130 PART THREE | DELIRIUM Table 3. Incidence of therapy-related adverse events (intention-to-treat population). Adverse event Haloperidol (n= 49) Olanzapine (n= 49) Any grade Grade 3 Grade 4/5 Any grade Grade 3 Grade 4/5a All TRAEs, n (%) 16 (32.7) 10 (20.4) 0 13 (26.5) 4 (8.2) 1 (2.0) Sedation, n (%) 10 (20.4) 7 (14.3) 0 9 (18.4) 4 (8.2) 1 (2.0) EPS Tremors, n (%) 3 (6.1) 1 (2.0) 0 2 (4.1) 0 0 Muscle stiffness, n (%) 2 (4.1) 1 (2.0) 0 1 (2.0) 0 0 Dizziness, n (%) 0 0 0 1 (2.0) 0 0 QTc prolongation, n (%) 1 (2.0) 1 (2.0) 0 0 0 0 Abbreviations: EPS, extrapyramidal symptom; TRAE, therapy-related adverse event aGrade 5 TRAEs did not occur in both arms. Delirium-related distress Sixteen patients in each treatment arm completed the DEQ. Mean delirium-related distress level (on a 0-4 numerical rating scale) was 2.1 (SD, 1.4) in the olanzapine arm, and 2.3 (SD, 1.4) in the haloperidol arm. The mean delirium-related distress level rated by spouses and/or caregivers was 2.7 (SD, 1.1) in the haloperidol arm, and 3.0 (SD, 1.2) in the olanzapine arm. Mean delirium-related distress level rated by attending nurses was 0.9 (SD, 0.9) in the haloperidol arm, and 1.1 (SD, 1.1) in the olanzapine arm. Discussion This multicenter, phase III RCT demonstrated no statistically significant difference in efficacy between olanzapine and haloperidol for the treatment of delirium in hospitalized adult patients with advanced cancer. Treatment with olanzapine did not result in a better DRR or shorter TTR compared to haloperidol. This trial met criteria for early stopping due to futility. The management of delirium is complex because of the considerable heterogeneity in terms of etiology and clinical subtype [22, 23]. A number of brain neural networks and pathways have been implicated, but underlying pathophysiological mechanisms remain poorly understood [24, 25]. The complexity of delirium suggests that a variety of interventions is most likely needed, which combines both non-pharmacological and pharmacological strategies, as appropriate to the cancer trajectory and goals of care. The question remains whether antipsychotic drugs are clinically useful and safe for the treatment of delirium in patients with advanced cancer. If so, are atypical antipsychotics preferred because of their possibly better adverse effect profile and efficacy advantages in some patients? Collective data remain limited on the activity and safety of antipsychotic drugs for the treatment of delirium in patients with advanced cancer. A recently performed Cochrane
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