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      Neuropsychiatric Disease and Treatment (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on all aspects of neuropsychiatric and neurological disorders. Sign up for email alerts here.

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      Treatment of behavioral and psychological symptoms of dementias with psychopharmaceuticals: a review

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          Abstract

          Behavioral and psychological symptoms represent common complications in patients with different types of dementia. Predominantly, they comprise psychosis, agitation and mood disorders, disinhibited behavior, impairment of the sleep and wakefulness rhythm, wandering, perseveration, pathological collecting, or shouting. Their appearance is related to more rapid progression of the disease, earlier institutionalization, use of physical restraints, and higher risk of mortality. Consequently, appearance of behavioral and psychological symptoms of dementia leads to higher costs of care provided and greater distress for caregivers. Clinical guidelines recommend nonpharmacological approaches as the first choice in the treatment of behavioral and psychological symptoms. Pharmacological therapy should be initiated only if the symptoms were not the result of somatic causes, did not respond to nonpharmacological interventions, or were not caused by the prior medication. Acetylcholinesterase inhibitors, memantine, antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines are used. This review summarizes the current findings about the efficacy and safety of the treatment of the neuropsychiatric symptoms in dementias with psychopharmaceuticals. Recommendations for treatment with antipsychotics for this indication are described in detail as this drug group is prescribed most often and, at the same time, is related to the highest risk of adverse effects and increased mortality.

          Most cited references53

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          The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial.

          Data from 12-week placebo-controlled trials have led to mounting concerns about increased mortality in patients with Alzheimer's disease (AD) who are prescribed antipsychotics; however, there are no mortality data from long-term placebo-controlled trials. We aimed to assess whether continued treatment with antipsychotics in people with AD is associated with an increased risk of mortality. Between October, 2001, and December, 2004, patients with AD who resided in care facilities in the UK were enrolled into a randomised, placebo-controlled, parallel, two-group treatment discontinuation trial. Participants were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone) for 12 months or to switch their medication to an oral placebo. The primary outcome was mortality at 12 months. An additional follow-up telephone assessment was done to establish whether each participant was still alive 24 months after the enrollment of the last participant (range 24-54 months). Causes of death were obtained from death certificates. Analysis was by intention to treat (ITT) and modified intention to treat (mITT). This trial is registered with the Cochrane Central Registry of Controlled Trials/National Research Register, number ISRCTN33368770. 165 patients were randomised (83 to continue antipsychotic treatment and 82 to placebo), of whom 128 (78%) started treatment (64 continued with their treatment and 64 received placebo). There was a reduction in survival in the patients who continued to receive antipsychotics compared with those who received placebo. Cumulative probability of survival during the 12 months was 70% (95% CI 58-80%) in the continue treatment group versus 77% (64-85%) in the placebo group for the mITT population. Kaplan-Meier estimates of mortality for the whole study period showed a significantly increased risk of mortality for patients who were allocated to continue antipsychotic treatment compared with those allocated to placebo (mITT log rank p=0.03; ITT p=0.02). The hazard ratio for the mITT group was 0.58 (95% CI 0.35 to 0.95) and 0.58 (0.36 to 0.92) for the ITT population. The more pronounced differences between groups during periods of follow up longer than 12 months were evident at specific timepoints (24-month survival 46%vs 71%; 36-month survival 30%vs 59%). There is an increased long-term risk of mortality in patients with AD who are prescribed antipsychotic medication; these results further highlight the need to seek less harmful alternatives for the long-term treatment of neuropsychiatric symptoms in these patients. UK Alzheimer's Research Trust.
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            The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia.

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              Best practice in the management of behavioural and psychological symptoms of dementia

              Behavioural and psychological symptoms of dementia (BPSD) occur in most patients with dementia. They cause great suffering in patients and caregivers, sometimes more so than the cognitive and functional decline inherent to dementia. The clinical features of BPSD include a wide variety of affective, psychotic and behavioural symptoms and signs. The causes and risk factors for BPSD are multiple and include biological, psychological and environmental variables. Frequently, their combination, rather than any specific factor, explains the occurrence of BPSD in an individual patient. Thus, a sound etiopathogenetic investigation including the patient and the family or care team is essential. The aim is to develop an individualized treatment plan using a therapeutic decision tree modified by the individual and environmental risk profile. Still, treatment may be difficult and challenging. Clinical empiricism often steps in where evidence from controlled studies is lacking. Psychosocial treatment approaches are pivotal for successful treatment of BPSD. Often a combination of different non-pharmacological approaches precedes drug treatment (most of which is off-label). Regular assessments of the treatment plan and any prescriptions must be carried out to detect signs of relapse and to stop any medicines that may have become inappropriate. Even with optimal management, BPSD will not disappear completely in some cases and will remain challenging for all involved parties. This article is a narrative review based closely on the interprofessional Swiss recommendations for the treatment of BPSD. To establish the recommendations, a thorough research of the literature has been carried out. Evidence-based data were provided through searches of Medline, Embase, ISI and Cochrane-Database research. Evidence categories of the World Federation of Biological Societies were used. Additionally, the clinical experience of Swiss medical experts was considered.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                2018
                09 May 2018
                : 14
                : 1211-1220
                Affiliations
                [1 ]Department of Psychiatry, Charles University in Prague, Prague, Czech Republic
                [2 ]Faculty of Medicine in Hradec Kralove and University Hospital, Hradec Kralove, Czech Republic
                [3 ]Department of Neurology, Charles University in Prague, Prague, Czech Republic
                [4 ]National Institute of Mental Health, Klecany, Czech Republic
                [5 ]Department of Applied Linguistics, University of Hradec Kralove, Hradec Kralove, Czech Republic
                Author notes
                Correspondence: Blanka Klímová, Department of Applied Linguistics, University of Hradec Kralove, Rokitanského 62, Hradec Kralove 500 03, Czech Republic, Tel +420 6047 3745, Fax +420 49 333 2235, Email blanka.klimova@ 123456uhk.cz
                Article
                ndt-14-1211
                10.2147/NDT.S163842
                5953267
                29785112
                0654240f-6081-4a51-b709-0bdc33a35ea0
                © 2018 Masopust et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Neurology
                dementia,behavioral and psychological symptoms,treatment,psychopharmaceuticals,adverse effects

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