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 Table of Contents  
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 60-62

The pharmacological treatment of behavioral alterations in the course of dementia

Department of Health Mental, ASP, Ragusa, Italy

Date of Submission25-Apr-2022
Date of Decision07-Jun-2022
Date of Acceptance12-Jun-2022
Date of Web Publication03-Aug-2022

Correspondence Address:
Dr. Davide Cristina
Department of Health Mental, ASP, Ragusa
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jgmh.jgmh_18_22

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How to cite this article:
Cristina D. The pharmacological treatment of behavioral alterations in the course of dementia. J Geriatr Ment Health 2022;9:60-2

How to cite this URL:
Cristina D. The pharmacological treatment of behavioral alterations in the course of dementia. J Geriatr Ment Health [serial online] 2022 [cited 2022 Dec 2];9:60-2. Available from:


The World Health Organization in its report made dementia a global public health priority. The prevalence of dementia is increasing in our aging population at a pressing rate. In Italy, there are estimated to be over one million patients affected by dementia, and of these around 600,000 with Alzheimer's dementia. Despite the treatment of dementia, it makes use of different strategies present at the level of the territory, the hospital is the main reference for patients suffering from dementia only in emergency conditions such as severe behavioral imbalances, epilepsy, delirium, and trauma.[1],[2] Thus, however, it is possible to incur improper hospitalizations or revolving doors in a psychiatric unit. In fact, the Behavioral and Psychological Symptons in Dementia (BPSD) is a frequent psychopathological condition characterized by psychotic symptoms such as delusions usually not bizarre and poorly structured with a persecutory background, visual hallucinations secondary to arousal or alteration of the state of consciousness, false recognitions of oneself and of others, psychomotor agitation, aggression, sexual disinhibition, altered eating behavior, the phenomenon of wondering, apathy, depression, anxiety, and sleep-wake cycle disorders.

BPSDs reduce the quality of life, also increasing the possibility of institutionalization of the patient. More than 90% of patients with dementia develop at least one of these symptoms.[3]

The treatment of BPDS in general should be initially addressed by modifying the cavinger's behavior or reducing environmental stimuli, involving family members in support or psychoeducational programs offered by the various associations for dementia, and by clinical care pathways, with integrated management. For example, taking charge on the territory must provide assistance to the patient and familie (Integrate/specialist home visits, primary care of the general practitioner, etc.) preventing the load on the hospital emergency room.[2]

Studies relating to the treatment of BPSD have not found particular innovations with regard to psychopharmacological treatment. Drugs for the treatment of dementia currently are based on anticholinesterase and N-Metil D Aspartic Acid (NMDA) antagonists which only have the function of slowing down the progressive cognitive decline.

The lack of approval by the regulatory bodies in charge of the various classes of psychiatric drugs means that the use of psychiatric drugs is an off-label practice with any related medicolegal problems, especially with regard to NL-based treatment which for about a decade has become more complex as a result of scientific data correlating typical and atypical neuroleptics with a 2%–4% increased risk of cerebrovascular-type adverse events. In fact, the publication of two “warnings” by the Food and Drug Administration (FDA) in 2005 and 2008 and subsequently, the European Medicines Agency reported increased mortality in patients suffering from dementia.[4] Thus, in all the technical data sheets of the typical and atypical NL drugs, the possible increased risk of cerebrovascular adverse events in patients with dementia is found in the warnings. In addition to NLs, various mood stabilizers are used off-label that have no indication for dementia such as valproic acid, valpromide, oxacarbamazepine, carbamazepine, gabapentin, and pregabalin, especially in manic symptoms or aggression. These stabilizers act with different mechanisms of action on neurons of the central nervous system.

NLs are FDA-approved antipsychotic drugs used in schizophrenic disorders and bipolar disorders. Conventional or typical NLs have been used extensively for decades and also initiated drug research into finding new molecules for the development of atypical NLs. Atypical NLs were initially used for patients who experienced side effects with typical NLs.[5] Among the NLs, a classification was made according to their appearance on the market.

  1. NL first generation or typical with the main pharmacological mechanism of action of D2 dopaminergic receptor antagonist: haloperidol, chlorpromazine, promazine, pimozide, and clotiapine. The most important side effects are Extra Pyramidal Syndrome (EPS) and dystonias including late forms, which are effects unwanted products usually associated with the use of first-generation (typical) high-potency antipsychotic drugs that chronically block the dopaminergic D2 receptors present mostly in the nigrostriatal pathway, exert a prolonged antidopaminergic action which would ultimately favor the cholinergic tone.[6] Adverse effects, especially in elderly people can be multiple: hypotensive effects, dysphagia, EPS, tardive dyskinesias, muscarinic effects (urinary retention), delirium, cognitive decline, endocrine effects, weight gain, lengthening of the QTc tract, and an abnormal electrocardiogram, which may result in ventricular arrhythmias.[7] Above all, the prevalence of multiple NL use in therapy reported by several studies highlighted people who took more NL were more likely to experience at least one side effect than monotherapy users[8]
  2. NL of second generation or atypical with the multivalent main pharmacological mechanism of action of the antagonist of the 5-HT2 serotonergic receptors, and less on D2 receptors, therefore they are safer than typical NLs, especially for fewer undesirable effects such as EPS. For many of them, quetiapine, olanzapine, clozapine, and risperidone may lead to weight gain and high blood glucose

  3. Neurotransmitter receptors play a crucial role in metabolic regulation and are also targets of NL drugs. Mutual interaction can lead to an imbalance of metabolic regulation (eating behavior, energy balance).[9] NLs of the second generation or atypical are olanzapine, quetiapine, amisulpride, risperidone, paliperidone, aripiprazole, clozapine, asenapine, ziprasidone, and lurasidone.

