Haloperidol Plus Promethazine for Psychosis Induced Aggression

A Cochrane review [Abstract] 1 included 6 studies with a total of 1367 subjects with psychosis-induced aggression.

• Haloperidol plus promethazine (H + P) vs. haloperidol alone: The combination treatment was clearly more effective (RR 0.65, 95% CI 0.49 to 0.87; 1 RCT, n=316) for the outcome not tranquil or asleep at 30 minutes. There were 10 cases of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.
• H + P vs. olanzapine: Both approaches were tranquillising. The combination of H + P seemed to be more effective, but the difference did not reach statistical significance (RR 0.60, 95% CI 0.22 to 1.61; 1 RCT, n=300). The risk of unwanted excessive sedation was less with the combination approach (RR 0.67, 95% CI 0.12 to 3.84; 2 RCTs, n=116).
• H + P vs. ziprasidone: The average sedation score (Ramsay Sedation Scale, RSS) was lower for the combination approach but not statistically significant (MD -0.1, 95% CI - 0.58 to 0.38; 1 RCT, n=60). The H + P combination appeared to cause less excessive sedation but the difference was not statistically significant (RR 0.30, 95% CI 0.06 to 1.43; 2 RCTs, n=111).
• H + P vs. haloperidol + midazolam: Average RSS scores suggest the combination of haloperidol and midazolam to be the most sedating (MD - 0.6, 95% CI -1.13 to -0.07, 1 RCT, n=60). The risk of excessive sedation was considerably less with H + P (RR 0.12, 95% CI 0.03 to 0.49; 2 RCTs, n=117). H + P seemed to decrease the risk of needing restraints by around 12 hours (RR 0.24, 95% CI 0.10 to 0.55; 1 RCT, n=60). It may be that use of midazolam with haloperidol sedates swiftly, but this effect does not last long.
• H + P vs. lorazepam: The combination treatment seemed to more effectively cause sedation or tranquillisation by 30 minutes (RR 0.26, 95% CI 0.10 to 0.68; 1 RCT, n=200). The secondary outcome of needing restraints or seclusion by 12 hours was not clearly different between groups, with about 10% in each group needing this intrusive intervention. Sedation data were not reported, however, the combination group did have less 'any serious adverse event' in 24-hour follow-up, but there were not clear differences between the groups.
• H + P vs. midazolam: Midazolam is more swiftly tranquillising of an aggressive situation than H + P (RR 2.90, 95% CI 1.75 to 4.8; 1 RCT, n=301). Midazolam seems to be swift and effective in tranquillising people who are aggressive due to psychosis. There was no difference in risk of serious adverse event overall (RR 1.01, 95% CI 0.06 to 15.95; 1 RCT, n=301). However, one out of 150 H + P patients had a swiftly reversed seizure, and one out of 151 midazolam patients had swiftly reversed respiratory arrest.

References

• Huf G, Alexander J, Gandhi P et al. Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database Syst Rev 2016;11():CD005146. [PubMed].