Drug therapy for delirium in terminally ill adults

Finucane, Anne; Jones, Louise; Leurent, Baptiste; Sampson, Elizabeth L; Stone, Patrick; Tookman, Adrian; Candy, Bridget

doi:10.1002/14651858.cd004770.pub3

Cited by 45 publications

(54 citation statements)

References 103 publications

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“…Antipsychotic drugs and benzodiazepines are widely used for the treatment of delirium in palliative care. A 2020 Cochrane review of four trials testing drug treatment for delirium in terminally ill adults 276 found that the efficacy of drug therapy was unclear owing to the mostly low to very low quality of evidence in these studies; however, there was some evidence of adverse effects of haloperidol and risperidone.…”

Section: Pharmacological Treatment Of Deliriummentioning

confidence: 99%

Delirium

Wilson

Mart

Cunningham

et al. 2020

Nat Rev Dis Primers

585

602

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Section: Pharmacological Treatment Of Deliriummentioning

confidence: 99%

Delirium

Wilson

Mart

Cunningham

et al. 2020

Nat Rev Dis Primers

585

602

View full text Add to dashboard Cite

“…Haloperidol is a major antipsychotic medication prescribed to diminish psychosis in schizophrenia patients 54 . However, its action is limited due to its elicitation of Parkinsonian-like bradykinesia, which affects a majority of patients and is commonly called haloperidol-induced EPS 55 , 56 . To date, there are no effective treatments available for haloperidol-induced EPS.…”

Section: Discussionmentioning

confidence: 99%

The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior

et al. 2020

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The mammalian target of rapamycin (mTOR) is a ubiquitously expressed serine/threonine kinase protein complex (mTORC1 or mTORC2) that orchestrates diverse functions ranging from embryonic development to aging. However, its brain tissue-specific roles remain less explored. Here, we have identified that the depletion of the mTOR gene in the mice striatum completely prevented the extrapyramidal motor side effects (catalepsy) induced by the dopamine 2 receptor (D2R) antagonist haloperidol, which is the most widely used typical antipsychotic drug. Conversely, a lack of striatal mTOR in mice did not affect catalepsy triggered by the dopamine 1 receptor (D1R) antagonist SCH23390. Along with the lack of cataleptic effects, the administration of haloperidol in mTOR mutants failed to increase striatal phosphorylation levels of ribosomal protein pS6 (S235/236) as seen in control animals. To confirm the observations of the genetic approach, we used a pharmacological method and determined that the mTORC1 inhibitor rapamycin has a profound influence upon post-synaptic D2R-dependent functions. We consistently found that pretreatment with rapamycin entirely prevented (in a time-dependent manner) the haloperidol-induced catalepsy, and pS6K (T389) and pS6 (S235/236) signaling upregulation, in wild-type mice. Collectively, our data indicate that striatal mTORC1 blockade may offer therapeutic benefits with regard to the prevention of D2R-dependent extrapyramidal motor side effects of haloperidol in psychiatric illness.

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“…Recently, a network meta‐analysis to evaluate pharmacological intervention for delirium treatment 37 and a Cochrane review 38 for drug therapy of delirium in terminally ill adults concluded that pharmacotherapy is not useful in alleviating delirium symptoms. However, if delirium in terminal phase is not being appropriately evaluated, we need to reconsider the conclusion of these meta‐analyses.…”

Section: Discussionmentioning

confidence: 99%

Are common delirium assessment tools appropriate for evaluating delirium at the end of life in cancer patients?

et al. 2020

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Objectives: The objectives of this study are to investigate how many advanced cancer patients became unconscious or non-communicative after pharmacological treatment for delirium, and to explore whether existing delirium assessment tools can successfully evaluate its severity at the end of life. Methods: This was a secondary analysis of a registry study that examined the efficacy and safety of antipsychotics for advanced cancer patients with delirium. A total of 818 patients were recruited from 39 specialized palliative care services in Japan. The severity of delirium was measured using the Richmond Agitation-Sedation Scale-Palliative care version, the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Nursing Delirium Screening Scale (Nu-DESC) on Day 3. Data from 302 patients with motor anxiety with an Agitation Distress Scale score ≥2 on Day 0 were analyzed for this study. The patients were categorized into four treatment response groups: complete response (CR: no agitation and fully communicative), partial response (PR: no/mild agitation and partially communicative), unconscious/non-communicative (UC), and no change (NC). Results: On Day 3, 29 (10%; 95% confidence intervals [CI], 7-13) and 2 (1%; 95% CI, 0-2) patients became unconscious and non-communicative, respectively. Forty-four patients were categorized as CR, 97 as PR, 31 as UC, and 96 as NC. The scores of the DRS-R-98 and Nu-DESC in the UC group were rated higher than patients in the NC group were. Conclusions: A considerable number of cancer patients with delirium became unconscious or non-communicative. Existing delirium assessment tools may be inappropriate for measuring the severity of delirium in end-of-life.

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Drug therapy for delirium in terminally ill adults

Abstract: Trusted evidence. Informed decisions. Better health.

Cited by 45 publications

References 103 publications

Delirium

Delirium

The mammalian target of rapamycin (mTOR) kinase mediates haloperidol-induced cataleptic behavior

Are common delirium assessment tools appropriate for evaluating delirium at the end of life in cancer patients?

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