Original Study - Brief Report| Volume 22, ISSUE 6, P1313-1316.e2, June 2021

Pharmacologic Treatment for Hypoactive Delirium in Adult Patients: A Brief Report of the Literature

Published:February 04, 2021DOI:



      The purpose of this report was to identify medications that can be used to treat hypoactive delirium.


      A systematic search of PubMed and Web of Science from inception through September 20, 2020.

      Setting and Participants

      Reports evaluating different pharmacologic treatments for hypoactive delirium in adults (age 18 years and older) and geriatric patients were included.


      Three independent investigators reviewed the abstracts, using the Rayyan QCRI review tool to decide which articles were eligible for inclusion. Hereafter, articles were read completely for final inclusion. Study quality was assessed using the guidelines from the National Institute for Health and Care Excellence for cohort studies and randomized control trials.


      Of the 52 relevant articles, only 4 (8%) met the selection criteria. Two were cohort studies whereas the other 2 were randomized control trials. After further review, one of the reports was excluded because the same data were used as in one of the randomized control trials. In total, 4 different pharmacologic therapies were used in the selected studies: haloperidol, ziprasidone, aripiprazole, and methylphenidate. Aripiprazole showed a complete resolution of hypoactive delirium (P < .001), and methylphenidate showed a significant amelioration in cognitive function (P < .001). Ziprasidone and haloperidol did not show significant differences compared with placebo.

      Conclusions and Implications

      A limited number of clinical studies on the treatment of hypoactive delirium are available. Aripiprazole and methylphenidate showed promising results in the treatment of hypoactive delirium.


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        • Hosker C.
        • Ward D.
        Hypoactive delirium.
        BMJ. 2017; (j2047): 357
        • Oh E.S.
        • Fong T.G.
        • Hshieh T.T.
        • Inouye S.K.
        Delirium in older persons.
        JAMA. 2017; 318: 1161
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        5th ed. 2013 (Arlington, VA: Author)
        • Meagher D.
        Motor subtypes of delirium: Past, present and future.
        Int RevPsychiatry. 2009; 21: 59-73
        • Kim S.-Y.
        • Kim S.-W.
        • Kim J.-M.
        • et al.
        Differential associations between delirium and mortality according to delirium subtype and age.
        Psychosom Med. 2015; 77: 903-910
        • Krewulak K.D.
        • Stelfox H.T.
        • Leigh J.P.
        • et al.
        Incidence and prevalence of delirium subtypes in an adult ICU.
        Crit Care Med. 2018; 46: 2029-2035
        • Inouye S.K.
        • Westendorp R.G.
        • Saczynski J.S.
        Delirium in elderly people.
        The Lancet. 2014; 383: 911-922
        • Lipowski Z.J.
        Delirium in the elderly patient.
        N Engl J Med. 1989; 320: 578-582
        • National Institute for Health and Care Excellence
        The social care guidance manual PMG10, 2013.
        (Available at:) (Accessed February 2020)
        • Boettger S.
        • Breitbart W.
        An open trial of aripiprazole for the treatment of delirium in hospitalized cancer patients.
        Palliat Support Care. 2011; 9: 351-357
        • Boettger S.
        • Friedlander M.
        • Breitbart W.
        • Passik S.
        Aripiprazole and haloperidol in the treatment of delirium.
        Aust N Z J Psychiatry. 2011; 45: 477-482
        • Girard T.D.
        • Exline M.C.
        • Carson S.S.
        • et al.
        Haloperidol and ziprasidone for treatment of delirium in critical illness.
        N Engl J Med. 2018; 379: 2506-2516
        • Gagnon B.
        • Low G.
        • Schreier G.
        Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: A prospective clinical study.
        J Psychiatry Neurosci. 2005; 30: 100-107
        • O’Keeffe S.T.
        Clinical subtypes of delirium in the elderly.
        Dement Geriatr Cogn Disord. 1999; 10: 380-385
        • O’Keeffe S.
        Clinical significance of delirium subtypes in older people.
        Age Ageing. 1999; 28: 115-119
        • Liptzin B.
        • Levkoff S.E.
        An empirical study of delirium subtypes.
        Br J Psychiatry. 1992; 161: 843-845
        • Morita T.
        Successful palliation of hypoactive delirium due to multi-organ failure by oral methylphenidate.
        Support Cancer Care. 1999; 8: 134-137
        • Michaud C.J.
        • Bullard H.M.
        • Harris S.A.
        • Thomas W.L.
        Impact of quetiapine treatment on duration of hypoactive delirium in critically ill adults: a retrospective analysis.
        Pharmacotherapy. 2015; 35: 731-739
        • Boettger S.
        Pipamperone and delirium: A preliminary evaluation of its effectiveness in the management of delirium and its subtypes.
        Swiss Med Weekly. 2017; 147: 2930