scholar
Shinkfield, G, Ogloff, J (2014). A review and analysis of routine outcome measures for forensic mental health services. International Journal of Forensic Mental Health 13, 252–271.Google Scholar
Sweileh, WM, Odeh, JB, Shraim, NY, Zyoud, SH, Sawalha, AF, Al-Jabi, SW (2014). Evaluation of Defined Daily Dose, percentage of British National Formulary maximum and chlorpromazine equivalents in antipsychotic drug utilization. Saudi Pharmaceutical Journal 22, 127–132.Google Scholar
Taylor, D, Paton, C, Kapur, S (1994). The Maudsley Prescribing Guidelines in Psychiatry. John Wiley & Sons: London.Google Scholar
Tune, LE (2001). Anticholinergic effects of medication in elderly patients. Journal of Clinical Psychiatry 62, 11–14.Google Scholar
van Haren, NE, Schnack, HG, Cahn, W, van den Heuvel, MP, Lepage, C, Collins, L, Evans, AC, Hulshoff Pol, HE, Kahn, RS (2011). Changes in cortical thickness during the course of illness in schizophrenia. Archives of General Psychiatry 68, 871–880.Google Scholar
Vinogradov, S, Fisher, M, Warm, H, Holland, C, Kirshner, MA, Pollock, BG (2009). The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia. American Journal of Psychiatry 166, 1055–1062.Google Scholar
Wechsler, D (2011). Test of Premorbid Functioning – UK Edition (TOPF UK) . Pearson Assessment: London.Google Scholar
WHO (1986). Ottawa Charter for Health Promotion. In First International Conference on Health Promotion Ottawa, 21 November 1986 (http://www.who.int/healthpromotion/conferences/previous/ottawa/en/).Google Scholar
Woods, SW (2003). Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry 64, 663–667.Google Scholar
Wunderink, L, Nieboer, RM, Wiersma, D, Sytema, S, 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
Zavitsanou, K, Katsifis, A, Mattner, F, Xu-Feng, H (2004). Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder. Neuropsychopharmacology 29, 619–625.Google Scholar