Haloperidol (Haldol): reminder of risks when used in elderly patients for the acute treatment of delirium
We remind healthcare professionals that elderly patients are at an increased risk of adverse neurological and cardiac effects when being treated with haloperidol for delirium. The lowest possible dose of haloperidol should be used for the shortest possible time, and cardiac and extrapyramidal adverse effects should be closely monitored.
Advice for healthcare professionals:
- special caution is required when using haloperidol for the acute treatment of delirium in frail, elderly patients
- only consider haloperidol for delirium when non-pharmacological interventions are ineffective and no contraindications are present (including Parkinson’s disease and dementia with Lewy bodies)
- before initiating treatment, a baseline electrocardiogram (ECG) and correction of any electrolyte disturbances is recommended; cardiac and electrolyte monitoring should be repeated during treatment (see below)
- prescribe the lowest possible dose for the shortest possible time, ensuring that any dose up-titration is gradual and reviewed frequently
- monitor for and investigate early any extrapyramidal adverse effects, such as acute dystonia, parkinsonism, tardive dyskinesia, akathisia, hypersalivation, and dysphagia
- report suspected adverse reactions associated with haloperidol on a Yellow Card
Review of haloperidol use in elderly patients with delirium
Haloperidol is a first-generation antipsychotic authorised for treatment of neurological and psychiatric disorders, including the acute treatment of delirium in adults when non-pharmacological treatments have failed – see the Summary of Product Characteristics (SmPC) for full indications.
The MHRA received concerns from a patient representative regarding the use of haloperidol for the acute treatment of delirium in elderly people in the UK. The MHRA conducted a review of UK safety information for haloperidol in the treatment of delirium in frail, elderly patients. The review included safety data from the Yellow Card scheme as well the published literature and current clinical guidance. We sought advice on the review assessment from the Pharmacovigilance Expert Advisory Group of the Commission on Human Medicines and experts in neurology and psychiatry. We have made available a Public Assessment Report.
The review did not identify any new safety concerns relating to use of haloperidol in elderly patients and no changes will be made to the safety advice in the product information. However, the review identified that the practical use of haloperidol in patients with delirium is variable and is known to be especially associated with adverse effects of the central nervous system.
We issue this reminder to healthcare professionals, especially prescribers of haloperidol, to emphasise the need for special caution when using this medicine in elderly people. This advice is consistent with current clinical advice for management of delirium in this population.
Clinical advice available on treatment of delirium
Delirium or ‘acute confusional state’ is a common and complex condition that is known to occur more frequently in older people. Diagnosis and treatment of newly presenting delirium in elderly people can be challenging as it is often multifactorial.
Clinical guidance recommends that patients are reviewed, and screening tools used. Delirium may also overlap with dementia or other precipitating factors such as polypharmacy or infection, which can be especially relevant in elderly patients. Frailty (defined by NHS England as ‘a loss of resilience that means people don’t bounce back quickly after a physical or mental illness, an accident or other stressful event’) can further increase the risk.
Clinical guidance recommends that pharmacological interventions for acute treatment of delirium are kept to a minimum with non-pharmacological interventions used first-line. However, in cases of delirium where these methods have failed and the patient is distressed or there is a risk to their safety or those around them, then clinical guidance recommends low-dose, short-term haloperidol unless contraindicated.
Full contraindications can be found in the Summary of Product Characteristics (SmPC). Haloperidol is contraindicated in patients with Parkinson’s disease and dementia with Lewy bodies. Relevant clinical guidance should be consulted for care of these patients.
Clinical guidance, especially on dosing and monitoring for patients with delirium, should be referred to such as NICE guidance on delirium, SIGN guidance risk reduction and management of delirium, and British Geriatrics Society guidance on patients presenting with confusion and delirium.
During the coronavirus (COVID-19) pandemic, haloperidol has also been used for the treatment of delirium associated with COVID-19.
Reminder of dosing recommendations in elderly patients
Elderly patients may have a lower clearance and longer elimination half-life of haloperidol. Dose adjustment is therefore recommended for patients with hepatic or renal impairment, as well as patients who are elderly. Prescribers should refer to local and national prescribing guidelines, as well as the dosing principles in the SmPC.
First dosing should always be very cautious, especially in elderly people, and the minimum effective dose should be prescribed for the shortest possible time. Any dose up-titration should be gradual and reviewed frequently. Regular reviews should be conducted, with the aim of discontinuing haloperidol treatment as soon as is feasible.
Reminder of neurological and cardiac side effects of haloperidol
Since 1964 and up to 4 September 2021, the MHRA had received a total of 1341 Yellow Card reports containing 3385 suspected adverse drug reactions relating to haloperidol. Of these, 242 reports related to patients from 60 years of age or older and the majority of the reactions (171) related to adverse effects in the nervous system.[footnote 1]
Elderly patients may be particularly susceptible to extrapyramidal side effects with haloperidol. These can be potentially serious and should be carefully monitored and promptly investigated. Extrapyramidal side effects may include acute dystonias, parkinsonism, or tardive dyskinesia, each of which may impair a patient’s ability to swallow, a complication of which can be inhalation of throat or stomach contents and eventually aspiration pneumonia. Healthcare professionals are encouraged to undertake early monitoring and investigation of drug-induced dysphagia in elderly patients.
Haloperidol is also associated with QTc prolongation and ventricular arrhythmias. Accordingly, use of haloperidol is contraindicated in patients with known QTc prolongation, congenital long QTc syndrome and in patients taking other drugs known to prolong the QTc interval – examples are provided in the Interactions section of the SmPC. A baseline ECG is recommended before treatment, particularly in patients with cardiovascular risk factors or a history of cardiovascular disease. The need for further ECGs during treatment should be assessed on an individual basis, and blood pressure monitoring during treatment is also advised.
Dose-related orthostatic hypotension is known to occur in elderly people treated with haloperidol, which may increase the risk of falls.
Other adverse reactions listed in the product information include rhabdomyolysis and rare cases of neuroleptic malignant syndrome, for which prompt medical intervention is required.
Clinical evidence base for use of haloperidol in delirium
The review identified that there are limited randomised controlled trials of haloperidol for the treatment of delirium, particularly in elderly patients, an issue contributed to by the practical and ethical difficulties associated with studies of this kind. However, haloperidol has been used extensively worldwide for many years.
Current clinical guidelines on delirium rely on expert opinion in this area of antipsychotic prescribing. Further study of the behavioural disturbances associated with delirium in elderly patients is needed and current clinical guidelines include recommendations for more research.
Report suspected reactions on a Yellow Card
Please continue to report suspected adverse drug reactions to the Yellow Card scheme. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:
- the Yellow Card website
- the Yellow Card app; download from the Apple App Store or Google Play Store
- some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.
Report suspected side effects to medicines, vaccines, medical device and test kit incidents used in coronavirus (COVID-19) testing and treatment using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.
Article citation: Drug Safety Update volume 15, issue 5: December 2021: 1.
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In interpreting these data, caution should be exercised as data may not be complete, and the reporting rates can be influenced by many factors. Reporters are asked to submit Yellow Card reports even if they only have a suspicion that the medicine may have caused the adverse drug reaction. ↩