  4. Third-generation NLs with the main pharmacological mechanism of action of a partial agonist of D2 receptors: aripiprazole, cariprazine, and brexpiprazole certainly have a less metabolic impact and less cardiac toxicity than all other NLs. However, they remain contraindicated in dementias like all other NLs.[10]

Observational studies suggest that atypical antipsychotics are associated with a lower risk of mortality from all causes and extrapyramidal symptoms, but with a higher risk of stroke than conventional antipsychotics. To manage agitation in adults with progressive dementia, physicians may recommend atypical antipsychotics with continuous monitoring of behavioral symptoms. Aripiprazole, risperidone, and olanzapine but not quetiapine result in a modest improvement in neuropsychiatric symptoms.[11]

Although the differences between atypical and typical NLs have been clarified with regard to the increased risk for cardiovascular events to the detriment of atypical NLs, there are different data, in fact, some observational studies including a retrospective cohort study of 22,890 elderly patients not necessarily demented in treatment with NL for the first time showed that the risk of death associated with NL is variable in the time of exposure to treatment and is higher in treated patients in all time periods of treatment with typical NLs.[12],[13] A comparison study in patients in long-term residences found that conventional NLs are less safe than atypical NLs in elderly patients with BPSD and should not be used.[14] The use of haloperidol is not recommended for a long time in patients with dementia except in delirium.[15]

Many studies have shown that atypical NLs compared to placebo have relative efficacy and in the treatment of BPSD are unsafe and the risk of mortality is increased.[3] Generation (partial D2 agonists) compared to first-generation NLs (typical) have a low toxicity profile (low risk of EPS, Neuroleptc Malignant Syndrome (NMS), tardive dyskinesia, orthostatic hypotension, less or no lengthening of the QTc tract), on the other hand, they are not indicated (not recommended) in the treatment of behavioral alterations in degenerative and vascular dementias,[16] except the atypical NL risperidone which in Italy is indicated for the short-term treatment of aggression in moderate-to-severe Alzheimer's dementia, and tiapride with indications of behavioral disorders with acute and chronic agitation and anxiety in the elderly but not in dementia.

In clinical practice, the use of low-dose atypical NLs (quetiapine, olanzapine, aripiprazole, and risperidone) is frequent, which in any case has proved to be sufficiently tolerated. In the first instance, only if necessary, the short-term use of typical NLs such as haloperidol (in low doses) with an indication of psychomotor agitation in case of dementia and with a poorly sedative profile and promazine is generally well-tolerated, but considering instead sedative effects.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Raz L, Knoefel J, Bhaskar K. The neuropathology and cerebrovascular mechanisms of dementia. J Cereb Blood Flow Metab 2016;36:172-86.  Back to cited text no. 1
Linee of National Adress on Diagnostic Therapeutic Assistance Pathways. juliy o5.2017.  Back to cited text no. 2
Yunusa I, Alsumali A, Garba AE, Regestein QR. Tewodros eguale assessment of reported comparative effectiveness and safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms of dementia: A network meta-analysis JAMA Netw Open 2019;2:e190828. doi:10.1001/jamanetworkopen.2019.0828.  Back to cited text no. 3
Vita A, Rossi A, Amore M, Carpiniello B, Fagiolini A, Maina G, et al. Manuale di Psichìatria. Milano: Edra; 2019. p. 159.  Back to cited text no. 4
Maher AR, Theodore G. Summary of the comparative effectiveness review on off-label use of atypical antipsychotics. J Manag Care Pharm 2012;18:S1-20.  Back to cited text no. 5
Cristina D. Description of a Case of Tardive Dyskinesia. Psychogeriatrics Year XV n. 1; January-April, 2020. p. 95.  Back to cited text no. 6
Karim S, Eleonor BJ. Treatment of psychosis in elderly people. Adv Psychiatr Treat 2005;11:286-96.  Back to cited text no. 7
Westaway K, Sluggett JK, Alderman C, Procter N, Roughead E. Prevalence of multiple antipsychotic use and associated adverse effects in Australians with mental illness. Int J Evid Based Healthc 2016;14:104-12.  Back to cited text no. 8
Siafis S, Tzachanis D, Samara M, Papazisis G. Antipsychotic drugs: From receptor-binding profiles to metabolic side effects. Curr Neuropharmacol 2018;16:1210-23.  Back to cited text no. 9
Stahl SM. Psycofarmacologia Essenziale – Guida Alla Prescrizione. 2nd ed. Milano: Edi-Ermes; 2014. p. 51.  Back to cited text no. 10
Farlow MR, Shamliyan TA. Benefits and harms of atypical antipsychotics for agitation in adults with dementia. Eur Neuropsychopharmacol 2017;27:217-31.  Back to cited text no. 11
Wang PS, Schneeweiss S, Avorn J, Fischer MA, Mogun H, Solomon DH, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005;353:2335-41.  Back to cited text no. 12
Gill SS, Bronskill SE, Normand SL, Anderson GM, Sykora K, Lam K, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007;146:775-86.  Back to cited text no. 13
Huybrechts KF, Schneeweiss S, Gerhard T, Olfson M, Avorn J, Levin R, et al. Comparative safety of antipsychotic medications in nursing home residents. J Am Geriatr Soc 2012;60:420-9.  Back to cited text no. 14
David Tayloe, Thomas R.E.Barnes, Allan H.Young. The Maudsley Prescribing guidelines in Psychiatry 13th edition. Wiley Blackwell: 2018 This thirteenth edition first published 2018. 13th edition Hoboken, NJ : Wiley, 2019 p. 574-5.  Back to cited text no. 15
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