11 Therapeutic Equivalences in Long-term Antipsychotics

Abstract

Study Objectives

The concept of dose equivalence is very useful when it comes to using drugs. In the case of antipsychotics, the first comparison was established by Davis in 1974, called the classical comparison method. Subsequently, other methods have appeared, such as the minimum effective dose method, the dose response method, the consensus among experts such as consensus method by Gardner, and the Daily Dose method of the World Health Organization. In 2016, Leucht et al performed the meta-analysis comparing the equivalence by the alternative methods of second-generation antipsychotics orally, based on Olanzapine. However, therapeutic equivalences between injectable antipsychotics have not yet been made.

The objective of the study is to establish a pattern of therapeutic equivalences between long-acting antipsychotics, based on the method of the Defined Daily Dose (DDD).

Method

The DDD is the dose of the maintenance medium of a drug for its main indication in adults of 70kg. In the case of antipsychotics, psychosis is the most important indication. DDDs are different for each route of administration, especially if the bioavailability of the drug varies between one route and another. To establish the DDD of a drug, 3 measures are taken: firstly, the dose ranges of the drug approved by at least 1 major regulatory authority. Secondly, doses used in clinical trials. Thirdly, post marketing data on dose used in clinical practice when the drug is commercialized. Depot formulations are usually assigned the same DDDs as the ordinary oral dosage form. Based on the DDD according to the WHO classification at http://www.whocc.no/.

For comparison, Olanzapine 210mg was used as the main drug and equivalences were established from it. Therapeutic deposit of Aripiprazole (ARI), Flufenazine decanoate (FLU), Haloperidol Decanoate (HAL) Olanzapine pamoate (OLA), Paliperidone palmitate (PAL), Risperidone depot (RIS), and Zuclopenthixol decanoate (ZUC).

Results

The results will be shown in a 8x8 table.

Conclusions

DDD is available for almost all antipsychotics and is an accepted method as well as a clinical level as a researcher. They are based on a wide variety of data from different sources. Several studies have found a strong correlation between this method and other methods of equivalence. This method also has limitations. First, the DDDs were not established for the purpose of therapeutic equivalences. Secondly, the daily dose can be applied mainly to the efficacy of the drug, when the dose could cause some adverse effects.

The establishment of therapeutic equivalences may help when a clinician needs to change one long-term antipsychotic. This could reduce psychotic relapses. It may enhance therapeutic adherence avoiding undesirable side effects. On the other hand, long-acting antipsychotics have corroborated the adherence and decrease of relapses, which is why it is increasingly used as a good alternative to oral drugs.