Psychiatry - October 2008 - (Page 32)

lorazepam was more moderate at 4.6mg per day. As mentioned in a review paper on delirium by Pae, et al., in a larger, placebo-controlled study comparing haloperidol to olanzapine, an atypical antipsychotic discussed in more detail later, little difference between active medication groups but superiority to placebo was demonstrated.12,13 In this study, low to moderate doses of haloperidol and olanzapine were used, 4.5mg versus 7.1mg respectively, and the instrument measure was the Delirium Rating Scale. The size of the active medication groups for haloperidol and olanzapine were 72 versus 74 patients with 29 patients receiving placebo and the mean time to improvement being 3.4 days versus 2.8 days and 5.2 days for those receiving placebo. Other typical antipsychotics have been the subject of investigation for treatment of delirium (acute organic mental syndrome), but many of these studies are 20 to 30 years old and do not always utilize diagnostic nomenclature compatible with contemporary medical practice. In the 1980s, a single blind study of haloperidol and thiothixene on 14 patients showed that both drugs were effective in relieving delirium with a possible slight advantage for thiothixene as measured by the Brief Psychiatric Rating Scale.14 The dose of haloperidol was between 4.8 and 15mg and the thiothixene dose was between 2 and 7mg per day. Earlier studies from the 1970s of thiothixene, loxapine, and thioridazine are difficult to incorporate into the evidence base given their admitted diagnostic heterogeneity and small sample sizes. One double-blind, placebo-controlled study of thiothixene dosed at 2 to 5mg up to three times a day failed to find superiority of the drug for chronic organic brain syndrome. The outcome measures of this study were the Brief Psychiatric Rating Scale and Nursing Observational Scale for Inpatient Evaluation.15 Another study contained two individual, double-blind trials of loxapine versus thioridazine for the treatment of chronic organic brain syndromes. One of these studies 32 Psychiatry 2008 [ O C T O B E R ] found loxapine at 10 to 150mg per day to be superior to thioridazine at 150 to 750mg per day for the treatment of chronic organic brain syndrome while the other demonstrated equal efficacy. The outcome measures were the Brief Psychiatric Rating Scale and Nursing Observational Scale for Inpatient Evaluation along with the Clinical Global Impressions Scale.16 Finally, one case report describes a patient who did not respond to higher-dose olanzapine, 20mg per day, but did respond to lower-dose loxapine, 45mg per day. Because rating scales for delirium were not utilized, equivalent doses of these medications were not established, and olanzapine is particularly sedating at higher doses, this case report is difficult to interpret.17 A brief case series of four patients with HIV-associated delirium demonstrated that molindone in doses of 40 to 140mg per day was effective in controlling delirium in each of the patients treated. Caution should be applied in coming to a conclusion from this report as the patients were on other typical antipsychotics at times, such as haloperidol and thioridazine, and no delirium rating scales were utilized.18 The evidence for use of typical antipsychotics in delirium is presented in Table 3. With the advent of atypical antipsychotics and their decreased risk of extrapyramidal side effects, there has been increased interest in using these agents for delirium. After clozapine, which clearly has serious limitations (lethal agranulocytosis) to its use for any disorder other than refractory schizophrenia or schizoaffective disorder, risperidone was the next atypical antipsychotic approved for use in the United States. An early case report in two patients with hypoxic brain injury demonstrated the potential capability of risperidone to be effective in treating delirium.19 After this, five separate studies in patients with a variety of underlying medical illnesses demonstrated the effectiveness of risperidone at doses ranging from 0.75mg per day to 3.1mg per day in the treatment of delirium with the majority of patients showing moderate to marked improvement of their delirium on the Clinical Global Impressions Scale, Brief Psychiatric Rating Scale, and Trzepacz Delirium Rating Scale. Common side effects of risperidone included sedation, dizziness, and extrapyramidal symptoms (EPS). The average length of treatment in these studies was approximately one week.20–24 In a small case series conducted in Israel, three elderly patients were administered risperidone and subsequently developed delirium. One of these patients was also receiving lithium at a therapeutic level, another was in the middle of a course of electroconvulsive therapy (ECT) treatment, and the last was mildly hyponatremic and receiving fluvoxamine and diuretics along with the risperidone. Clearly, other etiological factors for the delirium could have been operative.25 A doubleblind trial of risperidone and haloperidol demonstrated equivalence in treatments in efficacy and response rates. The mean daily dose of risperidone was 1.02mg and the mean daily dose of haloperidol was 1.71mg.26 The Trzepacz Delirium Rating Scale was again the main rating scale utilized. One large double-blind, placebo-controlled study using risperidone for the treatment of delirium in doses of 0.5mg to 4.0mg per day did not demonstrate efficacy for this agent. Nonetheless, a major confounding factor was the fact that the Positive and Negative Symptom Scale was used to measure delirium though this scale is not a measure of delirium specifically and measures multiple other aspects of mental functioning.27 Olanzapine would appear to have sufficient evidence to sustain a claim for delirium treatment. An early case report of the successful treatment of delirium in a cancer patient with olanzapine appeared in the literature in 1998.28 In two open trials of hospitalized patients using similar doses of olanzapine, the outcome was a 50-percent reduction in the

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Psychiatry - October 2008 Editor’s Message Editorial Advisory Board Contents Psych Rx Treatment of Migraine and the Role of Psychiatric Medications Play Therapy: A Case-based Example of a Nondirective Approach Delirium and Antipsychotics: A Systematic Review of Epidemiologyand Somatic Treatment Options Severely Mood-disordered Youth Respond Less Well to Treatment in a Community Clinic than Youth with Bipolar Disorder Beyond Informed Consent: The Ethics of Informing, Anticipating, and Warning Asthma: Wheezing, Woes, and Worries Classified Advertising Journal Watch Information for Authors

Psychiatry - October 2008

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