Appropriate management of the underlying condition(s) and the drugs that the patient is taking, remains the mainstay of delirium treatment.
Stopping drugs that cause delirium
The importance of reducing or ceasing drugs that exacerbate delirium cannot be overemphasised. This highlights the importance of a thorough medication review. While anticholinergics and psychoactive medications (including antiepileptic and pain medications) are important, other drugs such as NSAIDs and sotalol may also contribute to the problem (see box). Even drugs that are used to treat delirium, particularly if given in excess, can prolong or worsen delirium. It is also important to enquire about over-the-counter and complementary medications, such as European mandrake or scopolia which have marked anticholinergic properties, as these may precipitate delirium.
Drug therapy for delirium
Drug therapy is reserved for patients who are at risk of harming themselves or others, for example by pulling out essential medical devices or lines. Drug treatment for delirium is an understudied area, with only a limited number of small trials to guide management. There are very few data comparing different drugs. The choice of drug is not guided by an understanding of the pathophysiology of delirium, which remains imprecise.
Antipsychotics
If drugs are needed, antipsychotics are generally accepted as first-line, except in delirium tremens. However, phenothiazine antipsychotic drugs such as chlorpromazine, which have prominent anticholinergic properties, should be avoided in older patients. Always remember the essential aphorism of geriatric pharmacology: start low and go slow. Suggested initial doses are haloperidol 0.5 mg, risperidone 0.5 mg or olanzapine 2.5 mg. Depending on the response additional doses can be given after 2–4 hours, otherwise daily. However for the more frequent dosing, the patient should be closely monitored for over-sedation.
Efficacy
A number of small trials have shown that typical (particularly haloperidol) and atypical antipsychotics improve hyperactive symptoms, such as agitation, restlessness, thought and perceptual disturbance, and shorten the duration of delirium. Hypoactive symptoms such as drowsiness and sedation may be exacerbated. There is no clear evidence that atypical antipsychotics are more effective than typical antipsychotics, but they appear to have fewer extrapyramidal adverse effects.
Adverse effects
Extrapyramidal effects include akathisia (motor restlessness and muscular tension especially in the legs) and parkinsonism. These may occur in over half of older patients on antipsychotics, with the risk increasing with higher doses and longer duration of treatment.
Antipsychotics may prolong the QT interval. Neuroleptic malignant syndrome, a rare but potentially fatal disorder, is also more common with typical antipsychotics. It develops over 1–3 days, and symptoms include fever, extrapyramidal dysfunction with tremor and marked rigidity, autonomic disturbance including tachycardia and hypo- or hypertension, elevated creatine kinase and white cell count, and myoglobinuria. If suspected, antipsychotics should be ceased immediately and supportive measures instituted, including intravenous fluids.
Other adverse effects of antipsychotic drugs that affect older people during short-term treatment are sedation, orthostatic hypotension, epileptic seizures, weight gain and disturbed glucose and lipid metabolism. Sedation may, at times, be a desired effect but at other times it is an adverse effect, prolonging the delirium and increasing the risk of falls and fractures.
Evidence has emerged of an increased risk of stroke in older patients with dementia taking atypical antipsychotics, however the risk is thought to be similar with typical drugs.
Other drugs
Benzodiazepines are the treatment of choice for delirium tremens and delirium associated with benzodiazepine withdrawal. They can also be used in patients with neuroleptic malignant syndrome, Parkinson's disease or Lewy body dementia. However, the atypical antipsychotics may be used with caution in the latter two conditions.
Although anticholinergic drugs can contribute to the development of delirium, and ceasing them often helps improve delirium, there is no randomised evidence that the cholinergic drugs used to treat dementia (donepezil, galantamine or rivastigmine) have a role in the treatment of delirium.