Delirium and Antipsychotics
Posted on 30th April 2020 by Roshan Arjun Ananda
In this blog, Roshan, a final year medical student at Monash University, provides his own summary of a 2018 Cochrane Systematic Review “Antipsychotics for treatment of delirium in hospitalised non-ICU patients“.
Delirium is an acute medical condition with features of altered conscious state accompanied by disturbances in attention, cognition, awareness and perception. Moreover, it is a multifactorial disorder that is common among hospitalised elderly people especially those with underlying brain pathology including Parkinson’s disease and stroke. Developing over a short period of time (usually within hours or days), symptoms tend to fluctuate throughout the day. While polypharmacy and infection (e.g. urinary tract infection, pneumonia) are major precipitating factors of delirium, other precipitating factors include metabolic derangement, physical disorders (e.g. burns) and systemic organ failure (e.g. cardiac failure) (1).
Delirium is classified into hyperactive, hypoactive or mixed. Hyperactive delirium is characterized by elevated motor activity, agitation and delusions, whereas hypoactive delirium is characterized by decreased motor activity, drowsiness, and lethargy. Some people experience a mixture of both clusters of symptoms. Clinical features of delirium include difficulties in focusing or sustaining attention, fluctuating consciousness, speech or language disturbances and memory loss. Delirium is diagnosed based on history of the course and onset of mental state changes in the patient, supported by standardised delirium diagnostic assessment tools – Confusion Assessment Method (CAM) (2, 3).
Management of Delirium
Multidisciplinary teamwork is essential in the management of delirium. The management approach includes two pathways that are followed simultaneously: one to identify and treat the underlying medical disorder, and the other to manage symptoms of delirium. Specific therapy targeting medical conditions is administered after identifying the medical cause of delirium. However, the main approach to management of the symptoms is nursing care with non-pharmacological and pharmacological interventions. Nursing care includes adequate hydration, constant reorientation strategies, relaxation techniques, carer education, normalising sleeping pattern, adequate pain relief, vision and hearing aid use, and encouraging activity. Antipsychotic medications are indicated in patients with severe behavioural disturbances including severely agitated or aggressive (3).
A Cochrane review looked at the efficacy and safety of antipsychotics compared to non-antipsychotics (e.g. benzodiazepines) or placebo in the treatment of delirium in hospitalised non-ICU patients. The review also compared the use of typical and atypical antipsychotics (4).
Antipsychotics Vs Placebo
The systematic review included randomized and quasi-randomized trials with participants over 16 years old, randomly allocated to antipsychotics or non-antipsychotics or placebo. Randomized trials that focused on critically ill patients were excluded. The review included 9 randomized trials with 727 participants. Four studies compared antipsychotics to non-antipsychotics or placebo while seven trials compared typical to atypical antipsychotics (4).
The primary outcome of the review, total duration of delirium in days, was not reported in the trials. The evidence does not support antipsychotics administration in decreasing delirium severity (assessed by Delirium Rating Scale or Memorial Delirium Assessment Scale), decreasing mortality, reducing adverse events and shortening time to resolution as the pooled results indicate no statistical differences in the outcomes. Besides, the evidence does not support the superiority of typical over atypical antipsychotics (4).
Most of the randomized trials had unclear risk of bias except a study with low risk of bias, therefore downgrading the quality of evidence although only randomized trials were included in this review.
Clinical Practice and Future Research
The studies included in this review focus on hospitalized non-ICU patients, excluding those who are critically ill. Hence, limited evidence is available to support the use of antipsychotics in the critically ill population. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms may not be more frequent with antipsychotics compared to non-antipsychotic drug regimens, and may be of little or no difference for typical compared to atypical antipsychotics, although the evidence is very-low certainty.
Further review comparing antipsychotics with other pharmacological or non-pharmacological interventions would be a valuable guidance for clinical practice. Randomized trials comparing total duration of delirium symptoms in an antipsychotics group and a placebo group would be beneficial.