Treatment of terminal restlessness: a review of the evidence

Terminal restlessness is an important issue in the management of symptoms at the end of life with between 25% and 88% of dying patients exhibiting this condition. (1-5) The purpose of this review was to examine the empiric evidence about the pharmacological treatment for terminal restlessness. All available literature, in all languages, from 1966-2002 including randomized trials, concurrent observations, retrospective chart reviews, single case studies, clinical practice guidelines, expert consensus, single expert opinion articles, and editorials were reviewed as "best available evidence." Of the 72 articles reviewed, 14 met the criteria and were chosen for analysis. Despite the majority of authors recommending neuroleptic medications as a first or second line pharmacological treatment of restlessness, a number of studies demonstrated the effectiveness of other medications such as benzodiazepines (notably midazolam and lorazepam), or phenothiazines, either alone or in combinations. There is insufficient evidence to suggest that a single medication or class of medications is appropriate for terminal restlessness. There is a clear need for additional trials of neuroleptics, benzodiazepines, barbiturates, and combination protocols to determine which protocols are the most effective and have the least side effects.