Benzodiazepines and/or neuroleptics for the treatment of delirium in palliative care?—a critical appraisal of recent randomized controlled trials

Abstract

Delirium is a frequent condition in patients in a palliative care situation and most often associated with substantial burden or even danger for the persons concerned as well as caregivers and healthcare-professionals. Despite the lack of randomized-controlled-trials (RCTs) benzodiazepines and neuroleptic agents are used extensively in palliative care for the pharmacological management of delirium. A focused review for RCTs assessing pharmacotherapy with benzodiazepines and neuroleptics for the treatment of delirium in patients treated in a palliative care or hospice setting published in 2017 was performed in PubMed. A narrative summary of the findings of the RCTs and practical recommendation are presented. Of 42 publications, two RCTs could be included. One trial assessed the use of lorazepam (in addition to haloperidol) in case of agitation, the other placebo or risperidone or haloperidol in delirious palliative care patients. Neither risperidone nor haloperidol were superior compared to placebo, but were associated with higher mortality and morbidity. Lorazepam (along with haloperidol) reduced agitation in patients with delirium compared to placebo (along with haloperidol), but was unable to reduce the severity and incidence of delirium. It is of importance to note that psychopharmacotherapy with antipsychotics is mainly indicated for the hyperactive form of delirium and psychotic symptoms (e.g., delusions or hallucinations) in the hyperand hypoactive delirium. Severe agitation and aggressivity can be an indication for neuroleptics, when nonpharmacological interventions fail, whereas the use of benzodiazepines has to be limited to critical situations where neuroleptics cannot be applied and cases of delirium due to alcohol withdrawal. Both substances can aggravate, precipitate or mask delirium, result adverse events with substantial distress or unfavorable survival outcomes for the patients. Thus, they should only be used in severely symptomatic patients and the duration of the medication has to be limited in time. When delirium symptoms decay the psychopharmacotherapy has to be tapered. More important than psychopharmacotherapy, the thorough investigation and treatment of potentially reversible causes of delirium (e.g., pharmacotherapy, infection) and the routine identification of patients at risk for delirium along with prophylactic measures are essential. The recently published landmarks RCTs provide moderate evidence to adopt recommendations from other medical specialties (i.e., intensive care, geriatrics) to the field of palliative care.

The affinity and selectivity of α‐adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D‐adrenoceptors

“…These drugs are used to manage schizophrenia where their effect on blood pressure in agitated patients is less likely to be an issue. However, antipsychotics are also widely used to manage delirium in sick patients including the intensive care unit 58,59 and in palliative case 60,61 even though recent studies have questioned their effectiveness. 62 Delirium is common in older unwell patients who are more likely to be suffering from conditions…”

Delirium in cancer patient

“…Jest ono mało efektywne i wiąże się z ryzykiem wystąpienia działań niepożądanych. Zastosowanie terapii jest dopuszczalne, gdy pacjent zaczyna stanowić bezpośrednie zagrożenie dla swojego bezpieczeństwa lub osób w jego otoczeniu bądź też nie pozwala na udzielenie sobie pomocy medycznej [16,25,26,42].…”

“…Nie udowodniono skuteczności leków przeciwpsychotycznych w zapobieganiu ani leczeniu majaczenia (skróceniu jego czasu trwania czy też zmniejszeniu śmiertelności). Leki są jednak nadal powszechnie stosowane objawowo w pobudzeniu psychoruchowym oraz w przypadku wystąpienia objawów wytwórczych (myśli urojeniowe, iluzje, omamy) [3,42]. Farmakoterapii nie należy stosować w majaczeniu hipoaktywnym [25].…”

Abordagem do Delirium na Comunidade

“…O delirium desenvolve--se ao longo de um curto período (horas a dias) e flutua em gravidade durante o decurso de um dia. 24…”

“…Assim, eles devem apenas ser usados em doentes sintomáticos e a duração da terapêutica deve ser limitada. 9,24 Paradoxalmente, num estudo preliminar com doentes hospitalizados com delirium associado a agitação no contexto de cancro avançado, a adição de lorazepam ao haloperidol, comparativamente com o haloperidol isoladamente, resultou numa redução significativamente superior da agitação ao final de 8 horas. 58 Alguns estudos mostram benefício na utilização de agonistas alfa-2 dexmedetomidina.…”