Pharmacological interventions for pruritus in adult palliative care patients.

Background: Pruritus is not the most prevalent but one of the most puzzling symptoms in palliative care patients. It can cause considerable discomfort and has a major impact on patients' quality of life. In the field of palliative care, pruritus is a symptom occurring in patients with disparate underlying diseases and based on different pathologic mechanisms but ending in the same phenomenon. The pathogenesis of pruritus is complex and not fully elucidated. Thus, it is still very difficult to treat pruritus effectively. Evidence-based treatment approaches are needed.

Objectives: The objective was to evaluate the efficacy of different pharmacological treatments for preventing or treating pruritus in adult palliative care patients.

Search Methods: A systematic literature search up to January 2012 was performed and it was updated in August 2012. The following databases were searched: The Cochrane Library (CENTRAL, DARE, CDSR) (2012, issue 8 of 12); MEDLINE (1950 to August 2012); EMBASE (1980 to August 2012) and three other databases. In addition, we searched trials registries and checked the reference lists of all relevant studies, key textbooks, reviews, and websites, and contacted investigators and specialists in pruritus and palliative care regarding unpublished data.

Selection Criteria: We included randomised controlled trials assessing the effects of different pharmacological treatments on preventing or treating pruritus in palliative care patients.

Data Collection And Analysis: Two review authors independently assessed identified titles and abstracts. Three independent review authors performed assessment of all potentially relevant studies, data extraction, assessment of risk of bias and methodological quality. Results were summarised descriptively according to the different pharmacological interventions and the type of underlying pruritus. Where possible, results were presented in meta-analyses.

Main Results: In total, 38 reports comprising 40 studies and 1286 participants were included in the review. Altogether, 30 different treatments for pruritus in four different patient groups were included.The findings of this review indicated that the treatment of pruritus for palliative care patients is challenging and requires an individualistic approach. Results showed that effective therapeutic choices have to be guided by the pathophysiology of the pruritus. Various forms of pruritus occur, especially in the field of palliative care, and sometimes the origin of the pruritus is difficult to determine. Therefore, identifying the underlying cause of pruritus is of prime importance in order to develop tailored treatment plans, even if in palliative care the treatment is focused towards the symptom and not necessarily the underlying disease.Results show that in palliative care patients with pruritus of different natures, treatment with the drug paroxetine, a selective serotonin reuptake inhibitor, may be beneficial. For patients suffering from pruritus associated with HIV infection, indomethacin was described as the most effective drug, although the evidence was weak. For patients suffering from chronic kidney disease-associated pruritus, gabapentin may be an option. An alternative treatment for this patient group seems to be the κ-opioid receptor agonist nalfurafine, which has shown significant amelioration of pruritus and acceptable adverse effects. As they have exhibited a low incidence of adverse effects, rifampicin and flumecinol may be recommended for patients with cholestatic pruritus. The opioid antagonist naltrexone has been shown to offer a therapeutic alternative for patients suffering from uraemic or cholestatic pruritus. However, these drugs are often inappropriate in the palliative population because of the risk of reducing analgesia when giving high doses of naltrexone.

Authors' Conclusions: The findings of this review indicate that the number of systemic and topical drugs used for the different subforms of pruritus is increasing. Different interventions have been shown to be effective in the treatment of pruritus of different origins. Nevertheless, an optimal therapy for pruritus is constrained due to the limited understanding of crucial itch mediators and receptors in the various subforms of itch. Ideal antipruritic therapies are still lacking, especially for palliative care patients.This systematic review also indicates that there is insufficient evidence to give any concrete recommendations regarding treatment of pruritus in palliative care patients. Due to the very small sample sizes and poor methodological quality of the majority of studies that were included, the results of this review need to be interpreted with caution. Furthermore, the generalizability is questionable. Additional studies, and particularly carefully designed treatment trials, are needed to provide valid evidence for adequate treatment of pruritus in palliative care patients.