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Impact of opioid initiation on antipsychotic and benzodiazepine and related drug use among persons with Alzheimer's disease

  • Aleksi Hamina (a1) (a2), Piia Lavikainen (a1), Antti Tanskanen (a3) (a4), Anna-Maija Tolppanen (a1) (a5), Jari Tiihonen (a3) (a4), Sirpa Hartikainen (a1) (a2) and Heidi Taipale (a1) (a2)...

We analyzed the impact of opioid initiation on the prevalence of antipsychotic and benzodiazepine and related drug (BZDR) use among community-dwelling persons with Alzheimer's disease (AD).


We utilized the register-based Medication use and Alzheimer's disease (MEDALZ) cohort for this study. We included all community-dwelling persons diagnosed with AD during 2010–2011 in Finland initiating opioid use (n = 3,327) and a matched cohort of persons not initiating opioids (n = 3,325). Interrupted time series analyses were conducted to compare the prevalence of antipsychotic and BZDR use in 30-day periods within six months before opioid initiation to 30-day periods six months later.


Before opioid initiation, prevalence of antipsychotic use among opioid initiators was 13.3%, 18.3% at opioid initiation, and 17.3% six months later. Prevalences of BZDR use were 27.1% six months prior, 28.9% at opioid initiation, and 26.9% six months later. After opioid initiation, antipsychotic and BZDR use declined by 0.3 percentage points (pps, 95% confidence interval 0.1–0.5) and 0.4 pps (0.2–0.7) per month, respectively, until the end of the follow-up. Compared to persons not initiating opioid use, opioid initiation immediately resulted in an increase in prevalence of 1.9 pps (0.9–2.8) for antipsychotics and of 1.6 pps (0.9–2.2) for BZDR use. However, in total there was a comparative decrease of 0.5 pps (0.3–0.8) per month for antipsychotics and of 0.4 pps (0.2–0.6) for BZDR use until the end of the follow-up.


Our results suggest that opioid initiation may reduce antipsychotic and BZDR use among persons with AD.

