Medication therapy has become commonplace in the treatment of patients with delirium/dementia during hospitalization. Ideally, patient confusion/aggression can be controlled with non-pharmacologic therapy, however when changes in mental status become a threat to patient and health care worker safety, medications can be helpful.
Antipsychotics are generally categorized as first (typical) and second (atypical) generation drugs. As the name suggests, second generation drugs were developed later, where the term "atypical" neuroleptics was introduced in 1998. These were developed to control psychiatric illness, while minimizing side effects. Both classes of drugs antagonize dopamine (D2) receptors, improving hallucinations and delirium. Atypical antipsychotics bind the D2 receptor with less affinity and higher specificity for the mesolimbic area of the brain. This is felt to cause similar efficacy with less extrapyramidal side-effects, which include rigidity, spasticity, and tardive dyskinesia as well as negative symptoms (psychomotor retardation), attributed to blockade in the nigrostriatal and prefrontal regions respectively.
Neuroleptic medications are amongst the most common drugs used to treat delirium and behavioral dementia. In 2005, the FDA issued a warning statement for these medications as a group, citing a small but significant association with increased mortality with their use. This increased mortality was secondary to an increase in infectious (pneumonia) and cardiovascular (sudden death/CHF/stroke) events. An increase in cerbrovascular events was seen with multiple atypical antipsychotics (ex. risperidone, olanzapine). This has led to controversy regarding the use of these drugs in clinical practice.
Psychotropic medications should be used judiciously in response to delirium, but are sometimes warranted. These drugs should not be provided prophylactically, considering they have not been shown to reduce delirium incidence, but duration following it's occurrence, which was examined in an RCT of postoperative delirium (kalisvaart et al. 2005). The efficacy between agents is similar, where comparisons of haldol (typical) and risperidone, qeutiapine, olanzapine and ziprasidone (atypicals) have been performed. To manage aggressive behavior in patients with dementia, risperidone has been investigated the most and showed mild benefits in multiple trials. The meta-analysis (2005 JAMA), examined 15 RCTs of atypical antipsychotics and placebo in delirium and found a grouped reduction in mortality in the placebo group, however amongst the specific drug subgroups, no increased mortality was identified. Long term follow up patients randomized to continue their current medication (haloperidol, risperidone, thioridiziner, chlorpromazine etc) or placebo. Results showed an associated increase in mortality in those taking antipsychotics over a 12 week period. There tends to be a dose dependent response and increased risk with haloperidol. Intramuscular haloperidol may be less arrythmogenic making oral/IM the routes of choice.
Physicians should constantly re-evaluate the need for antipsychotic use and discontinue when possible. See the link below for one of many citations.
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