**7.2 Symptomatic treatment**

Drugs useful for managing delirium may include antipsychotics and in selected cases benzodiazepines including diazepam, lorazepam, and midazolam. The latter class of drug can be indicated in the case of alcohol withdrawal or epilepsy delirium. Other drugs such as α-2 receptor agonists, psychostimulants, cholinesterase inhibitors, and melatonergic drugs are also used although no recommendations have been released so far.

About antipsychotics, it was demonstrated that both conventional (e.g., haloperidol) and atypical antipsychotics including olanzapine, risperidone, quetiapine, aripiprazole are effective in the treatment of delirium. Of note, the efficacy and safety of haloperidol at low doses (up to 10 mg/day) are comparable to those of atypical antipsychotics such as risperidone, olanzapine, and quetiapine [27].

In palliative care, haloperidol is one of the most used drugs. It is commonly administrated for the treatment of delirium and for the prevention and/or

treatment of nausea/vomiting (including the opioid-induced ones) [28]. Even if it represents the preferred drug in the treatment of delirium, its use is limited by concern for side effects. Usually, the onset of extrapyramidal disorders is dosedependent and cardiotoxicity — QTc prolongation or torsades de pointes (with a QTc > 450–500 ms immediate drug withdrawal is recommended) — generally rarely occurs for low doses [29]. However, in patients under palliative care, many factors such as the severity of the underlying disease and organ damage, comorbidities, cachexia, hypoproteinemia, advanced age, and polytherapy can increase the risk of side effects. For example, haloperidol pharmacokinetics (**Table 2**) mostly depends on CYP2D6 functioning.

About doses, in mild delirium with no underlying psychiatric illness haloperidol can be used at the dose of 0.5–1 mg bid, both oral or subcutaneous (0.25–0.5 mg for elderly patients). In moderate delirium, the dose can be doubled. In severe and terminal delirium the dose is 0.5–4 mg both oral or subcutaneous (possibly repeated every 45–60 min) with a maximum of 2–20 mg/day.

Among the other antipsychotics, risperidone (0.5–4 mg/day) could be useful in patients requiring high doses of haloperidol or at high risk of developing haloperidol-induced extrapyramidal or cardiac effects. Olanzapine (2.5–10 mg/day, orally or i.m.) has an efficacy comparable to haloperidol but can induce sedation due to its antihistaminergic action; thus, it is not recommended in elderly patients with dementia or hypoactive delirium, although its use can be beneficial for the regulation of the sleep–wake rhythm [30]. Quetiapine (from 12.5–25 mg/day up to an average dose of 50–175 mg/day) has an intense antihistaminergic activity which can worsen confusion. It can also cause hypotension. Finally, the first-generation antipsychotic agent levomepromazine is also used to address intractable nausea or vomiting, and for severe delirium in the last days of life. This phenothiazine is administered orally or by subcutaneous bolus injection (10–25 mg, repeatable as required after 2 hours) or continuous subcutaneous infusion (25–100 mg/day).

It must be emphasized that the efficacy of antipsychotics and other pharmacological interventions for the treatment of delirium in palliative care is still under debate [31, 32]. The use of antipsychotics and/or other medications becomes inevitable for the management of hyperactive or mixed delirium with severe agitation and anxiety but they must be given short-term and at the lowest effective dose. Symptomatic therapy of delirium is also mandatory if it becomes a source of suffering.


*Abbreviations: p.o., oral; i.m., intramuscular; s.c., subcutaneous; i.v., intravenous; Vd: Volume of distribution; PPB, Plasma protein binding; Cl, Clearance.*

**9**

**Author details**

Marco Cascella

Pascale, Napoli, Italy

Department of Supportive Care, Istituto Nazionale Tumori-IRCCS-Fondazione

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: m.cascella@istitutotumori.na.it

provided the original work is properly cited.

multicomponent non-pharmacological approaches.

*Introductory Chapter: Delirium in Palliative Care DOI: http://dx.doi.org/10.5772/intechopen.98654*

Non-pharmacological approaches such as behavioral and educational interventions, and cognitive activities as well as methods aimed at improving sleep, vision, and hearing functioning, are useful for addressing the issue of delirium. Encouraging family visits is another effective non-pharmacological strategy to be

Communication strategies play a role of fundamental importance. Among the many examples reported, those proposed by the Mother Élisabeth Bruyère health care organization seem to be simple and effective. According to these suggestions, it is mandatory to use a calming voice, speak slowly and in short simple sentences, present one idea at a time and if needed, repeat the sentence. It is also suggested to avoid contradicting the person, accepting his/her arguments. Finally, rapid movements or gestures that can be misinterpreted as aggressive must be avoided [33].

Although clinical experience and scientific evidence underline that delirium can lead to multiple clinical and healthcare problems and that its timely recognition and treatment can induce a remission of the clinical picture, screening of cognitive conditions and delirium remains an unmet need. As the efficacy of pharmacological treatments has not yet been proven, greater efforts must be focused on prevention and early diagnosis. In short, the strategies to be adopted for prevention are quite codified. It is crucial to recognize potential risk factors and, since according to the ICD-11, delirium is essentially featured by disturbed attention and awareness, a careful evaluation of changes in usual behaviors is mandatory. The suspicion, in turn, must direct towards the administration of validated tools. Although the effectiveness of antipsychotics and other pharmacological treatments is still questioned, the use of these drugs is especially necessary for the treatment of hyperactive or mixed delirium featuring severe agitation and self or hetero-injurious behaviors. The hypoactive subtype, although very frequent, is little recognized and requires

**7.3 Non-pharmacological strategies**

strengthened.

**8. Conclusion**