Corresponding author
Correspondence should be addressed to: Aleksi Hamina, MSc (Pharm), Kuopio Research Centre of Geriatric Care, School of Pharmacy, University of Eastern Finland, PO Box 1627, 70211 Kuopio, Finland. Phone: +358503537868; Fax: +35817162424. Email:
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Abdulla, A. et al. (2013). Guidance on the management of pain in older people. Age and Ageing, 42, i1–57.
American Geriatrics Society (2015). American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 63, 22272246.
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Press.
Azermai, M. et al. (2012). Systematic appraisal of dementia guidelines for the management of behavioural and psychological symptoms. Ageing Research Reviews, 11, 7886.
Bakken, M. S., Engeland, A., Engesæter, L. B., Ranhoff, A. H., Hunskaar, S. and Ruths, S. (2014). Risk of hip fracture among older people using anxiolytic and hypnotic drugs: a nationwide prospective cohort study. European Journal of Clinical Pharmacology, 70, 873880.
Beardon, P. H., McGilchrist, M. M., McKendrick, A. D., McDevitt, D. G. and MacDonald, T. M. (1993). Primary non-compliance with prescribed medication in primary care. BMJ (Clinical Research Edition), 307, 846848.
Chibnall, J. T., Tait, R. C., Harman, B. and Luebbert, R. A. (2005). Effect of acetaminophen on behavior, well-being, and psychotropic medication use in nursing home residents with moderate-to-severe dementia. Journal of the American Geriatrics Society, 53, 19211929.
Corbett, A. et al. (2012). Assessment and treatment of pain in people with dementia. Nature Reviews Neurology, 8, 264274.
Doody, R. S. et al. (2001). Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56, 11541166.
Haasum, Y., Fastbom, J., Fratiglioni, L., Kåreholt, I. and Johnell, K. (2011). Pain treatment in elderly persons with and without dementia: a population-based study of institutionalized and home-dwelling elderly. Drugs & Aging, 28, 283293.
Hamina, A. et al. (2017b). Long-term use of opioids for nonmalignant pain among community-dwelling persons with and without Alzheimer disease in Finland. Pain, 158, 252260.
Hamina, A., Taipale, H., Tanskanen, A., Tolppanen, A. M., Tiihonen, J. and Hartikainen, S. (2017a). Differences in analgesic use in community-dwelling persons with and without Alzheimer's disease. European Journal of Pain, 21, 658667.
Hawley, S. et al. (2016). Anti-osteoporosis medication prescriptions and incidence of subsequent fracture among primary hip fracture patients in England and Wales: an interrupted time-series analysis. Journal of Bone and Mineral Research, 31, 20082015.
Hunt, L. J. et al. (2015). Pain in community-dwelling older adults with dementia: results from the national health and aging trends study. Journal of the American Geriatrics Society, 53, 15031511.
Husebo, B. S., Ballard, C., Cohen-Mansfield, J., Seifert, R. and Aarsland, D. (2014a). The response of agitated behavior to pain management in persons with dementia. The American Journal of Geriatric Psychiatry, 22, 708717.
Husebo, B. S., Ballard, C., Fritze, F., Sandvik, R. K. and Aarsland, D. (2014b). Efficacy of pain treatment on mood syndrome in patients with dementia: a randomized clinical trial. International Journal of Geriatric Psychiatry, 29, 828836.
Husebo, B. S., Ballard, C., Sandvik, R., Nilsen, O. B. and Aarsland, D. (2011). Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ (Clinical Research Edition), 343, d4065.
Jensen-Dahm, C., Gasse, C., Astrup, A., Mortensen, P. B. and Waldemar, G. (2015). Frequent use of opioids in patients with dementia and nursing home residents: a study of the entire elderly population of Denmark. Alzheimer's and Dementia, 11, 691699.
Lövheim, H., Karlsson, S. and Gustafson, Y. (2008). The use of central nervous system drugs and analgesics among very old people with and without dementia. Pharmacoepidemiology and Drug Safety, 17, 912918.
Manfredi, P. L., Breuer, B., Wallenstein, S., Stegmann, M., Bottomley, G. and Libow, L. (2003). Opioid treatment for agitation in patients with advanced dementia. International Journal of Geriatric Psychiatry, 18, 700705.
Matowe, L. K., Leister, C. A., Crivera, C. and Korth-Bradley, J. M. (2003). Interrupted time series analysis in clinical research. The Annals of Pharmacotherapy, 37, 11101116.
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease. Neurology, 34, 939944.
Mittal, V., Kurup, L., Williamson, D., Muralee, S. and Tampi, R. R. (2011). Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence. American Journal of Alzheimer's Disease and Other Dementias, 26, 1028.
NICE (2006). Dementia: Supporting People with Dementia and Their Carers in Health and Social Care. Clinical Guideline 42. National Institute for Health and Clinical Excellence. Available at:
Penfold, R. B. and Zhang, F. (2013). Use of interrupted time series analysis in evaluating health care quality improvements. Academic Pediatrics, 13, S38S44.
Rabins, P. V. et al. (2007). American psychiatric association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Second edition. The American Journal of Psychiatry, 164, 556.
Rajkumar, A. P. et al. (2017). Epidemiology of pain in people with dementia living in care homes: longitudinal course, prevalence, and treatment implications. Journal of the American Medical Directors Association, 18, 453.e1453.e6.
Saarelainen, L. et al. (2015). The incidence of benzodiazepine and related drug use in persons with and without Alzheimer's disease. Journal of Alzheimer's Disease, 49, 809818.
Scherder, E., Herr, K., Pickering, G., Gibson, S., Benedetti, F. and Lautenbacher, S. (2009). Pain in dementia. Pain, 145, 276278.
Schneider, L. S., Dagerman, K. S. and Insel, P. (2005). Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA, 294, 19341943.
Shega, J. W., Hougham, G. W., Stocking, C. B., Cox-Hayley, D. and Sachs, G. A. (2004). Pain in community-dwelling persons with dementia: frequency, intensity, and congruence between patient and caregiver report. Journal of Pain and Symptom Management, 28, 585592.
Taipale, H. et al. (2017). Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease. Canadian Medical Association Journal, 189, E519–E529.
Taipale, H., Koponen, M., Tanskanen, A., Tolppanen, A. M., Tiihonen, J. and Hartikainen, S. (2014). Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland. Journal of Clinical Psychopharmacology, 34, 435440.
Taipale, H., Tanskanen, A., Koponen, M., Tolppanen, A. M., Tiihonen, J. and Hartikainen, S. (2016). Agreement between PRE2DUP register data modeling method and comprehensive drug use interview among older persons. Clinical Epidemiology, 8, 363371.
Tanskanen, A. et al. (2015). From prescription drug purchases to drug use periods – a second generation method (PRE2DUP). BMC Medical Informatics and Decision Making, 15, 21.
Tolppanen, A.-M. et al. (2016a). Antipsychotic use and risk of hospitalisation or death due to pneumonia in persons with and without Alzheimer's disease. Chest, 150, 12331241.
Tolppanen, A.-M. et al. (2016b). Cohort profile: the Finnish medication and Alzheimer's disease (MEDALZ) study. BMJ Open, 6, e012100.
van Dalen-Kok, A. H., Pieper, M. J., de Waal, M. W., Lukas, A., Husebo, B. S. and Achterberg, W. P. (2015). Association between pain, neuropsychiatric symptoms, and physical function in dementia: a systematic review and meta-analysis. BMC Geriatrics, 15, 42. Available at:
Vidal, J. S. et al. (2008). Evaluation of the impact of memantine treatment initiation on psychotropics use: a study from the French national health care database. Neuroepidemiology, 31, 193200.
Wagner, A. K., Soumerai, S. B., Zhang, F. and Ross-Degnan, D. (2002). Segmented regression analysis of interrupted time series studies in medication use research. Journal of Clinical Pharmacy and Therapeutics, 27, 299309.
WHO Collaborating Centre for Drug Statistics Methodology (2017). ATC classification index with DDDs, 2017. Oslo, Norway. Available at:
Wills, P., Claesson, C. B., Fratiglioni, L., Fastbom, J., Thorslund, M. and Winblad, B. (1997). Drug use by demented and non-demented elderly people. Age and Ageing, 26, 383391.
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International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
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