In their excellent paper Alexander et al (Reference Alexander, Tharyan and Adams2004) systematically conducted a comparison trial of intramuscular lorazepam and haloperidol-promethazine in violent or agitated patients. The authors utilised a prospective follow-up design and used proper diagnostic assessment measures, thus taking care of most of the methodological pitfalls that have plagued research in this area.

However, a few concerns about the study persist. Ideally, there is a need for a viable placebo arm to compare the efficacy of both interventions. A comparison of a new agent with a drug previously shown to be active without a placebo comparator is uninterpretable unless one agent is superior to the others. Concluding that a drug is efficacious without a placebo comparator can lead to an incorrect assumption of efficacy if neither the investigational drug nor the active drug was, in that trial, any better than placebo would have been if included. Introducing a drug into therapeutic use on the basis of such a trial would expose patients to a compound with no greater benefit than placebo (Reference Temple and EllenbergTemple & Ellenberg, 2000). A placebo is also important in the assessment of the safety profile, as it provides a base for determining which adverse events are truly related to the investigational drug. For these reasons, placebo-controlled trials are almost universally demanded by regulatory bodies to demonstrate efficacy for any pharmacological intervention.

The authors have not described any investigations carried out to exclude toxic states, epilepsy and other organic conditions. They failed to comment on vital parameters during and after administration of both interventions. They could have assessed the level of satisfaction of the treatment team with the intervention (Reference Petrack, Marx and WrightPetrack et al, 1996). They could also have applied any scale for aggression, agitation, alertness and psychopathology (Reference Battaglia, Moss and RushBattaglia et al, 1997).

Certain issues merit consideration before accepting the authors' conclusion. The better outcome of the haloperidol-promethazine group compared with the lorazepam group could be because the combination group had more patients with mania than the lorazepam group and the combination group had more moderately ill and less severely ill patients than the lorazepam group. In addition, details of additional medications were not mentioned. It remains possible that some improvement was due to additional medications in both groups.

The authors commented that 23 patients failed to sleep at all during the 4-h follow-up compared with only 8 in the combination group, which is difficult to understand from Table 2. There were some inconsistent findings in the paper: sleep outcome in the combination group at 120 min were 69% and 88% in Table 2 and Table 5, respectively. Similarly, there was a discrepancy in the number of patients in the combination group who were never tranquil (Results and Table 2).

Nevertheless, we feel that the authors have taken a useful step in this relatively neglected area. Further studies are required on the effectiveness of these interventions in the hope that better understanding can lead to better treatment of violent patients.