What is the best pharmacological treatment for delirium? Am Jl Psy.Feb.2014


Delirium is  a neurotoxic state and is associated with acute new brain damage . Longer duration of the delirium episode is associated with greater global brain atrophy, white matter disruption, and cognitive decline .

There are three subtypes of delirium: hyperactive delirium, hypoactive delirium and mixed delirium. 75% of delirium cases are either of the hypoactive or mixed type. hyperactive form is most often characterised by hallucinations, delusions, agitation, and disorientate and often attract medical attention. Hypoactive subtype is characterised by confusion and sedation and is less often associated with psychotic features, which are more difficult to identify even if present.Patients with hypoactive delirium usually have longer hospital stays and are more likely to develop pressure sores and hospital-acquired infections.

Joseph I. Friedman et al review the pharmacological options to prevent and treat  delirium in this article.

Prevention: IV haloperidol and oral risperidone  is shown to reduce delirium in post operative patients. Choline esterase inhibitors are not better than placebo in this. Anaesthetic techniques do not make much difference. Ketamine and melatonin might reduce post operative delirium.

Treatment: Antipsychotic use in ongoing delirium is less effective than prophylactic treatment. RCTs comparing different antipsychotics show that haloperidol, ziprasidone, and quetiapine were not associated with  higher rates of delirium resolution during the treatment period than was placebo.Two quetiapine studies showed early resolution of delirium, but differences in subject characteristics could have contributed to the differences in response. Prevention studies showed that haloperdiol can reduce duration and severity of delirium where as SGA s reported no such effect.

Subtypes: Some studies suggest aripiprazole as more effective in hypoactive delirium and haloperidol in both hyperactive and hypoactive states. Olanzapine showed lower response in hypoactive states.  

Antipsychotics were generally safer to use in delirium states.

Conclusion: Haloperidol’s effectiveness in preventing postoperative delirium is accompanied by its effectiveness in decreasing delirium duration and severity when it occurs but was not observed in the placebo-controlled haloperidol treatment study of ongoing delirium. Limited evidence demonstrates that quetiapine shortens the duration of episodes in ongoing delirium, while other second-generation antipsychotics (olanzapine and risperidone) used in delirium prevention trials had no such effect on delirium duration or severity.

Summary of the article:

Pharmacological treatments of non-substance-withdrawal delirium: a systematic review of prospective trials. Friedman JI, Soleimani L, McGonigle DP, Egol C, Silverstein JH. Am J Psychiatry. 2014 Feb 1;171(2):151-9.


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