Dose equivalents for second generation long-acting injectable antipsychotics: The minimum effective dose method

Background: The concept of dose equivalence of depot medication is important for many scientific and clinical purposes. Methods: A systematic literature search on four second-generation antipsychotics available as long-acting injectable drugs and haloperidol was conducted. We used the minimum effective dose method which is based on randomized fixed dose studies where the smallest dose which was significantly more efficacious than placebo in the primary outcome was declared as minimum effective dose. We calculated equivalent doses from acute phase studies but we also reported the minimum effective doses found in relapse prevention studies. Results: The acute phase minimum effective doses/olanzapine equivalents were: aripiprazole lauroxil 441 mg (300 mg aripiprazole)/4wks/0.71; aripiprazole 400 mg/4 weeks/0.95 (aripiprazole maintena); paliperidone palmitate 25 mg/4 weeks/0,06; risperidone 25 mg/2 weeks/0,12; RBP-7000 90 mg/4 weeks/0,21; olanzapine 210 mg/2 weeks/1. Conclusions: The minimum effective dose method is an operationalized and evidence-based approach for determining antipsychotic dose equivalence which can also be applied to long-acting injectable formulations. Doses may not have been chosen low enough to find the truly minimum effective dose. Comparisons with other methods will be necessary to come to ultimate conclusions.