Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes followingmajor gastrointestinal surgery: a randomized clinical trial and systematic review
- Pearse RM, Harrison DA, MacDonald N, OPTIMISE Study Group
In Reply Dr Fleischhacker suggests that high dropout rates limit the generalizability of our findings. This effectiveness study included participants that clinicians selected as candidates for long-acting injectable antipsychotic medications (ie, they were expected to benefit from depot treatment because they were at risk of poor outcomes due to a history of poor adherence or substance abuse). Thus the findings should be generalizable to typical patients for whom treatment with long-acting injectable antipsychotics is considered. Fleischhacker speculates that some differences in extrapyramidal symptom ratings did not reach statistical significance due to low power.With a large enough sample, all such differencesbecomestatistically significant;however,weagree that small differences in adverse eventsmay be clinically important for individuals. Any results that did not meet statistical significancemust be considered relative to clinically and statistically significant differences (eg, the mean 2 kg weight gain with paliperidone palmitate vs the 1 kg weight loss with haloperidol decanoate). We plan to investigate possible differences in injection site pain, but it is already clear that any effect favoring one of the drugs did not result in an overall effectiveness advantage. Fleischhacker correctly points out that oral haloperidol rather than oral haloperidol decanoate was the comparator in the haloperidol-risperidone trial mentioned in our article. A correction accompanies this letter. Dr Suzuki suggests that the mean doses of paliperidone used formaintenance treatment inour trialmayhavebeen too high.His analysis,which initiated froma study about relative doses of antipsychotics that did not include paliperidone palmitate, suggests that themeanmaintenance dose of paliperidone palmitate in our study should have been approximately 50mgpermonth.Weare aware of no evidence to support this as a typicalmaintenance dose, which is less than half the recommendedmaintenance dose found in the paliperidone palmitate package insert. Because our study was not restricted to people with an acute exacerbation, it is not surprising that the participants were on average moderately ill. We used randomization to address measured and unmeasured factors, including baseline medications, that might theoretically advantage one group. Adjunctive psychotropics, excluding the sustained need for antipsychotic medications after 8 weeks, were allowed throughout the trial, and we found similar rates of starting new medications in the 2 groups for the following indications: anxiety (16.6% for paliperidone vs 15.2% for haloperidol); depression (19.3% for paliperidone vs 17.2% for haloperidol); agitation, excitement, or mania (8.3% for paliperidone vs 4.8% for haloperidol); aggression or violence (1.4% for paliperidone vs 0.7% for haloperidol); and insomnia (22.1% for paliperidone vs 24.8% for haloperidol). The study found that paliperidone palmitate and haloperidol decanoate were similar in avoiding efficacy failure. We could not rule out a clinically meaningful difference favoring one of the drugs, but did find significant differences in akathisia favoring paliperidone palmitate and in weight and prolactin levels favoring haloperidol decanoate.