Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis

JAMA Psychiatry. 2019 May 1;76(5):526-535. doi: 10.1001/jamapsychiatry.2018.4365.


Importance: Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear.

Objective: To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention.

Data sources: PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and from inception to May 17, 2018.

Study selection: Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention.

Data extraction and synthesis: To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model.

Main outcomes and measures: The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium.

Results: A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1% male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4% male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95% CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95% CI, 0.01-0.66 for ramelteon; OR, 0.25; 95% CI, 0.09-0.69 for olanzapine; OR, 0.27; 95% CI, 0.07-0.99 for risperidone; and OR, 0.50; 95% CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control.

Conclusions and relevance: This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Delirium / drug therapy
  • Delirium / prevention & control*
  • Drug Therapy, Combination
  • Haloperidol / administration & dosage
  • Haloperidol / therapeutic use
  • Humans
  • Indenes / administration & dosage
  • Indenes / therapeutic use
  • Lorazepam / administration & dosage
  • Lorazepam / therapeutic use
  • Network Meta-Analysis
  • Treatment Outcome


  • Antipsychotic Agents
  • Indenes
  • ramelteon
  • Haloperidol
  • Lorazepam